Iranian Society of ISSN 0021 - 082X Dermatology IRANIAN ...zums.ac.ir/files/IT/pages/magiran/56333.pdf · ISSN 0021 - 082X Summer 2011 . Vol. 14, No.2 Serial No. 56 Published Quarterly

ISSN 0021 - 082X

Summer 2011 . Vol. 14, No.2 Serial No. 56Published Quarterly by the Iranian Society of Dermatology

JOURNAL OFIRANIAN

Iranian Society of Dermatology

انجمن متخصصين پوست ايران

Editor-in-ChiEf

Parviz Toossi, MD, Tehran, Iran

dEputy Editors

Habib Ansarin, MD, Tehran, IranReza Robati, MD, Tehran, Iran

Mohammad Golshani, MD, Tehran, Iran

Editorial Board

intErnational advisory Board

ExECutivE Board

Editorial offiCE

Ali Asilian, MD, Isfahan, IranMir Hadi Aziz-Jalali: MD, Tehran,IranCelalettin R. Celebi, MD, Ankara, TurkeyCheyda Chams-Davatchi, MD, Tehran, IranMaryam Daneshpazhooh, MD, Tehran, IranYahya Dowlati, MD, PHD, Tehran, IranHee Chul Eun, MD, Seoul, KoreaMahmoud Farshcian, MD, Hamedan, IranAlireza Firooz, MD, Tehran,IranChristoph C. Geilen, MD, Berlin, GermanyAziz Ghahary, PhD, Vancouver, CanadaReza Ghohestani, MD, PhD, SanAntonio, USAFarhad Handjani, MD, Shiraz, IranHemangi Jerajani, MD, Mumbaie, IndiaDavid A. Mehregan, MD, Monroe, USAAli Khamesipour, PhD, Tehran, IranFarhad Malekzad, MD, Tehran, IranParvin Mansouri, MD, Tehran, Iran

Mohammad Javad Nazemi, MD, Tehran, IranSoheila Nassiri, MD, Tehran, IranMansour Nassiri Kashani, MD, Tehran, IranKoushik Lahiri, MD, Kalkata, IndiaMohammad Ali Nilforoosh Zadeh, MD, Tehran, IranConstantin E. Orfanos, MD, Berlin, GermanyTerrence Ryan, MD, Oxford, UKParvaneh Saket, MD, Tehran, IranMohammad Shahidi-Dadras: MD, Tehran,IranSaad-Allah Shamsaddini, MD, Kerman, IranBahram Sina, MD, Baltimore, USARobert A. Schwartz, MD, MPH, Newark, USAHossein Tabatabaei, MD, Tehran, IranAgneta Troilius, MD, Malmoe, SwedenMahin Valikhani, MD, Tehran, IranShyam Verma, MD, Vadodara, IndiaLuitgard G. Wiest, MD, Munich, GermanyReza Yaghoobi, MD, Ahvaz, Iran

Razaq Ahmed, MD, Boston, USAHassan A. Alabdulla, MD, Doha, QatarYassin Al-Qubati, Taiz, YemenAshraf Badawi, MD, Saudi ArabiaBijan Dowlati, MD, Long Beach, USAAhmad Fathi, MD, Munster, USA

Martin Kassir, MD, Dallas, USADarius R. Mehregan, MD, Monroe, USAFarrokh Modabber, PhD, Seattle, USAThada Piamphongsant, MD, Bangkok, ThailandBijan Safai, MD, Valhalla, USA

Parviz Toossi, MDReza Robati, MD

Mohammad Golshani, MDZohreh Mahfooz

Iranian Society of DermatologyUnit 1, No 14, Sharifi St, North Gandi Ave, Tehran, IranPost Box: 14155-6157Tel: +98 - 21 - 88202914-15Fax: +98 - 21- 88784721Website: www.iranjd.org; www.iranjd.ir; www.iransocderm.comEmail: [email protected]

The Iranian Journal of Dermatology is indexed in Index Copernicus, CABI Abstracts, IranMedex, Scientific Information Database (SID), Eastern Mediterranean Region (EMR) Index Medicus and Regional Library of Science and Technology (RLST) and approved by Medical Journals Commission of the Ministry of Health and Medical Education. In addition, clinical trials published in the Journal are indexed by the Cochrane Skin Group.

