Giant Onychomatricoma: a case report

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Volume 12 ● Number 3 ● July - September 2020

Anticoagulants in dermatological surgical practice

Effectiveness of 4% tranexamic acid cream and low-fluence QS Nd:YAG 1064-nm laser on melasma: a double-blind, randomized and controlled study

Pustular rash after dermal filler injection should not be interpreted as Herpes Simplex infection

Giant Onychomatricoma: a case report

www.surgicalcosmetic.org.br

SCIENTIFIC SUPPORT:

Surgical& Cosmetic Dermatology

Publicação Oficial da Sociedade Brazileira de DermatologiaPublicação Trimestral

www.surgicalcosmetic.org.br

Periodicidade TrimesTral

EDITOR-CHEFE Hamilton Ometto Stolf

Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas (SP),Brazil.Faculdade de Medicina, Universidade Estadual Paulista, Botucatu (SP),Brazil.

CO-EDITORES Bogdana Victoria Kadunc

Pontifícia Universidade Católica de Campinas, Campinas (SP), Brazil. Hospital do Servidor Público Municipal, São Paulo (SP), Brazil.

Ricardo Vieira Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.

Surg Cosmet Dermatol. | Rio de Janeiro | v. 12 | n. 3 | Jul-Set. 2020 | p. 193-294

ISSN: 1984-5510 Online ISSN: 1984-8773

Review Articles / Artigos de Revisão

Anticoagulantes na prática cirúrgica dermatológica 203 Anticoagulants in dermatological surgical practice Ivander Bastazini Junior, Marina Carrara Camillo Barbosa Uso dos probióticos em Dermatologia - Revisão 208 Use of probiotics in Dermatology - Review Célia Luiza Petersen Vitello Kalil, Christine Chaves, Artur Stramari de Vargas, Valéria Barreto Campos

Original Articles / Artigos Originais

Eficácia do creme com ácido tranexâmico a 4% e laser QS Nd: YAG 1064 nm de baixa fluência 215 no melasma: um estudo duplo-cego, randomizado e controlado Effectiveness of 4% tranexamic acid cream and low-fluence QS Nd:YAG 1064-nm laser on melasma: a double-blind, randomized and controlled study Dhesi Ariembi, Retno Indar Widayati, Diah Adriani Malik

Estudo clínico do carcinoma basocelular facial: estudo retrospectivo de 5 anos de 70 casos 222 em um hospital universitário Clinical study of basal cell carcinoma on the face: a 5-year retrospective study of 70 cases in a teaching hospital Welly Wijayanti, Khairuddin Djawad

Estudo comparativo da aplicação regional de peeling de fenol e toxina botulínica: 230 ainda um tratamento acessível e eficiente para rugas periorais e periorbitárias Regional phenol peel and botulinum toxin: still an efficient and affordable treatment for periorbital and perioral wrinkles Daniela Alves Pereira Antelo, Jaqueline Barbeito de Vasconcellos, Rosane Orofino-Costa

O comportamento do consumidor de protetor solar: influência dos aspectos sensoriais 237 no hábito de fotoproteção e motivação de compra Sunscreen’s consumer behavior: influence of sensory aspects in the photoprotection habit and purchase motivation Mariane Massufero Vergilio, Pedro Alves da Rocha Filho

Avaliação do reconhecimento das expressões faciais em pacientes com melasma facial: 245 um estudo transversal Evaluation of facial expression recognition in patients with facial melasma: a cross-sectional study Maria Laura Marconi França, Hélio Amante Miot, Juliano Vilaverde Schmitt, Thales Vianna Coutinhoß

Uso de nutricosmético à base de proteoglicanos em alopecias não cicatriciais 251 em crianças e adolescentes Use of nutricosmetic based on proteoglycan in non-cicatricial alopecia in children and adolescents Rogério Nabor Kondo, Airton Dos Santos Gon, Paulo Muller Ramos

Tolerância à dor e resultado estético da remoção de acrocórdons com crioterapia 258 de contato em comparação à eletrocoagulação Pain tolerance and aesthetic result of removing acrochordons with contact cryotherapy compared to electrocoagulation Flávia Trevisan, Gabriela Ferreira Kalkmann, Emerson Luis Batista Filho

Surgical & Cosmetic Dermatology

Publicação Oficial da Sociedade Brazileira de DermatologiaJULY / AUGUST / SEPTEMBER 2020 l VOLUME 12 l NUMBER 3ISSN:1984-5510Online ISSN: 1984-8773

201

Table of contents / Sumário

Surg Cosmet Dermatol. Rio de Janeiro v.12 n.3 jul-set. 2020 p. 201-2.

Infiltração intralesional de corticosteroide x laser fracionado ablativo associado 264 a drug delivery de corticosteroide no tratamento de queloides: um estudo comparativo Intralesional corticosteroid injection versus ablative fractional laser associated with corticosteroid drug delivery in the treatment of keloids: a comparative study Thais Furtat Marques, Manoella Freitas Santos, Isadora da Luz Silva, Fabiane Kumagai Lorenzini, Ana Paula Dornelles da Silva Manzoni

Diagnostic Imaging / Diagnóstico por Imagem

Melanoma sobre nevo spilus 270 Melanoma on nevus spilus Bruna Ramos da Silva, Flávia Thomé França, Nathalia Fahl Cicotti, Maria Paula Barbieri D’elia, Jorge Logan Furtado Costa

How I do? / Como eu faço? Reconstrução de defeitos auriculares extensos após cirurgia micrográfica de Mohs: 274 relato de dois casos clínicos Reconstruction of extensive ear defects after Mohs micrographic surgery: two case reports Raíssa Rigo Garbin, Fernando Eibs Cafrune, Gabriela Leiria Bencke, Ciro Paz Portinho

Técnica de penteado em fileiras com elásticos para realizaçao de procedimentos 278 em couro cabeludo Strips hairstyle technique with elastic hair bands for scalp procedures Leticia Arsie Contin

Case Reports / Relatos de Caso

Erupção cutânea pustulosa após injeção de preenchimento dérmico não deve ser 281 interpretada como infecção por Herpes Simplex Pustular rash after dermal filler injection should not be interpreted as Herpes Simplex infection Marina Landau, Erica M. Lin, Carlos Wambier

Onicomatricoma gigante: relato de um caso 286 Giant Onychomatricoma: a case report Manoella Freitas Santos, Maria Emilia Vieira de Souza, Laura Luzzatto, Leonardo Albarello, Renan Minotto

Miíase por Dermatobia hominis simulando lipoma 290 Myiasis due to Dermatobia hominis simulating lipoma Ana Beatriz Antunes Funes, Ana Carolina Gama Martins, André Matheus Camelo Neves, Marilda Aparecida Milanez Morgado de Abreu,

Ana Cláudia Cavalcante Espósito

Table of contents / Sumário

202


203

Review ArticlesAuthors:Ivander Bastazini Junior1

Marina Carrara Camillo Barbosa1

1 Post-graduate - Dermatology, Instituto Lauro de Souza Lima, Bauru, São Paulo, SP - Brazil

Corresponding author:Marina Carrara Camillo BarbosaRod. Cmte. João Ribeiro de Barros, s/n Distrito Industrial Marcus Vinícius Feliz Machado - Bauru (SP)CEP: 17034-970E-mail: [email protected].

Receipt date: 27/07/2020 Approval date: 29/05/2020

Study conducted at the Lauro de Souza Lima Institute, Bauru, São Pau-lo, (SP), Brazil

Financial Support: None.Conflict of Interest: None.

Anticoagulants in dermatological surgical practiceAnticoagulantes na prática cirúrgica dermatológica


DOI: http://www.dx.doi.org/10.5935/scd1984-8773.20201233659

ABSTRACTinTroducTion: In the last decades, anticoagulants have become more frequent in the popu-lation and younger age groups. Objective: This article aims to address the risk of the most used anticoagulant medications in dermatological surgeries. Methods: We reviewed the most common anticoagulant medi-cations. Results: The pre-surgical consultation performed correctly, emphasizing the patient's clinical history (including renal function in cases of use of new oral anticoagulants), the anatomical site addressed, and the surgical treatment schedule is essential for a satisfactory outcome. Conclusions: The use of anticoagulant medications is increasingly common in medical prac-tice. In patients receiving anticoagulant medications, strict adherence to good surgical prac-tices is essential. Special attention to adequate hemostasis of the surgical field, adequate and compressive dressings and postoperative care must be given. The patient should be adequately informed about the most significant risks to which he is subject.Keywords: Dermatology; Anticoagulants; Surgery

RESU MOIntrodução: Nas últimas décadas, o uso de anticoagulantes vem se tornando mais frequente na população e em faixas etárias mais jovens. objetIvo: O objetivo desse artigo é abordar o risco das medicações anticoagulantes mais utilizadas em cirurgia dermatológica. Métodos: Foi realizada revisão das medicações anticoagulantes mais utilizadas. Resultados: A consulta pré-cirúrgica realizada adequadamente, com ênfase ao histórico clínico do paciente (incluindo função renal nos casos de uso dos novos anticoagulantes orais), a localização anatômica abordada e a exata programação do tratamento cirúrgico são essenciais para um desfecho adequado. ConClusões: A utilização de medicações anticoagulantes é cada vez mais frequente na prática médica. Em pacientes recebendo medicações anticoagulantes é essencial a estrita adesão às boas práticas cirúrgicas, com es-pecial atenção à hemostasia adequada do campo cirúrgico, aos curativos adequados e compressivos e aos cuida-dos pós-operatórios, sendo o paciente devidamente informado sobre os maiores riscos aos quais está sujeito.Palavras-chave: Anticoagulantes; Centro cirúrgico hospitalar; Dermatologia

INTRODUCTIONIn the last decades, anticoagulant use has become more

frequent in the population and younger age groups. This class of drug, which was initially limited to vitamin K inhibitors and acetylsalicylic acid (ASA), grew with the introduction of new antiplatelet agents and new oral anticoagulants (NOAC). These new medications have their pharmacological profile and drug interactions, and they are very different from their predecessors. The dermatological literature on the anticoagulant’s impact on the surgical procedures performed by dermatologists is scarce. Furthermore, the international “guidelines” on anticoagulation are unspecific, considering all procedures as low bleeding risk, which, in the end, can lead to inappropriate conduct in the face of more invasive interventions performed by the dermatological surgeon. This article aims to review of the most used anticoa-gulant medications and their risks for dermatological surgeries.

WarfarinWarfarin is a vitamin K epoxy reductase (VKOR) inhibi-

tor. It starts to act in 90 minutes and has a half-life from 36 to 42 hours (Table 1).1 It has been one of the most widely used anti-coagulants for decades. However, due to the narrow therapeutic window and the INR volatility, recent studies showed that only 61% of patients undergoing treatment remained on the desi-red therapeutic target.2,3 Due to its intense protein binding and metabolism by cytochrome P2C9, many drugs and supplements interfere with its action. Administration of vitamin K or fresh frozen plasma can reverse its effect.

Hemorrhagic events are the most frequent adverse event, and their occurrence is closely linked to INR values, especially when they are higher.4,5 Previous studies suggest that dermato-logical surgeries can be performed with a lower risk of hemor-rhagic complications in patients using warfarin, provided that the INR value is lower3,5 (Table 2), with special attention to intraoperative hemostasis.4 Two other studies assessing patients who underwent surgery with a low bleeding rate using warfarin found a risk of bleeding ranging from 2.28% to 2.5%.5,6

For many years, warfarin suspension and the use of bri-dging therapies with heparin have been recommended preope-ratively. Currently, the literature strongly recommends not using these substitutions for dermatological surgeries due to the in-creased bleeding risk (9.6% vs. 2.5% while maintaining warfarin) and thromboembolic phenomena.6,7

Acetylsalicylic acidThe acetylsalicylic acid (ASA) is an irreversible inhibi-

tor of cyclooxygenase,1 which hinders platelets from producing thromboxane A2, promoting their aggregation, vasoconstriction, and increased activation.8 It has a rapid onset of action (30-40 minutes) and a short half-life (three hours) (Table 1). The effect is reversible only after platelet renewal. Although some authors have described an increased risk of postoperative bleeding with ASA,9 others found a slight risk (1.42%)6 or did not find increa-sed bleeding when using acetylsalicylic acid and other non-hor-monal anti-inflammatory drugs.5,10

ClopidogrelClopidogrel is an irreversible platelet adenosine diphos-

phate P2Y12 receptor inhibitor, activated after vascular injuries or plaque ruptures. It has an onset of action in two hours and a half-life of six hours.

Drugs metabolized by cytochrome P450 interfere with clopidogrel metabolism by decreasing antiplatelet activity (e.g., proton-pump inhibitors).

Some authors describe a 28-fold increased risk of severe bleeding in patients using clopidogrel compared to non-anticoa-gulants, and a six-fold increased risk compared to patients using acetylsalicylic acid.9 Studies comparing the association of clopi-dogrel with other antiplatelet agents (ASA) found an eight-fold increased risk of severe bleeding complications, compared to monotherapy.8 Koenen et al., in a prospective multicenter study with 9,154 surgical procedures, found a bleeding risk of 3.57% in individuals taking two anticoagulants (ASA and clopidogrel); 2.13% for the association of ASA and coumarins; and 1.32% for of ASA combined with heparin. Moreover, those not anticoagu-lated presented a risk of hemorrhagic complications of 0.55%.11

TicagrelorTicagrelor is a P2Y12 receptor inhibitor with the onset

of action (15-30 minutes) and recovery of platelet function (72 hours) faster than clopidogrel. However, some studies suggest a higher risk of hemorrhagic events (central nervous system and gastrointestinal tract). It presents a 6-8 hour half-life (Table 1).8

PrasugrelPrasugrel is another irreversible platelet receptor P2Y12

inhibitor, also with faster action than clopidogrel. It has an onset of action in 15-30 minutes and a half-life of 2-15 hours (Table 1). Its maximum antiplatelet effect occurs within 48 hours, and reco-very occurs gradually after two days of medication suspension.8

DipyridamoleDipyridamole is a phosphodiesterase inhibitor used as a

coronary vasodilator. It has an antiplatelet effect due to decrea-sed platelet aggregation and vasodilation. As a single agent, it does not increase the risk of bleeding.8

NEW ORAL ANTICOAGULANTSRivaroxabanRivaroxaban is a direct factor Xa inhibitor, reversibly

blocking the conversion of prothrombin to thrombin.12 It has an onset of action between two and four hours and a half-life of 5-12 hours (Table 1). Its elimination is mainly renal.8

It is administered in fixed doses and does not require routine control due to predictable pharmacodynamic and phar-macokinetic characteristics.8

There are no specific laboratory tests for monitoring, but, in emergencies, the activated partial thromboplastin time (APTT) and the prolonged prothrombin time (PT) can be used qualitatively to assess Factor Xa inhibitors.1

204 IB Junior, Barbosa MCC


It undergoes hepatic metabolism through the cytochro-me CYP3A4/5 and CYP2J2 pathways, revealing important drug interactions. Azoles, cyclosporins, and erythromycin increase the anticoagulant effects. Phenytoin and rifampicin have the opposite effect, reducing this action. Also, P glycoprotein (P-gp) inhibitors lead to prolonged and increased anticoagulant action (verapamil, amiodarone, and quinidine) due to the competitive inhibition of renal clearance.12

There is no specific antidote, but prothrombin complex concentrate can be administered in emergencies.1 Two new agents for reversing anticoagulant effects are under investigation (andexanet alfa and ciraparantag), the first of which has already been approved by the Food and Drug Administration (FDA) in May 2018.1,13,14

ApixabanApixaban is a direct reversible factor Xa inhibitor, whose

mechanism of action is identical to rivaroxaban and edoxaban.1,8 It has fast absorption (1-3 hours) and a half-life of 10 to 15 hours (Table 1). Its excretion is renal (25%) and biliary, and cytochrome P 450/3A4 and enzymatic pathway P-gp metabolizes it. There-fore inhibitors of these pathways increase blood levels of the me-dication (interactions similar to rivaroxaban).1,8 It also does not require routine monitoring, and patients with mild or moderate renal and hepatic dysfunction do not need dose correction. An-dexanet alfa recently obtained authorization as a reverse agent from the FDA.1,13

EdoxabanEdoxaban is the newest direct factor Xa inhibitor.1,12 It

has an identical mechanism of action to other factor Xa inhibi-tors. However, cytochrome P 450 poorly metabolizes it, thus re-ducing the risk of drug interactions.1,12 Furthermore, medicines that are metabolized by the enzymes of the P-gp system interfere with their effectiveness.

DabigatranDabigatran is a direct thrombin inhibitor by constraining

factor IIa1 and reversibly blocking the fibrinogen conversion to fibrin.1,8,12 It starts to act in 1-3 hours and has a half-life of 8-17 hours (Table 1). The kidneys excrete it (80%) and, thus,

renal dysfunctions can prolong its half-life, being contraindicated in severe renal changes (creatinine clearance <30 ml/min).1,8,12 Cytochrome P does not metabolize it; however, the glycopro-tein P (P-gp) inhibitors can raise its plasma levels.

Like other new oral anticoagulants, routine monitoring is unnecessary, but the thrombin time (TT) can be used to infer its effect.1 In emergencies, hemodialysis can be used to reduce its action. More recently, idarucizumab has been approved in Euro-pe as a reversing agent.1,15 Ciraparantag has also been suggested for this purpose.14

ANTICOAGULANTS AND ANTIPLATELETS IN SURGICAL PRACTICEThe use of anticoagulant medications is increasingly

common in medical practice. Consequently, the dermatological surgeon faces daily the need for invasive procedures in patients using one of these medications. In this context, careful preopera-tive anamnesis focused on daily medications and clinical indica-tions for such use is essential. It’s vital to measure the complexity of the planned procedure, together with the bleeding risk.

There is significant controversy in the literature about the degree of complexity of surgical procedures performed by the dermatologist. However, in general, we must consider those with large detachments and with large tissue movements as pro-cedures with higher bleeding risk. Anatomical location is also directly linked to this risk, with the incidence of bleeding com-plications in the nose being much more frequent than in other areas of the head and neck region (21% x 6%).16

There are no specific criteria in the dermatological li-terature on the definition of surgical bleeding. Some authors consider everything from mild events, such as changing the dres-sing, to severe events, ranging from surgical revision and necro-sis to blood transfusion. 11 It can explain different numbers and different interpretations. In general, it is accepted that the risk of bleeding in dermatological surgeries performed on patients who are not using any medication is low, being estimated at approximately 1%.8,11,13 The highest bleeding risk is demonstra-ted in patients undergoing surgical procedures under the use of anticoagulants.8,11 The literature describes that the association of two or more agents significantly increases hemorrhagic even-ts.8,11,12 However, the increased risk of thromboembolic events associated with discontinuation of anticoagulant medications is well documented.17,18,19 The magnitude of potential events that present high morbidity and mortality dramatically surpasses the risk of hemorrhagic complications at the surgical site in derma-tological surgery.

Therefore, the pre-surgical consultation performed pro-perly with an emphasis on the patient's clinical history (inclu-ding renal function in cases of new oral anticoagulants use), the anatomical location addressed, and the exact surgical schedule treatment is essential for a satisfactory outcome. Whenever feasi-ble, it’s crucial to consider reconstructions with the least possible detachment,18 mainly for complex and riskier areas such as the face. At that time, medications used prophylactically can be dis-continued for procedures with higher hemorrhagic potential.

Anticoagulants and dermatological surgery 205


Table 1: Pharmacological characteristics of anticoagulants

Anticoagulant Onset of action Half-life

Warfarin 90 minutes 36 to 42 hours

Acetylsalicylic acid 30 minutes 3 hours

Clopidogrel 150 minutes 6 hours

Ticagrelor 15 minutes 6 to 8 hours

Prasugrel 15 minutes 2 a 15 hours

Dipyridamole 10 minutes 3 hours

Rivaroxaban 120 minutes 5 to 12 hours

Apixaban 60 minutes 10 to 15 hours

Edoxaban 60 minutes 10 to 15 hours

Dabigatran 120 to 180 minutes 8 to 17 hours

Regarding warfarin, a multicenter study with 9,154 sur-gical procedures 11 demonstrated the INR value as a significant factor for the bleeding risk in multivariate analysis. In the uni-variate analysis, the study found that, with a lower INR,1,3 the risk of bleeding was 0.46%; and with a higher INR,1,3 the risk of bleeding increased to 3.7% (p<0.0001).

Syed et al.4 reported a bleeding risk of 60% with INR >3.5 and 27% for INR <3.5. However, the withdrawal of war-farin increases the risk of thromboembolism, in addition to the rebound hypercoagulability state observed when it is interrup-ted.8 Bridging therapies with heparin are a common practice in moments of warfarin suspension. However, there is an extensive demonstration of increased bleeding events,6,8,20,21 and currently it is not advised in dermatological surgery.22 It is currently con-sidered that INR <3 does not contraindicate the dermatological surgery, even those with more complex reconstructions such as flaps or grafts.8,18,25 If the INR is >3, it is suggested to postpone the surgery until the INR can be within the safety margin.8,18

The use of clopidogrel increases the risk of hemorrhagic events with data ranging from 2.86% to 9%.9 Acetylsalicylic acid increased the risk from 1.42% to 2-3%.8,9 Other authors have not found an increased risk of bleeding with the ASA use com-pared to controls.5,10 The risk of severe ischemic events and even death with the interruption of these medications is abundant.18,23

Therefore, it is currently recommended not to interrupt medi-cation in patients on antiplatelet monotherapy,5,8,18 except for

those with exclusively preventive indication.8 In such cases, they should be suspended seven to 10 days before the surgery date. In cases of a combination of two antiplatelet agents and proce-dures with a higher bleeding potential, one should evaluate the possibility of operating after the patient is on monotherapy.11 If not possible, the surgical procedure is performed without inter-rupting the medications.24

Regarding the new oral anticoagulants, we need to con-sider three main factors in the pre-surgical evaluation: the extent of the surgical procedure, the bleeding risk, and the patient's renal function. The bleeding risk is similar to that of warfarin. Some guidelines, such as the European Heart Rhythm Asso-ciation (EHRA), consider unnecessary to interrupt NOAC in superficial surgery in patients with normal kidney function (Table 2).12,25 For more aggressive surgeries, it is recommended to interrupt the medication 24 hours before the procedure and not restart it before one hour after the procedure, due to predic-tability and short half-lives.11,24 In patients with creatinine clea-rance <30 ml/minute, the medication interruption time should be longer.1

Strict adherence to good surgical practices is essential in patients receiving anticoagulant medications, paying particular attention to adequate hemostasis of the surgical field, proper compressive dressings, and postoperative care. It’s also important to properly inform the patient about the highest risks they are subject to. l

206 IB Junior, Barbosa MCC


Table 2: Recommendations of anticoagulants in dermatological surgical practice

Anticoagulant Recommendation

General orientations

1. Medicines and supplements with potential anticoagulant and / or antiplatelet action in prophylactic use can be suspended seven days before surgery.

2. Medications used for medical indication (previous heart attack, stroke) should be maintained.3. Special attention is paid to intraoperative surgical techniques to control bleeding, in addition to occlusive

dressings for an adequate time.

Warfarin1. One week before surgery, request INR. If INR is >3.5, weigh the risk / benefit of the surgery immediately and if

possible postpone the procedure until the INR is within the safety margin (2-3, 5).

Acetylsalicylic acid1. Do not suspend.2. If prophylactic or analgesic use, it can be discontinued 7- 10 days before the procedure.

Clopidogrel, Ticagrelor and Prasu-grel

1. Do not suspend

Dipyridamole 1. Do not suspend

Dabigatran, Rivaroxaban, Apixaban 1. If surgery with greater bleeding potential, discontinue only the dose prior to the day of surgery.

Anticoagulants and dermatological surgery


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AUTHOR'S CONTRIBUTION:

Ivander Bastazini Junior | 0000-0003-0300-1263Statistical analysis; approval of the final version of the manuscript; study design and planning; preparation and writing of the ma-nuscript; data collection, analysis, and interpretation; active participation in research orientation; intellectual participation in pro-paedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Marina Carrara Camillo Barbosa: 0000-0001-8906-0242Statistical analysis; approval of the final version of the manuscript; study design and planning; preparation and writing of the ma-nuscript; data collection, analysis, and interpretation; active participation in research orientation; intellectual participation in pro-paedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Review ArticlesAuthors:Célia Luiza Petersen Vitello Kalil 1 Christine Chaves 2 Artur Stramari De Vargas 2 Valéria Barreto Campos 3

1 Célia Kalil Clinic, Porto Alegre (RS), Brazil.

2 Farmatec - Compounding Pharmacy, Porto Alegre (RS), Brazil.

3 Valéria Campos Clinic, Jundiaí (SP), Brazil.

Corresponding author:Clínica Célia Kalil Rua Padre Chagas, 230 Moinhos de VentoPorto Alegre (RS)90570-080E-mail: [email protected]

Receipt date: 20/07/2020Approval date: 07/09/2020

Study conducted at the Célia Kalil Clinic, Porto Alegre (RS),


Use of probiotics in Dermatology - ReviewUso dos probióticos em Dermatologia - Revisão


RESU MOTem crescido o número de evidências dando suporte à existência de uma correlação “eixo in-testino-pele”. Há indícios também de que a modulação da microbiota intestinal pode ter um papel importante nas doenças dermatológicas. Estudos têm mostrado que o uso de probióticos pode ter efeitos benéficos no tratamento de doenças de pele com origens inflamatórias, como dermatite atópica, acne, entre outras. Todavia, não há uma padronização sobre em que doses ou quais espécies devem ser utilizadas para os tratamentos. Este artigo tem o objetivo de elaborar um panorama a respeito do uso de probióticos como tratamento de doenças dermatológicas, com foco em mecanismos de ação e resultados clínicos relatados na literatura.Palavras-chave: Dermatopatias; Pele; Probióticos

ABSTRACTThe number of evidence supporting the existence of a “gut-skin axis” correlation has grown. There is also a suggestion that the intestinal microbiota modulation may play an essential role in dermatological dis-eases. Studies have shown that probiotics' oral use can have beneficial effects in treating skin diseases with inflammatory origins such as atopic dermatitis, acne, and others. However, there is no standardization as to what doses or species should be used for the treatments. We provide an overview of the use of probiotics as a treatment for dermatological diseases, focusing on mechanisms of action and clinical results reported in the literature.Keywords: Probiotics; Skin; Skin diseases

208


Use of probiotics in Dermatology 209


Table 1: Clinical studies using probiotics

Title Dermatological disease Treatment Result

A randomized trial of Lactobacillus plantarumCJLP133 for the treatment of atopic dermatitis19 Atopic dermatitis

Two daily doses of L. plantarum 5x109UFC for 12 weeks

Reduction of the SCORAD index significantly higher than the placebo group with a reduction in eosinophil counts and levels of IFN-gamma and IL-4 at the end of treatment.

Lactobacillus16 plantarum IS-10506 supplementa-tion reduced SCORAD in children with atopic dermatitis16

Atopic dermatitis

Two daily doses of L. plantarum 10x109UFC for 12 weeks

SCORAD and IL-4, INF-gamma, and IL-17 levels were significantly lower at the end of the study in the treated group compared to placebo. IgE levels have not changed sig-nificantly.

Effects of probiotics on atopic dermatitis: a ran-domized controlled trial17 Atopic dermatitis

Two daily doses of L. fermentum VRI-033 PCC 1x109UFC for eight weeks

Significant reduction in the SCORAD index in the treated group compared to placebo.

Children with atopic dermatitis show clinical improvement after Lactobacillus exposure18 Atopic dermatitis

A daily dose of L. paracasei 2x109UFC, L. fermentum 2x109UFC or a mixture of L. paracasei and L. fermentum 4x109UFC for three months

The treated groups showed a signif-icant reduction in the SCORAD index and an improvement in the quality of life indices compared to placebo. There was no significant difference between groups in the reduction of IgE levels.

Supplementation with Lactobacillus rhamnosus SP1 normalizes skin expression of genes implicat-ed in insulin signaling and improves adult acne26

Acne

Daily dose of L. rhamnosus SP1 3.0x109UFC for 12 weeks

Significant improvement in the appearance of acne on the skin. Normalization of the expression of genes related to insulin signaling, without this effect in the placebo group.

Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut39 Psoriasis

Daily dose of B. infantis 35624 10 × 109 CFU for eight weeks

Significant decrease in plasma levels of TNF-a and C-reactive protein, when compared to placebo.

Clinical Evidence of Effects of Lactobacillus plantarum HY7714 on Skin Aging: A Random-ized, Double Blind, Placebo-Controlled Study53

Rejuvenation

Daily dose 10 × 109 CFU/day of L. plantarum HY7714 for three months

Reduction in transepidermal water loss, in the depth of wrinkles, and increase in skin brightness after treatment. Significant 21.73% increase in skin elasticity in the treated group compared to placebo.

INTRODUCTIONThe importance of the human microbiome for health

has been extensively researched in the last decade. Studies have shown that the microbiota and the host share a positive depen-dency, and the disruption in the balance between them can have significant consequences.1 In 2001, the World Health Organiza-tion (WHO) defined probiotics as living microorganisms that benefit humans and animals when consumed in adequate quan-tities.2

The intestinal microbiome strongly influences the host’s immune system by protecting against external pathogens and initiating immunoprotective responses.3 Thus, changes in the in-testinal microbiome can lead to the development of inflamma-tory or autoimmune diseases in organs distant from the intesti-ne, such as the skin.3 A considerable change in the relationship between the microorganisms that inhabit the intestine charac-terizes the intestinal dysbiosis, as well as the expansion of new

bacterial groups, generating an imbalance in the microbiome and possible clinical effects in the human body.4 The number of evidence pointing to a correlation between the disease and intestinal dysbiosis has increased in common inflammatory der-matological diseases, such as atopic dermatitis (AD), acne vulga-ris, psoriasis, rosacea, and even melasma (Table 1). Also, there is evidence that some peptide-secreting cells with regulatory func-tion present in the skin, brain, and intestine would have the same embryonic origin in the ectoderm.5 This type of information corroborates and supports the existence of the “skin-gut axis”6 and “gut-brain-skin axis”, considering that the emotional state can influence the individual’s inflammatory state.7 Furthermo-re, recent research and hypotheses have suggested that the main mechanism by which the skin and the intestine microbiota can affect each other is through modulation of the endocrine and immune system.3

210 Kalil CLPV, Chaves C, De Vargas AS, Campos VB


The use of probiotics to manipulate the intestinal flora and thus obtain positive results in organs distant from the in-testine, such as the skin, is an old practice. However, there is no standardization regarding which doses or species should be used for treatments. This study aims to overview the use of probio-tics as a treatment for dermatological diseases, focusing on me-chanisms of action and clinical results reported in the literature. METHODS

In April 2020, we researched the PubMed database for publications covering the use of probiotics in the treatment of atopic dermatitis, acne, psoriasis, rosacea, aging, and melasma. Studies explaining the mechanism of action and clinical trials were prioritized, including original articles and reviews or me-ta-analyzes regarding the topics covered.