Original articles

� Efficacy of topical 5% imiquimod with cryotherapy versus intralesional meglumine antimoniate in the treatment of anthroponotic cutaneous leishmaniasisSimin Shamsi Meymandi, Manzumeh Shamsi Meymandi, Soodabeh Zandi, Shahriar Dabiri, Mahin Aflatoonian ............................................................................................................................................... 42

� The effect of different concentrations of topical podophyllin on cutaneous leishmaniasisNasrin Hamidizadeh, Behrooz Barikbin, Maryam Yousefi, Abbas Sahraei, Ali Khamesipour, Shima Younespour, Hanif Sadeghitehrani ........................................................................................................................................... 48

� Clinical efficacy and tolerability of valacyclovir versus acyclovir in treatment of herpes zosterArun Achar, Partha Pratim Chakraborty, Tarapada Ghosh, Biswanath Naskar, Tapobrata Guharay, Samiran Bisai ...................................................................................................................................................... 52

� 308-nm excimer laser plus topical calcipotriol in the treatment of vitiligo; A single blind randomized clinical studyHassan Seirafi, Maryam Daneshpazhouh, Somayeh Khezri, Pardis Kiani, Sara Sabouri Rad, khadijeh Moghadam, Farzaneh Khezri ............................................................................................................... 58

� Erythroderma in Khuzestan province, southwest of IranMohammad Ali Mapar, Amir Hosein Roozbeh, Mohammad Bagher Mohammad Hasani ................................... 64

case repOrts

� Bilateral congenital nevus of Ota in association with Mongolian spotHoda Rahimi, Maryam Yousefi, Mina Mirnezami, Zahra Asadi-Kani ................................................................... 68

� Localized genital bullous pemphigoid; A case reportAfshar Ramezanpour, Abdolamir Feizi ................................................................................................................ 71

� Unilateral generalized morphea: A case reportPerihan Ozturk .................................................................................................................................................... 73

Quiz

� Acquired hyperpigmented lesion on the footPouran Layegh, Nona Zabolinejad, Naghmeh Zabolinejad, Akram Momenzadeh ............................................. 76

letter tO editOr

� A case of contact dermatitis due to green beanViroj Wiwanitkit .................................................................................................................................................... 79

IranIan Journal of Dermatology

Summer 2011; Vol. 14, No. 2

Contents

C© 2011 Iranian Society of Dermatology

Instructions for Authors

1. Aims and Scope: The “Iranian Journal of Dermatology” is the official scientific quarterly publication of the Iranian Society of Dermatology.

2. This Journal accepts Original Papers, Review Articles, Case Reports, Quiz, Short Communications and Letters to the Editor in the fields of clinical dermatology, dermato-pathology, dermatologic surgery and basic sciences related to dermatology.

3. Submission: Manuscript submission to the Iranian Journal of Dermatology is only possible through the Journal’s URL: http://www.iranjd.ir. Manuscript must be accompanied by a covering letter to the Editor-in-Chief, including title and author(s) name and undertaking that it has not been published or submitted elsewhere. In case the manuscript was earlier submitted to some other journals and was rejected, the authors must provide full information for proper analysis. Manuscript should be typed as a Microsoft Word document in double space on the A-4 size page set up with clear margins on both sides. Tables as well as illustrations should be typed and drawn at the end of the manuscript after the references. Do not submit tables as photographs. All text documents should be uploaded in Microsoft Word format as an attachment. The figures should be sent in a format of JPEG or GIF which will produce high quality images in the online edition of the journal.

4. The manuscript should include: Title page; Abstract; Introduction; Materials & Methods; Results; Discussion; Acknowledgement and References.

5. The title page: The complete title of the manuscript, the name of all the authors with their highest qualifications, the department or institution to which they are attached, address for correspondence with telephone numbers, e-mail, and fax number.

6. The Abstract: All original articles must accompany a structured abstract up to 250 words. It should be structured as Background, Methods, Results and Conclusion followed by 3 to 5 Keywords. Keywords will assist indexers in cross indexing the article as they are published with abstract. Use terms from the Medical Subject Headings (MeSH) list of Index Medicus (http://www.nlm.nih.gov/mesh/MBrowser.html). Authors need to be careful that the abstract reflects the content of the article accurately.

7. Introduction: This should summarize the purpose and the rationale for the study. It should neither review the subject extensively nor should it have data or conclusions of the study.

8. Materials & Methods: This should include exact method or observation or experiment. If an apparatus is used, its manufacturer’s name and address should be given in parenthesis. If the method is established, give reference but if the method is new, give enough information so that another author is able to perform it. If a drug is used, its generic name, dose and route of administration must be given. For patients, age, sex with mean age ± standard deviation must be given. Statistical method must be mentioned and specify any general computer programme used. The Info system used should be clearly mentioned.

9. Results: It must be presented in the form of text, tables and illustrations. The contents of the tables should not be all repeated in the text. Instead, a reference to the table number may be given. Long articles may need sub-headings within some sections (especially the Results and Discussion parts) to clarify their contents.

10. Discussion: This should emphasize the present findings and the variations or similarities with other work done in the field by other workers. The detailed data should not be repeated in the discussion again. Emphasize the new and important aspects of the study and the conclusions that follow from them. It must be mentioned whether the hypothesis mentioned in the article is true, false or no conclusions can be derived.

D Iranian Journal of Dermatology

11. Acknowledgement: All contributors who do not meet the criteria for authorship should be covered in the acknowledgement section. It should include persons who provided technical help, writing assistance and departmental head who only provided general support. Financial and material support should also be acknowledged.

12. Tables: In limited numbers should be submitted with the captions placed above. Do not submit tables as photograph. Place explanatory matters in footnotes, not in the heading.

13. Figures: Should be in limited numbers, with high quality art work and mounted on separate pages. The captions should be placed below. The same data should not be presented in tables, figures and text, simultaneously.

14. References: All manuscripts should be accompanied by relevant references. The author should ensure reference to locally published studies by doing proper literature search. It may not be possible for the editor and reviewers to check the accuracy of all reference citations. To minimize such errors author should verify references against the original documents. The Reference should provide the following information as stated in the presented models as follows:

a. Article: Tallab TM, Bahamdam KA, Mirdad S, et al. Cutaneous leishmaniasis: Schedules for intralesional treatment with sodium stibogluconate. Int J Dermatol 1996;35:594-7.

b. Chapter: Bigby M. The hierarchy of evidence. In: Williams HC, Bigby M, Diepgen T, et al (Eds). Evidence-based dermatology. Oxford: BMJ Publishing Group; 2003. 44-8.

c. Book: Norman IJ, Redfern SJ (Eds). Mental health care for elderly people. New York: Churchill Livingstone; 1996.

15. Abbreviations and symbols: Use only standard abbreviations. Avoid using them in the title and abstract. The full term for which an abbreviation stands should precede its first use in the text unless it is a standard unit of measurement.

16. The corresponding author: Will be supplied with 3 free printed issues.

17. Ethical guidelines: Ethical considerations must be addressed in the Materials and Methods section. 1) Please state that informed consent was obtained from all human adult participants and from the parents or legal guardians of minors. Include the name of the appropriate institutional review board that approved the project. 2) Indicate in the text that the maintenance and care of experimental animals complies with National Institutes of Health guidelines for the humane use of laboratory animals, or those of your Institute or agency.

18. Conflicts of interest: Authors must acknowledge and declare any sources of funding and potential conflicting interest, such as receiving funds or fees by, or holding stocks and shares in, an organization that may profit or lose through publication of your paper. Declaring a competing interest will not lead to automatic rejection of the paper, but we would like to be made aware of it.

19. Page charges: There are no charges for publication in this Journal.

20. Copyright: The entire contents of the ‘Iranian Journal of Dermatology are protected under international copyrights. This Journal is for your personal noncommercial use. You may not modify copy, distribute, transmit, display, or publish any materials contained on the Journal without the prior written permission of it or the appropriate copyright owner.

21. Peer review process: All manuscripts are considered to be confidential. They are peer-reviewed by at least 2 anonymous reviewers selected by the Editorial Board. The corresponding author is notified as soon as possible of the editor decision to accept, reject, or require modifications. If the manuscript is completely acceptable according to the criteria set forth in these instructions, it is scheduled for the next available issue.

22. Disposal of material: Once published, all copies of the manuscript, correspondence and artwork will be held for 6 months before disposal.

E© 2011 Iranian Society of Dermatology

The Final Checklist

The authors must ensure that before submitting the manuscript for publication, they have taken care of the following:

1. Title page should contain title, name of the author/co-authors, their qualifications, designation & institutions they are affiliated with and mailing address for future correspondence, e-mail address, and phone and fax number.