Atopic dermatitisExcessive colonization of pathogenic bacteria on the skin

due to epidermal barrier dysfunction and immune deregulation that affects patients characterizes the AD.8 There is a reduction in the microbiome’s diversity,8,9 mainly during episodes of wor-sening of the disease, 9 in addition to the high colonization by bacteria such as Staphylococcus aureus, which is directly related to the severity of the disease.10 In the same direction, effective treat-ments were associated with the microbiota’s re-colonization and greater diversity of bacteria.8 Evidence suggests a connection between the disease and microbiota dysbiosis, without a specific invading pathogen, in addition to the already known disorders characteristic of atopic dermatitis, such as filaggrin genes muta-tions and Th-2 response deregulation.9

Modulation of the intestinal microbiota has emerged as an alternative in treating atopic dermatitis since it is related to the clinical disease’s outcome. A study showed that children with eczema associated with IgE have a lower proportion of bifidobacterium species and less microflora’s diversity during childhood.11 Another study revealed that the early colonization of the intestine by Escherichia coli, during the second month of life, could bring long-term health benefits, since a lower in-cidence of atopic dermatitis was noticed in colonized patients when they reached six years.12

AD treatment in children using probiotics has been wi-dely studied in recent years. Although the results found may be divergent, a recent meta-analysis showed that intestinal modu-lation in children could reduce the values of Scoring Atopic Dermatitis (SCORAD).13 Still, information about the effective dose, the best time for administration, and which strains are most effective for the treatment remains unclear.14

A literature review assessed different complementary and integrative therapies (CIT) to treat atopic dermatitis in chil-dren.15 The study observed that supplementation of probiotics remains the best CIT validated by studies for the childhood AD treatment.

The most robust evidence is related to treatment with Lactobacillus plantarum and Lactobacillus fermentum in children aged 12 months or older. Two different randomized clinical trials evaluated each probiotic, with a duration of 12 months. The stu-

dies showed a reduction in SCORAD when administered alone, without other probiotics strains.16-19 The improvement was cli-nically significant because, on average, an improvement of 8.7 points on the SCORAD scale resulted in an improvement of 1.0 point on the global severity scale. However, although another study on the treatment with L. plantarum has not shown effec-tiveness.20 Nevertheless, the latter lasted only six weeks while the others lasted 12 weeks, potentially indicating the beneficial effect of longer treatments.

AcneAcne is a dermatological disease related to the piloseba-

ceous unit. It can manifest itself in an inflammatory form, with papules and pustules, or non-inflammatory, with open or closed comedones. Overproduction of sebum, follicular hyperkeratini-zation, and increased secretion of pro-inflammatory cytokines characterize the condition.21

Several factors may be related to the onset of the disease. Western carbohydrate diets have a well-established relationship with acne.22 High glucose loads induce insulin and insulin-like growth factor (IGF -1) production, promoting sebocyte and keratinocyte proliferation, and causing the lipids production in the sebaceous glands.23 The Cutibacterium acnes bacteria role in acne’s pathogenesis has been widely studied, although it has not been completely elucidated. Just as the intestinal flora can induce IGF-1,24 it has been shown that C. acnes can stimulate the IGF-1 system/ IGF-1 receptors on the skin.25 Thus, it can be suggested that an imbalance of the intestinal flora may lead to a higher production of sebum and higher colonization of the skin by C. acnes, disturbing the close balance between the skin flora’s members and creating a disease’s synergistic cycle.

Oral supplementation of probiotics can be an adjuvant therapy in acne treatment. A study with humans observed that the consumption of Lactobacillus rhamnosus SP1 3x109 UFC/day improved the acne appearance on the adults’ skin. The therapy could normalize the expression of genes related to insulin signa-ling, and this change was not seen in the control group.26 Also, a clinical study assessed the synergistic effect of probiotics and minocycline consumption in the treatment of acne compared with the probiotic and antibiotic alone. All groups showed clini-cal improvement, but the group treated with the association had the lowest number of total lesion, with a significant difference from the other two groups. Also, two patients in the minocycli-ne-treated group had to leave the study because they had vaginal candidiasis, and the probiotic supplementation was an option for possible prevention of adverse events secondary to chronic antibiotic use.27

The use of lactobacilli topically can also be beneficial in reducing acne symptoms. In vitro studies have shown that some probiotics strains can inhibit C. acnes and other non-beneficial species through bacteriocins’ secretion.28 In vitro and in vivo stu-dies with Streptococcus thermophiles demonstrated that the pro-biotic could increase the production of beneficial lipids in the stratum corneum, such as ceramides, which can retain moisture in the skin,29 and phytosphingosine, which acts against C. acnes.30 Topical probiotics can also act by an immunomodulatory me-



chanism on keratinocytes and epithelial cells. The Streptococcus salivarius K12 strain was able to inhibit the production of pro--inflammatory cytokines, such as IL-8, in epithelial cells and ke-ratinocytes, most likely by inhibiting the NK-kappa B pathway.31

PsoriasisPsoriasis is an immune-mediated genetic disease that

manifests itself in the skin, joints, or nails. It has different clini-cal manifestation forms, which can be more or less intense, but with typical symptoms such as scaling and plaques on the skin, inflammation, and stiffness of the tissue.32 Although its patho-genesis is not fully understood, Th17 cells and the cytokines produced by them, such as IL-17, IL-22, and IL-23, play criti-cal roles in psoriasis’ pathogenesis. The intestinal microbiome is believed to be involved in the development of psoriasis, as well as in the activation of pro-inflammatory Th17 cells.33 It has been shown that patients with psoriasis and inflammatory bowel disease (IBD), two inflammatory conditions, have a similar pa-ttern of dysbiosis, suggesting the presence of a “gut-microbio-me-skin axis” in psoriasis and IBD. The lower presence of sym-biotic bacteria, including Lactobacillus spp., Bifidobacterium spp., Faecalibacterium prausnitzii,34 characterize this dysbiosis, as well as the colonization by certain pathobionts, such as Escherichia coli, Salmonella sp., Helicobacter sp., Campylobacter sp., Mycobacterium sp. and Alcaligenes sp.35 Also, S. aureus colonizes more abundantly the skin of psoriasis patients than that of individuals without the disease.36,37 These reduced levels of beneficial bacteria can lead to deleterious consequences, including changes in specific inflammatory proteins and poor regulation of intestinal immune responses that can affect distant organs.

Probiotic supplementation can play a significant role in the treatment of psoriasis. One study showed that oral admi-nistration of Lactobacillus pentosus GMNL-77 significantly de-creased erythematous lesions and epidermal thickening in mice with imiquimod-induced psoriasis when compared to placebo. The treatment significantly reduced mRNA levels of pro-in-flammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6 and IL-23/IL-17A. Also, the study found that treatment with Lactobacillus pentosus GMNL-77 also decreased the spleen weight of the group treated with imiquimod and re-duced the number of CD4þ T cells producing IL-17 and IL-22 in the spleen.38

Furthermore, a placebo-controlled study showed that su-pplementation with Bifidobacterium infantis 35624 in patients with psoriasis led to a significant decrease in plasma levels of pro-inflammatory markers, such as TNF-a and C-reactive pro-tein, when compared to placebo.39 A case study observed that supplementation with Lactobacillus sporogens three times daily combined with 10 mg biotin once daily was able to improve a severe case of pustular psoriasis not responsive to steroids, dapso-ne, and methotrexate.40

RosaceaThe possibility that intestinal bacteria and their products

may contribute to the development of skin lesions, such as rosacea, has also been studied. In a clinical study, it was found that patients

with inflammatory skin diseases had an imbalanced intestinal mi-crobiome. Rosacea patients had a significantly higher prevalence of small intestinal bacterial overgrowth (SIBO) than patients without the disease. Also, and more importantly, the SIBO eradication indu-ces an almost complete regression of skin lesions in patients with rosacea.41 In a case study, it was seen that the treatment of a patient affected by rosacea on the scalp with low dose doxycycline and Bifidobacterium breve BR03 together with Lactobacillus salivarius LS01 was able to promote improvement in skin and eye symp-toms.42 Although more research in this area are necessary, patients can be counseled on measures to maintain a healthy intestinal mi-crobiome, including consumption of a diet rich in fiber (prebiotics) or modulation of intestinal microflora via oral probiotics.

Photoaging and melasmaUltraviolet radiation (UVR) is considered the most po-

tent inducer of extrinsic aging. Studies have shown that exposure to UVR can induce significant changes in the human immune system, such as reducing the number of Langerhans cells, chan-ge in their morphology, and their ability to present antigens.43 Also, an increase in immunosuppressive cytokines like IL-10 has already been reported.44 The use of lactobacilli may represent an alternative skin protection to UVR.

A study with mice demonstrated that supplementation with Lactobacillus johnsonii (La1) was able to protect the skin from the harmful effects of UVR, such as a reduction in the number of Langerhans cells and a higher level of IL-10, post-ex-posure to radiation.45 A study with humans tested, for ten weeks, the oral administration of Lactobacillus johnsonii and 7.2 mg of carotenoids to healthy women, pre-exposed to simulated or natural sunlight. Compared to placebo, dietary supplementation prevented the UVR-induced decrease in Langerhans cell densi-ty and accelerated the recovery of immune system homeostasis after exposure to UVR. The comparison of the minimum ery-thema dose (MED) showed that, in those who received supple-mentation, MED increased by 20%.46

The study evidenced the association’s benefit, despite re-quiring the comparison between treatment with carotenoids and isolated probiotics. Another study also assessed the association of carotenoids and probiotics. A study with humans tested the effectiveness in treating melasma with a supplement containing beta-carotene, lycopene, and Lactobacillus johnsonii. The results showed that the treated group had a significant melasma impro-vement when it evaluated the Taylor scale and the Melasma Area and Severity Index (MASI) scale.47

A study with hairless mice indicated that oral adminis-tration of Bifidobacterium breve prevented URV-induced tran-sepidermal water loss compared to mice that received placebo. Also, the administration of B. breve suppressed the URV-indu-ced increase in hydrogen peroxide levels, protein oxidation, and xanthine oxidase activity in the animals’ skin.48 Another study with mice showed that oral administration of Lactobacillus aci-dophilus reduced the formation of fine lines induced by expo-sure to UVB radiation. The study attributed this protection to the reduction in the expression of metalloproteinases, such as MMP-1 and MMP-9.49



RejuvenationThe use of probiotics can also benefit other aspects rela-

ted to skin aging. The use of probiotics can influence intrinsic factors, such as genetics, hormonal status, and oxidative meta-bolic reactions, and extrinsic factors, such as exposure to solar radiation, tobacco, and psychological stress.

Healthy, normal skin exhibits a slightly acidic pH in the range of 4.2 to 5.6, which helps prevent pathogenic bacterial colonization, regulates enzyme activity, and maintains a moistu-re-rich environment.50 However, after the age of 70, the skin’s pH increases significantly, stimulating the proteases’ activity.51 As probiotic metabolism frequently produces acidic molecules, de-creasing the pH of the environment,52 using probiotics could restore the normal pH of the skin and, consequently, return the levels of proteases’ activity to closer to those observed in young and healthy skin.

A clinical study, controlled by placebo, assessed patients between 41 and 59 years, who had dry skin and wrinkles. The study showed that the administration of 1×1010 CFU/day of Lactobacillus plantarum HY7714 significantly suppressed the loss of transepidermal water, reduced the depth of wrinkles, and increased the skin brightness after three months of treatment compared to day zero. Furthermore, at the end of the study, the group’s skin elasticity treated with probiotics increased by 21.73%, with a significant difference in relation to the placebo group.53 These data suggest that the use of probiotics may work as a nutricosmetic (Table 1).

CONCLUSIONThe balance or imbalance of the human’s microbiome

can produce effects in different body organs, such as the skin and the intestine. Various dermatological diseases, usually with inflammatory factors involved, end up responding to the imba-lance or modulation of the intestinal microbiota significantly. It occurs mainly due to the suppression or activation of the immu-ne system caused by the modulation of cytokine production and activation of the body’s defense cells, which interferes with the disease’s pathophysiology.

Probiotic supplementation to treat dermatological disea-ses has been studied for many years. Although it is seen main-ly as a complementary therapy in clinical practice, the use of probiotics alone can present a positive result. When combined with conventional therapy, it manages to improve the clinical outcome of the treatment further. Also, its use reduces the ad-verse events of more aggressive therapies, such as systemic anti-biotics. With clear benefits, concrete results have emerged more and more with the growing number of studies on this subject. However, there are still gaps in knowledge and information that need to be better understood, such as the best strains to be used, the effective doses, or best dosing schedule. l

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Célia Luiza Petersen Vitello Kalil | 0000-0002-1294-547XApproval of the final version of the manuscript; preparation and writing of the manuscript; critical literature review; critical revision of the manuscript.

Christine Chaves | 0000-0001-8861-6499Approval of the final version of the manuscript; preparation and writing of the manuscript; critical literature review; critical revision of the manuscript.

Artur Stramari de Vargas | 0000-0001-5773-8039Approval of the final version of the manuscript; preparation and writing of the manuscript; critical literature review; critical revision of the manuscript.

Valéria Barreto Campos | 0000-0002-3350-8586pproval of the final version of the manuscript; preparation and writing of the manuscript; critical literature review; critical revi-sion of the manuscript.

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Surg Cosmet Dermatol. Rio de Janeiro v.12 n.1 jan-mar. 2020 p. 215-21.

Original ArticlesAuthors:Dhesi Ariembi1,2

Retno Indar Widayati1,2

Diah Adriani Malik1,2

1 Diponegoro University, Semarang, Central Java, Indonesia; 2Hospital Dr. Kariadi Semarang, Semarang, Indonesia.

2 Hospital Dr. Kariadi Semarang, Semarang, Indonesia.

Corresponding author:Dhesi Ariembi Jalan Prof. Sudarto No.13, Tembalang, Semarang, Central Java50275 E-mail: [email protected]


Study conducted at the Medical School of the Diponegoro University and the Hospital Dr. Kariadi Sema-rang, Indonesia.


Effectiveness of 4% tranexamic acid cream and low-fluence QS Nd:YAG 1064-nm laser on melasma: a double-blind, randomized and controlled studyEficácia do creme com ácido tranexâmico a 4% e laser QS Nd: YAG 1064 nm de baixa fluência no melasma: um estudo duplo-cego, randomizado e controlado


ABSTRACTIntroduction: Melasma is acquired symmetric hyperpigmentation that affects most com-monly in sun-exposed areas. Objective: This study aim to prove the effectiveness of 4% tranexamic acid cream (AT) treatment for melasma patients treated with low-fluence QS Nd:YAG 1064-nm laser. Methods: The study subjects were divided into two groups A and B who received low--fluence QS Nd:YAG 1064-nm laser therapy at baseline, fourth week, and eighth week. Group A received Tranexamic acid 4% (TA) cream, and group B received a placebo cream, applied twice a day for 12 weeks. The assessment uses MASI and MELASQoL scores. Results: The result showed that TA 4% cream was effective in reducing MASI and ME-LASQoL scores in melasma patients treated with low-fluence QS Nd:YAG 1064-nm laser. Conclusions: TA 4% cream was effective in reducing the MASI and MELASQoL scores in melasma patients treated with low-fluence QS Nd:YAG 1064\\\-nm laser.Keywords: Melanosis; Laser Therapy; Skin Cream

RESU MOIntrodução: O melasma é uma hiperpigmentação simétrica adquirida que afeta mais comumente as áreas expostas ao sol. Objetivo: Este estudo tem como objetivo provar a eficácia do tratamento com creme com ácido tranexâ-mico a 4% em pacientes com melasma tratados com laser QS Nd:YAG 1064 nm de baixa fluência. Métodos: Os sujeitos do estudo foram divididos em dois grupos, A e B, que receberam terapia a laser QS Nd:YAG 1064 nm de baixa fluência dia inicial do estudo, e após 4 e 8 semanas. O grupo A recebeu creme com ácido tranexâmico a 4% (AT) e o grupo B recebeu creme com placebo, aplicado duas vezes ao dia durante 12 semanas. A avaliação utilizou as pontuações MASI e MELASQoL. Resultados: O resultado mostrou que o creme AT a 4% foi eficaz na redução dos escores MASI e MELASQoL em pacientes com melasma tratados com laser QS Nd:YAG 1064 nm de baixa fluência. Conclusões: O creme AT 4% foi eficaz na redução dos escores MASI e MELASQoL em pacientes com melasma tratados com laser QS Nd:YAG 1064 nm de baixa fluência.Palavras-chave: Creme para a Pele; Melanose; Terapia a Laser

216 Ariembi D, Widayati RI, Malik DA


INTRODUCTIONMelasma comes from the Greek melas, which means bla-

ck patches, or chloazein, which means green. Melasma is more common in women than in men. This disorder runs chronic and tends to recur.1,2 Melasma mainly occurs in Fitzpatrick III–V skin types, living in areas with high-intensity ultraviolet light.3

Melasma can affect all races, mostly Asian, Hispanic, La-tin American, and Arabic. Handel et al. mentioned a melasma prevalence of 8.4% of dermatology cases in Brazil, 14.5% in the Arabian population in Detroit (USA), and 8.8% in the Latin population in Texas (USA).4 Melasma covers 50% of the aesthe-tic cases in Asia.5,6 The incidence of melasma in Southeast Asia was 40% of women and 20% of men.5 In Indonesia, the ratio of women and men who suffers from melasma is 24:1.7

The pathogenesis of melasma is not clear until now. The main predisposing factors include genetic, ultraviolet rays, and hormonal exposure.2,3 The clinical features of melasma are brown, dark brown, or black macules, symmetrical, with irregular borders, single or multiple, found in the forehead, temple, upper lip, cheeks, and other parts exposed to sunlight. Melasma based is divided into three distinctive patterns on the distribution of lesions: centrofa-cial (65%), malar (20%), and mandibular (15%).8,9

Wood’s lamps and histopathological examination can be used to determine the depth of the melasma pigment. Based on Wood’s lamp examination, melasma is divided into three types: epidermal, dermal, and mixed.7 Research that assesses the validi-ty of Wood’s lamp to identify melasma patterns compared to his-topathology showed the level of sensitivity, low specificity, and low accuracy (46%) in all three types of melasma pathology.10

The basic principles of melasma management are su-ppressing melanocyte proliferation, inhibiting melanosome formation, and increasing melanosome degradation.8 Research on melasma therapy has been conducted with varying results. However, until now, there has not been a single effective therapy with satisfactory results.11,12

Tranexamic acid is a synthetic derivative of the lysine amino acid, which reduces the activity of melanocyte tyrosinase involved in melanogenesis.11,13 Tranexamic acid can be adminis-tered systemically or topically; however, serious adverse events have been reported on tranexamic acid when given systemically. Still, it is safer when given topically.14

Low-fluence Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG) 1064-nm laser is one of the modalities used in melasma therapy, through a sub-thermolytic mechanism. Research on low-fluence QS Nd:YAG 1064-nm laser in melasma has been carried out. Still, high recurrence rates after laser therapy and poor long-term results are observed when low-fluence QS Nd:YAG 1064-nm laser is used as monothera-py.15 Some of the researchers concluded that to get better results in melasma treatment with low-fluence QS Nd:YAG 1064-nm laser, it should be combined with other therapies including topi-cal agents such as tranexamic acid.16

Research combination of tranexamic acid 4% cream and low-fluence QS Nd:YAG 1064-nm laser has not been conduc-ted in Indonesia. It led to a high recurrence rate in melasma and

various adverse events arising from the treatment. Thus, effecti-ve combination therapy with minimal adverse events is needed. We conducted this study to prove the effectiveness of tranexa-mic acid 4% cream in melasma treatment with low-fluence QS Nd:YAG 1064-nm laser.

The difference between this study and the previous re-search conducted by Laothaworn et al. is the sample number’s research design, as many as 16 people, and how the subjects were treated. The treatment duration was 12 weeks, and the parame-ters assessed in this study were MASI and MELASQoL scores.

METHODSThis study is a double-blind, randomized, controlled,

two-groups, pre and post-design trial. This study population’s criteria were all melasma patients seeking treatment at the Der-matology and Venereology Clinic of the Diponegoro National Hospital from August to October 2019. The study subjects com-prised 16 melasma patients diagnosed clinically and by Wood’s lamp examination, who were over 20 years of age, had Fitzpatri-ck skin type IV-V, and willing to participate and obtain therapy in the research. Patients received an explanation of the therapeu-tic procedure and signed informed consent.

Exclusion criteria included a history of allergy to trane-xamic acid, pregnancy or breastfeeding, using hormonal contra-ception, active infection in the area of melasma, and history of hypertrophy or keloid scar. Patients with a history of oral retinoid consumption or topical facial lightening treatment products must stop these medications at least one year and one month before the first visit. Furthermore, patients with a history of receiving oral tranexamic acid therapy or undergoing cosmetic procedures on the face (laser, dermabrasion, chemical peels) must stop these medications at least six months before the first visit.

Consecutive sampling, conducted upon the patient’s ar-rival, selected research subjects, and we performed block rando-mization. The study subjects were divided into two groups: A and B. Both groups received low-fluence Q-switched Nd:YAG 1064-nm laser therapy at baseline, fourth, and eight weeks. After the laser therapy, group A received tranexamic acid 4% cream, and group B received placebo cream, applied twice a day for 12 weeks. MASI and MELASQoL scores were assessed in both groups at baseline and after twelve weeks.

MASI score parameters are expressed as mean and stan-dard deviations because they are normally distributed. In con-trast, MELASQoL scores are expressed as medians, minimum, and maximum values due to abnormal distribution. The Shapi-ro-Wilk test conducted the normality test because the sample size was small (number of samples <50).

The hypothesis tested the mean difference of MASI sco-res before and after treatment with paired t-test. An unpaired t-test carried out the hypothesis test of differences in MASI sco-res and delta MASI scores between the treatment and control groups.

The Wilcoxon test assessed the hypothesis of MELAS-QoL average scores before and after treatment. The Mann–

Effectiveness of tranexamic acid 4% cream 217


Whitney test carried out the hypothesis testing of MELASQoL score differences between the treatment and control groups. An unpaired t-test examined the difference in MELASQoL delta scores between the treatment and control groups.

Differences were considered significant if p<0.05. Data analysis used the IBM SPSS program version 25.

The Health Research Ethics Commission of the Faculty of Medicine, Diponegoro University granted the study proto-col’s ethical clearance under the No.222/EC/KEPK/FK UN-DIP/V/2019.

RESULTSStudy subjects as many as 16 people completed all the

series of therapies in this research. Figure 1 shows the number of subjects in the treatment and control group during the study.

The research subjects were 16 melasma individuals: nine presented centrofacial distribution (56.3%), and seven, malar dis-tribution (43.7%). The results of Wood’s lamp examination fou-nd a mixed type of melasma in 13 subjects (81.3%), followed by epidermal types in three individuals (18.2%).

Table 1 presents the MASI analysis scores in both groups, showing decreased MASI scores in both groups.

The average MASI score of the treatment group at the beginning of the research was 14.6 ± 8.40; at the end of the study, it dropped significantly to 7.3 ± 5.12 (p = 0.001; paired t-test). The average MASI score of the control group at the be-ginning was 18.8 ± 7.53 and also dropped significantly to 17.6 ± 7.76 (p = 0.007; paired t-test).

At baseline, the average of MASI score in the treatment group was 14.6 ± 8.40, lower than the control group’s sco-re, which was 18.8 ± 7.53. However, the statistical test results showed the difference of the MASI score before the treatment was not significant (p = 0.3; unpaired t-test).

The average MASI score after treatment was 7.3 ± 5.12. This score was lower than the average MASI score of the control group, 17.6 ± 7.76. Statistical test results showed that the diffe-

rence in MASI score after treatment was significant (p = 0.007; unpaired t-test).

The treatment group’s average MASI score was 7.4 ± 3.79, which was significantly higher than the control group’s MASI score, 1.3 ± 0.95 (p<0.001; unpaired t-test). Graphic 1 shows the average change in MASI scores from before to after treatment.

Table 2 presents an analysis of MELASQoL scores in both groups. There was a decrease in MELASQoL scores in both groups. The MELASQoL average score of the treatment group at baseline was 34.5 ± 14.67, and at the end of the stu-dy, it dropped significantly to 21.3 ± 9.72 (p = 0.01; Wilcoxon test). The MELASQoL average score of the control group at the beginning was 30.0 ± 17.69; at the end of the study, it dropped significantly to 22.1 ± 16.81 (p = 0.01; Wilcoxon test).

The MELASQoL score of the treatment group was 13.3 ± 5.68, significantly higher than the control group, which was 7.9 ± 3.04 (p = 0.002; unpaired t-test).

Graphic 2 presents the comparison of ΔMELASQoL scores between the treatment and control groups.

DISCUSSIONMelasma is an acquired hyperpigmentation disorder

that is most commonly found in Asian women. Management of melasma is difficult due to the high recurrence rate.17 First--line therapy includes controlling risk factors, using sunscreen, stopping hormonal therapy or photosensitizer drugs, and using topical anti-tyrosine and topical exfoliants. The second-line uses an association of first-line and chemical peels. The third-line is the combination of the first-line with a non-ablative fractional laser or fractional radiofrequency. The fourth-line is the first-line combined with Intense Pulse Light or Q-switch laser.15

Topical therapy is more effective for epidermal melas-ma. Patients can obtain it at an affordable price, but it requires regular daily use. Procedural treatment, such as chemical peels and micro-needling, can also be used in the epidermal type of melasma. Lasers and other light-based energy are an alternati-ve for dermal and mixed type melasma or recalcitrant melasma. However, the treatment costs are high, and the treatment must be repeated for several months. Thus, the physician must inform the patient before starting the therapy. Systemic therapy can use oral Tranexamic Acid (TA) for dermal or mixed melasma, or me-lasma resistant to topical treatment. Still, users must be careful with systemic adverse events, including gastrointestinal disorders, menstrual disorders, and the most severe event reported, deep vein thrombosis.2,16

The choice of melasma therapy depends on the melas-ma type, Fitzpatrick’s skin type, history of previous therapy, and patient expectations. In addition to the patient’s adherence and the treatment costs, melasma therapy also requires a long time because the therapeutic effect is usually seen only after one-two months.8 Combination therapy with topical and procedural preparations is the most widely used melasma therapy option currently, including QS Nd:YAG laser modality combined with topical preparations.11,12Figure 1: Diagram of the number of subjects in the treatment and control

groups during the research


Hydroquinone is the best standard for depigmenting agents for melasma. Nevertheless, long-term hydroquinone can cause exogenous ochronosis.2,5 Other alternative topical the-rapies not containing hydroquinone are available, for example, tranexamic acid.2 Janney et al. compared 5% TA solution and hydroquinone cream: the combination achieved a 27% MASI decrease in the TA solution group and 5% and 26.7% in the hy-droquinone group, with erythema and irritation adverse events found in the hydroquinone group. This study showed that the TA 5% solution effectiveness as melasma therapy was almost the same as hydroquinone.18

Tranexamic acid (trans-4-(aminomethyl) cyclohexane--carboxylic acid) is a synthetic derivative of the amino acid lysi-ne, a competitive inhibitor of activation of plasminogen activator (PA) through reversible interactions at lysine-binding sites. Tra-nexamic acid (TA) reduces PA activity, thereby preventing the conversion of plasminogen to plasmin.19 Another mechanism of action of tranexamic acid is the melanocyte tyrosinase activity reduction to prevent the binding of plasminogen to keratino-cytes, resulting in decreased prostaglandin and arachidonic acids

Graphic 1: MASI score boxplot in the treatment (n = 8) and control groups (n = 8) at the end of the study


Table 1. MASI score of melasma patients in treatment (n = 8) and control groups (n = 8)

Group

MASI Score

Treatment (n = 8) Control (n = 8)

p*Average ± SB; Average ± SB;

Median (Min–Max) Median (Min–Max)

Before14.6 ± 8.40;

15.4 (5.0–25.6)18.8 ± 7.53;

19.0 (6.9–27.6)0.3*

After7.3 ± 5.12;

6.8 (1.7–14.8)17.6 ± 7.76;

18.3 (5.9–27.6)0.007*

Δ MASI score 7.4 ± 3.79;

6.9 (3.0–12.2)1.3 ± 0.95;

1.0 (0.0–2.7)<0.001

p ** before vs. after 0.001 0.007Δ MASI score: MASI score before–MASI score after*unpaired t-test**paired t-test

Table 2. MELASQoL score in the treatment (n = 8) and control groups (n = 8)

Group

MASI Score

Treatment (n = 8) Control (n = 8)

p¶Average ± SB; Average ± SB;

Median (Min–Max) Median (Min–Max)

Before34.5 ± 14.67;

30.5 (18.0–64.0)30.0 ± 17.69;

23.5 (14.0 – 70.0)0.4¶

After21.3 ± 9.72;19.0 (10–40)

22.1 ± 16.81;16.5 (10.0–62.0)

0.06¶

ΔMELASQoL 13.3 ± 5.68;12.5 (6–24)

7.9 ± 3.04;7.5 (4.0–13.0)

0.002*

p§ before vs. after 0.01 0.01

ΔMELASQoL score: MELASQoL score before–MELASQoL score after¶Mann–Whitney test; §Wilcoxon test; *unpaired t-test


Graphic 2: Boxplot diagram of MELASQoL scores in the treatment (n = 8) and control groups (n = 8) at the end of the study

involved in melanogenesis.11,13,18

Tranexamic acid as a therapy for melasma is available in topical, oral, and intradermal injection preparations. Moreover, it can be combined with other therapeutic modalities. Melasma therapy with topical tranexamic acid has minimal adverse events in the form of erythema and irritation, and it is safe for long--term use. 20,21

The laser is one of the most critical therapeutic instru-ments in the dermatology field, including melasma.22 Traditional QS laser (high fluence) is effective for pigmented lesions treat-ment through selective targets for melanin. However, several stu-dies have shown some adverse events, including hyperpigmen-tation, hypopigmentation, and melasma recurrence.5 The new variant of the QS Nd: YAG laser is called low-fluence or sub--thermolytic. The laser is the same but with lower fluence than traditional QS. Low-fluence therapy mostly uses a wavelength of 1064 nm, which penetrates deeper into the dermis, avoiding damage to the epidermis, and can be used on darker skin.23 Sub-thermolytic therapy is based on the theory that pigment disorders occur through photoacoustic mechanisms that dama-ge the melanin pigment, whereas keratinocytes and melanocytes are protected from the damage.24 Low-fluence laser causes mini-mal thermal damage, decreases the number of melanosomes (es-pecially stage IV melanosomes), not damaging the melanocytes, but lowering its volume and dendrites.25 Nevertheless, there is still damage that accompanies QS sub-thermolytic therapy, but this damage is reported to be less than that caused by traditional photothermal therapy.15,26

Low-fluence Q-switched Nd:YAG laser is used as a the-rapy for melasma, despite the reported transient response and adverse events including erythema, edema, hypopigmentation spots, recurrence, and hyperpigmentation rebound. The litera-ture recommends this laser not to be used in too many sessions (>6–10 times) or too often (intervals every week) to avoid ad-verse events.27

In this study, the treatment group’s MASI score was signi-ficantly lower than before the treatment (p<0.001). The study’s

results are consistent with the research conducted by Ebrahimi et al. in 50 melasma patients. The study compared a TA 3% solution with hydroquinone solution 3% combined with dexamethasone 0.01%, and showed a significant decrease in MASI scores in both groups.28 Other studies conducted by Atefi et al. in 60 melasma patients compared those who received TA 5% topical to those who received hydroquinone 2%. The research showed a more significant decrease in the TA group’s MASI score, proving that topical TA can reduce the MASI scores, being effective and safe as a melasma therapy with minimal adverse events compared to hydroquinone.11,29

MASI scores in the control group after treatment were significantly lower than before treatment. Research conducted by Suh et al. on 23 melasma individuals treated with a low--fluence QS Nd:YAG 1064-nm laser every week for ten weeks showed a significant decrease in MASI score at week seven (7.57 ± 2.91) and week 10 (9.15 ± 2.74) compared to before treat-ment (14.15 ± 1.47), with a p-value <0.05.30 Another study conducted by Kar found a significant reduction in MASI score of 47.93% (p<0.05) in group A that received low-fluence QS Nd:YAG 1064-nm laser therapy, followed by 40.44% (p<0.05) in group B, which received Glycolic Acid peeling therapy, and 20.81% (p<0.05) in group C, which received high-fluence QS Nd:YAG 1064-nm laser therapy. Most adverse events were fou-nd in group C.17 Thus, low-fluence QS Nd:YAG 1064-nm laser is effective for melasma.

Statistical test results of MASI score of the treatment group were significantly higher than the control group (p<0.001; unpaired t-test). Research conducted by Laothaworn et al. used MASI scores and showed a significant decrease in the treatment group combination of low-fluence QS Nd:YAG 1064 nm and TA 3% cream since four weeks after the first laser, and this con-tinued to decline until final observation.12

This study conducted low-fluence QS Nd:YAG 10640-nm laser three times at 4-week intervals. The TA 4% cream was applied morning and afternoon for three consecutive months and stopped one day after the laser therapy administration. Parti-cipants got some clinical photos before and after treatment with TA 4%, shown in Figure 4 and Figure 5. Previous research had proven the effectiveness of low-fluence QS Nd:YAG 1064-nm laser therapy and topical tranexamic acid for melasma. A research conducted by Laothaworn et al. evaluated the use of tranexamic acid 3% cream and low-fluence QS Nd:YAG 1064-nm laser combination.12

This study also assessed the MELASQoL score to see how melasma affected the patients’ quality of life.31 Significant decreases in MELASQoL scores were found in the treatment group after treatment (p=0.01). A substantial reduction in the MELASQoL score was also found in the control group after treatment (p=0.01). The statistical test results of the MELAS-QoL score in the treatment group were significantly greater than those in the control group (p = 0.002; unpaired t-test), (Figure 2 and 3).

Two subjects in this study complained of redness after the laser action, but the redness disappeared within 20–30 minutes


Figura 2: A - (A) Participant’s clinical photo before therapy, melasma appeared on both cheeks. (B) Clinical photos of participants at weeks four, eight, and twelve after the first laser therapy and TA 4% cream twice daily. There was an improvement in melasma on both cheeks.

A

B

Figura 3: (A) Clinical photograph of the participant before treatment, showing melasma on the cheeks, temples, and upper lip. (B) Clinical photos of participants at weeks four, eight, and twelve after the first laser therapy and TA 4% cream twice daily. There was an improvement in melasma on the cheeks, temples, and upper lips.

A

B





after a cold compress. Based on Suh et al.’s research, 23 study subjects who received low-fluence QS Nd:YAG 1064-nm laser therapy had transient erythema and no other serious adverse events.30

CONCLUSIONMASI and MELASQoL scores in the treatment group

decreased significantly compared to the control group. This

study concluded that the TA 4% cream effectively reduced the MASI and MELASQoL scores in melasma patients treated with low-fluence QS Nd:YAG 1064-nm laser.

Observations in this study were only carried out within 12 weeks due to time constraints. Thus, we couldn’t observe the long-term effects of combination therapy of low-fluence QS Nd:YAG 1064-nm laser and TA 4% cream. We suggest future studies to use tools to measure pigment depth more objectively, with longer observation times. l

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19. Zhang L, Tan WQ, Fang QQ, Zhao WY, Zhao QM, Gao J, et al. Tranexamic acid for adults with melasma: a systematic review and meta-analysis. Biomed Res Int. 2018;2018:1683414.

20. George A. Tranexamic acid: an emerging depigmenting agent. Pig-ment Int. 2016;3(2):66.

21. Laothaworn, Deeanandlarp, Pattaraarchachai, Juntongjin. Effect of adjuvant tranexamic acid on melasma-a pilot study. Thai J Pharm Sci. 2016;40:184-7.

22. Haley D, Pratt O. Basic principles of lasers. Anaesth Intensive Care Med. 2017;18(12):648-50.

23. Jordão JM, Rebellato PRO. Energy-based devices for treatment of me-lasma. J Surg Dermatol. 2017;2(T1):130-8.

24. Tse TW, Hui E. Tranexamic acid: an important adjuvant in the treatment of melasma. J Cosmet Dermatol. 2013;12(1):57-66.

25. Cho HH, Choi M, Cho S, Lee JH. Role of oral tranexamic acid in melasma patients treated with IPL and low fluence QS Nd:YAG laser. J Dermatol Treat. 2013;24(4):292-6.

26. Park YW, Yeo UC. Mottled hypopigmentation from laser toning in the treatment of melasma: a catastrophic or manageable complication? Med Lasers. 2015;4(2):45-50.

27. Bevec Fotona T. Treating melasma with sub-thermolytic Q-Switched Nd:YAG. J LAHA 2011;2011(1):53-5.

28. Ebrahimi BNF. Topical tranexamic acid as a promising treatment for me-lasma. J Res Med Sci. 2014;19(8):753-7.

29. McKesey J, Tovar-Garza A, Pandya AG. Melasma treatment: an eviden-ce-based review. Am J Clin Dermatol. 2020;21(2):173-225.

30. Lieu TJ, Pandya AG. Melasma quality of life measures. Dermatol Clin. 2012;30(2):269-80.

31. Suh KS, Sung JY, Roh HJ, Jeon YS, Kim YC, Kim ST. Efficacy of the 1064-nm Q-switched Nd:YAG laser in melasma. J Dermatolog Treat. 2011;22(4):233-8


Dhesi Ariembi | 0000-0002-0835-2938Data collection, analysis, and interpretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Retno Indar Widayati | 0000-0002-5529-1963Statistical analysis; approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review.

Diah Adriani Malik | 0000-0003-0268-0655Statistical analysis; approval of the final version of the manuscript; study design and planning; active participation in research orientation.


ABSTRACTIntroduction: Basal cell carcinoma (BCC) is the most common cancer in the world. Al-though rarely metastasizes, BCC can cause high levels of morbidity due to its locally destruc-tive nature. Local flaps provide reasonable option for reconstruction of facial defects with good result. Objective: Describe the clinical profile of BCC in South Sulawesi, Indonesia. Methods: A retrospective analysis was performed in all patients with BCC who had under-gone surgical resection in our center. Patient charts were reviewed for demographic informa-tion, tumor size, anatomic location, clinical subtype, and surgical method. Results: There were 70 BCC cases consisting of 18 (25.7%) men and 52 (74.3%) women. The most frequent age group was 46 to 65-year-old group (49 patients, 70%). The most common aesthetic unit affected was the nasal unit (24 patients, 34.3%) with lesions measured 1 cm to 2 cm in diameter (45 patients, 64.29%). The most common clinical subtype was nod-ular type (37 patients, 52.86 %). Advancement flap was the most frequent technique used (32 patients, 45.71%). Conclusions: BCC more frequently occurs in females, on the nose, and in the age range of 46 to 64 years old. Local flaps resulted in an excellent aesthetic result and are the first choice for reconstruction of the face. Keywords: Basal cell; Carcinoma; Retrospective studies; Surgical flaps

RESU MOIntrodução: O carcinoma basocelular (CBC) é o câncer mais comum no mundo. Embora raramente metas-tatize, o CBC pode causar altos níveis de morbidade devido à sua natureza localmente destrutiva. Retalhos locais fornecem opção razoável para reconstrução de defeitos faciais com bom resultado. Objetivo: Descrever o perfil clínico do CBC no sul de Sulawesi, Indonésia. Métodos: Uma análise retrospectiva foi realizada em todos os pacientes com CBC submetidos à ressecção cirúrgica em nosso centro. Os prontuários dos pacientes foram revisados para informações demográficas, ta-manho do tumor, localização anatômica, subtipo clínico e método cirúrgico. Resultados: Ocorreram 70 casos de CBC, sendo 18 (25,7%) homens e 52 (74,3%) mulheres. A faixa etária mais frequente foi de 46 a 65 anos (49 pacientes, 70%). A unidade estética mais acometida foi a nasal (24 pacientes, 34,3%) com lesões de 1 cm a 2 cm de diâmetro (45 pacientes, 64,29%). O subtipo clínico mais comum foi o nodular (37 pacientes, 52,86%). Retalho de avanço foi a técnica mais utilizada (32 pacientes, 45,71%). Conclusões: O CBC ocorre mais frequentemente no sexo feminino, no nariz e na faixa etária de 46 a 64 anos. Os retalhos locais resultaram em excelente resultado estético e são a primeira escolha para reconstrução da face.Palavras-chave: Carcinoma basocelular; Cirurgia de Mohs; Estudos retrospectivos


222

Original ArticlesAuthors:Welly Wijayanti 1 Khairuddin Djawad 1

1 Hasanuddin University, Makassar, Indonésia.

Corresponding author:Welly WijayantiJl. Perintis Kemerdekaan KM.11 Tama-lanrea, Makassar, South Sulawes, Indonésia.90245E-mail: [email protected]


Trabalho realizado no Departamento de Dermatologia e Venereologia, Faculdade de Medicina, Hasanuddin University, Makassar, Indonésia.


Agradecimentos: Os autores gos-tariam de agradecer a Ivan Kurniadi, MD, por seu suporte técnico.

Clinical study of basal cell carcinoma on the face: a 5-year retrospective study of 70 cases in a teaching hospitalEstudo clínico do carcinoma basocelular facial: estudo retrospectivo de 5 anos de 70 casos em um hospital universitário

Facial basal cell carcinoma: 5-year study 223


INTRODUCTIONSkin cancer is the most common type of cancer. It can

be differentiated based on the type of cells found in each lesion into basal cell carcinoma (BCC) (77%), squamous cell carcino-ma (SCC) (20%), malignant melanoma (3%), and rare tumors originating from the skin (<1%). Anatomical distribution mostly favors the head and neck region, where this location constitutes 85% of BCC and 75% of SCC.1

Among all skin cancers, BCC is the most common type. Although it rarely metastasizes or leads to death, BCC can cause high morbidity due to its locally destructive nature. The high prevalence of BCC allows us to understand better the disease characteristics, pathogenesis, clinical and histopathological fea-tures.2

The finding that BCC occurs mainly on sun-exposed sites and that sun protection can reduce its frequency provides indirect but crucial evidence for the role of ambient solar radi-ation.3 Intermittent intense episodes of UV exposure and sun-burns at any age appear to increase the BCC risk. In contrast, cumulative long-term UV exposure and childhood sunburns in-crease the risk of developing SCC.4 Geographic location also has been implicated as a risk factor for BCC, and populations living in geographic regions with latitudes closer to the equator have reported higher rates of BCC than other populations.5

BCC generally occurs in individuals older than 50 years, but not much is known about its incidence in subjects younger than 40 years. To date, studies that aimed to investigated BCC in younger populations were unable to find any trends.6

Surgical excision may be the most effective treatment for primary BCC, and it has been traditionally the main treatment of choice. BCC is typically removed with a pre-set excision margin of 0.3-0.4 centimeter (cm). In BCC cases on the face, grafts and flaps are more recommended for wound closure than direct closure.7

In the past decade, several studies have examined the re-lationship between age, gender, and anatomical distribution re-garding different BCC variants, including nodular, superficial, and morpheaform BCC. Recent literature suggests that the an-atomical location of BCC may favor the development of par-ticular subtypes.8 Yet further studies are needed to clarify these associations. This study aims is to describe the clinical profile of BCC in South Sulawesi, Indonesia.

METHODSWe retrospectively analyzed data of all patients with facial

BCC who presented to the Tumor and Skin Surgery Clinic of the Department of Dermatology and Venereology, at Makassar, from January 2015 to January 2020.

We reviewed patient charts for demographic informa-tion (age and sex), anatomical location, tumor size in diameter, clinical subtype, and surgical treatment method. Six age cate-gories were established: (1) younger than 5 years of age, (2) 5 to 12 years of age, (3) 13 to 25 years of age, (4) 26 to 45 years of age, (5) 46 to 65 years of age, (6) older than 66 years of age. Anatomical location divided into 12 aesthetic units according to

Gonzales-Ulloa, 1975: (1) frontal, (2) temporal, (3) auricular, (4) supraorbital, (5) orbital, (6) infraorbital, (7) zygomatic, (8) buccal, (9) nasal, (10) labial, (11) mental, and (12) parotid-mesenteric (Figure 3). Tumors were divided into four subtypes, according to Fitzpatrick et al. (2019): (1) nodular, (2) pigmented, (3) superfi-cial, and (4) morpheaform. The method of surgical treatment by local flap was divided into five groups: (1) advancement flap, (2) rotation flap, (3) transposition flap, (4) combination of rotation and advancement flap, and (5) combination of transposition and advancement flap.

We were able to generate meaningful summary statis-tics, and we summarized the results, reporting them as mean or percentage, chart, and table. Mean and standard deviation was calculated for the age at presentation and size of the lesion. Fre-quency and percentages were calculated for all data. The data were analyzed using SPSS version 25.0 software (SPSS Inc., Chi-cago, IL, USA).

RESULTSWe retrieved a total of 70 facial BCC cases. Of these cas-

es, 18 (25.72%) patients were men, and 52 (74,29%) were wom-en with overall men to women ratio of 1:2.8 (Figure 1). The age distribution ranged from 30 to 80 years old. The most frequent age group was 46-65 years old (mean 60.06 ± 4.33 years), fol-lowed by 66 years old and above (Figure 2). Of these groups, the sixth decade was found to be the peak age of presentation.

Anatomic DistributionWe further analyzed the location of face tumors by re-

viewing the preoperative photographs and categorizing each tumor to 12 aesthetic units of the face, according to Gonza-les-Ulloa, 1975.9 The most common site was the nose, where tumors occurred in 24 (34%) cases, followed by the infraorbital area, which was involved in 19 (27%) cases (Figure 3).

Tumor SizeThe smallest tumor was 0.5 cm in diameter, and the larg-

est was 3.5 cm. The majority of tumors had a diameter between 1 cm and 2 cm in 45 (64,29%) cases, followed by 2 cm to 3 cm in 20 (28,57%) cases. The average tumor diameter was 1.8 cm (Figure 4).

BCC Clinical Subtypes The BCC clinical subtype was divided into four types

(nodular, pigmented, superficial, and morpheaform) using pre-operative photographs (Figure 5). The most common clinical subtype was the nodular type, seen in 37 (52,86%) cases, fol-lowed by the pigmented type in 29 (41,43%) cases (Figure 6).

Surgical TreatmentAll 70 tumors were treated by excision with surgical

margins of 0.4 cm to 0.5 cm. There was no recurrence in one to five years follow-up. The most commonly used method of wound closure was local flap. In all cases of local flaps, the most common technique was advancement flap (32 cases, 45.71%), followed by rotation flap (20 cases, 28.57%) (Figure 7).

224 Wijayanti W, Djawad K.


We also analyzed the operative methods by aesthetic units. Among all advancement flaps cases, the most commonly treated area was the nose (9 cases, 28.12%) and the infraorbital unit (9 cases, 28.12%). Rotation flap was commonly used in the infraorbital unit (8 cases/40.00%), and transposition flap was fre-quently used in the nose (8 cases, 61.54%). The combination of rotation and advancement flap was commonly used in the nasal unit (2 cases, 66.67%), and the combination of transposition and advancement flap was mostly used in the nasal and infraorbital unit (Table 1).

DISCUSSIONSkin cancer is the most frequent type of malignancy

with a gradually increasing incidence throughout the world. Al-though it rarely metastasizes or leads to death, BCC can cause high morbidity due to its locally destructive nature.2

In the present study, the subjects’ age ranged from 30 to 80 years, with a mean age of 59.25 ± 10.11 years. The age group with the highest incidence of BCC was the 46-65 years (mean 60.06 ± 4.33 years). The mean age was similar to that reported by Matthew et al., 66.9 ± 15.1 years, and by Martha et al., of 60 years.(10,11) The most common variety of carcinoma is BCC, which accounts for 77% of all skin cancer cases and is more frequent in the elderly population, reflecting the connection between accumulative sun exposure and cancer development.1

BCC occurs mainly on sun-exposed sites. It suggests that

Figure 1: Distribution of BCC Patients by Gender

Figure 2: Distribution of BCC Patients by Age



cumulative lifetime sun exposure has a strong dose-response as-sociation with BCC.3 Chronic UV exposure is the highest risk factor for BCC, with a typical latency period of 15 to 20 years between the UV damage and the clinical onset. The UV dose, exposure duration and intensity all play a role in BCC develop-ment.12 UV exposure, particularly the UVB spectrum, is accept-ed as the most important causal factor for BCC development. UV light is believed to directly induce DNA mutations via co-valent bonding between adjacent pyrimidines (UVB) and form reactive oxygen species (UVA).13 Geographic location has also been implicated as a risk factor for BCC, where populations liv-ing in geographic areas with latitudes closer to the equator have reported higher rates of BCC than other populations.5 Thus, the

fact that Indonesia is located in the equator and has about 5000 km or 1/8 of the equatorial circumference in longitude played a significant role in the occurrence of BCC in our cohort.14

This study presented men to women ratio of 1 to 2.8. BCC is traditionally more commonly in men due to their more extensive exposure to sunlight. However, in a previous retro-spective review assessing a period between 2005 and 2012, Choi et al. found BCC to be more common among women, with men to women ratio of 1:1,38.9 Nicolo et al. found that BCC is more common in women than men, with a ratio of 1:0.9. This greater incidence among women was believed to be due to female population’s the higher life expectancy.15 Mancuso et al. study showed that the development of skin cancer might be

Figure 3: Distribution of BCC Patients by Aesthetic Units of the Face

Figure 4: Distribution of BCC patients by Lesion Diameters


related to sex hormones such as estrogen, but such relationship has not been studied extensively in the clinical or epidemio-logic setting. An animal study found that endogenous estrogen antagonized basal and squamous skin tumorigenesis induced by physical or chemical agents.16

In the current study, there were 70 BCC cases in the facial region. Neoplasm of the skin is more frequently found on the face because it is continuously exposed to UV radiation with no protection.17 Cosmetically, the face is the most significant an-atomic space for many patients. Thus, malignant facial neoplasms pose a challenge in treatment: to have an oncologically account-able surgery and, at the same time, optimal cosmetic outcome.18 Analysis on the anatomical site for the occurrence of 70 cases BCC showed that the nose was the most common location, with 24 cases (34%), followed by the infraorbital area, with 19 (27%) cases. A study on 138 cases of BCC by Kang et al. showed a sim-ilar finding, where the nose was the most common site for BCC (44 of 138 cases, 31.9%).1 Omer et al. retrospectively reviewed 171 cases of BCC in the head and neck region and reported that BCC was more frequent in the nose (53 cases, 46,3%).19 Firas

et al. showed in 335 cases of BCC that the face was the most commonly affected site in both men (77%) and women (83%). It reflects the importance of solar radiation as the main causative factor in the pathogenesis of this condition.20

BCC on the nose is expected, including on the nasal tip, because the nose is the most projected portion of the face and is more exposed to UVR.15 Larger tumors can infiltrate and eventually destroy the neighbor areas due to muscle infiltration in the distal half of the nasal area, and, subsequently, the cartilage. BCCs of the lateral sidewall may also extend to the nasolabial fold and infiltrate the muscles and the orbicularis oculi in ad-vanced stages. Also, BCCs present on the nasal root, albeit rare, present a challenging defect closure due to its proximity with the medial canthus.21

In the present study, the mean tumor diameter was 1.8 cm. Most tumors measured between 1 cm and 2 cm in diameter (45 cases, 64.29%). In a previous retrospective review, Kang et al. found the most common tumor size was from 1 cm to 2 cm in 69 cases (50%), with a mean of 1.5 cm.1 Metastasis is expected to occur in tumors larger than 3 cm in diameter, with a risk of

Figure 5: Basal Cell Carcinoma Subtypes. (A) Nodular, (B) Pigmented, (C) Superficial, (D) Morpheaform


A

C

B

D


metastasis up to 1-2%. This risk increases to 20-25% and 50% in tumors with 5 cm and larger than 10 cm in diameter, respective-ly. A BCC larger than 10 cm in diameter is referred to as “giant” and poses a significant risk for morbidity and mortality.6

In our population, nodular BCC was the most frequently observed subtypes, and it was seen in 37 (52,86%) cases. This result is similar to that found by Codazzi et al., who observed the nodular subtype in 62.4% cases. This subtype more frequent-ly develops on sun-exposed areas.22 It typically presents a shiny, pearly papule or nodule with a smooth surface, rolled borders, and arborizing telangiectasias. Moreover, slow-growing, ad-vanced tumors can become large and ulcerate, classically referred to as a “rodent ulcer”. Advanced, infiltrative tumors can distort the structures they invade.23

All 70 tumors were treated by excision with surgical margins of 0.4-0.5 cm for complete clearance, and there was no recurrence in one to five years follow-up. The European Der-matology Forum (EDF) guidelines on surgical excision margin recommended the excision of BCC measuring less than 2 cm in diameter with 0.3 cm to 0.4 cm margin. In contrast, in cases of high-risk BCC, larger than 2 cm, the Forum recommended a margin of 0.5 cm to 1 cm. The EDF cited that previous studies showed complete clearance in 95% cases when such margins were used.24 Current guidelines suggest a range of peripheral margins between 0.2 cm and 0.5 cm in low-risk BCC and from 0.5 cm to 1.5 cm in high-risk lesions.25

All reconstructions in this study were successful with-out any significant aesthetic or functional deformity. The most

Figure 6: Distribution of BCC by Clinical Subtype

Figure 7: Distribution of BCC by Surgical Treatment



commonly used method of wound closure was local flap. All flaps survived without complications; there were no reports of hematoma, seroma, or severe infection. Advancement flap was the most frequently used flap technique (32 cases, 45.71%). The local flap was also the method of choice in a previous study (102 cases, 74.4%) and consisted of advancement flap, rotation flap, forehead flap, and transposition flap.26

In the advancement flap (Figure 8), the movement goes in a straight line parallel to its major axis, from the donor site to the recipient. This maneuver is possible due to the skin donor’s elasticity, resulting in a gain directly proportional to the flap’s length. On the other hand, to prevent ischemic necrosis of the flap’s apex, it is essential to respect a ratio of at least 3:1 between the major and minor axis of the flap.27 The mobilization can be facilitated by the excision of two Burrow’s triangles (exhaus-tion method) on the flap base. Dual opposing (H-plasty) can be advantageously exploited in specific anatomic sites where it is

necessary to keep aesthetic continuity (eyebrow, forehead, nose bridge, helix rhyme).28

The small number of subjects, and the inclusion of only one institution, limited our study. Future large-scale studies with additional data such as onset and recurrences will help better to delineate the BCC’s nature and corresponding optimal treat-ment.

CONCLUSIONBasal cell carcinoma is the most common type of ma-

lignant facial skin lesion. Our study showed that BCC more frequently occurs in women, on the nose, and in the group age of 46 to 64 years. The nodular subtype is the most common subtype with a 1-2 cm diameter, consistent with previously published reports. The advancement flap resulted in satisfactory facial reconstructive results, both cosmetically and functionally, following surgical excision. l


Figure 8: Bilateral advancement flaps on the nasal subunit. a) Pre-operative photograph

A B C

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Welly Wijayanti | 0000-0003-4862-8617Análise estatística; aprovação da versão final do manuscrito; concepção e planejamento do estudo; elaboração e redação do ma-nuscrito; obtenção, análise e interpretação dos dados; participação intelectual em conduta propedêutica e/ou terapêutica de casos estudados; revisão crítica da literatura; revisão crítica do manuscrito.

Khairuddin Djawad | 0000-0002-2316-1339Aprovação da versão final do manuscrito; concepção e planejamento do estudo; elaboração e redação do manuscrito; revisão crítica do manuscrito.


230

Original ArticlesAuthors:Daniela Alves Pereira Antelo 1 Jaqueline Barbeito de Vasconcellos 1

Rosane Orofino-Costa 1

1 Universidade do Estado do Rio de Janeiro, Rio de Janeiro (RJ), Brazil.

Corresponding author:Rosane Orofino-CostaAv. 28 de Setembro, 77, 2º andar Vila Isabel, Rio de Janeiro (RJ)20551-030E-mail: [email protected]


Study conducted at the Universidade do Estado do Rio de Janeiro, Rio de Janeiro (RJ), Brazil.


Acknowledgements:The authors would like to thank Allergan, Dermatus and Dermage for donating the botulinum toxin, phe-nol solution 88%, and the photopro-tector used in this study, and Andréa Reis de Souza Bernardes-Engemann for the guidance in making the figu-res, graphs, and tables.

Regional phenol peel and botulinum toxin: still an efficient and affordable treatment for periorbital and perioral wrinklesEstudo comparativo da aplicação regional de peeling de fenol e toxina botulínica: ainda um tratamento acessível e eficiente para rugas periorais e periorbitárias


ABSTRACTIntroduction: Patients often request anti-aging treatments of the perioral and periorbital regions. Most of the time, it is necessary to use a combination of procedures to meet the patient’s expectations. Objective: This is a prospective, single-center, and comparative study assessing the rejuvena-tion of the perioral and periorbital regions after treatment with medium depth chemical peel using phenol 88% with or without the previous application of botulinum toxin. Methods: Sixteen patients underwent regional peel with phenol 88%; eight received botuli-num toxin application two weeks before. The assessment was conducted using standard pho-tographs and evaluation scales by doctors and patients. Results: The overall evaluation by doctors and patients on the 45th day was considered ex-cellent or good for all patients, with little advantage for combined treatment in the periorbital region. Conclusion: Combining these two relatively low-cost procedures, often overlooked by dermatologists, resulted in a significant improvement in the changes related to aging in these areas.Keywords: Botulinum toxins type A; Chemexfoliation; Phenol; Rejuvenation

RESU MOIntrodução: Com frequência, pacientes solicitam avaliação e tratamento para o rejuvenescimento das regiões perioral e periorbitária. Na maioria das vezes, é preciso usar uma combinação de procedimentos para que o resultado atenda às expectativas. Objetivo: Por meio de um estudo prospectivo, unicêntrico e comparativo, comparar o rejuvenescimento das regiões perioral e periorbital, após tratamento com peeling químico médio com fenol 88% com ou sem a aplicação prévia de toxina botulínica.Métodos: O peeling regional de fenol 88% foi utilizado em 16 pacientes; em oito delas houve aplicação de toxina botulínica duas semanas antes. A avaliação foi feita por meio de fotografias padronizadas e escalas de avaliação por médicos e pacientes.Resultados: A avaliação global por médicos e pacientes no 45º dia foi considerada excelente ou boa para todas as pacientes, com pequena vantagem para o tratamento combinado na região periorbital.Conclusão: A combinação desses dois procedimentos de custo relativamente baixo, muitas vezes negligen-ciado pelos dermatologistas, resultou na melhora significativa das alterações do envelhecimento dessas áreas. Palavras-chave: Abrasão química; Fenol; Rejuvenescimento; Toxinas botulínicas tipo A


INTRODUCTIONPerioral (POR) and periorbital (POB) aging is a frequent

complaint of patients who seek to improve their facial appearan-ce. It consists of static and/or dynamic wrinkles, flaccidity, and actinic changes in the skin, such as elastosis, caused by ultraviolet radiation, senescence, and smoking. These factors contribute to the change in texture and rhytids in areas where the skin is sub-ject to frequent movement.1

It is necessary to combine procedures to obtain a satis-factory result, such as ablative lasers (Erbium or CO2), chemical peels, injections of botulinum toxin (BT) and hyaluronic acid, microfocused ultrasound, microneedling, and dermabrasion.1,2 Some of these procedures have high costs and results that do not always meet patients' expectations.

Unlike the deep peel obtained with the Baker-Gordon formula, phenol 88% is considered an average chemical peel. It affects the superior reticular dermis, promotes neocolagenesis, and attenuates static rhytids.3,4,5

BT injection causes a decrease in muscle contraction. Its application in small doses in the POR and POB regions impro-ves dynamic rhytids and attenuates the static ones.6

This study aims to compare the POR and POB regions’ rejuvenation through the treatment with localized phenol (PP) 88% peeling with and without prior application of botulinum toxin (BT).

STUDY DESIGN Prospective, single-center, and comparative study.

PATIENTS AND METHODSSixteen healthy women with static and dynamic wrinkles

in the POR and POB regions, classified into Fitzpatrick skin phototypes I to III and from the Dermatology Clinic of the State University of Rio de Janeiro, RJ, Brazil, participated in this project after signing the informed consent form. This study was conducted according to the rules issued by the Declaration of Helsinki, revised in 2013.

Electrocardiogram, blood count, and biochemical tests were performed with urea and creatinine levels before applica-tion. All patients used the triple combination at night (hydroqui-none 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%) topically for two weeks before the procedure and sunscreen SPF 30, daily, in the morning. The patients were divided into two groups of eight individuals. Group I (GI) received only with PP, and group II (GII) received PP and BT.

We diluted the onabotulinum toxin (onaBT) in 1 mL of sodium chloride 0.9% (final concentration of 100 U/mL) and applied it to eight patients (GII) two weeks before the peeling. Then, we injected 4 U BT in the POR region and 12 U on each side of the POB region (Figure 1).