2. Abstract in structured format up to 250 words.

3. References mentioned as stated in the Instruction to Authors section.

4. Make sure for headings of tables, their numbers and captions of illustrations. Don’t repeat the information in tables if it is covered in the text.

5. Photographs / illustrations along with their captions.

6. Letter of Undertaking signed by all the authors.

7. Disclosure regarding source of funding and conflict of interest if any besides approval of the study from respective Ethics Committee/Institution Review Board.

8. Covering Letter

9. Main Manuscript document

Parviz Toossi, MDThe Editor-in-ChiefIranian Journal of DermatologyUnit 1, No 14, Sharifi St, North Gandi Ave, Tehran, IranPost Box: 14155-6157Tel: +98 - 21 - 88202914-15Fax: +98 - 21 - 88784721Website: www.iranjd.irE-mail: [email protected]

42

Original article

Iranian Journal of Dermatology © 2011 Iranian Society of Dermatology

Efficacy of topical 5% imiquimod with cryotherapy versus intralesional meglumine antimoniate in the treatment of anthroponotic cutaneous leishmaniasis

Background: Cutaneous leishmaniasis (CL) is a major world problem. Several types of treatment regimens have been suggested. Imiquimod demonstrated a leishmanicidal activity by increasing local cytokine production. The aim of this study was to determine the efficacy of topical 5% imiquimod with cryotherapy vs. intralesional meglumine antimoniate (MA) in treatment of anthroponotic (dry type) CL.

Method: This is a prospective, randomized, open trial study (from Iran) from September 2008 to September 2010, including 50 patients (25 patients in the combined imiquimod and cryotherapy group and 25 patients in the intralesional MA group). Patients were randomly assigned to receive combined cryotherapy biweekly with imiquimod three times per week or intralesional MA weekly until complete cure or up to 12 weeks, whichever earlier. The primary end point was clinical cure, defined as complete re-epitelialization of 100%, complete flattening of induration compared with baseline at weeks 2, 6, 12 and follow up were done 1, 2 and 3 months after complete cure.

Results: 50 participants divided into 25 patients in group A and 25 patients in group B completed the study. Complete cure was 65.5% (16/24 patients) in group A and 83.3% (19/23 patients) in group B. No complication was detected in patients treated with MA. Pain and eczematous reaction were detected by 4 patients and local infection in 1 patient treated with imiquimod.

Conclusion: Although Meguimine antimoniate seems to be a more effective therapy for cutaneous leishmaniasis, this study revealed no significant difference in clinical response between combination of imiquimod and cryotherapy with intralesional MA in patients with cutaneous leishmaniasis in an endemic area of L. tropica.

Keywords: cutaneous leishmaniasis, imiquimod, cryotherapy, meglimine antimoniate

Simin Shamsi Meymandi, MDManzumeh Shamsi Meymandi, PhDSoodabeh Zandi, MDShahriar Dabiri, MDMahin Aflatoonian, MD

Dermatology And Leishmaniasis Research Center, Kerman University Of Medical Sciences, Kerman, Iran

Corresponding Author:Simin Shamsi Meymandi, MDDermatology And Leishmaniasis Research Center, Kerman University Of Medical Sciences, Kerman, IranEmail: [email protected]

Conflict of interest: None to declare

Register code: K/88/58

InTRoDuCTIon

Cutaneous leishmaniasis (CL) is a major health problem, which is increasing in incidence 1. Leishmaniasis is endemic in more than 60 countries worldwide 2. More than 90 percent of CL occurs in Iran, Afghanistan, Syria, Saudi Arabia, Brazil

and Peru 3.Leishmaniasis is a disease caused by the

protozoa of the heterogeneous Leishmania species, transmitted by the bite of a female sandfly and from the sub–family of phlebotominae 4.

CL caused by Leishmania tropica (anthroponotic, ACL in urban areas) or by Leishmania major

Iran J Dermatol 2011; 14: 42-47

Received: February 22, 2011Accepted: June 15, 2011

Imiquimod with cryotherapy for treatment of cutaneous leishmaniasis

43Iranian Journal of Dermatology, Vol 14, No 2, Summer 2011

(zoonotic, ZCL in rural areas) is endemic in Iran 5,6.CL initially starts as a papule at the site of

a sandfly bite which then increases in size and eventually ulcerates. It may take 3-18 months to heal in over 90% of cases 7. The incubation period lasts from 2 weeks to several months and cases up to 3 years have been reported 8,9. CL is a self healing disease, but this can take months or even years 3. Treating of CL will accelerate cure and reduce scarring and risk of transmission. This is especially important at cosmetically important sites 10.