The 16 patients used oral acyclovir (200 mg 8/8h) for five days, starting two days before the PP. After demarcation of the target areas, PP was conducted, using an applicator made by wooden chopsticks wrapped with cotton, containing a small amount of the phenol solution, for application in just one pass.

Between the applications of phenol in the two regions, a time interval of approximately 15 minutes was waited, offering water intake (flowchart, Figure 2). Jessner's solution and trichlo-roacetic acid (TCA) 35% were applied to the rest of the face, with a layer of Jessner followed by a layer of TCA until homoge-neous frosting was obtained.

After the PP, the patients were instructed to use solid va-seline on the whole face and gentamicin cream in the POB and POR areas for seven days, to maintain physical photoprotection during the protocol period and to take analgesics if necessary. The triple formula was reintroduced two weeks after the peels.

Face-to-face and photographic follow-up was performed one week (D7), two weeks (D14), and 45 days (D45) after the peel. The doctor subjectively classified the rhytids before and 45 days after the end of the treatment by their intensity in 1+, 2+ or 3+ (the most intense). The overall final result on D45 was classified as excellent, good, no change, or poor by the doctor and the patient, independently.


Perioral and periorbital phenol and BT 231

Figure 1: Doses (U) and points of application of the onabotulinum toxin, at a concentration of 100 U/mL. A. Periorbital region; B. Perioral region

A

B

RESULTSPatients’ age ranged between 41 and 78 years, with an

average of 56 years (53 in GI and 58 in GII).In the global assessment of GI and GII at D45, both phy-

sicians and patients considered the result as excellent, most of the time. There was no “no change” or “poor” results in any of the treated groups (Table 1).

Regarding the intensity of wrinkles in the POB region, GII decreased the score in 5/8 (62.5%) patients, while in GI, only 1/8 (12.5%) patients presented a reduction in the score

(Figures 3 and 4A). In the POR region, 3/8 (37.5%) patients in GII achieved the score reduction, while the other 5/8 (62.5%) remained unchanged. In GI, the score decreased in 2/8 (25.0%) patients, while 5/8 (62.5%) remained unchanged, and 1/8 (12, 5%) presented worsening of the score (Figures 4B, 5 and 6).

Regarding adverse events, post-inflammatory hyperchro-mia in the region treated with PP was observed in 2/8 (25%) patients, being resolved with the reintroduction of the triple for-mula and maintenance of sunscreen. There were no episodes of herpes simplex in the 16 patients treated.

232 Orofino-Costa R, Vasconcellos JB, Antelo DAP


Table 1: Global assessment 45 days after treatment with phenol and botulinum toxin for perioral and periorbital rhytids

Group I (s6 PP) n = 8 Group II BT+ PP n = 8

Doctor Patient Doctor Patient

N (%) N (%) N (%) N (%)

Excellent 6 (75.0%) 5 (62.5%) 5 (62.5%) 5 (62.5%)

Good 2 (25.0%) 3 (37.5%) 3 (37.5%) 3 (37.5%)

No change 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

Poor 00 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

BT - botulinum toxin, PP - 88% phenol peeling

Figure 2: Flow chart for phenol 88% peeling in the periorbital and perioral regions

Triple formula Minimum 2 weeks before

Aciclovir 200 mg 3x/d 2 days before + 3 days

ECG, blood count, urea, creatinine

Asepsis with alcohol 70% INPM

Phenol 88% LITTLE amount do not pass again!

Wait 15 minutes between regionsWater orally with straw in these intervals

Solid petroleum jelly, cleansing lotion, SOS analgesic

PHYSICAL PHOTOPROTECTION!

DISCUSSIONThe rhytids of the periorificial regions of the face are

usually considered markers of aging.7 They are also difficult to approach by dermatologists and plastic surgeons due to the skin

delicacy, in addition to the mouth and eyes movement and func-tion. Blepharoplasty, dermabrasion, BT, fillers, peels, and ablative lasers are some of the procedures used.8,9

The POR and POB regions’ treatment with PP is a tra-ditional technique, with significant results in static rhytids and low cost. However, some dermatologists restrict their use due to the publication of complications,10 mainly localized hypo-chromia. Limiting its use to skin phototypes I to III patients and associating Jessner's solution and TCA 35% in the adjacent area are useful measures. They increase safety since the face as a whole receives the skin renewal benefits. The post-inflammatory hyperchromia observed in two of our cases is relatively com-mon in countries with a hot climate and a mixed population. It is usually easy to treat with depigmenting agents and adequate photoprotection.11 Phenol is nephrotoxic and arrhythmogenic, regardless of its concentration or application technique. Therefo-re, it is essential to conduct laboratory and electrocardiographic evaluations after the anamnesis and physical examination.12 It is advisable to take an interval between applying it in the different regions to accelerate the elimination of phenolic metabolites in the urine, thus reducing the possibility of systemic complica-tions.13



Figure 3: Clinical result before and 45 days after the application of phenol 88% peeling in the periorbital region. A and B. phenol only; C and D. botulinum toxin and phenol peeling

A

C

B

D

Figure 4: Comparative graph of the pre-treatment clinical result and 45 days post-treatment, measured by the intensity of the rhytids (1+ to 3+) between the GI (group I - phenol only) and GII (group II - phenol + botulinum toxin). A. Periorbital region (GI p = 0.35 and GII p = 0.01)

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BT mainly treats dynamic wrinkles, being indicated in the face’s periorificial areas, whose movement can leave lines marked permanently.

Combining a procedure to treat static rhytids associated with another for dynamic wrinkles has benefits, as its results will be more evident and more durable. Although the amount of BT used in these regions is small,

Figure 4: Comparative graph of the pre-treatment clinical result and 45 days post-treatment, measured by the intensity of the rhytids (1+ to 3+) between the GI (group I - phenol only) and GII (group II - phenol + botulinum toxin). B. perioral region (GI p = 0.60 and GII p = 0.08)

PP’s neocolagenesis will have a longer duration.14 For healthy and fair-skinned people, PP is an excellent therapeutic option, at an affordable cost compared to ablative lasers. BT in-jections before peels also act in the reepithelization and remode-ling of collagen in a relatively adynamic environment.15

In this study, despite the small treatment groups and the

A

C

B

D

Figura 5: Clinical result before and 45 days after application of phenol 88% peeling in the perioral region, at rest. A and B. Phenol only; C and D. Botulinum toxin and phenol peeling



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subjective medical evaluation, a slight difference can be observed between monotherapy with PP and the combined treatment with BT and PP. This result is more evident in the POB region, given that most patients in the GII showed improvement in this area, in contrast to the improvement in only one patient in the GI. When globally assessing the POR and POB treatment, most patients considered the result excellent.

A

C

B

D

Figura 6: Resultado clínico antes e 45 dias depois da aplicação de peeling de fenol 88% na região perioral, contraindo. A e B – somente fenol; C e D – toxina botulínica e peeling de fenol

CONCLUSIONIn this comparative study, the treatment of POR and

POB rhytids with the association of botulinum toxin and PP was superior to monotherapy with PP and might be another safe and cost-effective option in managing these regions. The best results were obtained in the POB region. l




Daniela Alves Pereira Antelo | 0000-0001-8203-1772Aprovação da versão final do manuscrito; concepção e planejamento do estudo; elaboração e redação do manuscrito; obtenção, análise e interpretação dos dados; revisão crítica da literatura; revisão crítica do manuscrito.

Jaqueline Barbeito De Vasconcellos | 0000-0002-9726-0719Aprovação da versão final do manuscrito; elaboração e redação do manuscrito; obtenção, análise e interpretação dos dados; revi-são crítica da literatura; revisão crítica do manuscrito.

Rosane Orofino-Costa | 0000-0002-1603-418XContribuição no artigo: Aprovação da versão final do manuscrito; concepção e planejamento do estudo; elaboração e redação do manuscrito; obtenção, análise e interpretação dos dados; revisão crítica da literatura; revisão crítica do manuscrito.


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BV, Palermo E, Addor F, Metsavaht L, Rabello L, Mattos R, et al. Tratado de

Cirurgia dermatológica, cosmiatria e laser da Sociedade Brazileira de Der-

matologia. Rio de Janeiro: Elsevier; 2012. p.322-30.

2. Tamura BM. Avaliação de uma técnica simplificada para tratamento de

rítides da região perioral e periorbicular com laser de CO2. Surg Cosmet

Dermatol 2012;4(3):237-40.

3. Soleymani T, Lanoue J, Rahman Z. A. Practical approach to chemical peels:

a review of fundamentals and step-by-step algorithmic protocol for treat-

ment. J Clin Aesthet Dermatol. 2018;11(8):21-8.

4. Velasco MVR, Okubo FR, Ribeiro ME, Steiner D, Bedin V. Rejuvenescimento

da pele por peeling químico: enfoque no peeling de fenol. An bras Derma-

tol. 2004;79(1):91-9.

5. Lee KC, Sterling JB, Wambier CG, Soon SL, Landau M, Rullan P, et al. Seg-

mental phenol-Croton oil chemical peels for treatment of periorbital or

perioral rhytides. J Am Acad Dermatol. 2019;81(6):e165-6.

6. Dorizas A, Krueger N, Sadick NS. Aesthetic uses of botulinum toxin. Derma-

tol Clin. 2014;32(1):23-36.

7. Honigman R, Castle DJ. Aging and cosmetic enhancement. Clin Interv

Aging. 2006; 1(2):115-9.

8. Ozturk CN, Huettner F, Ozturk C, Bartz-Kurycki MA, Zins JE. Outcomes as-

sessment of combination face lift and perioral phenol-croton oil peel. Plas-

tic and Reconstructive Surgery. 2013;132(5):743-53.

9. Danhof RS, Cohen JL. A combination approach to perioral rejuvenation. J

Drugs Dermatol. 2016;15(1):111-2.

10. Bagatin E, Hassun K, Talarico S. Revisão sistemática sobre peelings. Surg

Cosmet Dermatol. 2009;1(1):37-46.

11. Davis EC, Callender VD. Postinflammatory hyperpigmentation: a review of

the epidemiology, clinical features, and treatment options in skin of color.

J Clin Aesthet Dermatol. 2010;3(7):20-31.

12. Kadunc BV, Vanti AA. Avaliação da toxicidade sistêmica do fenol em pee-

lings faciais. Surg Cosmet Dermatol. 2009;1(1):10-4.

13. Starkman SJ, Mangat DS. Chemical Peel (Deep, Medium, Light). Facial Plast

Surg Clin North Am. 2020;28(1):45-57

14. Gart MS, Gutowski KA. Overview of botulinum toxins for aesthetic uses.

Clin Plastic Surg. 2016;43(3):459-71.

15. Zimbler MS, Holds JB, KokoskaMS, Glaser DA, Prendiville S, Hollenbeak CS,

et al. Effect of botulinum toxin pretreatment on laser resurfacing results.

Arch Facia Plast Surg. 2001;3(3):165-9.


Original ArticlesAuthors:Mariane Massufero Vergilio 1 Pedro Alves da Rocha Filho 1

1 Universidade de São Paulo (USP), Ribeirão Preto (SP), Brazil.

Corresponding author:Mariane Massufero VergilioFaculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São PauloAvenida do Café, s/n Monte Alegre - Ribeirão Preto (SP)CEP: 14040-903 Email: [email protected]


Study conducted at the School of Pharmaceutical Sciences of the Ri-beirão Preto da Universidade de São Paulo, Ribeirão Preto (SP), Brazil


Sunscreen’s consumer behavior: influence of sensory aspects in the photoprotection habit and purchase motivationO comportamento do consumidor de protetor solar: influência dos aspectos sensoriais no hábito de fotoproteção e motivação de compra


ABSTRACTIntroduction: Using sunscreen is a behavior that reduces the risk of skin cancer, among other diseases. The consumer's preferences for sunscreen types can assist dermatologists in recommending the best product to their patients. Objective: This study aims to indicate consumption and photoprotection habits, investi-gating answers to sun protection problems. Methods: An exploratory cross-sectional study, conducted through a questionnaire, with data collected directly from the participants. Results: Among the 300 interviewees, 249 declared to consume sunscreens. We found that most consumers misused sunscreens, and this problem may be related to sensory perception after applying sunscreen to the skin. Also, consumers highlighted the importance of sensory perception, whether visual, tactile, or olfactory, when purchasing this type of product. Conclusions: This research reveals that the sensory characteristics, compliance, real effective-ness under normal conditions of use, and the market demand for sunscreens are interconnect-ed. Thus, we suggest that dermatologists balance the importance of sensory aspects, cost, and sunscreens brand when recommending them to consumers.Keywords: Behavior; Cosmetics; Dermatology; Questionnaires; Perception; Sunscreening agents; Sensation.

RESU MOIntrodução: O uso de protetor solar é um comportamento que pode ajudar a reduzir o risco de câncer de pele, entre outras doenças. Uma melhor compreensão das preferências do consumidor de protetores solares pode auxiliar os dermatologistas na recomendação deste produto aos seus pacientes. Objetivo: Indicar os hábitos de consumo e de fotoproteção, buscando respostas aos problemas relacionados à proteção solar. Métodos: Estudo exploratório do tipo transversal, realizado por meio de questionário, tendo os dados sido coletados diretamente com os participantes. Resultados: Dentre os 300 entrevistados, 249 mostraram-se consumidores de protetor solar. Detectou-se que grande parte dos consumidores faz uso incorreto de protetores solares, e esse problema pode estar rela-cionado à percepção sensorial após a aplicação do produto na pele. Além disso, destacou-se a importância da percepção sensorial, seja visual, tátil ou olfativa, como fator decisivo no momento da compra deste tipo de produto. Conclusões: Esta pesquisa revela que características sensoriais, uso efetivo, real eficácia em condições normais de uso e demanda do mercado de protetores solares estão interligados. Dessa forma, sugere-se que os derma-tologistas levem em consideração os aspectos sensoriais, o custo e a marca dos protetores solares ao fazerem suas recomendações aos pacientes. Palavras-chave: Comportamento; Cosméticos; Dermatologia; Protetores solares; Percepção; Ques-tionários; Sensação.

237


INTRODUCTION AND OBJECTIVESkin cancer is a serious public health problem worldwi-

de. It is the most common malignant tumor in humans, affecting individuals from all countries, regardless of age, sex, or social status.1 The main risk factor for skin cancer, melanoma, and non--melanoma, is excessive exposure to genotoxic and mutagenic ultraviolet (UV) solar radiation.2 Other factors, such as skin co-lor, light-colored eyes and hair, family or personal history of skin cancer, virus infection (human papillomavirus), immuno-suppression (mainly transplant patients), environmental and oc-cupational factors, may increase the risk of developing skin can-cer.3,4 Considering that the self-defense mechanisms against solar radiation are limited, the need to offer other means of photopro-tection whenever there is exposure to the sun becomes evident. Thus, photoprotection measures include primary, effective, and low-cost preventive actions, through health education, such as wearing specific clothing, hats, and glasses for sun protection and avoiding exposure to the sun during times of higher radiation. Correct use of a suitable sunscreen is the most effective way to ensure adequate sun protection.3,5,6

In 2018, Brazil was in the third position in the wor-ld sunscreen consumption ranking, and it is the largest Latin American market.7 However, most of the population misu-ses sunscreens, especially regarding the product’s amount that should be applied to the skin, the uniformity, the frequen-cy and the extension of the application area, as well as the need for reapplication every two hours.8-12 The recommended amount of sunscreen is 2 mg/cm2, which is the dosage used by manufacturers during performance tests and in vivo protection factor determination.8

According to the 2019-2020 Trends Notebook of the Brazilian Personal Hygiene Industry Association, one factor is essential in the category of sun protection products: a pleasant sensation.13 Consumers usually choose a product that spreads easily, with a moderately moist tactile sensation during the appli-cation, quick drying, followed by a smooth, dry post-application sensation, a mattifying effect, and little or no noticeable residue on the skin.13,14

This study aims to assess the consumer market for suns-creens, consumers’ lifestyle and usage, and to analyze how dif-ferent attributes influence the sensory perception of the leading brands of sunscreen for the body and face.

METHODSThis is an exploratory study of observational nature, with

a cross-sectional descriptive approach and structured primary data collection. It was conducted in a single moment, through a mixed questionnaire, with open and multiple-choice questions. The Research Ethics Committee of the Faculty of Pharma-ceutical Sciences of Ribeirão Preto approved the study (CAAE 50815815.6.0000.5403). Clarifications about the study, as well as the link leading to the questionnaire were disseminated through social networks.

The questionnaire structure consisted of questions to de-termine the participant's profile, followed by questions to identi-

fy whether the participant fit the survey (whether he was a con-sumer of photoprotective products or not) and, finally, questions about the consumer behavior.

The sampling used in this work was non-probabilistic, of accessibility or convenience type, to reach and seek a popu-lation that consumes sunscreens. The questionnaire’s answer was voluntary, and the confidentiality of the identity was guaranteed, with the online questionnaire open to answers for 15 days, in April 2016, aiming to capture around 100 responses from con-sumers.

RESULTSDuring the study, 300 valid responses were obtained.

Those who answered the question “Do you usually use suns-creen?” were considered sunscreen consumers, indicating that they always use sunscreen or when they are exposed to the sun. Thus, those who answered that they never use sunscreen had their answers considered ineligible. In total, 249 sunscreen con-sumers participated. Among the 51 participants who indicated never using sunscreen, 25 were men, and 26 were women.

Through the distribution of consumers by age and sex, we found that the sample group was mainly composed of indi-viduals between 17 and 35 years old, being considered a young audience. Also, the women’s frequency was approximately five to six times higher than men, totaling 37 men and 211 women.

We classified the group of consumers according to the skin phototype through self-assessment, following the Fitzpatri-ck scale. There was a higher incidence of participants with skin type II (39%), followed by type III (35%), type IV (16%), type I (9%), and type V (1%).

Consumers were asked about the exposure time and the time of day when they were most exposed to the sun. Graph 1 describes the results. We observed that 52% of consumers (131 participants) answered that they expose themselves between 10 am and 4 pm, a period when solar irradiation is more harmful to the skin,15 and 11 of them claimed to be exposed to the sun by more than two hours a day.

After the sample was adequately characterized, the study addressed topics related to the choice, application, and motiva-tors for purchasing sunscreen. Initially, consumers were asked about the application of sunscreens. Graph 2 depicts the users' answers to the question “In which areas of the body does the sunscreen usually go?”. The results found that most of the con-sumers (99.06%) use the product on the face. However, only 62.65% of consumers protect other regions often exposed, such as the neck and chest. According to the answers, we found that 43.37%, 72.29%, and 81.93% of the participants do not habi-tually apply sunscreen to the upper limbs, ear and neck, and lower limbs, respectively.

In the answers to the questions “Which sun protection factor (SPF) do you use?” and “Do you follow the use indica-tions present on the product packaging?” almost half of the users (49.4%) stated SPF 30. In comparison, 47.8% stated using SPF greater than 30. Only 56.2% claimed following the instructions

238 Vergilio MM, Filho PAR



Sunscreen’s consumer behavior 239

for use described on the product packaging. To check whether they followed these instructions, users answered the questions “Do you reapply the sunscreen?” and "How often do you rea-pply it?" Graph 3 describes the answers. We observed that only 41.4% of sunscreen consumers reapply the product throughout the day (Graph 3A). Among those who reapply the sunscreen (103 individuals), 62.1% answered that they reapplied only once a day, while 33.0% reapplied twice a day, and 4.9%, three times a day (Graph 3B).

Regarding the questions related to consumers’ products texture, we observed that users prefer lotions since 56.2% of the participants replied using sunscreen with lotion texture. Within this category, 26.1% of users chose anti-grease lotion.

To better understand what causes the participants’ dif-ficulty using the product, they answered the question “If you don't use or stopped using sunscreen, explain the reason”.

In addition to six multiple-choice alternatives, this ques-tion presented an open-ended question, where the participan-

Graph 1: Frequency of responses classified by time of exposure and time of day when consumers are exposed to the sun

Graph 2: Percentage of consumers who have the habit of applying sunscreen to certain regions of the body

ts could describe their reasons in detail. Therefore, open-ended responses underwent thematic analysis and were subsequently integrated into multiple-choice answers. The categorization was conducted according to nine different themes: forgetfulness, fra-grance, always use sunscreen, difficult application, high cost, eye discomfort, skin sensation, easier tanning, and time. Seven res-ponses were not categorized because they did not fit the themes. From the analysis shown in Graph 4, we observed that 72.9% of the responses cited forgetfulness as a reason why consumers stopped using sunscreen. The second main reason for not using sun protectors was the sensation they cause on the skin, a theme mentioned in 11.7% of the responses.

Also, users had to answer the open-ended question “What do you like least about a sunscreen?”. Thus, each par-ticipant had the opportunity to describe their opinion wi-thout the influence of answers predefined by the questionnai-re. The thematic analysis of the obtained answers previously categorized the responses. The categorization was conducted according to seven different themes: tactile/ visual percep-tion of the skin, damage to health, application, fragrance, rea-pplication/ fixation, price, and nothing against it. Among the answers obtained, ten were not categorized because they did not fit the proposed themes. According to these data (Graph 5), most responses are related to the products’ sensory aspec-ts since 56.7% cited characteristics related to the tactile and visual perception of the skin, and 20.5% cited the fragrance of the products as the least pleasing feature in a sunscreen. Of the remaining responses, in decreasing order, 10.4% ci-ted characteristics related to price, 5.0% to the application of the product, 3.6% to reapplication/ fixation, 2.2% claimed to have nothing against sunscreens, and, finally, 1.8% of the answers were related to some health damage that they belie-ved to have during the use of photoprotection.

The question "When buying sunscreen, what defines your choice?" was added to the questionnaire to detect the pur-chasing motivators for sunscreens consumers. There was also an open-ended question in addition to eight multiple-choice ques-tions, where the participant could describe his answer. Therefore, the thematic analysis of responses obtained previously catego-rized the solutions for the assessment of free responses. For the final analysis, these data were integrated with those obtained in the multiple-choice options. The categorization was conducted according to nine different themes: brand, price, indication of third parties, design/ packaging, sensation on the skin, texture, fragrance, product appeal (claim), and effectiveness. According to the data obtained (Graph 6), no participant indicated the design/


Graph 3: Percentage of consumers who reapply sunscreen. A. Percentage of consumers who reapply. B. Among the consumers who reapply, the frequency, in percentage, of that reapplication

Graph 4: Reasons why consumers of sunscreens stop using them


packaging as a purchase motivator. However, the skin sensation was the most chosen theme, mentioned in 27.6% of the respon-ses. The sunscreen brand proves to be a great purchase motivator (16.0%), as well as price and texture, both frequent in 14.4% of answers. The importance of sensory perception, whether visual, tactile, or olfactory, is also highlighted as a decisive factor when purchasing a product. We also noticed the great importance of third party referrals (11.6%) at the time of the purchase decision, especially when health professionals make the referral. In the question “Regarding the guidance on the need to use sunscreen, who made the indication?”, the dermatologist proved to be the leader in indication (57%), followed by family members (18%), media (14%), other professionals (7%), and friends (4%).

In the question "When choosing a sunscreen, assuming you don't know the brands and prices of any of them, which sensory characteristic would be the most decisive?", pre-analysis and analysis were conducted in the same way as the previous question. The categorization was carried out according to six different themes: dry touch, visual aspect, fragrance, aqueous re-sidue formation, skin sensation, and oiliness. Among the answers obtained, four of them were not categorized because they did not fit the objective of the question (Graph 7). In decreasing order of frequency, dry touch was the most mentioned, followed by skin sensation, oiliness, fragrance, and visual aspect.

DISCUSSIONThis study evidenced that the respondents not using

sunscreens were lower than those found in the literature.16-21 However, it revealed that many people still do not use sunscreen when exposed to UV radiation. This research’s result is surpri-sing and highlights the health concern, as Brazil has a continen-tal dimension, with almost all the territory located between the Equator and the Tropic of Capricorn, and it is considered the country with the greatest territory extension close to the sun.5

This study reveals that more than half of consumers are exposed to the sun in the period when solar irradiation is more harmful to the skin. Therefore, educational measures for sun exposure should be intensified and disseminated in Brazil, to prevent the development of damage caused by sun exposure, considering that epidemiological data that points to a continuous increase in skin cancer incidence.4

In Saudi Arabia, the prevalence of regular sunscreen use was found at a rate of only 23.7% of participants.16 In Turkey, low levels of sun protection habits have also been reported in children and adolescents.19,21 In Australia, in studies focused on children, only 58% were protected against sun exposure through the use of sunscreens. 22 In comparison, only 37% of teenagers and 33% of adults reported using sunscreen during outdoor ac-


Graph 5: Percentage of responses, by theme, about what the participant least likes in a sunscreen

Graph 6: Features that define consumers' choice of sunscreen

Graph 7: Sensory characteristics that define the purchase choice of sunscreen


tivities on summer weekends, in addition to other methods of sun protection.18

In Brazil, studies applying a questionnaire to a sample of university students found that most university students in the city of Campinas (SP) do not adequately protect themselves from sun exposure.23 Still, more than 60% of medical students in Fortaleza never or rarely apply sunscreen.20 An analytical cross--sectional study of a Brazilian university in Taquaritinga (DF),17 reported that only 25% of university students used sunscreen daily.

We found that the number of women who answered the questionnaire was greater than the number of men, and it may be considered a limitation of this study. Still, it is curious that among the people who claimed never to have used suns-creen, approximately half are men. Moreover, among con-sumers, men represented only a little more than a fifth of the participants. Such data suggest that, even with the fact that women predominantly composed the study sample, the-re is a gender influence on sun protection habits and beha-vior.16,20,21,23–26 When there is a more equitable proportion of men and women, women are more likely to use sunscreen and be aware of the connection between sun exposure and skin cancer.16 Gender and also age, educational level, self--esteem, and skin type are factors that affect sun exposure habits and sun protection behavior.25 Analyzing the time and period of the day of sun exposure, our results were better. A similar study, covering students aged 14 to 18, found that the most common time interval and sun exposure period among students was two h/day between 10 am and 4 pm during the week.21 From the classification of the consumer phototype, a multiethnic sample was not observed. Respondent consumers predominantly had skin phototypes II and III. A recent study conducted in the USA observed in multiethnic sampling that, although the skin cancer incidence is higher among non-His-panic whites, minority populations are often diagnosed with more advanced disease and are more prone to poor results.27 Furthermore, the study concluded that this outcome is rela-ted to the fact that public health education and interventions to promote sun protection behaviors are consistently directed towards non-Hispanic whites.27–29 Therefore, leading public health education efforts and conducting interventions to pro-mote sun protection in minority populations can be a bene-ficial approach to discuss skin cancer morbidity and mortality in these groups.27

Corroborating the low rate of sunscreen reapplication revealed in this study, in Italy, it was observed that, in addition to the low adherence by adolescents, only 50.4% of them rea-pplied the sunscreen.30 This research also reveals that consumers tend to ignore the sunscreen application in some body areas, especially ears, neck, and lower extremities.31 Also, consumers are not comfortable using the adequate amount of formulation, and generally, they apply less than recommended.9–11 Thus, one can think that the desired protection would not be as effective as indicated on the label.11 Therefore, it is essential to highlight the need for greater attention concerning the user's adhesion for the

most appropriate use of the photoprotector, as recommended by the manufacturer, to reach the SPF indicated on the packaging when using the product.

In contrast to the old trends in sunscreens, there is cur-rently high consumer demand for products that present a plea-sant sensation and provide a more refined aesthetic appearan-ce.13,32 Thus, the vehicle used in the formulation impacts the product’s sensory attributes, inducing the consumer to use it.33 Consequently, sunscreens with bad sensory characteristics will be less used.33 Among the unwanted sensory aspects, there is the perception, after application, of oily, hot and sweaty skin; the presence of a film or residue on the skin surface; and opaque white colors, associated with many formulations, especially those consisting of inorganic filters.33

When consumers in this study were asked about the motivators for buying sunscreens, the skin sensation, the tex-ture, the brand, and the price stood out. The formulations' sensorial dry touch properties proved to be essential for the purchase decision among these sensory characteristics. It is in line with the scientific literature since the demand for suns-creens with a light consistency, and easy scalability was always more significant in the Brazilian market, as consumers pre-fer to keep their skin dry and not shiny.13,14 Also, consumer demands have increased with the amplified market offer of products manufactured in South Korea and Japan, due to the smooth sensation, ease of spreading, and suitability for mixed or oily skin.13

In 2017, a study assessed both purchase drivers and suns-creen use,34 and it identified that the primary use motivators were to prevent sunburn, skin cancer, and premature skin aging.34 Moreover, the main factors that influenced sunscreen purchase decisions were water and sweat resistance, price, recommenda-tions from friends and family, followed by fragrance and pleasant texture.34 A 2018 study, covering a sample of medical students, found that the most critical characteristics of sunscreens that in-fluenced the product choice were SPF, texture, and protection against solar radiation.20

Expanding to the clinical area, these are essential points for the dermatologist to observe when prescribing sunscreens. Questions related to purchase motivation become crucial for the knowledge of consumer behavior, but more than that, they be-come important allies for the dermatologist to understand how his patients behave.

CONCLUSIONSConsidering the answers obtained through the question-

naire, we notice that most consumers acquire sunscreen critically and rigorously. When choosing and buying, they consider fac-tors such as the perceived sensation when using them. However, consumers were still careless about the correct use of sunscreens: most of them do not follow the directions for use described on the packaging label; they apply the sunscreen only on some parts of the body; many forget to use it, and when they remem-ber, they don’t reapply the product throughout the day. Several factors indicated low adhesion and misuse of sunscreen. Among



them, the study revealed that part is related to the product's sen-sory properties.

Also, the consumer is not yet aware of the total benefit of the sunscreen. However, the sensory characteristics are essen-tial in the purchase process's preference, being as decisive as the brand and its price. This research reveals that the sensory aspects, the effective use, the real effectiveness under normal conditions of use, and the market demand are interconnected.

Knowledge of such topics reveals a range of essential in-formation for the dermatologist to achieve a more modern and effective therapeutic approach. Knowing patients' behavior helps understand what impacts treatment can have on their quality of life and assists the physician in understanding more modern and humane therapeutic approaches. l

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Original ArticlesAuthors:Maria Laura Marconi França 1 Hélio Amante Miot 1 Juliano Vilaverde Schmitt 1 Thales Vianna Coutinho 2

1 Faculdade de Medicina de Botucatu, Botucatu (SP), Brazil.

2 Clinical Neuroscience Research Laboratory, Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brazil.

Corresponding author:Juliano Vilaverde SchmittAv. Prof. Mário Rubens Guimarães Montenegro, s/n UNESP - Campus de Botucatu, Botu-catu (SP), BrazilCEP: 18618-687


Study conducted at the Botucatu Medical School, Botucatu (SP), Brazil.