To date, there is no vaccine against leishmaniasis and the available drugs are toxic, expensive and difficult to administer. Moreover, there are evidences of emerging resistance of the parasite to the commonly used drugs. Treatment of CL should be directed towards the eradication of amastigotes and reduction of the size of lesion with minimal scarring and possible toxicity. Several types of treatment regimens have been suggested for CL but until todays, there is no single treatment modality has been indisputably shown to be superior to others 11. Options in the treatment of CL include intralesional injection as pentavalent antimony, hypertonic sodium chloride solution and zinc sulphate; topical treatments as paromomycine ointment, 5% imiquimod cream, topical amphotericin B; physical therapy as cryotherapy, localized controlled heat, Co2 laser, photodynamic therapy; oral treatments as azoles, azithromycin, miltefosine, zinc sulphate and intramuscular or intravenous drugs such as systemic antimonials, pentamidine and amphotericin B 12.

Imiquimod is an imidazoquinoline amine that has been approved by Food and Drug Administration (FDA) as a 5% cream for external genital and perianal warts. Imiquimod is an immune response modifier that stimulates innate and adaptive immune pathways, resulting in antiviral, antitumor and immunoregulatory properties. Imiquimod induces cytokine production, most likely via activation of Toll-like receptor 7 (TLR7). Imiquimod is a stimulator of the innate immune response via the induction, synthesis of cytokines, such as IFN, IL6 and TNF 13.

Imiquimod demonstrated a leishmanicidal activity by inducing the expression of the inducible nitric oxide synthase (iNOS) gene and the release of nitric oxide 14. Imiquimod also stimulates of the

Th1 cytokine IFN. Imiquimod is generally well tolerated with the most frequent adverse reactions being mild to moderate inflammation with erythema, erosion, excoriation, flaking and edema 15.

In an open study of 12 patients with CL resistant to MA, Imiquimod in combination with MA cured 90% of the patients 16.

In a randomized double-blind clinical trial with use of Imiquimod, a 72 percent cure rate was observed when the cream was used in conjunction with MA in patients with CL who had failed to respond to antimony alone 17.

In this study, the efficacy of combination treatment with topical imiquimod cream and cryotherapy was compared with intralesional MA in a randomized, open trial clinical study.

PATIEnTS AnD METhoD

Participants

The study was done on patients aged between 5 to 65 years who had CL. The exclusion criteria were: chronic systemic disease such as renal failure, myocarditis, hepatitis and pancreatitis, immune suppression, breast feeding, pregnancy, sporotrichoid and lupoid forms, diameter of lesion >3 cm, disease duration >9 months, number of lesions >2, the past history of sensitization to MA or imiquimod, mucosal lesions and history of receiving other treatment in a recent month.

All the patients with positive smear or skin biopsy with positive Leishman body were enrolled in this study.

Participants, his or her guardian (patients younger than 18 years) were informed about the study and sign of consent form were taken.

Study setting and location

The study was carried out in the Kerman province of Iran which is an endemic area for ACL caused by L. tropica 18. The eligible patients were recruited among patients with CL who were referred to the Dermatology Clinic and Leishmaniasis research center of Afzalipour Hospital of Kerman, Iran.

Intervention

Of 105 patients screened, 75 were entered the

Meymandi et al

44 Iranian Journal of Dermatology © 2011 Iranian Society of Dermatology

treatment study. Patients were randomly allocated to one of two treatment groups. 39 Patients (24 female and 15 male) were enrolled in group A and 36 patients (21 female and 15 male) in group B (Figure 1).

Group A were treated with combined cryotherapy (biweekly) and 5% imiquimod (Aldara, 3M pharmaceuticals) cream 3 times per week.

Cryotherapy with liquid nitrogen was performed by dipstick technique. It consists of application of a saturated, cotton – tipped applicator on the lesion until 2-3 mm halo forms around it. The freeze time ranges between 10 and 25 seconds. This procedure was repeated every other week.