Financial support: FAPESP - Funda-ção de Amparo à Pesquisa do Estado de São Paulo.

Conflict of interest: None.

Acknowledgement: We thank FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo.

Evaluation of facial expression recognition in patients with facial melasma: a cross-sectional studyAvaliação do reconhecimento das expressões faciais em pacientes com melasma facial: um estudo transversal


ABSTRACTIntroduction: Melasma is frequent among women, and it is associated with a significant psychosocial impact. The facial expressions recognition is a cognitive process directly related to our emotional and psychosocial status. Objectives: This study evaluates the melasma patients' ability and healthy controls in identi-fying facial expressions reflecting six main emotions. Methods: This is a cross-sectional study, including 24 melasma patients and 24 healthy con-trols, matched for age. We collected demographic data, dermatology life quality index (DLQI), Hospital Anxiety and Depression Scale (HADS), and Social Phobia Inventory (SPIN). Also, we conducted a computerized facial emotion recognition test using 56 images. Results: The participants had a mean age of 39.8 (sd: 8.1), and the melasma patients reported a median of 84 months (p25-p75: 48-144) duration of the dermatosis and a median DLQI of 6 (2-10). Patients with melasma presented higher anxiety scores (9.4 [4] x 6.7 [4.3]; p=0.03) and showed higher accuracy in identifying emotions due to their greater success in recogniz-ing fear (35 [13-52] x 13 [3-25]; p=0.03). The non-biased right answers' difference remained significant after multivariate analysis adjusted for the anxiety scores (p<0.01). Conclusions: Women with melasma presented a higher accuracy in recognizing facial ex-pressions of fear, suggesting differentiated brain processing of emotions in this population.Keywords: Anxiety; Emotions; Melanosis

RESU MOIntrodução: O melasma é frequente entre mulheres, estando associado a significativo impacto psicossocial. O reconhecimento das emoções faciais é um processo cognitivo envolvido com o nosso status emocional e psicossocial. Objetivos: Avaliamos a habilidade de portadoras de melasma e controles hígidos em identificar expressões faciais das seis principais emoções. Métodos: Estudo transversal, com 24 portadoras de melasma e 24 controles, pareadas por idade. Foram coletados dados demográficos, qualidade de vida em Dermatologia (DLQI), escore hospitalar de ansiedade e depressão (HADS), fobia social (SPIN), e foi realizado um teste de reconhecimento de emoções faciais por computador com 56 imagens. Resultados: As participantes tiveram idade média de 39,8 (dp: 8,1) anos, e as portadoras de melasma relatavam uma mediana de 84 (p25-p75: 48-144) meses de duração da dermatose e um DLQI mediano de 6 (2-10). As portadoras de melasma apresentaram maior habilidade na identificação das emoções, devido a maiores acertos no reconhecimento do medo (35 [13-52] x 13 [3-25]; p=0,03), e maiores escores de ansiedade (9,4 [4] x 6,7 [4,3]; p=0,03). A diferença nos acertos não enviesados manteve-se significativa após análise multivariada ajustada pelos escores de ansiedade (p<0,01). Conclusões: Mulheres portadoras de melasma apresentaram maior habilidade no reconhecimento da ex-pressão facial de medo. Palavras-chave: Ansiedade; Emoções manifestas; Melanose

245



Figure 1: Examples of facial expressions of happiness and fear used in the facial emotion recognition test (8 examples x 7 emotions = 56 images per test).

246 França MLM, Miot HA, Schmitt JV, Coutinho TV

INTRODUCTIONMelasma is a frequent dyschromia among women and is

associated with significant psychosocial impact on patients’ qual-ity of life. It usually begins between the third and fourth decades of life in people with mixed color skin. Despite being associated with chronic sun exposure, genetic factors, and sex hormones, its etiopathogenesis is not fully understood. Changes such as solar elastosis, dermal inflammatory process, and basement membrane damage found in skin with melasma, suggest the role of inflam-matory cells such as mast cells and photoaging in the disease’s etiopathogenesis.1–3

Among the psychological changes related to melasma, there has been a greater propensity to stress and anxiety, and emotional processing may be altered in this population. Also, quality of life, understood as a general perception of well-being involving different aspects of the individual’s life, seems to be significantly affected in melasma patients.4,5

Recognition of facial emotions is a cognitive process directly involved with our emotional and psychosocial status. Emotional changes may be related to accuracy in recognizing the different emotions expressed by others.6–8 Recognition and interpretation of emotional facial expressions play a crucial role in adapting to the environment and facilitating social interac-tion.9

Since 1990, visual affective stimuli have been used in research on emotions, since image visualization has privileged access to the semantic network where affective information is stored.10

In the present study, we assessed the melasma patients’ ability and healthy controls to identify facial expressions of the six main emotions (fear, anger, joy, sadness, surprise, and dis-gust). We sought to verify if there is any differentiation in this cognitive capacity between groups and some correlation with questionnaires already translated and validated in Brazilian Por-tuguese about quality of life (DLQI), symptoms of anxiety or depression through the Hospital Anxiety and Depression Score (HADS), and social phobia through the Social Phobia Invento-ry (SPIN). These characteristics can affect the facial recognition ability of emotions.

METHODSA cross-sectional study was conducted with 24 melasma

patients and 24 previously age-matched controls without der-matological complaints. The study included women aged 18 to 60 years, recruited from the between January and October 2016, with no difficulties in understanding or communication, no de-creased visual acuity, and no accompanying psychiatric comor-bidities, according to the participant’s report, after signing the informed consent form.

The institution’s ethics committee approved the study.Demographic data were collected, and the Dermatolo-

gy Life Quality Index (DLQI), Hospital Anxiety and Depres-sion Scale (HADS), Social Phobia Inventory (SPIN) question-naires, all validated in Portuguese, were applied. Also, we used an emotion recognition test through a computer-assisted facial

image. The test randomly displayed, on a 16-inch monitor, eight copies of each illustrated emotion (anger, disgust, joy, neutral, sadness, surprise, and fear) totaling 56 images.11–16 Each image was preceded by a 3 seconds countdown and presented for 0.5 seconds before being hidden, in an adaptation of Calvo’s meth-od (2008).17 The interviewee had free time to indicate which emotion she had recognized after each photo presented, and the image could not be shown again. (Figure 1) The 56 open access facial expression images were obtained from the Karolinska In-stitute (Solnavägen, Solna, Sweden).18

The HADS questionnaire was used because it is an open-access tool, often used in research on anxiety in medical studies, which reported higher anxiety levels in women with melasma. The report of interference of this feature with the abil-ity to recognize emotions justifies the analysis of social phobia through SPIN, a tool validated for Portuguese.19

Continuous variables were analyzed between the case and control groups by the Student-parametric t-test or the Mann-Whitney non-parametric test according to the normality of the distributions assessed by the Shapiro-Wilk test.20 Categor-ical variables were compared by the chi-square or Fisher’s exact when the lowest expected value was less than 6. The ability to recognize emotions was assessed by the bias hit index adjust-ed by a mixed generalized linear model with gamma distribu-


Table 1: Demographic and psychometric features and accuracy on facial emotion recognition test for the study groups.

Features Melasma Controls OR (CI 95%) p

Age* 39.5 (7.5) 40.1 (8.7) - 0.81

Married / civil union** 15 (62.5) 16 (66.7) 0.83 (0.25 to 2.72) 0.77

Income up to 3 minimum wages** 18 (75) 17 (70.8) 1.23 (0.34 to 4.42) 0.76

Complete basic education** 10 (41.7) 12 (50) 0.71 (0.22 to 2.23) 0.56

Regular study years† 8.5 [4-11] 11 [5-11] - 0.25

Spin† 15.5 [10-25] 14 [7-25] - 0.57

HADS-depression† 7 [6-8] 6.5 [4-9] - 0.45

HADS-depression ≥ 8** 9 (38) 9 (38) 0.99

HADS-anxiety* 9.4 (4) 6.7 (4.3) - 0.03

HADS-anxiety ≥ 8** 18 (75) 11 (46) 0.04

Total hits (%)† 77 [70-80] 69 [58-76] - 0.04

Accuracy by emotion ‡

Anger† 59 [44-68] 50 [28-64] - 0.33

Disgust† 75 [45-76] 64 [52-76] - 0.72

Happiness† 100 [88-100] 97 [88-100] - 0.49

Neutral† 70 [62-80] 61 [38-89] 0.84

Sadness† 57 [28-75] 48 [22-57] - 0.27

Surprise† 59 [44-67] 45 [36-53] - 0.24

Fear† 34 [13-50] 13 [3-25] - 0.03

* Mean (standard deviation); Student’s t test; ** n (%); Fisher’s exact test ; † Median [1 quartile – 3 quartile]; Mann-Whitney’s test.‡ Significance corrected by the sequential Sidak method; unbiased scores: 100 * hits2 / (8 * total use of the option).

Evaluation of facial expression recognition in patients with facial melasma 247

tion and post-hoc significance adjusted by the Sidak sequential method.18,21,22

RESULTSTable 1 compares the demographic and psychometric

data between the groups, where there are higher HADS anxiety scores among melasma patients. Patients with melasma had a median of 84 (p25-p75: 48-144) months of disease duration and a median DLQI of 6 (2-10). There was no difference between the groups regarding marital status, income, education or social phobia scores and depression.

Women with melasma had a greater ability to identi-fy emotions due to better recognition of fear expression (Fig-ure 2). Multivariate analysis, adjusted for HADS anxiety values, confirmed this finding, with better performance only for fear expression (p <0.01). The difference between melasma patients and controls in fear recognition was significant for those with HADS anxiety above 7 (36 [13-50] x 8 [3-16]; p <0.01), but not for those with lower HADS anxiety levels (22 [4-33] x 13 [6-25]; p = 0.46).

There was no correlation between fear recognition scores and HADS anxiety (Rho = 0.08; p = 0.58) or DLQI (Rho = 0.23; p = 0.29) values.

DISCUSSIONPatients with melasma presented correct identification of

facial expression of fear, as well as higher anxiety scores. The significance of the correctness in recognizing emotions was ad-justed by Sidak’s sequential method to decrease the chance of such findings occurring at random due to multiple comparisons. Also, the groups were age-matched and had similar education, income, marital status, and depression and social phobia scores.

Previous studies have already identified a possible associ-ation between stress and anxiety with melasma, which may be related to facial recognition of emotions. In 2008, a study found that 26.3% of women reported melasma stress as an aggravat-ing factor of the disease, and 28.6% had a previous psychiatric diagnosis between depression and anxiety. 5 Similarly, Bimal et al. (2017) identified high anxiety scores in 36.6% of melasma patients in northern India.23

Wolf et al. (1991) reported two melasma cases that man-ifested two to three months after acute stressful events (death of family members), with no other obvious risk factors.24 Finally, Handel et al. (2014) found higher levels of anxiety and increased consumption of anxiolytics or antidepressants in women with melasma.4

Figure 2: Accuracy (unbiased hits) on the recognition of fear facial expression (Boxplot).



In addition to reports of the association between stress and anxiety with melasma, the symmetrical facial feature, regu-larly involving areas innervated by the trigeminal nerve, suggests that the nervous system may play a significant role in the patho-physiology of the disease. In this sense, Bak et al. (2009) identi-fied increased expression of nerve growth factor (NGF) recep-tors and neural endopeptidase in melasma lesions compared to normal adjacent skin.25

Significant evidence indicates that stress-associated events in animal and human models are associated with changes in NGF production or action. Also, NGF may promote the re-modeling of damaged tissues following acute or chronic stressful events.26

Peters et al. (2004) found in animal studies that NGF release is a major step in stress-induced capillary growth and fall, as well as the activation of mast cells and antigen-presenting cells in the skin.27

The present study’s findings indicate that melasma pa-tients have a greater ability to recognize fear facial expressions. Furthermore, Surcinelli (2006) found that people with high anxiety levels have a greater ability to recognize fear in facial expressions.6 Thus, our findings corroborate the observation of a higher anxiety level in women with melasma according to Handel et al.4

Different psychosocial and socioeconomic factors may influence facial recognition of emotions. However, considering age matching and the absence of significant differences regard-ing marital status, income, and education level between the two groups in the present sample, the findings suggest the existence of a significant relationship between melasma, anxiety, and the ability to recognize facial emotions.

Recognition of fear facial expression is particularly as-sociated with the amygdala’s function, with bilateral lesions in these parts of the brain leading to prominent impairment of this ability.28 Also, Stein et al. (2007) found that people prone to anx-iety show greater activation of the amygdala and insula during brain processing of emotions.29

By analyzing subgroups according to HADS anxiety levels, we found that the difference in recognition of fear ex-pression was significant only in participants with higher anxi-ety scores, suggesting that emotional processing of anxiety may differ between women with and without melasma, leading to different impacts on facial recognition of emotions.

The observed results suggest that melasma patients may present a greater amygdala activity and anxiety propensity; how-ever, causal relationships between this observation and skin changes cannot be concluded in the present study. The trigemi-nal nerve may be the connection between skin and psychologi-cal changes. Effective treatment of persistent generalized anxiety through percutaneous trigeminal electrical stimulation has been reported, indicating the propagation of facial stimuli to nuclei involved in the processing of emotions, such as the amygdala and insula, through extensive connections to the trigeminal nu-clei of the brain stem.30–32 Trigeminal stimuli related to amygdala activity could influence inflammatory and pigmentary changes observed in melasma.

The present study has limitations because it is mono-centric and only includes patients from the public healthcare system, which may impair the results’ external validity. On the other hand, the results corroborate previous findings from the literature on the subject.

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11. Martins GA, Arruda L, Mugnaini ASB. Validação de questionários de

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12. Osório FL, Crippa JA, Loureiro SR. Evaluation of the psychometric pro-

perties of the Social Phobia Inventory in university students. Compr

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13. Marcolino JAM, Mathias LA da ST, Piccinini Filho L, Guaratini AA, Suzuki

FM, Alli LAC. Hospital Anxiety and Depression Scale: a study on the va-

lidation of the criteria and reliability on preoperative patients. Rev Bras

Anestesiol. 2007;57(1):52-62.

14. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a sim-

ple practical measure for routine clinical use. Clin Exp Dermatol.

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15. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta

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16. Connor KM, Davidson JR, Churchill LE, Sherwood A, Foa E, Weisler RH.

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Evaluation of facial expression recognition in patients with facial melasma 249


CONCLUSIONWe can conclude that the women with melasma eval-

uated presented a better performance in recognizing the facial expression of fear, especially among those with higher anxiety levels, suggesting possible connections between the disease’s

pathophysiology and characteristics of brain processing of emo-tions. Although consistent with the literature, this finding should be extended to different groups and centers to verify their ex-ternal validity. l


Maria Laura Marconi França | 0000-0003-0379-4558Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data col-lection, analysis, and interpretation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Hélio Amante Miot | 0000-0002-2596-9294Statistical analysis; approval of the final version of the manuscript; active participation in research orientation; critical revision of the manuscript.

Juliano Vilaverde Schmitt | 0000-0002-7975-2429Statistical analysis; approval of the final version of the manuscript; study design and planning; preparation and writing of the ma-nuscript; data collection, analysis, and interpretation; active participation in research orientation; intellectual participation in pro-paedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Thales Vianna Coutinho | 0000-0002-7968-0154Study design and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; active parti-cipation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.



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tol. 1991;125(2):192.

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26. Aloe L, Alleva E, Fiore M. Stress and nerve growth factor: findings in ani-

mal models and humans. Pharmacol Biochem Behav. 2002;73(1):159-66.

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251


Original ArticlesAuthors:Rogério Nabor Kondo ¹ Airton Dos Santos Gon 1 Paulo Muller Ramos 2

1 Regional University Hospital of Northern Paraná, Universidade Estadual de Londrina (PR), Brazil.

2 Universidade Estadual Paulista Júlio de Mesquita Filho, Botucatu (SP), Brazil.

Corresponding author:Rogério Nabor KondoAv. Ayrton Senna da Silva, 1055, sala 1205Gleba Fazenda Palhano, Londrina (PR), BrazilCEP: 86050-460E-mail: [email protected]


Study conducted at the Dermatolo-gy Service of the Regional University Hospital of Northern Paraná, Univer-sidade Estadual de Londrina (PR), Brazil.

Financial support: None.Conflict of interest: None.

Acknowledgments: The authors would like to thank the patients for their voluntary participation, the SAME of the Specialties Ambulatory of the University Hospital, and the provision of samples by Momenta Pharmaceuticals.

Use of nutricosmetic based on proteoglycan in non-cicatricial alopecia in children and adolescentsUso de nutricosmético à base de proteoglicanos em alopecias não cicatriciais em crianças e adolescentes


ABSTRACTIntroduction: Nutricosmetics have been used as supplements for hair growth in the treatment of non-cicatricial alopecia. However, there are no studies on using of these products in individ-uals under 18 years of age. Objective: To assess the efficacy and tolerability of using a nutricosmetic product based on proteoglycans in individuals under 18 years of age with non-cicatricial alopecia. Methods: This is a clinical, uncontrolled, and prospective trial. Patients with non-cicatricial alopecia, of both sexes, aged between 6 years and 18 years, received nutricosmetics containing proteoglycan for six months. Three dermatologists independently evaluated standardized pre and post-treatment photos. A hair count was performed in a scalp area of 1 cm2, and the pa-tients answered a questionnaire about improvement or worsening. Results: Eleven patients (100% women) were included. Ten (91%) showed improvement after six months, observed through photographic evaluation, hair count, and self-assessment. No patient presented allergies. Two patients had transient epigastric pain. Conclusions: The use of proteoglycans-based nutricosmetics was effective and well-tolerat-ed in children and adolescents with non-cicatricial alopecia.Keywords: Alopecia; Hair follicle; Proteoglycans; Treatment outcome

RESU MOIntrodução: Nutricosméticos têm sido utilizados como suplementos para crescimento capilar no tratamento de alopecias não cicatriciais, porém não existem estudos sobre o uso desses produtos em indivíduos abaixo de 18 anos de idade. Objetivo: Avaliar a eficácia e a tolerabilidade do uso de um produto nutricosmético à base de proteoglicanos em indivíduos menores de 18 anos, portadores de alopecias não cicatriciais.Métodos: Ensaio clínico, não controlado e prospectivo. Portadores de alopecias não cicatriciais, de ambos os sexos, com faixa etária entre seis e 18 anos, receberam nutricosmético contendo proteoglicano por seis meses. Fotos padronizadas pré e pós-tratamento foram avaliadas independentemente por três dermatologistas. Foi realizada contagem de fios em área de 1cm2 do couro cabeludo, e os pacientes responderam a questionário sobre melhora ou piora. Resultados: Foram incluídas 11 pacientes (100% do sexo feminino), nas quais 10 (91%) apresentaram melhora após seis meses, constatada por meio de avaliação fotográfica, contagem de fios e autoavaliação. Nen-huma paciente apresentou alergia. Duas pacientes apresentaram desconforto epigástrico transitório. Conclusões: O uso de nutricosmético à base de proteoglicanos foi eficaz e bem tolerado em crianças e ado-lescentes portadores de alopecias não cicatriciais. Palavras-chave: Alopecia; Folículo piloso; Proteoglicanas; Terapêutica

252 Kondo RN, Gon AS, Ramos PM


Table 1: Distribution by sex, age, phototype and diagnosis

Sex Age Fothotype Diagnosis

01 F 16a +1m+4d III Eflúvio telógeno

02 F 13a+11m+8d IV Eflúvio telógeno

03 F 17a+2m+21d III Eflúvio telógeno

04 F 11a+2m IV Tricorrinofalangiano-1

05 F 17a+1m III Eflúvio telógeno

06 F 17a+4m+26d III Tricorrinofalangiano-1

07 F 9a+9m+25d III Alopecia areata

08 F 16a+2m+28d II Eflúvio telógeno

09 F 9a+11m+19d III Alopecia areata

10 F 13a+9m+19d IV Alopecia areata

11 F 13a+6m+16d III Moniletrix

F=female a=age; m=months; d=days;

Figure 1: Instrument with 1 cm2 for counting hair strands.

INTRODUCTION Hair does not play a vital role in humans. Still, aesthet-

ic impairment can bring psychological damage to patients, due to its loss or rarefaction (alopecia), especially in children and women.1,2,3 Hair loss is a frequent complaint in the dermatolog-ical office.4,5Alopecia can be subdivided into two large groups: non-scarring, potentially reversible; and scarring, characterized by permanent damage to the hair follicle.1,6 Non-scarring alo-pecia is the most common form.7

Nutricosmetics (NC) contain vitamins, minerals, colla-gens, proteoglycans, and other substances, that work with food supplements. They are not considered drugs.8,9,10 NCs have been widely used as an adjuvant therapeutic option in the treatment of alopecia, with the advantage, according to the pharmaceutical industry, 10-13 of presenting good results with few adverse events. However, few clinical studies support their use.11,12 They have even been studied in pregnant women,14 but there are no studies involving children and adolescents.

OBJECTIVEThe study’s objective was to evaluate the efficacy and tol-

erance of a nutricosmetic based on proteoglycans in individuals under 18 years of age with non-scarring alopecia.

METHODSWe conducted an open, prospective, and uncontrolled

clinical trial.By convenience sample, we selected patients with

non-scarring alopecia, of both sexes, less than 18 years old, seen at the Specialties Clinic of the Hospital Universitário de Londri-na from November 2016 to October 2019. Participants received nutricosmetics (NC) based on specific 300 mg proteoglycans (versicans, decorins, and syndecans) in addition to acerola extract (118 mg), biotin (30 mcg), and silicon (75 mg).

The exclusion criteria were: allergy to fish (one of the product’s components), scarring alopecia, and current use of any treatment for alopecia or other supplements.

The institution provided the NC, and it was self-admin-istered in two daily doses (tablets could be macerated for inges-tion, if necessary).

Hair counting was performed in an area of 1 cm2 at the scalp’s most affected area due to alopecia before and after treat-ment. The principal investigator counted all the hair strands in-side the mold with tweezers’ aid through a 1cm x 1cm square hole made in a plate (Figure 1). There was no cutting or shaving of the hair.

Three dermatologists, members of the Brazilian Society of Dermatology and not involved in the research, evaluated stan-dardized photos before and after treatment. The photos were as-

Use of nutricosmetic based on proteoglycan in non-scarring alopecia in children and adolescents. 253


Table 2: Main results of the use of nutricosmetics consisting of proteoglycans for the treatment of non-scarring alopecia in individuals less than 18 years of age.

Paciente T0 T6 p-valor

Densidade capilar (fios/cm2)

01 82 126

02 106 178

03 104 166

04 136 204

05 168 174

06 84 146

07 12 86

08 94 154

09 11 92

10 06 84

11 56 86

Densidade média dos participantes * 78 136 0,02

Avaliação fotográfica (3 dermatologistas)**

Piora importante - 0/33

Leve piora - 0/33

Inalterado - 3/33

Leve melhora - 16/33

Melhora importante - 14/33

Avaliação melhora leve/importante - 30/33 0,02

*(média de fios e contagem de fios por paciente): T0(pré-tratamento); T6 (após 6 meses de tratamento)**(avaliação de 3 dermatologistas cegos independentes no total de 33 respostas possíveis)

sessed both in chronological order (pre and post-treatment) and inverted to reduce the evaluator’s bias. The dermatologists were informed about it and assessed the photos without knowing their chronological order. Scores were: -2 (significant worsening); -1 (slightly worsening); 0 (unaltered); +1 (slight improvement); + 2 (important improvement). The analysis only considered pre and post-treatment assessments.

Patients also answered a self-assessment questionnaire at the end of 6 months, indicating worsening, no change, and im-proving.

The following data were collected and entered into an Excel spreadsheet: name, hospital patient registration number, gender, age, phototype, duration of hair loss, previous treatment, laboratory tests (blood count, platelets, ferritin, TSH, blood glu-cose, creatinine, and transaminases).

The data were analyzed and processed using the Graph-Pad Instat and Excel 2007 software. Statistical significance was performed using the chi-square test, considering the 5% sig-nificance level (p <0.05) and applied to compare sex and im-

provement. The outcomes were: density of hair in the target area, photographic evaluation, and self-evaluation of patients.

The Institution’s Ethics and Research Committee ap-proved the research, C.A.A.E number 57073416.9.0000.5231. The parents or guardians of the study participants signed the informed consent.

RESULTEleven patients were included, and their serum tests were

normal. Although the study was not gender exclusive, subjects were 100% women, significant compared to men (p = 0.001). Age ranged from 9 years to 17 years (average of 13.2 years). Ta-ble 1 presents the diagnoses, with telogen effluvium being more prevalent (5/11).

Ninety-one percent (10/11) of the patients improved af-ter six months of treatment when considering hair count and photo evaluation (Table 2 and Figures 2-5).

The invited dermatologists’ evaluation of photographs pointed to an improvement in most cases (16 responses for slight


A B

Figura 2: A - Patient with occipital alopecia areata (ophiasis). B. After 6 months of treatment

Figure 3: A - Patient with alopecia areata on scalp vertex. B. After 6 months of treatment

Figura 4: A - Patient with telogen effluvium B. After 6 months of treatment

A

A

B

B



Figure 5: A - Patient with monilethrix. B. After 6 months of treatment

A B


improvement and 14 responses as a significant improvement, in 33 possible responses). Three responses were left unaltered (Table 2).

The monilethrix patient (Figure 4) answered a question-naire stating no improvement during the six months. However, the photographs and hair count showed improvement.

One patient (Figure 5) answered the questionnaire stat-ing no improvement. The photographs showed no significant increase in volume. The increase in 6 hair strands (168 per cm2 to 174 hair strand) was not significant when compared to the increase in other patients (p = 0.59), with consistency between the three points of evaluation (hair count, clinical and self-eval-uation).

No patient reported allergies. The two youngest patients had an initial epigastric discomfort (nausea without vomiting) upon the ingestion of the nutricosmetic. None of the patients had abdominal pain or diarrhea related to product administra-tion.

DISCUSSIONAlopecia can bring psychological harm to patients, es-

pecially children, adolescents, and women.1,3 The 100% women sample can prove this (underage girls) since the study’s objective was not to exclude the men population.

Hair growth supplements are NC containing different vitamins, minerals, collagens, proteoglycans, and other substanc-es.8,11,12,15 Even pregnant women have been evaluated in previous studies,11 but there are no studies involving children and ado-lescents. It could be motivated by the difficulty in taking pills, little voluntary demand by children and adolescents for medical services, preference for topical treatments, and the difficulty in releasing parents for clinical trials.

The NC used in the present study contains 300 mg of proteoglycans (versicans, decorins, and syndecans) extracted from fish, in addition to acerola extract (118 mg), biotin (30 mcg), and silicon (75 mg), which help in the hemostasis of the

human hair follicle.Proteoglycans (PG) are the main components of the ex-

tracellular matrix (ECM), with direct and indirect cell signal-ing, presenting independent roles in regulating the hair follicle’s growth state. They can control the activation of growth factors and other anagen inducers. Therefore, their concentration is a determining factor for the interaction cascades that lead to an-agen initiation.8

Another key PG with anagen-inducing properties is decorin. It acts as a signal through the canonical insulin-like growth factor (IGF) signaling cascade and directly regulates cell death and the synthesis of other matrix constituents. Decorin actively blocks the transformation of growth factor-beta 1 (TGF-β1), a potent inducer of apoptosis and catagen, making it a potential anagen inducer.8

Also, PGs increase the stability of collagen fibrils and pro-tect them from proteolytic cleavage. Thus, they are key modu-lators of fibrillogenesis. Versican has been shown to enhance the expression of fibronectin and β1-integrin that facilitates cell-ECM adhesion.8

The NC’s adverse events are dyspepsia (gastric discom-fort) and itching, especially in people allergic to fish.11

Telogen effluvium is a frequent cause of hair loss. 1,7 However, there are no data on its incidence in children and ado-lescents. The diagnosis was based on clinical history, traction test, normal trichoscopy, and removal of other causes. The presence of the TRPS-1 gene confirmed Trichorhinophalangeal syndrome type-1.17 Clinical18 and dermoscopic examination diagnosed the alopecia areata and monilethrix.

At the beginning of the medication, the participants’ age range did not exceed 17 years + 6 months + 29 days to not reach the full 18 years after six months of treatment (Table 1). According to photographic evaluation, capillary density, and self-assessment questionnaire, 91% of the patients improved after


Figure 6: A - Patient with telogen effluvium. B. Patient after 6 months. Apparently no volume improvement.

A B


six months of treatment (Table 2 and Figures 2, 3, 4, and 5). Only one case showed no improvement (Table 2 and Figure 6).

The dermatologists’ evaluations of the photographs were in agreement with the result of the assessment of the capillary density of the most affected area. The option of not knowing which ones were the pre and post-treatment photos was meant for not inducing their responses.

None patient presented allergies. Two patients (the youngest) had to macerate the product and had nausea without vomiting at the beginning of the treatment, but completed the study. There were no complaints of epigastric pain, abdominal pain, or diarrhea.

The main limitations of the study are a small sample, not being controlled, the inclusion of participants with different di-agnoses, and the possibility of spontaneous improvement of alo-pecia areata and telogen effluvium.16,19

CONCLUSIONThe use of NC based on proteoglycans in monotherapy to

treat children and adolescents with non-scarring alopecia proved to be effective and well-tolerated. These preliminary findings need to be confirmed by controlled, larger sample studies. l



Rogério Nabor Kondo | 0000-0003-1848-3314Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; criti-cal literature review; critical revision of the manuscript.

Airton dos Santos Gon | 0000-0003-1219-5581Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; active participation in research orientation; critical literature review; critical revision of the manuscript.

Paulo Muller Ramos | 0000-0002-1561-414XApproval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; active

participation in research orientation; critical literature review; critical revision of the manuscript.

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19. Cranwell WC, Lai VWY, Photiou L, Meah N, Wall D, Rathnayake D, et al.

Treatment of alopecia areata: an australian expert consensus state-

ment. Australas J Dermatol. 2019;60(2):163-70.


258


Original Articles

Authors:Flávia Trevisan 1 Gabriela Ferreira Kalkmann 2

Isabela do Prado Nascimento 2

Emerson Luis Batista Filho 2

1 Dermatologist Master in Internal Medicine,Universidade Federal do Paraná, Curitiba (PR), Brazil.

2 Medical Student, Universidade Federal do Paraná, Curitiba (PR), Brazil.

Corresponding author:Flávia Trevisan R. Alcídio Viana, 916, sala 705 São Pedro, São José dos Pinhais (PR)83005-560 E-mail: [email protected]


Study conducted at the Universida-de Federal do Paraná, Curitiba (PR), Brazil.


Acknowledgments: We thank the residents of the Complex Dermatolo-gy Service of the Hospital de Clínicas, Universidade Federal do Paraná.

Pain tolerance and aesthetic result of removing acrochordons with contact cryotherapy compared to electrocoagulationTolerância à dor e resultado estético da remoção de acrocórdons com crioterapia de contato em comparação à eletrocoagulação


ABSTRACTIntroduction: Acrochordons are very prevalent in dermatological offices and can reach al-most 60% of the population over 70. One possible therapeutic approach is contact cryotherapy. Objectives: Compare pain tolerance, aesthetic results, and the preference of participants for electrocoagulation or contact cryotherapy techniques in the treatment of acrochordons. Methods: Ten participants, with at least four acrochordons each, had their lesions divided into two groups. One group was submitted to electrocoagulation and the other to contact cryotherapy. We measured pain tolerance using the analog pain scale (EAD). The aesthetic result was assessed by visual comparison between the treatment groups in each participant, and the patient’s preference was evaluated by asking the participant objectively. Results: All points analyzed had statistical significance. The participants gave lower scores in EAD for lesions submitted to contact cryotherapy. The esthetic result evaluated after 30 days was superior in the lesions of the electrocoagulation group. All participants preferred the contact cryotherapy technique. Conclusions: Contact cryotherapy is the preferred method with better pain tolerance in treating acrochordons, but the aesthetic result was better with electrocoagulation. Keywords: Cryosurgery; Cryotherapy; Electrocoagulation; Electrosurgery; Fibroma

RESU MOIntrodução: Podendo atingir quase 60% da população maior de 70 anos, os acrocórdons são muito prev-alentes em consultórios dermatológicos. Entre as abordagens terapêuticas possíveis estão a crioterapia de contato e a eletrocirurgia. Objetivos: Comparar a tolerância à dor, o resultado estético e a preferência dos participantes entre as técnicas de eletrocoagulação e crioterapia de contato no tratamento de acrocórdons. Métodos: Dez participantes, com no mínimo quatro acrocórdons cada um, tiveram suas lesões divididas em dois grupos. Um grupo foi submetido à eletrocoagulação e o outro à crioterapia de contato. A tolerância à dor foi medida pela escala analógica de dor (EAD). O resultado estético foi avaliado por comparação visual entre os grupos de tratamento, em cada participante. A preferência foi avaliada com perguntas objetivas ao participante. Resultados: Todos os pontos avaliados tiveram significância estatística. Os participantes deram notas mais baixas na EAD às lesões submetidas à crioterapia de contato. O resultado estético avaliado após 30 dias foi superior nas lesões do grupo da eletrocoagulação. Todos os participantes preferiram a técnica de crioterapia de contato. Conclusões: A crioterapia de contato é o método preferido e com melhor tolerância à dor no tratamento de acrocórdons, porém o resultado estético foi melhor com a eletrocoagulação. Palavras-chave: Criocirurgia; Crioterapia; Eletrocirurgia; Eletrocoagulação; Fibroma

INTRODUCTIONAcrochordons (or cutaneous fibroepithelial polyps or skin

tags) are benign skin neoplasms easy to diagnose clinically (Figure 1). They are present in about 0.9% to 1.2% of dermatological consultations in the Brazilian adult population.1 They occur in 46% of people over 40, reaching 59% of individuals over 70.2,3

Although benign, they can cause significant discomfort to patients. Treatment techniques include tangential exeresis, chemiocauterization, electrosurgery, and cryotherapy.3 Since cryo-jet therapy can cause hypochromia in the surrounding skin due to the increased sensitivity of melanocytes to freezing, contact cryotherapy is a useful approach. Two previous publications described a similar procedure.4,5 This study aims to compare pain tolerance, aesthetic results, and the participant’s preference between electrocoagulation (ECG) and contact cryotherapy (CC), techniques in the treatment of acrochordons.

METHODSThis is a prospective interventionist study with adult

participants of both sexes, selected at the Complex Dermatology Clinic of the Hospital de Clínicas of the Federal University of Paraná, in Curitiba (PR), Brazil, from August to December 2019. The individuals had a clinical diagnosis of at least four acrochordons measuring from 2 mm to 5 mm.

The lesions of each participant were randomized into two groups. Group 1 underwent electrocoagulation (ECG), and group 2 underwent contact cryotherapy (CC).

After antisepsis with aqueous chlorhexidine digluconate solution 1%, the acrochordons from group 1 were submitted to electrocoagulation treatment with a high-frequency scalpel (Wavetronic 5000 Digital® Loktal, São Paulo, SP, Brazil, 60-100 Watts, coag mode, power 7), by direct contact of the active tip in the dry lesion, for four seconds.

The lesions in group 2 were submitted to contact cryotherapy. After immersing the 10 cm anatomical forceps for 15 seconds in liquid nitrogen, the lesion was clamped. The

contact with the surrounding skin was minimized for as long as possible during 10 seconds until bleaching, with defrost time equal to or greater than freezing time ( Figure 2).

The degree of pain for each method was assessed using the pain analog scale (0 to 10, where 0 was no pain, and 10 was the worst pain the participant ever felt). The aesthetic result was assessed based on standardized photographs taken before and 30 days after the treatment. Fourteen experienced dermatologists analyzed the images on a computer screen, without knowing which treatment group each lesion was part of, choosing the one presenting the best aesthetic result.

The research ethics committee released the study under CAAE number 15233019.7.0000.0096. Statistical analysis was performed by parametric methods and comparison of means in the analysis of pain tolerance and non-parametric methods for the participant’s aesthetic result and preference (chi-square).

RESULTSWe selected 30 participants and, after applying the

inclusion and exclusion criteria, we reached n = 10. There were four men and six women, with an average age of 61.4 years and an average number of lesions of 18.1. The most affected region was the cervical.

The degree of pain in group 1 ranged from 2 to 8, with a mean of 4.6 (SD = ± 2.41, var 5.82, mode 3) and in group 2, it ranged between 0 and 1, with a mean of 0.4 (SD = ± 0.52, var = 0.63, mode 0) (Table 1). All participants rated pain with the lowest score in group 2. The best pain tolerance in group 2 was statistically significant, with p<0.0001 (difference -4.20, CI -5.84 to -2.56) (Figure 3).

Six participants returned after 30 days. When assessing the aesthetic result (Table 2), the average percentage of preference was 80.95% for electrocoagulation and 19.05% for contact cryotherapy (p = 0.0013, CI 25.04% to 79.91%).

All participants preferred the contact cryotherapy technique. No participant had postoperative complications in any of the groups.

Figure 1: Acrochordons in the cervical region of a female participant

Acrochordon removal with contact cryotherapy versus electrocoagulation 259


260 Trevisan F, Kalkmann GF, Nascimento IP, Batista Filho EL


DISCUSSIONPain sensitivity is very variable among participants. Its

graduation can be entirely subjective, and EAD tries to make this analysis objective. In addition to the interpersonal difference in pain tolerance, the same individual may experience the painful sensation differently at different times and on each side of the body. Therefore, we compared the two techniques on the same participant, on the same day, and with a random selection of lesions.

Open cryo-jet therapy is widely used in dermatological practices. It has good applicability and low operating cost. However, the opening diameter can influence the level of

pain, the halo of action, and the aesthetic result. Also, the outlet pressure of liquid nitrogen can cause apprehension and fright in the patient.

As the jet of liquid nitrogen forms a cone, a larger opening should be further away from the target, achieving more healthy skin. It creates a greater risk of sequelae, such as dyschromia, blistering, increased diameter, and the action halo’s deepening.4

With contact cryotherapy, the better accuracy to reach the target reduces this risk, especially in cases of pedunculated lesions such as the acrochordons.4,5

Table 1: Clinical profile and pain degree scale in both groups

Patient Sex Age Number of lesions

Treatment siteEAD Grade

Group 1 (ECG) Group 2 (CC)

01 F 73 7 Cervical 6 1

02 F 61 30 Cervical 4 0

03 M 65 4 Infra-armpit 8 0

04 F 57 12 Cervical 2 0

05 F 51 16 Periorbital 2 0

06 M 64 23 Armpit 3 1

07 M 72 7 Armpit 3 1

08 F 54 19 Cervical 7 0

09 F 48 23 Cervical 8 0

10 M 73 40 Cervical 3 1

Source: The author (2020) F: Female; M: Male; ECG: Electrocoagulation; CC: Contact cryotherapy

Figure 2: Application technique by contact cryotherapy using anatomical forceps

Most participants (6 out of 10) gave a score of 0 on EAD for the CC method, which demonstrated superiority in pain tolerance with good statistical significance (p<0.0001). This less painful sensitivity is extremely useful in the acrochordons treatment close to the eyes. It reduces the reflex of instinctive escaping or closing the eyes, very common in ECG cases without anesthesia or in open cryo-jet therapy.

The lower painful sensitivity of CC also allows excellent comfort to the patient, making it possible to treat a large number of acrochordons at the same time without the need for infiltrative anesthesia. It reduces the exposure to its risks, such as bruising, pain, or, exceptionally, intoxication, in addition to benefiting patients with needles phobia.

The good efficacy and the easiness of treating acrochordons by electrocoagulation are not denied. Still,



Table 2: Preference of the aesthetic result of each evaluator in each case.

Evaluator Case 1 Case 2 Case 3 Case 4 Case 5 Case 6

01 ECG ECG ECG ECG ECG CC


03 ECG ECG ECG ECG ECG ECG

04 ECG ECG ECG ECG CC ECG


06 ECG ECG ECG CC ECG ECG


08 ECG ECG ECG CC ECG ECG

09 ECG ECG ECG ECG ECG ECG



12 CC ECG ECG ECG CC CC

13 CC ECG ECG CC ECG ECG

14 ECG ECG ECG CC CC ECG

Total ECGCC

122

140

140

104

85

104

Source: The author (2020) F: Female; M: Male; ECG: Electrocoagulation; CC: Contact cryotherapy

Figure 3: Graph of scores on the analog pain scale per participant. Red: group 1 (ECG). Blue: group 2 (CC). Full line: reported note. Dotted lines: linear trend

EAD

gra

de

Participants

Group 1

Group 2

Linear (Group 1)

Linear (Group 2)

contact cryotherapy adds up the advantages of its easy access in dermatological offices, fast learning, low technical complexity, non-interference with participants’ electronic devices (such as pacemakers and hearing aids), and the absence of need for sterile instruments such as the active tip of the electronic scalpel.

To assess the aesthetic result of the two techniques, photographic images with lighting and standardized equipment reduced the interpretation bias. For evaluating dermatologists, the technique used in each location was not mentioned.

Lesions treated with ECG had an aesthetic result considered better than those treated with CC, with statistical significance when comparing the percentages of preferences using the chi-square method (Figures 4 and 5).

Although it was not the focus of this study, the authors observed that there were six cases of residual lesions in group 2 (submitted to contact cryotherapy). In one of the authors’ opinion, the larger acrochordons treated by contact cryotherapy need a time greater than 10 seconds or repetition of the freezing

A

C

B

D

A

C

B

D

Figure 4: Aesthetic result. The dashed arrows make it easy to compare the result between the two images. A. Pre-treatment. B. After 30 days of ECG treatment. C. Pre-treatment. D. After 30 days of CC treatment

Figure 5: Aesthetic result. A. Pre-treatment. B. After 30 days of ECG treatment. C. Pre-treatment. D. After 30 days of CC treatment

262 Trevisan F, Kalkmann GF, Nascimento IP, Batista Filho EL


cycles for two or even three times, until slight erythema or edema of the lesion is observed.

When asked about the preference of the method, all patients chose contact cryotherapy as the best. Possible motivations for this choice are the lower pain of the method, the possibility of rapid application in several acrochordons, and its enormous practicality.

CONCLUSIONSThe removal of acrochordons by contact cryotherapy

proved to be the preferred method among the participants, and it is less painful than the ECG. The aesthetic result after 30 days was superior for electrocoagulation. l

REFERENCES1. Sociedade Brazileira de Dermatologia. Perfil nosológico das consultas

dermatológicas no Brazil. An Bras Dermatol. 2006;81(6):549-58.

2. Banik R, Lubach D. Skintags: localization and frequencies according to

sex and age. Dermatologica. 1987;174(4):180-3

3. Belgam Syed SY, Lipoff JB, Chatterjee K. Acrochordon. [atualização em

24 de março de 2020]. In: StatPearls [Internet]. Treasure Island (FL):

StatPearls Publishing; 2020. Disponível em: https://www.ncbi.nlm.nih.

gov/books/NBK448169/

4. Goodheart HP. Surgical Pearl: a rapid technique for destroying small

skin tags and filiform warts. Dermatol Online J. 2003;9(5):34.

5. Taylor JE, Osmun WE. Just a pinch: technique for skin tag removal in

sensitive areas. Can Fam Physician. 2016;62(12):998-9.


Flávia Trevisan | 0000-0001-5855-3685Análise estatística; aprovação da versão final do manuscrito; concepção e planejamento do estudo; elaboração e redação do ma-nuscrito; obtenção, análise e interpretação dos dados; participação efetiva na orientação da pesquisa; participação intelectual em conduta propedêutica e/ou terapêutica de casos estudados; revisão crítica da literatura; revisão crítica do manuscrito.

Gabriela Ferreira Kalkmann | 0000-0003-0040-7591Obtenção, análise e interpretação dos dados; revisão crítica da literatura.

Isabela do Prado Nascimento | 0000-0002-3436-9311Obtenção, análise e interpretação dos dados; revisão crítica da literatura.

Emerson Luis Batista Filho: 0000-0002-2124-5715Obtenção, análise e interpretação dos dados; revisão crítica da literatura.



Original ArticlesAuthors:Thais Furtat Marques 1 Manoella Freitas Santos 1 Isadora da Luz Silva 1 Fabiane Kumagai Lorenzini 1 Ana Paula Dornelles da Silva Manzoni 1

1 Dermatoloy Service of the Santa Casa de Porto Alegre, Porto Alegre (RS), Brazil.

Corresponding author:Thais Furtat MarquesBorges de Medeiros, 154/802 Torres (RS)95560-000E-mail: [email protected]


Study conducted at the Dermatology service of the Santa Casa de Miseri- córdia de Porto Alegre, Porto Alegre (RS), Brazil.


Acknowledgments: The authors thank the resident colleagues and tutors who helped indirectly in this project.

Intralesional corticosteroid injection versus ablative fractional laser associated with corticosteroid drug delivery in the treatment of keloids: a comparative studyInfiltração intralesional de corticosteroide x laser fracionado ablativo associado a drug delivery de corticosteroide no tratamento de queloides: um estudo comparativo


ABSTRACTIntroduction: Keloids are known to impact the quality of life of their patients. Intralesional corticos-teroid injection (ICI) is still the most widely used therapeutic option, although with variable results and limitations. Numerous other strategies have been studied, including the association of lasers with drug delivery (DD). Objectives: To compare the therapeutic response between ICI with isolated triamcinolone acetonide and the association of ablative fractional laser (AFL) and DD of the same drug, and assess quality of life. Methods: We followed-up eight keloid patients who underwent three sessions with a one-month interval between them. ICI was performed in the right half of the scar and AFL and DD on the left. In assessing the results studied statistically, we used measurement and clinical and photographic comparison of the lesions, the Vancouver clinical and analog pain scales, and the Dermatology Life Quality Index questionnaire. Results: We observed a statistically significant improvement in keloids with both techniques. In comparison, ICI was significantly higher than the AFL with DD. On the other hand, the latter technique was statistically less painful. As for patients' quality of life, a significant improvement was observed after treatment in both cases. Conclusions: Both methods were significantly effective in improving keloids; however, ICI showed to be supe-rior. AFL with DD was better tolerated than ICI and is an interesting option for patients with extensive lesions or low pain tolerance.Keywords: Drug delivery systems; Injections, Intralesional; Keloid; Lasers; Triamcinolone acetonide

RESU MOIntrodução: Os queloides sabidamente impactam a qualidade de vida de seus portadores. A infiltração intralesio-nal de corticosteroide (IIC) ainda é a opção terapêutica mais utilizada, embora com resultados variáveis e limitações. Inúmeras outras estratégias vêm sendo estudadas, dentre elas a associação de lasers com drug delivery (DD). Objetivos: Comparar a resposta terapêutica entre a IIC com acetonido de triancinolona isolada e a associação do laser fracionado ablativo (LFA) e DD do mesmo fármaco bem como avaliar a melhora da qualidade de vida. Métodos: Foram acompanhados oito pacientes com queloides submetidos a três sessões com intervalo de um mês entre elas. Na metade direita da cicatriz, realizou-se ICC e, à esquerda, LFA e DD. Na avaliação dos resultados estudados estatisticamente foram utilizados: medição e comparação clínica e fotográfica das lesões, as escalas clínica de Vancouver e analógica de dor e o questionário conhecido como índice de qualidade de vida em Dermatologia. Resultados: Observou-se melhora estatisticamente significativa dos queloides com ambas as técnicas. Na compa-ração, a IIC foi significativamente superior ao LFA com DD. Por outro lado, a última técnica foi estatisticamente menos dolorosa. Quanto à qualidade de vida dos pacientes, observou-se melhora significativa após o tratamento em ambos os casos. Conclusões: As técnicas comparadas foram significativamente eficazes na melhora dos queloides, sendo que a IIC é superior. Já o LFA com DD foi mais bem tolerado do que a infiltração, sendo uma opção interessante para pacientes com lesões extensas ou com baixa tolerância à dor. Palavras-Chave: Cicatriz; Cicatriz Hipertrófica; Terapia a laser

264



Intralesional corticosteroid injection versus laser 265

INTRODUCTIONSkin healing is a physiological process in response to tis-

sue damage.1 However, when there is an imbalance between the destruction and deposition of fibroblasts, the appearance of unsi-ghtly lesions known as keloid or keloid scars can occur.1 Keloids are elevated, shiny scars that can exceed the limits of the original skin damage. Usually, they are accompanied by itching and/or pain and do not spontaneously involute.2 Its incidence varies be-tween 6-16% in the scientific literature, being more frequent in patients with high skin phototypes and regions such as ear lobe, arms, shoulders, back, and chest.2 Due to its unsightly appearan-ce and symptoms, publications describe a significant impact on these patients’ quality of life (QoL).3

Intralesional corticosteroid injection (ICI) is the most commonly used therapeutic option.6 However, it cannot always be used due to technical limitations such as extensive lesions and pain.9 According to the literature, its effectiveness varies between 50% and 100% of treated cases, and the recurrence rate ranges from 9% to 50%.4 Also, complications may accompany its use, such as the appearance of atrophy, telangiectasias, enlargement of the lesion, and perilesional hypochromia.5

To date, there is no report of a therapeutic method uni-versally accepted as the gold standard for keloids’ treatment.6 Numerous therapeutic strategies have been studied, some of them very promising.2,5 Ablative fractional lasers (AFL) are an option used since the publication of the study by Manstein et al.

5 It can be associated with the topical application of cor-ticosteroids on the micro-perforations resulting from AFL use, a technique known as drug delivery (DD), proposed by Waibel et al. as an alternative of combining treatments to optimize results.9

This study aims to compare the effectiveness between the therapeutic response to keloids from ICI and the association of AFL with corticosteroid DD. The degree of discomfort caused by each treatment modality will also be comparatively analyzed, as well as the impact on the quality of life of patients with ke-loids.

METHODSThis study is a quasi-experimental, self-controlled clinical

trial, in which the patient is in control of himself. Patients from the outpatient clinics of the Dermatology Service of the Federal University of Health Sciences of Porto Alegre with a clinical diagnosis of keloid were selected.

The sample consisted of individuals over 18 years old with keloids diagnosed clinically by dermatologists and without previous treatments. The patients could not have a previous his-tory of allergy to the components used in the formulation of triamcinolone acetonide, be pregnant, or use medications that reduced tissue healing during the study or in a period less than six months ago (e.g., immunosuppressants and isotretinoin).

All patients agreed to participate in the study by signing the Informed Consent Form. The Declaration of Helsinki’s ethi-cal guidelines were included in this research. A total of eight patients were treated and evaluated with loss to follow-up of one of them during the study.

ProceduresThree sessions were held at monthly intervals. Before

completing each treatment session and 30 days after its con-clusion, the researcher measured the total extent of the lesions (centimeters), marking a central point that divided them into two equal portions. The lesions were photographed in a stan-dardized way.

ICI and DD were performed with triamcinolone ace-tonide at a concentration of 5 mg/ml (Kenalog 50% 10 mg/ml suspension - Bristol-Myers Squibb Montréal, Canada – plus saline 50%), using the same volume (1 ml/cm3) for both techni-ques, in all sessions.

We applied the ICI on the right half of the lesion, and AFL + DD on the left half. The AFL 2940 nm of the Solon® pla-tform (LMG lasers, Guaxupé, MG, Brazil) was used in the abla-tive fractional mode with 17 J of energy. Immediately after the AFL, triamcinolone acetonide was massaged for 30 seconds over the microperforations, restricted to the keloid’s left half-side. The ICI was distributed homogeneously in the right half-side of the lesion using a 1 ml syringe and 27 G needle.

After applying each of the therapeutic modalities, patien-ts were asked to rate the pain felt using the pain analog scale (zero = no pain to 10 = unbearably painful). At each session, the order in which ICI and AFL + DD were applied was reversed, so it did not influence the pain assessment.

Before starting the treatment and 30 days after its conclu-sion, the Vancouver clinical scale was adapted to classify keloids in vascularity, pigmentation, texture, and thickness.7 Patients also answered the quality of life questionnaire known as the Derma-tology Life Quality Index (DLQI).3

One month after the last session, patients evaluated the improvement on each side of the keloid, according to their per-ception, giving scores between 0 (no clinical improvement) and 10 (total improvement of the keloid). We invited a dermatolo-gist who was not part of the study and was blinded about the treatments used to evaluate from 0 to 10 each side of the keloid. The grades were given through the pre-treatment analysis one month after therapy’s conclusion photographs, paired in a stan-dardized way in the Windows® Power-Point program. The cuto-ff point for considering clinical improvement was scores equal to or greater than 5.

STATISTICAL ANALYSISThe sample size calculation was performed based on a

reduction of 55% (6.8 ± 1.96 to 3.05 ± 1.70) on the Vancouver scale (d = 2.03) and considering a significance level of 5% and a power of 90%.

The minimum sample size was estimated at six patients. Statistical treatment was performed using descriptive statistics to characterize categorical variables (absolute and relative distribu-tion), and quantitative variables (measures of central tendency and variability). The Shapiro Wilk nonparametric normality test was applied to the latter. For symmetric variables, the mean and standard deviation were used; and for asymmetric, median,

266 Marques TF, Santos MF, Silva IL, Lorenzini FK, Manzoni APDS


interquartile range, maximum and minimum values were used. For the inference analysis in the comparison before and after the intervention, the t-Student or Wilcoxon tests were used for continuous variables, and the McNemar and Friedman test for categorical variables. The data received statistical treatment using the software SPSS 25.0 (Statistical Package to Social Sciences for Windows) in which, for decision criteria, the significance level (<) of 5% was adopted.

RESULTSTable 1 shows the patients’ profile regarding age, sex, skin

phototype, location, cause and time of evolution of the scar. The clinical analysis before and after treatment using the modified Vancouver clinical scale demonstrated statistically significant improvement of the keloid both on the side treated with ICI (p=0.000) and on the side treated with AFL + corticosteroids DD (p=0.005) (Table 2). When comparing which of the thera-peutic options showed the most significant clinical improvement using the modified Vancouver scale, the ICI was significantly hi-gher than the AFL + DD (p=0.003) (Table 3). The score gi-ven by the patient regarding the clinical improvement of each half-side of their lesion demonstrated that both the side that received ICI (p=0.014) and the side treated with AFL + DD (p=0.008) improved significantly (Table 4).

Regarding the analysis of the patients' quality of life using the DLQI scale, we found that the subjects obtained a statisti-cally significant improvement in their QoL after the treatment (p=0.012) (Table 2). There was also a significant total scar size reduction after the treatment (p=0.008) (Table 2). Regarding the patient's assessment of the degree of discomfort with each therapeutic modalities using the pain analog scale, the subjects classified the ICI as significantly more painful than the AFL + DD (p = 0.006) (Table 3).

During the five-month follow-up of the sampled patien-ts, complications with any of the treatment modalities were not evidenced.

DISCUSSIONDermatologists already use ICI widely to treat keloids,

and scientific publications already documented its ability to improve these lesions.6 AFL has its main scientific knowledge

based on the facial rejuvenation’s treatment through its ability to remodel collagen in the applied region.8 Similarly, it was pos-tulated that it could assist in the treatment of scars, in addition to inducing a correction of abnormal lymphoproliferative grow-th, localized tissue hypoxia, and reduced cell growth factors.6,8,10

Also, the microchannels created in tissue ablation can be used to deliver the corticosteroid intralesionally using the DD techni-que. Thus it’s possible to associate more than one therapeutic option in the same treatment session.6 One of the few consensu-ses that exist in the current literature on keloids is that we should combine treatments, leading to better outcomes.4,5,6

In this study, we found that three sessions with monthly intervals of the association of the AFL with the triamcinolo-ne acetone DD were significantly effective in obtaining a ke-loid’s clinical improvement (Figure 1) according to the criteria of the modified Vancouver clinical scale (p=0.005) and to the patient's self-assessment (p=0.008). There are few publications in the scientific literature on the treatment of keloids using AFL + DD, and, among them, our study is the one that demonstrated a significant improvement in keloids with the least number of sessions. The improvement in the side treated with ICI is also statistically significant (p=0.000), corroborating previous scien-tific findings.

Comparing the two techniques studied with each other, using the modified Vancouver scale score, found that the ICI was statistically superior to the AFL + DD in terms of clinical improvement (p=0.003). This result was different from the study by Alexander et al., the scientific publication that most resembles our study regarding the use of AFL + DD.

They demonstrated a superiority of the AFL + DD over the ICI that we believe is due to the more significant number of sessions held, in a total of five sessions with monthly intervals, compared to our work, which totaled three sessions.6

AFL + DD was significantly less painful than ICI (p=0.006) when assessing pain experienced with each thera-peutic modalities. We believe that in this finding lies the main highlight for the use of AFL + DD over ICI, as patients with extensive keloid areas tend not to tolerate pain caused by ICI in large extensions.9,10

Regarding the assessment of patients' quality of life befo-re and after the treatment, the results showed a significant impro-

Table 1: Profile of patients sampled regarding age, sex, phototype, lesion site, cause and time of scar evolution

Patient Age Sex Phototype Scar site Scar cause Scar evolution time

1 36 M II Lower abdomen Surgery 1 year

2 22 F III Inframammary Surgery 1 year

3 20 F II Back Acne 3 years

4 20 F II Back Acne 3 years

5 20 F II Shoulders Acne 3 years

6 36 F VI Anterior chest Surgery 5 years

7 36 F VI Chest Perforation by firearms 5 years

8 24 F II Elbow Glass cutting 1 year



vement after the therapy, corroborating the scientific literature’s findings.4,6 The holistic approach to keloid patients is essential to promote global health status. These patients deal with unsightly lesions, often symptomatic, and with psychosocial discomfort secondary to the condition. Thus, we should not underestima-te the suffering that even small keloid lesions can cause to the patient.3

It is noteworthy that no secondary effects were observed with the two treatment modalities during the study period. It demonstrates that both are safe when performed with the cor-rect technique in up to three sessions.

Table 3: Comparative analysis of Intralesional corticosteroid injection and ablative fractional laser with drug delivery on the Vancouver clinical scale: assessment of the patient and the dermatologist, using unidentified photographs, and assessment of the pain experienced by the

patient with each of the techniques

Comparative analysis of infiltration of corticosteroids with ablative fractional laser + drug delivery

ICI AFL + DD 95% CI P

Modified Vancouver scale -5.00 + 1.69 -2.75 + 1.91 -2.25 (-3.41; -1.09) 0.003

Analog pain scale 4.7 + 2.8 1.0 + 1.3 3.62 (1.4; 5.8) 0.006

Table 2: Comparative analysis of Intralesional corticosteroid injection and ablative fractional laser with drug delivery on the Vancouver clinical scale: assessment of the patient and the dermatologist, using unidentified photographs, and assessment of the pain experienced by the

patient with each of the techniques

Pre-treatment Post-treatment Difference 95% CI P

Modified Vancouver Scale: Corticoid injection 8.375 + 2.32 3.375+ 1.5 -5.0 0.000

Modified Vancouver Scale: ablative fractional laser + drug delivery

8.375 + 2.32 5.625+ 1.68 -2.8 0.000

Keloid Size (cm) 4.5875 + 2.84 4.4+ 2.8 -0.2 0.008

Improved quality of life (DLQI) 15.12+ 12.1 4.375+ 3.8 -10.75 (-18.2;-3.3) 0.012

Table 4: Analysis of the clinical improvement of the lesion for each treatment modality by both the patient and the dermatologist

Evaluation of clinical improvement after treatment AFL + DD P

Patient: Corticosteroids injection 7.75 ( + 2.38) 0.014

Patient: ablative fractional laser + drug delivery 7.13 + (1.64) 0.008

The present study's main limitation is the small sample of patients and the reduced number of sessions. Thus, we aim to expand both the number of patients and the number of total sessions performed. We will also increase the follow-up time to assess the risk of keloid recurrence and analyze whether collagen remodeling continues after the sessions. It was seen in Figure 2 patient who, two months after the final evaluation, demonstrated that the side that received the AFL + DD continued to improve even without further intervention.

We know that when using the same lesion to assess both therapeutic modalities, we face the risk that both procedures

Figure 1: Pairing of three keloids: A. Phase before the treatment start. B. One month after the end of the 3rd session. The median portion of the lesion was marked to limit the left and right sides. Left: Intralesional corticosteroid injection. Right: ablative fractional laser with corticosteroid drug delivery

1A 1B 1C

2A 2B 2C


would influence the keloid's middle portion. However, we be-lieve that the benefits were more significant than if we used two different keloid lesions. This perception was because we did not observe any difficulty in applying the modified Vancouver clinical scale to each keloid half-side or in the patient's self-as-sessment of the lesion.

Figure 2: Clinical analysis before and after keloid treatment using the modified Vancouver scale to each of the proposed therapies and evaluation of the reduction in lesion size in centimeters and the impact on the patient's quality of life before and after treatment

A - Pre-treatmentB - Após 1 mês do fim do trata-mento: 1 month after the end of treatment

C - 2 months after the end of treatment

CONCLUSIONSThe compared techniques were significantly effective in

improving keloids, and the ICI is superior. AFL + DD was better tolerated than ICI, and it is an interesting option for patients with extensive lesions or with low pain tolerance. l

268 Marques TF, Santos MF, Silva IL, Lorenzini FK, Manzoni APDS



Thais Furtat Marques | 0000000166765872Study design and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review.

Manoella Freitas Santos | 0000000250245976Data collection, analysis, and interpretation

Isadora Da Luz Silva | 0000000190848723Preparation and writing of the manuscript.

Fabiane Kumagai Lorenzini | 0000000163658705Critical revision of the manuscript.

Ana Paula Dornelles Da Silva Manzoni | 0000000161844440 Approval of the final version of the manuscript; active participation in research orientation; intellectual participation in propae-deutic and/or therapeutic conduct of studied cases; critical revision of the manuscript.

REFERENCES1. Arno AI, Gauglitz GG, Barret JP, Jeschke MG. Up-to-date approa-

ch to manage keloids and hypertrophic scars: a useful guide. Burns.

2014;40(7):1255-66.

2. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic

scarring and keloids: pathomechanisms and current and emerging

treatment strategies. Mol Med. 2011;17(1-2):113-25.

3. Furtado F, Hochman B, Ferrara SF, Dini GM, Nunes JM, Juliano Y, et al.

What factors affect the quality of life of patients with keloids? Rev As-

soc Med Bras. 2009;55(6):700-4.

4. Erlendsson AM, Anderson RR, Manstein D, Waibel JS. Developing tech-

nology: ablative fractional lasers enhance topical drug delivery. Der-

matol Surg. 2014;40(Suppl 12):S142-6

5. Lanoue J, Goldenberg G. Acne scarring: a review of cosmetic therapies.

Cutis. 2015;95(5):276-81.

6. Alexander S, Girisha BS, Sripathi H, Noronha TM, Alva AC. Efficacy of

fractional CO2 laser with intralesional steroid compared with intrale-

sional steroid alone in the treatment of keloids and hypertrophic scars.

J Cosmet Dermatol. 2019;18(6):1648-1656.

7. Lee YI, Kim J, Yang CE, Hong JW, Lee WJ, Lee JH. Combined therapeutic

strategies for keloid treatment. Dermatol Surg. 2019;45(6):802-810.

8. Waibel JS, Rudnick A, Shagalov DR, Nicolazzo DM. Update of ablative

fractionated lasers to enhance cutaneous topical drug delivery. Adv

Ther. 2017;34(8):1840-9.

9. Waibel JS, Wulkan AJ, Shumaker PR. Treatment of hypertrophic scars

using laser and laser assisted corticosteroid delivery. Lasers Surg Med.

2013;45(3):135-40.

10. Behrangi E, Jalilifar M, Lajevardi V, Razavi V, Azizian Z. Comparative

effect of ablative fractional CO2 laser plus triamcinolone acetonide

cream versus intralesional injection of triamcinolone acetonide in ke-

loid and hypertrophic scars: a randomized clinical trial. J Skin Stem Cell.

In Press(In Press):e69394. Epub 2018 Sept 1.


Melanoma on nevus spilusMelanoma sobre nevo spilus


ABSTRACTThe nevus spilus (NS), also known as speckled lentiginous nevus or nevus on nevus, is represented by a brownish macule on which small macules of darker shades appear. It is more common on the trunk and lower limbs. The general population's prevalence is 0.2% to 2.3%, and they have a benign character. The exact risk for malignant transformation is still unknown; thus, it demands a routine clinical-dermoscopic follow-up. We present a case of malignant melanoma on acquired nevus spilus, in which early an excision was per-formed, with no recurrence, highlighting the importance of follow-up of these patients.Keywords: Melanoma; Nevi and melanomas; Nevus

RESU MOO nevo spilus (NS), também chamado de nevo lentiginoso mosqueado ou nevus so-bre nevus, é representado por mancha acastanhada sobre a qual surgem pequenas má-culas de tons mais escuros. É mais comum no tronco e em membros inferiores. A preva-lência na população geral é de 0,2% a 2,3% e tem caráter benigno. O risco exato para transformação maligna ainda é desconhecido, por isso demanda seguimento clínico-dermatoscópico rotineiro. Apresentamos um caso de melanoma maligno sobre nevo spilus adquirido, no qual foi rea-lizada exérese precoce, sem recidiva, ressaltando a importância do acompanhamento desses pacientes.Palavras-chave: Melanoma; Nevo; Nevos e melanomas

Diagnostic ImagingAuthors:Bruna Ramos da Silva 1 Flávia Thomé França 1

Nathalia Fahl Cicotti 2 Maria Paula Barbieri D’elia 2 Jorge Logan Furtado Costa 3

1 Department of Dermatology of the Clinical Hospital, Universidade Estadual de Campinas, Campinas (SP), Brazil.

2 Department of Medicine, Universidade Federal de São Carlos, São Carlos (SP), Brazil.

3 Department of Pathology, School of Medicine Botucatu, Botucatu (SP), Brazil.

Corresponding author:Bruna Ramos da Silva R. Pedro Vieira da Silva, 64, Bloco San Diego, apto 13Jardim Santa GenebraCampinas (SP)13080-570 E-mail: [email protected]


Acknowledgments: We thank Dr. Vinicius de Souza for his dermos-copic description, photographer Eliete Soares from the Department of Dermatology at Universidade Estadual Paulista, and Dr. Hamilton Stolf for their encouragement.

Study conducted ant the Clinical Hospital of the Universidade Estadual de Campinas, Campinas (SP), Brazil.


270


Melanoma on nevus spilus 271

INTRODUCTIONNevus spilus (NS), also known as nevus on nevus or

speckled lentiginous nevus, presents small macules and/or hyperchromic papules on a larger and slightly brownish ma-cula. It is usually located on the trunk and lower limbs. A single or multiple lesion clinically characterizes NS, and this lesion may acquire a zosteriform aspect on the dermatome. It can be congenital or acquired, being more common in chil-dhood, but there are reports of its appearance at any age, and there is no predisposition for a skin type.1 Its prevalence in the general population is 0.2% to 2.3%, and it is benign. Al-though malignant transformation is rare, NS must be moni-tored. This article aims to report an 84-year-old patient with nevus spilus with malignant transformation to melanoma.

CASE REPORTAn 84-year-old man sought help at the Dermatology

Clinic of the School of Medicine of Botucatu to treat four pancellular carcinomas on the face. In 2005, we observed an irregular stain measuring 15 x 10 cm in length, hyperpig-mented, with a café-au-latte color in the trunk’s lateral region

during the consultation. Upon the stain, there were multiple dark brown, lenticular macules.

In the stain’s center, we noticed a dark brown, asym-metrical macula, with irregular edges, measuring 15 mm in the largest diameter (Figures 1 and 2). Dermoscopy revea-led an irregular pigmentation area, containing an atypical pigment network with thickening and abrupt termination (Figure 3). Physical examination presented the absence of palpable lymph nodes.

Because this was a lesion suspected of malignancy, sur-gical excision was performed. The anatomopathological exa-mination revealed extensive superficial malignant melanoma with evident lymphocytic infiltrate, Clark level III, and Bres-low index 0.4 mm, associated with junctional nevus (Figures 4 and 5).

The patient underwent clinical follow-up with a phy-sical examination, dermoscopy, and tests for tumor staging, which resulted in no changes. There was no change in the remaining nevus and/or evidence of local recurrence or dis-tant metastasis during seven years of follow-up. The patient was lost to follow-up in the Dermatology Clinic from 2012. In 2016, he died at 95 years of age from pneumonia, decom-pensated heart failure, and acute chronic kidney failure.

DISCUSSIONThe nevus spilus (NS) is a hyperpigmented stain, resul-

ting from lentiginous melanocytic hyperplasia. Smaller macu-les from 1 mm to 3 mm, with darker shades, compose the le-sion, resulting in a mottled appearance. There is no preference for gender or race. It can be congenital or acquired. However, its etiology remains unknown.5 The first case of melanoma in NS was reported in 1957.2 Since then, less than 40 cases have been published.4 In Brazil, two case reports of malignant melanoma were found on nevus spilus.3,4 Some studies believe

Figure 1: Irregular light brown hyperpigmented patch, with multiple small lenticular macules, also called nevus on nevus, and with a blackened macula

in the center, in the trunk’s lateral region

Figure 2: Detail of the macula located centrally with various shades, from brown to black

Figure 3: Dermoscopy: irregular pigmentation area, containing atypical pigment network with thickening and abrupt termination. Presence of blackish and milky-red areas without structure, associated with a whitish-blue veil. Some hypopigmentation areas irregularly distributed in the lesion


272 Silva BR, Cicotti NF, Costa JLF, França FT, D’Elia MPB.


that the risk of malignancy can vary from 0.13% to 0.2%.13,14 Under microscopy, the darkest spots reflect junctional nevus cells nests, compound and intradermal, and more rarely Spitz nevus and blue nevus.6

It is crucial to detect clinical elements that suggest a higher risk of developing of melanoma in these patients’ follow-up. Rhodes and Mihm assumed that clinically irregu-lar lesions could be associated with atypical histopathologi-cal features, designating them as “dysplastic” nevus spilus, and thus differentiating them from the “typical” nevus spilus.10 Our patient presented a nevus spilus of the acquired type. The lesion was suspected of malignancy, represented by the asymmetric macula, blackened, with irregular edges over the nevus. Dermoscopy showed an irregular pigmented network, with thickening and abrupt termination points on the le-sion’s periphery. Histopathological examination confirmed the hypothesis of malignancy, showing extensive superficial melanoma in the area corresponding to the macula, with se-veral shades of black, observed clinically.

There is a probability that the nevus spilus have a hi-gher risk of developing into a melanoma.7,8,9 An increased risk

of malignancy would be theoretically possible since nevus spilus is a subtype of congenital melanocytic nevus (CMN), that is, a hamartomatous proliferation of melanocytes. There is still no evidence that the presence of hair predisposes to melanoma.6

However, the nevus spilus appears to have a noticea-bly lower risk of malignant transformation than other classic CMNs of the same size. One explanation would be that the CMN's nevus cells are found in deeper layers of the dermis. Also, it is known that the greater the number of melanocytes, the greater the potential for malignant degeneration.6 There is still no protocol in the literature for the management or follow-up of nevus spilus.4 In the case presented, there was no recurrence or metastasis during the follow-up. This report and the other publications teach the importance of clinical follow-up associated with dermoscopy for the early detec-tion and treatment of malignant lesions. Self-examination is advisable for patients with nevus spilus, paying attention to changes in color or irregular elements. Excisional biopsy in lesions suspected of malignancy on the nevus is essential for the early diagnosis of melanoma.9,12,15 l

Figure 4: Nevus spilus, Hematoxylin & eosin staining, 200x. Histopathological subtype: melanocytic junctional nevus. Presence

of melanocytic cell nest at a dermoepidermal junction, with adjacent lentiginous melanocytic hyperplasia

Figure 5: Extensive superficial melanoma, Hematoxylin & eosin stain, 60x. Asymmetric lentiginous proliferation of atypical melanocytes, atrophy of the epidermis, with the formation of irregularly distributed nests, amidst

intense lymphocytic infiltrate and pigmentary effusion


Melanoma on nevus spilus 273


Bruna Ramos da Silva | 0000-0002-2912-0474Preparation and writing of the manuscript; critical literature review; critical revision of the manuscript.

Nathalia Fahl Cicotti | 0000-0001-9893-8184Preparation and writing of the manuscript; data collection, analysis, and interpretation.

Jorge Logan Furtado Costa | 0000-0003-4312-7506 Preparation and writing of the manuscript.

Flávia Thomé França | 0000-0003-0830-7317Critical literature review; critical revision of the manuscript.

Maria Paula Barbieri D’elia | 0000-0003-1524-721X Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; active participation in research orientation; critical literature review; critical revision of the manuscript.

8. Singh S., Jain N., Khanna N. Nevo peludo spilus: uma série de casos.

Pediatr Dermatol . 2013;30:100-4.

9. Haenssle HA, Kaune KM, Buhl T. Melanoma surgindo no nevo spilus

segmentar: detecção por dermatoscopia digital seqüencial. J Am Acad

Dermatol . 2009;61:337-41.

10. Yoneyama K, Kamada N, Mizoguchi M, Utani A, Kobayashi T, Shinkai H.

Malignant melanoma and acquired dermal melanocytosis on congeni-

tal nevus spilus. J Dermatol. 2005;32(6):454-8.

11. Karam SL, Jackson SM. Malignant melanoma arising within nevus spi-

lus. Skinmed. 2012;10(2):100-2.

12. Meguerditchian AN, Cheney RT, Kane JM. Nevus Spilus with synchro-

nous melanomas: case report and literature review. J Cutan Med Surg.

2009;13(2):96-101.

13. Corradin MT, Giulioni E, Fiorentino R, Santeufemia DA, Re GL, Vettorello

A. In situ malignant melanoma on nevus spilus in an elderly patient.

Acta Dermatovenerol Alp Pannonica Adriat. 2014;23(1):17-9.

14. Corradin MT, Zattra E, Fiorentino R, Alaibac M, Belloni-Fortina A. Nevus

spilus and melanoma: case report and review of the literature. J Cutan

Med Surg. 2010;14(2):85-9.

15. Piana S, Gelli MC, Grenzi L, Ricci C, Gardini S, Piana S. Multifocal melano-

ma arising on nevus spilus. Int J Dermatol. 2006;45(11):1380-1.

REFERENCES1. Fernandez-Flores A. Eponyms, morphology, and pathogenesis of

some less mentioned types of melanocytic nevi. Am J Dermatopathol;

2012;34(6):607-18.

2. Perkinson NG. Melanoma arising in a café au lait spot of neurofibroma-

tosis. Am J Surg. 1957;93(6):1018-20.

3. Tavoloni Braga JC, Gomes E, MacEdo MP, Pinto C, Duprat J, Begnami

MD, et al. Early detection of melanoma arising within nevus spilus. J Am

Acad Dermatol. 2014;70(2):e31-2.

4. De Brito MHTS, Fernandes CMBM, Rosa MJM de PM da C, Dionísio CSN

de M, Ferreira JCM, Garcia MMAP da S. Synchronous melanomas arising

within nevus spilus. An Bras Dermatol. 2017;92(1):107-9.

5. Vaidya DC, Schwartz RA, Janniger CK. Nevus spilus. Cutis.

2007;80(6):465-8.

6. Gathings RM, Reddy R, Bhatia AC, Brodell RT. Nevus spilus: is the pre-

sence of hair associated with an increased risk for melanoma?. Cutis.

2016;98(3):171-4.

7. Schaffer JV, Orlow SJ, Lazova R. Nevo lentiginoso salpicado: den-

tro do espectro de nevos melanocíticos congênitos. Arch Dermatol.

2001;137:172-8.

How I do?Authors:Raíssa Rigo Garbin ¹Gabriela Leiria Bencke ¹Ciro Paz Portinho ²Fernando Eibs Cafrune ¹

1 Dermatology Service, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre (RS), Brazil.

2 Department of Plastic Surgery, do Hospital de Clínicas de Porto Alegre, Porto Alegre (RS), Brazil.

Corresponding author:Raíssa Rigo GarbinAvenida Independência, 75Porto Alegre (RS)90035-074 E-mail: [email protected]


Study conducted at the Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre (RS), Brazil.


Acknowledgments: We thank to the Dermatology Service staff at the Santa Casa de Misericórdia in Porto Alegre.

Reconstruction of extensive ear defects after Mohs micrographic surgery: two case reportsReconstrução de defeitos auriculares extensos após cirurgia micrográfica de Mohs: relato de dois casos clínicos


ABSTRACTThe ear is one of the regions with the highest prevalence of cutaneous tumors. The recons-truction of auricular defects resulting from its excision tends to be complicated, especially when extensive and of the total thickness. We report two cases of reconstruction of surgi-cal defects due to the resection of auricular basal cell carcinomas by Mohs micrographic surgery. One case was reconstructed through an interpolated island flap mobilized from the retroauricular region through the primary defect itself, and the other by retroauricular skin flap with anterior rotation through the primary defect. Both presented satisfactory aesthetic and functional results.Keywords: Mohs Surgery; Skin Neoplasms; Surgical Flaps

RESU MOA orelha é uma das regiões com maior prevalência de tumores cutâneos, e a reconstrução dos defeitos auriculares resultantes de sua excisão, especialmente quando extensos e de espessura total, tende a ser complexa. São relatados dois casos de reconstruções de defeitos cirúrgicos auriculares, decorrentes da ressecção de carcinomas basocelulares por cirurgia micrográfica de Mohs, sendo um por meio de retalho em ilha interpolado mobilizado da região retroauricular através do próprio defeito primário, e outro por retalho de pele retroauricular com rotação anterior através do defeito primário - ambos com resultados estético e funcional satisfatórios. Palavras-Chave: Cirurgia de Mohs; Neoplasias cutâneas; Retalhos cirúrgicos

274

Surg Cosmet Dermatol. Rio de Janeiro v.12 n.3 jul-set. 2020 p. 274-7

INTRODUCTIONNon-melanoma cutaneous neoplasms are prevalent and

affect preferentially photoexposed areas, especially head and neck. Its treatment is eminently surgical, aiming to obtain tu-mor-free margins. Areas of aesthetic and functional importance are usually affected, which refers to the complexity of the sur-gical defects reconstruction in these places, such as the auricular pavilion.1,2 The objective of this study was to report two cases of total thickness auricular defects reconstruction through cuta-neous flaps.

Case 1A 68-year-old man presented infiltrative basal cell car-

cinoma in the left ear, affecting the anti-helix, triangular fossa,

Reconstruction of extensive ear defects after Mohs micrographic surgery: two case reports 275

A

D

G

B

E

H

C

F

I

A

D

G

B

E

H

C

F

I

Figure 1: (A) Preoperative lesion aspect; (B) Surgical defect after the lesion excision, stage I; (C) Final surgical defect, stage II; (D) Island Flap - incision of the donor area; (E) Anterior traction of the island flap, maintaining the pedicle; (F) Defect covered after suturing; (G) Secondary defect closure; (H) Final appearance 35 days after the procedure.

Figure 2: (A) Preoperative lesion aspect; (B) Surgical marking during the intraoperative period; (C) Surgical defect after excision of the lesion, stage I; (D) Preauricular advance for anterior closure; (E) Incision posterior to the retroauricular groove; (F) Passage of the flap through the primary defect; (G) Positioning and fixation of the flap to the auricle; (H) Immediate postoperative; (I) Final appearance 21 days after the procedure.


and the anterosuperior portion of the helix (Figure 1A). He was submitted to two-stage Mohs micrographic surgery (Figures 1B and 1C) with total excision of the invading lesion, in addition to the anterior ear skin and posterior ear cartilage and skin. Removal of the tumor resulted in an extensive full-thickness auricular defect. We chose an interpolated island flap brought from the retroauricular region to the anterior auricular region for the reconstruction. After anesthesia with bupivacaine, the ear was folded anteriorly, and the donor area was demarcated imme-diately posterior to the retroauricular groove. An island-shaped incision was performed, maintaining an intact subcutaneous pe-dicle (Figure 1D). The flap was then mobilized to the anterior auricular region through the primary defect, attempting to avoid twisting, traction, or compression of the pedicle, causing vascular involvement (Figure 1E). After placing the flap on the primary defect, it was sutured with 5-0 mononylon (Figure 1F). The ear’s upper face was later drawn towards the secondary defect and fi-xed to the retroauricular region (Figure 1G), leaving only a small

area to heal by secondary intention. The surgery was performed in a single stage, under sedation and local anesthesia, without complications and with adequate aesthetic and functional results (Figure 1H).

Case 2An 85-year-old woman presented extensive infiltrative

basal cell carcinoma affecting the entire concha auricular, exten-ding to the external acoustic meatus, tragus, crus of helix, and antihelix (Figure 2A and B). Previous magnetic resonance ruled out invasion of deep structures (vascular and neural). Under local anesthesia with bupivacaine and sedation, the patient was sub-mitted to Mohs micrographic surgery, with total tumor excision in the second stage. The procedure resulted in an extensive and complex full-thickness surgical defect involving cartilage, sub-cutaneous tissue, and distal part of the external acoustic canal (Figure 2C). We performed closure with a retroauricular skin flap with anterior rotation through the primary defect. Initially,

276 Garbon RR, Cafrune FE, Bencke GL, Portinho CP


the anterior portion of the defect was closed with a pre-au-ricular flap followed by an incision in the central area to re-create the external acoustic meatus (Figure 2D). Afterward, we made a semilunar incision posterior to the retroauricular groove (Figure 2E) and, after detachment of the flap, we folded it forward through the surgical defect (Figure 2F) and sutured it to the concha (Figure 2G). A longitudinal fusiform incision was then made in the flap’s posterior region, so the anterior border was rotated toward the acoustic canal, against the preauricular flap, and the posterior border toward the mastoid region, setting the back face of the ear. A drain was maintained in the first seven postoperative days to avoid collections (Figure 2H) and evolved with good aesthetic and functional results (Figure 2I).

DISCUSSIONApproximately 90% of cutaneous neoplasias affect the

head and neck, and basal cell carcinoma is the most prevalent histological type.3 The ear is one of the anatomical sites with the highest occurrence of carcinomas because of its projection to the head, making it more susceptible to ultraviolet radiation.4

Mohs micrographic surgery is the recommended treat-ment for extensive, infiltrative, and/or poorly delimited auri-cular basal cell carcinomas. The auricular defects reconstruction presents a challenge to the dermatological surgeon due to its curved and concave shape, the small amount of adjacent skin, and the difficulty in preserving the original auricular shape and support.2,3,5

The main options for anterior auricular defects correc-tion, in which the primary closure would distort the ear format, are the use of grafts, flaps, or closure by secondary intention. When the defect is extensive, as in the cases reported, healing

by secondary intention may cause contraction with consequent auricular form and auditory function alteration. The use of skin and cartilage grafts also has limited role for extensive defects, as their contraction tends to distort the ear’s structural support. Moreover, its aesthetic result is usually inferior to the use of flaps, especially due to the difficult equivalences of skin color and tex-ture between the donor and recipient area.1,2,4,6

The retroauricular region functions as a skin reservoir. Because of its proximity to the defect, it is ideal for anterior ear surface reconstruction, resulting in similar skin color and texture, as well as mild scarring.7 The pull-through flap (Case 1) is based on the idea of passing a retroauricular flap through a tunnel in the cartilaginous structure (the primary defect itself, in the case reported) to reach the anterior auricular surface.1

The interpolated flap is an appropriate closure option for defects with significant auricular impairment, such as the subcutaneous pedicle flap, transferred from the retroauricular re-gion to the anterior auricular region through the primary defect (Case 2).1,4,8 Masson first described it, and the procedure was cal-led revolving door flap or flip-flop flap.3,4 Its advantages include the possibility of correcting large defects, the use of adjacent protected and vascularized skin, and the completion of the pro-cedure in a single step.1,4,5,8

Surgical defects of the outer ear are especially challen-ging when extensive or affecting the cartilage because of auri-cular support loss. The small amount of adjacent free skin makes it difficult to reconstruct this anatomical region. Some closure options, such as primary, secondary intention, or use of grafts, have limited roles. In such cases, reconstruction with cutaneous flap is preferential, with favorable results. l


Raíssa Rigo Garbin | 0000-0002-9771-1209Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; critical literature review; critical revision of the manuscript.

Fernando Eibs Cafrune | 0000-0002-6645-0122Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; criti-cal literature review; critical revision of the manuscript.

Gabriela Leiria Bencke | 0000-0002-1521-0452Author’s contribution: Study design and planning; preparation and writing of the manuscript.

Ciro Paz Portinho: 0000-0001-7188-9423Author’s contribution: Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases.

REFERENCES1. Adler n, Ad-El D, Azaria R. Reconstruction of nonhelical auricular de-

fects with local flaps. Dermatol Surg 2008;34(4):501-7.

2. Carrol BT, Gillen WS, Maher IA. Transpositional modification of the

posterior auricular pull-through flap: a new twist. Dermatol Surg

2014;40(1):79-82.

3. Humphreys TR, Goldberg LH, Wiemer DR. The postauricular (Revolving

Door) island pedicle flap revisited. Dermatol Surg 1996;22(2):148-50.

4. Nemir S, Hunter-Ellul L, Codrea V, Wagner R. Reconstruction of a large

anterior ear defect after mohs micrographic surgery with a cartilage

graft and postauricular revolving door flap. Case Rep Dermatol Med

2015:484819. Epub 2015 Sep 3.

5. Larcher L, Plotzeneder I, Tasch C, Riml S, Kompatscher P. Retroauricular

pull-through island flap for defect closure of auricular scapha defects

- a safe one-stage technique. Journal of Plastic, Reconstr Aesthet Surg

2011;64(7):934-6.

6. Redondo P, Lloret P, Sierra A, Gil P. Aggressive tumors of the concha:

treatment with postauricular island pedicle flap. J Cutan Med Surg

2003;7(4):339-43.

7. Ali E, Nasrin N, Azin E. Aesthetic reconstruction of the upper antihe-

lix in external ear with banner pullthrough flap. J Cutan Aesthet Surg

2015;8(4):218-221.

8. Braun JR M, Cook J. The Island Pedicle Flap. Dermatol Surg 2005;31(8

Pt 2):995-1005.

Reconstruction of extensive ear defects after Mohs micrographic surgery: two case reports 277


The scalp is a difficult area to approach due to a signifi-cant amount of hair. Keeping this area aseptic and using topical anesthesia is a challenge, as well as following a logical pattern to perform procedures such as microneedling, mesotherapy, LLLT, lasers, or surgery.1,2 These treatments have been used more fre-quently nowadays for the treatment of androgenetic alopecia 3,4 and alopecia areata.5

This technique consists of dividing rows of hair with a fine-tooth comb (Figure 1) and using hairbands to fix them in the vertex and parietal areas (Figure 2).

These hairbands can be sterilized in an autoclave or put into alcohol 70% if necessary. This approach allows moving rows

How I do?Authors:Leticia Arsie Contin 1

1 Hospital do Servidor Público Municipal de São Paulo, São Paulo (SP), Brazil.

Corresponding author:Leticia Arsie Contin R. Castro Alves, 60. 5o andar. Sao Paulo-SP 01532-000 E-mail: [email protected]


Study conducted at the Hospital do Servidor Público Municipal de São Paulo, São Paulo (SP), Brazil.


Strips hairstyle technique with elastic hair bands for scalp proceduresTécnica de penteado em fileiras com elásticos para realizaçao de procedimentos em couro cabeludo


ABSTRACTStrips hairstyle technique with elastic hair bands is a way of managing hair to help on scalp procedures and to facilitate dermatologists' practice.Keywords: Hair; Laser therapy; Laser therapy, low-level; Needles

RESU MOA técnica de penteado em fileiras com elásticos consiste em uma maneira de prender os cabelos para auxiliar a realizaçao de procedimentos de couro cabeludo e facilitar a prática dos dermatologistas. Palavras-Chave: Agulhas; Cabelo; Terapia a Laser; Terapia a Laser de baixa Intensidade

278


Figure 1: Row separation with fine-tooth comb

Hair band technique 279


laterally and opens a space for topical anesthesia or medications. (Figure 3).

Also, microneedling can be conducted neatly and in the same direction, avoiding hair breakage and losing of a logical sequence.

It is possible to open a space inside one of the rows with a simple hand gesture and access the area between them. (Figure 4).

Figure 2: Hair columns tied with elastic hairbands Figure 4: Exposure of an area within the rows using fingers

Figure 3: Displacement of the rows to expose the area to be treated Figure 5: Microneedling in the exposed area

Using this technique makes it possible for a professional to work alone, making everyday practice with hair procedures easier. (Figure 5) l

280 Contin LA



Leticia Arsie Contin | 0000-0002-4783-9909Statistical analysis; approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

REFERENCES1. Bagazgoitia L, Moreno Y. A simple and effective technique for hair con-

trol in dermatologic surgery. J Am Acad Dermatology 2017, sep;77(3):e-

73-e74.

2. Baker M, Fox L, Davis C. A "french twist":practical hair control in plastic

surgery. Plast Reconstr Surg. 2013;131(3):456e-457e.

3. Fertig RM, Gamet AC, Cervantes J, Tosti A. Microneedling for the treat-

ment of hair loss? J Our Acad Dermatol Venereol. 2018. April; 32(4) 564-

569.

4. Contin L. Male androgenetic alopecia treated with microneedling alo-

ne or associated with injectable minoxidil by microinfusion of drugs

into the skin.

5. Strazzulla LC, Avila L, Lo Sicco K, Shapiro J. An overview of the Biology

of Platelet Rich Plasma and Microneedling as Potential Treatments for

Alopecia Areata. J invest Dermatol 2017. Nov 3.

281

Case ReportsAuthors:Marina Landau1 Erica M Lin2 Carlos Wambier2

1 Arena Dermatology, Herzliya, Tel Aviv, Israel

2 Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA

Corresponding author:Erica M LinDepartment of Dermatology Rhode Island Hospital593 Eddy Street, Ambulatory Patient Center, 10th Floor Providence, EUA.02903 E-mail: [email protected]


Institution: Arena Dermatology, Herzliya, Tel Aviv, Israel


Pustular rash after dermal filler injection should not be interpreted as Herpes Simplex infectionErupção cutânea pustulosa após injeção de preenchimento dérmico não deve ser interpretada como infecção por Herpes Simplex



ABSTRACTFiller-induced arterial obstruction can mimic other dermatological conditions. In this case series, the authors describe four patients with filler-induced arterial obstruction presenting with pustular rash that was misdiagnosed as a herpetic infection. Since correct and timely diagnosis is crucial for scar prevention, pustular rash has to be recognized by injectors as a clinical expression of vascular obstruction induced by dermal filler injection. Keywords: Hyaluronic acid; Herpes simplex; Ischemia; Injections, intra-arterial

RESU MOA obstrução arterial induzida por materiais de preenchimento pode simular outras condições derma-tológicas. Nesta série de casos, os autores descrevem quatro pacientes com obstrução arterial induzida por preenchimento, os quais se apresentaram como erupção cutânea pustulosa que foi diagnosticada erroneamente como infecção herpética. Como o diagnóstico correto e precoce é crucial para a prevenção de cicatrizes, a erupção cutânea pustulosa deve ser reconhecida como uma expressão clínica da obstrução vascular induzida pela injeção cutânea. Palavras-Chave: Ácido hialurônico; Herpes simples; Isquemia; Injeções, intra-arteriais

INTRODUCTIONHyaluronic acid (HA) filler injections are popular min-

imally invasive procedures performed on healthy individuals looking for cosmetic enhancement.1 Vascular compromise fol-lowed by skin necrosis is a devastating potential complication.2-6 Early recognition of vascular occlusion and proper treatment, including hyaluronidase injection, are required to avoid irrevers-ible changes such as scarring.6-11 However, symptoms of vascular occlusion are occasionally misinterpreted. In such circumstances, treatment is delayed, significantly reducing the chances of full recovery.

Clinical presentation of dermal ischemia includes skin blanching, livedo reticularis, redness, skin sloughing, crusting, and scars. Pustules are only rarely mentioned as a manifestation of impending skin necrosis.3,12 In the past year, we evaluated four cases in which patients presented with a pustular eruption 3-4 days after HA-based dermal filler injection. In all cases, the injecting/treating physician made the diagnosis of a herpetic outbreak. Detailed medical history indicated that the pustules resulted from impending skin necrosis due to filler-induced vas-cular occlusion rather than viral infection.

CASE REPORTSCase 1A 44-year-old woman presented for a consultation five

days after being injected for upper lips wrinkles with HA-based filler elsewhere. Twenty-four hours after injection, she com-plained of pain accompanied by skin discoloration along the right nasolabial fold and upper lip. Her complaint was dismissed as a simple bruise. On the third day after the injection, a pustular eruption developed in the same area. The injecting physician examined the patient and clinically diagnosed the eruption as a herpetic outbreak, initiating the systemic anti-herpetic treat-ment. When we examined the patient in our office, a confluent pustular eruption along the right nasolabial with focal crusts was present (Figure 1a). Widespread erosions were evident on the mucosal side of the left lip (Figure 1b).

Based on the patient’s history and clinical findings, diag-nosis of impending skin necrosis due to intraarterial injection of HA was made. Bacterial and viral cultures were taken and came back negative. The patient was treated with 300 units hyaluro-nidase in the affected area, topical 2% Nitroglycerin cream, 100 mg Aspirin, and antibiotic ointment. After re-epithelization, we performed three sessions of vascular laser treatment (VBeam by Syneron Candella). Following the treatment, full skin recovery was achieved with minimal post-inflammatory hyperpigmenta-tion at the site (Figure 1c).

Case 2A 32-year-old woman was injected elsewhere with HA-

based filler for nose enhancement. Twenty-four hours after the injection, the patient experienced severe pain accompanied by skin discoloration. The treating physician’s office staff dismissed these complaints as a normal post-procedural effect. On the third day after the injection, the patient was seen in a hospital emer-gency room with a pustular eruption, and we were tele-con-

282 Landau M, Lin EM, Wambier C.


Figure 2: Pustular eruption along the nose, medial cheeks and glabellar area in Case 2 (3 days post-injection)

A

B

C

Figure 1: Case 1 (A). Pustular eruption along the right nasolabial folds and upper lip (5 days post-injection) (B). Erosions on the mucosal side of the left lip (5 days post-injection) (C). Full recovery with minimal post inflammatory

Figure 3: Case 3 (A). Skin discoloration (1 day post-injection) (B). Pustular eruption in the upper lip and left lower nasolabial areas (5 days post-injection) (C). Erosions on the mucosal side of the upper left lip (5 days post-injection) (D). Resolution with residual crusting

Pustular rash after dermal filler injection should not be interpreted as Herpes Simplex infection 283


sulted. At this stage, erythema and swelling of the nose, medial cheeks, and glabellar area, along with pustules on the distal and proximal parts of the nose, were observed (Figure 2). The diag-nosis of impending skin necrosis due to intravascular obstruction was made. Nevertheless, the patient was admitted to the hospital, and intravenous antibiotic and antiherpetic treatment were ini-tiated. The patient was lost to follow-up.

Case 3A 53-year-old woman was examined in our office three

days after a HA-based filler injection for upper lip wrinkles elsewhere. Skin discoloration was noted 24 hours post-injec-tion and photographed by the patient (Figure 3a). On the third day post-injection, a pustular eruption appeared, and the patient contacted the treating physician’s office. A diagnosis of Herpes simplex was made, and treatment with systemic antiherpetic was initiated.

At this stage, we examined the patient in our office. On examination, we observed erythema and swelling of the upper lip and left lower nasolabial areas. Pustules were seen in two distinct foci on the upper lip (Figure 3b). Painful erosion was found on the upper left lip mucosa (Figure 3c). The diagnosis of impending skin necrosis due to intravascular filler injection was made. The patient was treated with 300 units of hyaluronidase, topical 2% Nitroglycerin cream, and topical anesthetic gel on the mucosal aspect to alleviate the pain. After an additional seven

days, the mucosal erosions had healed completely, but residual crusting of the upper lip skin was still visible (Figure 3d).

Case 4A 23-year-old woman was injected with HA-based filler

into the nasolabial folds elsewhere. On the fourth day post-in-jection, the patient developed a pustular rash along the left na-solabial fold, nostril, and medial cheek (Figure 4a). After an ad-ditional three days, some of the pustules began to crust (Figure 4b). At this stage, the treating physician contacted our office for advice regarding systemic antiherpetic treatment. A diagnosis of intravascular HA injection was made. The patient was treated with a hyaluronidase injection into the affected area. Two weeks later, the treating physician reported that the skin had complete-ly healed (Figure 4c).

DISCUSSIONIntra-arterial injection of dermal filler is rare, but not

completely preventable. Slow injection of small boluses, thor-ough knowledge of regional anatomy, use of blunt cannulas in-stead of sharp needles, and pre-injection aspiration can all reduce the risk of arterial obstruction, but not completely eliminate its occurrence.12-15 Therefore, diagnosing this condition based on clinical manifestations and providing timely treatment are cru-cial in preventing devastating outcomes, such as scarring, and skin and soft tissue necrosis.12,16

A

C

B

D


While increasing pain and cutaneous discoloration are well known clinical signs, the pustular rash is a less well-recog-nized manifestation of vascular obstruction. As a result, misdiag-nosis of pustular rash as herpes simplex infection delays proper management. The mechanism of pustular rash is potentially re-lated to polymorphonuclear cell attraction to the site via com-plement activation during ischemic or thrombotic events, as re-ported in other tissues.17-19

The “golden time” for the first intervention is classically limited to the first three days after an ischemic event.20 Accord-ing to our experience and the cases presented, the pustular phase is included within this “tissue saving” time frame.

CONCLUSIONSEvery injector should recognize the pustular phase as a

part of the full clinical spectrum of filler-induced arterial ob-struction to provide timely treatment. l

284 Landau M, Lin EM, Wambier C.

Figure 4: Case 4 (A). Pustular eruption along the left nasolabial folds (4 days post-injection) (B). Erosions with crusting (7 days post-injection) (C). Full recovery with minimal post inflammatory hyperpigmentation

A B C



Marina Landau | 0000-0001-9016-6394Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data col-lection, analysis, and interpretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Erica M Lin | 0000-0002-7641-6040Approval of the final version of the manuscript; preparation and writing of the manuscript; critical literature review; critical revision of the manuscript.

Carlos Wambier2 | 0000-0002-4636-4489Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data col-lection, analysis, and interpretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

REFERENCES1. The American Society for Aesthetic Plastic Surgery. 2016 Cosmetic Sur-

gery National Data Bank Statistics. [Internet]. New York: ASAPS Commu-

nications Office; [updated 2016; cited December 2019]. Available from:

https://www.surgery.org/sites/default/files/ASAPS-Stats2016.pdf.

2. Kassir R, Kolluru A, Kassir M. Extensive necrosis after injection of hyalu-

ronic acid filler: case report and review of the literature. J Cosmet Der-

matol. 2011;10(3):224-231.

3. Beleznay K, Humphrey S, Carruthers JSA, Carruthers A. Vascular com-

promise from soft tissue augmentation. experience with 12 cases

and recommendations for optimal outcomes. J Clin Aesth Dermatol.

2014;7(9):37-43.

4. Sun ZS, Zhu GZ, Wang HB, Xu X, Cai B, Zeng L, et al. Clinical outco-

mes of impending nasal skin necrosis related to nose and nasolabial

fold augmentation with hyaluronic acid fillers. Plast Reconstr Surg.

2015;136(4):434e-441e.

5. Bravo BSF, Balassiano LKDA, Da Rocha CRM, Padilha CBDS, Torrado

CM, Da Silva RT, et al. Delayed-type necrosis after soft-tissue augmen-

tation with hyaluronic acid complication. J Clin Aesthet Dermatol.

2015;8(12):42-7.

6. Chen Q, Liu Y, Fan D. Serious vascular complications after nonsur-

gical rhinoplasty: a case report. Plast Reconstr Surg Glob Open.

2016;4(4):e683.

7. Glaich AS, Cohen JL, Goldberg LH. Injection necrosis of the glabella:

Protocol for prevention and treatment after use of dermal fillers. Der-

matol Surg. 2006;32(2):276-81.

8. Beer K, Downie J, Beer J. A treatment protocol for vascular occlusion

from particulate soft tissue augmentation. J Clin Aesthet Dermatol.

2012;5(5):44-7.

9. Dayan H, Arkins JP, Mathison CC. Management of impending ne-

crosis associated with soft tissue filler injections. J Drugs Dermatol.

2011;10(9):1007-12.

10. Abduljabbar MH, Basendwh MA. Complications of hyaluronic acid

fillers and their managements. J Dermatol and Dermatol Surg.

2016;20(2):100-6.

11. Signorini M, Liew S, Sundaram H, De Boulle KL, Goodman GJ, Monheit

G, et al. Global Aesthetics Consensus: Avoidance and Management of

Complications from Hyaluronic Acid Fillers-Evidence- and Opinion-Ba-

sed Review and Consensus Recommendations. Plast Reconstr Surg.

2016;137(6):961e-71e.

12. DeLorenzi C. Complications of injectable fillers, part 2: vascular compli-

cations. Aesthet Surg J. 2014;34(4):584-600.

13. Breithaupt AD, Jones DH, Braz A, Narins R, Weinkle S. Anatomical ba-

sis for safe and effective volumization of the temple. Dermatol Surg.

2015;41(Suppl 1):S278-83.

14. Sundaram H, Weinkle S, Pozner J, Dewandre L. Blunt-tipped micro-

cannulas for the injection of soft tissue fillers: a consensus panel as-

sessment and recommendations. J Drugs Dermatol. 2012;11(8):s33-39.

15. Funt D, Pavicic T. Dermal fillers in aesthetics: an overview of adver-

se events and treatment approaches. Clin Cosmet Invest Dermatol.

2013;6:295-316.

16. Gilbert E, Hui A, Meehan S, Waldorf HA. The basic science of dermal

fillers: past and present Part II: adverse effects. J. Drugs Dermatol.

2012;11(9):1069-77.

17. Tuttolomondo A, Di Sciacca R, Di Raimondo D, Renda C, Pinto A, Licata

G. Inflammation as a therapeutic target in acute ischemic stroke treat-

ment. Curr Top Med Chem. 2009;9(14):1240-60.

18. Distelmaier K, Adlbrecht C, Jakowitsch J, Winkler S, Dunkler D, Gerner C,

et al. Local complement activation triggers neutrophil recruitment to

the site of thrombus formation in acute myocardial infarction. Thromb

Haemost. 2009;102(3):564-72.

19. Behm CZ, Kaufmann BA, Carr C, Lankford M, Sanders JM, Rose CE, et al.

Molecular imaging of endothelial vascular cell adhesion molecule-1 ex-

pression and inflammatory cell recruitment during vasculogenesis and

ischemia-mediated arteriogenesis. Circulation. 2008;117(22):2902-11.

20. Hong JY, Seok J, Ahn GR, Jang YJ, Li K, Kim BJ. Impending skin necrosis

after dermal filler injection: A "golden time" for first-aid intervention.

Dermatol Ther. 2017;30(2):e12440.

Pustular rash after dermal filler injection should not be interpreted as Herpes Simplex infection 285

286

Case ReportsAuthors:Manoella Freitas Santos1,2 Maria Emilia Vieira de Souza1,2

Laura Luzzatto 2 Leonardo Albarello 2 Renan Minotto 2

1 Department of Dermatology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre (RS), Brazil.

2 Department of Dermatology, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre (RS), Brazil.

Corresponding author:Manoella Freitas SantosDepartamento de Dermatologia da Irmandade Santa Casa de Misericór-dia de Porto Alegre Av. Independên-cia, 75 Independência - Porto Alegre (RS)CEP: 90035-074E-mail: [email protected]


Study conducted at the Department of Dermatology, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre (RS), Brazil.


Acknowledgments: We thank the Department of Dermatology of the Santa Casa de Misericórdia, Porto Alegre.

Giant Onychomatricoma: a case reportOnicomatricoma gigante: relato de um caso


ABSTRACTIntroduction: Onychomatricoma is a rare benign tumor characterized by a clinical tetrad of a yellowish longitudinal band of varying thickness, splinter hemorrhages, longitudinal and transverse hypercurvature of the nail plate, and digitiform projections emerging from the nail matrix, leaving cavitations in the nail plate. We report a case of a female patient, 49 years old, with a history of a tumoral lesion in the third left toe for about four years, with a progressive increase in this period. Physical examination revealed an exuberant tumor lesion clinically compatible with onychomatricoma, confirmed by pathological examination after complete tumor excision.Keywords: Nails; Nail diseases; Neoplasms

RESU MOIntrodução: Onicomatricoma é um tumor benigno, raro, caracterizado pela tétrade clínica de faixa longitu-dinal amarelada de espessura variável, hemorragias em estilhaço, hipercurvatura longitudinal e transversa da placa ungueal e projeções digitiformes que emergem da matriz ungueal, deixando cavitações na placa un-gueal. Relatamos um caso de paciente feminina, 49 anos, com queixa de lesão tumoral em terceiro quirodác-tilo esquerdo há cerca de quatro anos, com aumento progressivo no período. Ao exame, apresentava lesão tumoral exuberante clinicamente compatível com onicomatricoma, confirmado pelo exame anatomopatológico após exérese completa do tumor. Palavras-chave: Doenças da unha; Neoplasias; Unhas


INTRODUCTIONOnychomatricoma is a rare benign tumor characterized

by digitiform projections from the matrix, being the only tumor in which the lesion actively produces nail plate alteration.1,2 We report a case of an onychomatricoma presenting an exuberant aspect, highlighting the clinical characteristics and the diagnosis of the lesion.

Case ReportA 49-years-old woman, who works in the shoe indus-

try, presented at the Dermatology Department with a tumoral lesion in the third left toe for about four years, with a progres-sive increase in this period. The patient denied pain or other injury-related symptoms. She had undergone several treatments for onychomycosis, without improvement. Physical examination revealed nail plate thickening, transverse hypercurvature, xan-thonychia, hemorrhagic splinters, and small holes in the nail’s free edge (Figures 1 and 2). Dermoscopy of the blade surface al-lowed better visualization of the hemorrhagic splinters, and the free edge showed the presence of perforations (Figures 3 and 4).

Due to suspected onychomatricoma, an excisional sur-gery of the lesion was performed. Two incisions were made in the proximal nail fold, which was rebound, exposing the tu-mor. The nail excision allowed the visualization of digitiform projections in the matrix area (Figures 5 and 6). We performed complete tumor excision and primary closure of the incisions in the proximal nail fold (Figure 7). The histopathologic exam demonstrated squamous epithelial digitiform hyperplasia form-ing projections, confirming the diagnosis of onychomatricoma (Figure 8).

Giant Onychomatricoma 287


Figure 1: Nail plate thickening, transverse hypercurvature, xantonychia

Figure 2: Nail plate thickening, transverse hypercurvature and small holes in the nail’s free edge

Figure 3: At dermoscopy examination, hemorrhagic splinters

Figure 4: Dermoscopy of the nail’s free edge: perforations

288 Santos MF, Souza MEV, Luzzatto L, Albarello L, Minotto R


DISCUSSIONA clinical tetrad characterizes the onychomatricoma,

consisting of a yellowish longitudinal band of varying thickness, splinter hemorrhages, longitudinal and transverse hypercurva-ture of the nail plate, and digitiform projections emerging from the nail matrix, leaving cavitations in the nail plate.3,4 It may

also manifest with longitudinal melanonychia, subungual hema-toma, nail dystrophy, proximal nail fold verrucosity, dorsal pte-rygium, giant variant, pseudofibrokeratoma type, and may have characteristics similar to onychomycosis.4,5 Plaque dermoscopy demonstrates perforations in the distal portion of the nail plate, hemorrhagic striae, and white longitudinal grooves correspond-ing to the nail plate channels.1,4,6

Differential diagnoses include subungual exostosis, fibro-keratoma, vulgar wart, onychomycosis, squamous cell carcino-ma, keratoacanthoma, superficial acral fibromyxoma, melanoma, bacterial infections, dermatofibrosarcoma protuberans, poro-carcinoma, and osteochondroma. Onychomycosis is cited as a

Figure 5: Transoperative: folding of the proximal nail fold, exposing the tumor

Figure 6: Transoperative: digitiform projections

Figure 7: Primary closure of the incisions

Figure 8: The histopathological examination demonstrated squamous epithelial digitiform hyperplasia forming projections (HE, 4x magnification)

predisposing factor for the emergence of onychomatricoma (re-active lesion theory). On the other hand, the tumor can also be considered a predisposing factor for onychomycosis.6,7

Imaging exams such as radiography, ultrasound, and MRI may help in the diagnosis of the lesion. Still, in most cases, the clinical and dermoscopic examination associated with the patho-logical examination is sufficient for the diagnosis, as in the case reported.8,9 Anatomopathological examination demonstrates a fibroepithelial tumor composed of two portions. The first por-tion, proximal, is located under the posterior nail fold, charac-

terized by epithelial invaginations filled with a thick V-shaped keratinized zone, well-defined fibrillar and fibrocystic stroma, and thickening of the nail plate. Digitiform projections, perfo-rations in the nail plate and deep, poorly delimited penetration of the connective stroma in the dermis characterize the second portion, the distal area in the lunula.10

The treatment of onychomatricoma is surgical, and a complete tumor excision should be performed. The long-term prognosis is generally favorable, but nail dystrophies are com-mon.11 l

Giant Onychomatricoma 289


REFERENCES1. Haneke E, Franken J. Onychomatricoma. Dermatol Surg.

1995;21(11):984-7.2. Ko CJ, Shi L, Barr RJ, Molne L, Ternesten-Bratel A, Headington JT. Un-

guioblastoma and unguioblastic fibroma an expanded spectrum of onychomatricoma. J Cutan Pathol. 2004;31(4):307-11.

3. Thomas L, Zook EG, Haneke E, Drapé JL, Baran R. Tumors of the nail apparatus and adjacent tissues. In: Baran R, de Baker DAR, Holzberg M, Thomas L. Baran and Dawber''s diseases of the nails and their manage-ment. 4th ed. USA: Wiley-Blackwell; 2012. p. 637-743.

4. Perrin C, Baran R. Onychomatricoma with dorsal pterygium: pathoge-nic mechanisms in 3 cases. J Am Acad Dermatol. 2008;59(6):990-4

5. Goettmann S, Zaraa I, Moulonguet I. Onychomatricoma with ptery-gium aspect: unusual clinical presentation. Acta Derm Venereol. 2006;86(4):369-70.

6. Baran R, Nakamura R. Doença das Unhas: do diagnóstico ao tratamen-to. Rio de Janeiro: Elsevier; 2011.

7. Cañueto J, Santos-Briz Á, García JL, Robledo C, Unamuno P. Onychoma-tricoma: genome-wide analyses of a rare nail matrix tumor. J Am Acad Dermatol. 2011;64(3):573-8.

8. Rosamary Soto, Ximena Wortsman, Yamile Corredoira. Onycho-matricoma: Clinical and Sonographic Findings. Arch Dermatol. 2009;145(12):1461-2.

9. Goetmann S, Drapé JL, Baran R, Perrin C, Haneke E, Belaïch S. Onycho-matricome: 3nouveaux cas: intérêt de la résonance magnétique nu-cléaire. Ann Dermatol Venereol. 1994;121(Suppl 1):S145.

10. Perrin C, Goettmann S, Baran R. Onychomatricoma: clinical and his-topathologic findings in 12 cases. J Am Acad Dermatol. 1998;39(4 pt 1):560-4.

11. Di Chiacchio N, Richert B, Haneke E. Surgery of the matrix. In: Richert B, Di Chiacchio N, Haneke E. Nail Surgery. New York: Informa Healthcare. 2011; p 103-32.


Manoella Freitas Santos | 0000-0002-5024-5976Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Maria Emilia Vieira de Souza | 0000-0001-6717-8362Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Laura Luzzatto | 0000-0002-4193-6943Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Leonardo Albarello | 0000-0002-8785-6885Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Renan Minotto | 0000-0002-1451-0461Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data collection, analysis, and interpretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

290


Case Reports

Authors:Ana Beatriz Antunes Funes 1

Ana Carolina Gama Martins1

André Matheus Camelo Neves1

Marilda Aparecida Milanez Morgado de Abreu1 Ana Cláudia Cavalcante Espósito 1

1 Medical School of the Universidade do Oeste Paulista, Presidente Prudente (SP), Brazil.

Corresponding author:Ana Cláudia Cavalcante EspósitoR. Estevan Peres Bomediano, 219Presidente Prudente (SP)19023-210 E-mail: [email protected]


Study conducted at the Universidade do Oeste Paulista, Presidente Pruden-te (SP), Brazil.


Myiasis due to Dermatobia hominis simulating lipomaMiíase por Dermatobia hominis simulando lipoma


ABSTRACTIntroduction: Dermatobia hominis is one of the main etiologic agents of furunculoid myia-sis. It is more common in intertropical countries and induces the formation of a papule or nodule in the skin with a central orifice. When the lesion's diagnosis is not made or when the larva does not go out, it can progress to a tumor’s formation. We report a rare case of a lipoma-simulating lesion in the lower limb of a man living in the countryside. The etiological diagnosis was made exclusively through histopathological examination, which showed a cyst with exogenous material to the center, compatible with D. hominis, in a clear degradation process.Keywords: Larva; Lipoma; Myiasis

RESU MOIntrodução: Dermatobia hominis é um dos principais agentes etiológicos da miíase furunculoide. É mais comum em países intertropicais e induz a formação na pele de pápula ou nódulo com orifício central. Quando o diagnóstico da lesão não é realizado ou quando a larva não é estruída, pode evoluir para a formação de uma tumoração. Relatamos um caso raro de lesão simuladora de lipoma no membro inferior de um homem morador da zona rural. O diagnóstico etiológico foi realizado por meio do exame histopatológico, sendo pos-sível visualizar um cisto com material exógeno ao centro, compatível com D. hominis, em nítido processo de degradação. Palavras-chave: Larva; Lipoma; Miíase

Subcutaneous nodule simulating lipoma 291


INTRODUCTIONDermatobia hominis, of the family Cuterebridae, is the

most common etiologic agent of furunculoid cutaneous myia-sis.1 Its life cycle has a particular characteristic, called foresia, in which the female lays its eggs in the abdomen of a blood-su-cking insect, establishing an interspecific harmonic relationship.2 More than 50 species can carry the eggs, especially Sarcopro-musca pruna, Musca domestica, and Haematobia irritans.3 When the insect bites an individual, the eggs come into contact with the human skin’s heat, hatching. Then, the larva penetrates the skin, even if it is intact.1 The larva remains inside the formed papule or nodule for five to ten weeks, and during this period, it passes through the first, second, and third larval stages. In the complete cycle, the mature larva emerges on the skin’s surface during the night, falls to the ground, and forms the pupa. One month after leaving the host, the adult insect hatches, keeping the cycle.¹

When the larva is placed on human skin, extraction is often done before the cycle is complete. However, in rare cases, the larvae encyst in the subcutaneous tissue and may progress to nodules’ formation. In the present article, we report the case of a patient with a subcutaneous tumor in the lower limb, with a long evolution, whose clinical characteristics simulated a lipoma. However, ultrasonography was compatible with a foreign body, and, after excision of the lesion, histopathological examination allowed the visualization of the larva.

CASE REPORTA 56-year-old man, farmer, residing in the countryside,

sought medical assistance due to the appearance, two years ago, of an asymptomatic lesion on the medial aspect of his left leg. The patient denied trauma preceding the development.

He presented a subcutaneous tumor of 4 cm in diameter on physical examination, with softened consistency, not adhered to the deep planes, painless on palpation, and without a central hole. The skin overlying the lesion did not show signs of in-flammation (Figure 1). The clinical hypothesis was of lipoma. However, as the patient presented varicose veins in the lower limbs, we requested ultrasonography with Doppler Color for surgical planning. The imaging showed a fusiform hypoechoic capsule located in the subcutaneous tissue, and, in the center, there was a 17x6 mm hyperechoic image, which could be com-patible with a foreign body.

The complete excision of the lesion was performed ac-cording to previous demarcation (Figure 2). Upon histopatholo-gical examination of the material, we macroscopically observed a nodular formation measuring 1.8 cm, with a single cavity fil-led with a yellowish liquid. There was an intense chronic in-flammatory process, with gigantocellular reaction of the foreign body type and granulation tissue with vascular neoformation and collagen degradation. In the center, there was an exogenous material compatible with D. hominis in a clear degradation pro-cess (Figures 3 and 4).

Figure 1: Subcutaneous nodule (4 cm in diameter), covered by normal skin, with softened consistency, not adhered to the deep planes, painless on

palpation, without central hole

Figure 2: Planning of the surgical excision of the lesion

292 Funes ABA, Martins ACG, Neves AMC, Abreu MAMM, Espósito ACC


The patient evolved with adequate wound healing (Fi-gure 5) and underwent routine dermatological follow-up for two years.

Figure 3: Histological section showing cystic lesion in soft tissues with central parasitic structure compatible with Dermatobia hominis. The

epidermis above the lesion is intact (Hematoxylin & eosin, 100x)

Figure 4: Cystic lesion with intense chronic inflammatory process, gigantocellular reaction of the foreign body type and granulation tissue, in addition to vascular neoformation. Presence of a parasite compatible with

Dermatobia hominis (Hematoxylin & eosin; 400x)

Figure 5: Fourteenth postoperative day

DISCUSSIONThe main agents of furunculoid cutaneous myiasis are

Dermatobia hominis, Cordylobia anthropophaga, Cuterebra sp, and Wohlfahrtia sp.4,5 It is more common in developing (intertropical) countries, such as those in Central America, South America, and sub-Saharan Africa.6 The incident cases in individuals coming from other areas of the globe result, in general, from travelers who were in an endemic area, implying a significant diagnostic challenge when returning to their country of origin.7,8

Dermatobia hominis has rows of dark backward spines, a pair of hooks in the mouth, striated muscles, as well as an external cuticle that involves the internal organs.9 Larva infesta-tion is related to poor hygiene habits, living in the countryside (as in the case reported), and low socioeconomic status.8

D. hominis' presence in the skin induces a papule or a nodule formation, with a central orifice of approximately 1 mm (corresponding to the invertebrate's respiratory pore and visua-lized by dermoscopy), from which a serosanguinous or purulent secretion leaks.7,8

In general, manual extraction of the larva is not a challen-ge, and the occlusion of the orifice with petroleum substances facilitates the process.5 However, when the diagnosis of the le-sion is not performed correctly or when the larva is not broken (spontaneously or under manipulation), it can evolve to the for-mation of a tumor that simulates an epidermal cyst, lipoma (as

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iasis caused by Dermatobia hominis: countries with increased risk for

travelers going to neotropic areas. Int J Dermatol. 2016;55(10):1060-8.

2. Safdar N, Young DK, Andes D. Autochthonous furuncular myiasis in

the United States: case report and literature review. Clin Infect Dis.

2003;36(7):e73-80.

3. Azevedo RR, Duarte JLP, Ribeiro PB, Krüger RF. Occurrence of Sarco-

promusca pruna (Diptera) in Southern Brazil as a vector of Dermatobia

hominis (Diptera) eggs. Arq Bras Med Vet Zootec. 2007;59(5):1348-50.

4. Ko JY, Lee I-Y, Park BJ, Shin JM, Ryu J-S. A case of cutaneous myiasis cau-

sed by Cordylobia anthropophaga larvae in a Korean traveler returning

from Central Africa. Korean J Parasitol. 2018;56(2):199-203.

5. Suárez JA, Ying A, Orillac LA, Cedeño I, Sosa N. First case of furuncu-

lar myiasis due to Cordylobia anthropophaga in a Latin American

resident returning from Central African Republic. Braz J Infect Dis.

2018;22(1):70-3.

6. Rodriguez-Cerdeira C, Gregorio MC, Guzman RA. Dermatobia Hominis

infestation misdiagnosed as abscesses in a traveler to Spain. Acta der-

matovenereol Croat. 2018;26(3):267-9.

7. Olsen J, Nejsum P, Jemec GBE. Dermatobia hominis misdiagnosed as

abscesses in a traveler returning from Brazil to Denmark. Acta Derma-

tovenerol Alp Pannonica Adriat. 2017;26(2):43-4.

8. Dunphy L, Sood V. Dermatobia hominis "the human botfly" presenting

as a scalp lesion. BMJ Case Rep. 2019;12(3).

9. Harbin LJ, Khan M, Thompson EM, Goldin RD. A sebaceous cyst with a

difference: Dermatobia hominis. J Clin Pathol. 2002;55(10):798-9.

10. Schembre DB, Spillert CR, Khan MY, Lazaro EJ. Dermatobia hominis

myiasis masquerading as an infected sebaceous cyst. Can J Surg.

1990;33(2):145-6.

11. Kahn DG. Myiasis secondary to Sermatobia hominis (human botfly)

presenting as a long-standing breast mass. Arch Pathol Lab Med.

1999;123(9):829-31.


Ana Beatriz Antunes Funes | 0000-0002-1224-8535Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; critical literature review; critical revision of the manuscript.

Ana Carolina Gama Martins | 0000-0002-8507-0774Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; critical literature review; critical revision of the manuscript.

André Matheus Camelo Neves | 0000-0001-8602-5724Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data col-lection, analysis, and interpretation; critical literature review; critical revision of the manuscript.

Marilda Aparecida Milanez Morgado de Abreu | 0000-0001-9099-6013Approval of the final version of the manuscript; preparation and writing of the manuscript; data collection, analysis, and inter-pretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Ana Cláudia Cavalcante Espósito | 0000-0001-9283-2354Approval of the final version of the manuscript; study design and planning; preparation and writing of the manuscript; data col-lection, analysis, and interpretation; active participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical literature review; critical revision of the manuscript.

Subcutaneous nodule simulating lipoma 293


the case presented), or even soft tissue malignancies.10,11 In these cases, the only effective procedure is surgical excision.

CONCLUSIONWe report the case of a patient with furunculoid cuta-

neous myiasis, in which the larva was not expelled, evolving

to form a large cystic lesion simulating a lipoma. This lesion persisted for two years, a period much longer than the usual. In endemic countries, especially in rural dwellers or under strict hygiene conditions, the possibility of larvae infestation should be considered. l

Surgical & Cosmetic DermatologyJuly / August / September 2020

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Surg Cosmet Dermatol. Rio de Janeiro v.12 n.3 jul-set. 2020 p. 192.

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