The patients were also treated with 5% imiquimod cream 3 times per week (Mondays, Wednesdays

and Fridays). Imiquimod was provided as 250 mg sachet. A box of sachets was given to each patient, asking them to apply a thin layer of cream on lesions at bedtime, to massage it into the skin thoroughly and wash the lesion 6 to 10 hours after application with soap and water.

Group B patients were treated with intralesional MA weekly (Glucantime, 1.5 gram in 5 cc solution as ampule; Rhodia laboratories, Rhonepoulenc, France). First the lesions were cleaned by povidon iodine. Thirty or 27 gauge needle was used for injection. The solution was injected intradermally in each lesion from all directions until the lesion had completely blanched (0.5 -2cc per lesion per week, depending on the size).

In both groups, the procedure was continued

Figure 1. A total of 50 patients completed follow – up after two types of treatments.



completed the follow- up treatment.The statistic analysis revealed no significant

difference in respect to gender, age, location and type of the lesions between two randomized groups (Table 1).

Twenty four patients in group A and 23 patients in group B completed the treatment and had follow-up for twelve weeks. In group A, 16 of 24 patients (65.5%) responded to treatment while in group B, 19 of 23 patients (83.3%) responded to treatment and had complete cure. No difference was observed between two groups (P=0.16) (Table 2).

Repeated measure model of ANOVA showed that temporal variation for size of lesions was significant for both groups (p= 0.000) and no difference was observed in regard to type of treatment (p=0.57) (Figure 2).

Cure rate in week 6 and 12 seemed to be greater in group B; 13.3% (9/25) in group A, 35% (3/25) in

until complete cure or up to 12 consecutive weeks, whichever was earlier. The patients were visited every week after initiation of treatment. Follow up evaluation was done by clinical assessment of treated lesions every month until 3 months.

Demographic information of the patients, characteristics of the skin lesions (such as induration, ulceration and edema) were registered by special designed observation recording form.

The induration size was defined as the greatest diameter of induration of the skin lesion in centimeter that was measured with the collis.

End points

The primary end point of this study was the clinical and laboratory cure of the lesions, defined as complete re-epitelialization of 100% (+/-scar), complete flattening of induration and negative smear of the lesions compared with baseline in each visit and also the time of completed cure.

The secondary end points included adverse-effects of two types of treatments and the relapse rate (defined as reappearance of lesions at the site or periphery of previously healed lesions or an increase in the size of lesions after initial improvement) that were assessed at months 1,2 and 3 after the end of treatment.

The proposal and consent form were reviewed and approved by the ethics committee of the center for research and training of Kerman University of medical sciences.

Statistical analysis

Data, expressed as Mean ± Standard deviation, were analyzed by SPSS sof tware package (version11.5). Chi-square-test and t-test were used for determining the significance of difference between the two groups of treatment. Repeated measure model of ANOVA was used to determine the temporal variation of size of lesion during 12 weeks and the effect of treatment. The difference was considered significant when p<0.05.

RESulTS

A total number of 75 patients with mean age of 15.6±12.2 were entered in the study and 50 (19 male and 31 female) of them (responding rate 88%)

Group VariableM.A

( N= 25)

Imiquimod + Cryotherapy

( N=25)P. Value

% No % NoSex

Female 61.9% 15 62.5% 160.59

Male 38.1% 10 37.5% 9Site

Upper limb 71.4% 19 28.2% 70.04Lower limb 4.8% 1 9.4% 2

Face 23.8% 5 62.6% 16Type of lesions

Plaque or ulcerated 57.1% 14 31.3% 70.056

Nodule 42.9% 11 68.8% 18

Table 1. Baseline Demographic and disease characteristics

Week Group Imiquimod+ Cryotherapy

P. valueM.A

TwoCure rate 0% 0%

0.52Mean size of lesion 1.39 ± 0.38 1.76 ± 0.39N 0 0

SixCure rate 35% 13.3


TwelveCure rate 83.3% 65.5%


Table 2. Analysis of cure rate between 2 groups based on weeks of follow-up

Meymandi et al


group B in week 6 and in week 12, 65.5% (16/24) in group A vs. 83.3% (19/23) in group B. But by using fisher exact test there was no significant difference between two groups in weeks 6 (P=0.09) and 12 (P=0.16) of treatment (Table 2). Three months after the end of treatment, relapse was observed in 2 of 25 patients treated with imiquimod and in 3 of 25 patients treated with MA.

The only adverse effects related to topical treatment were pain and eczematous reaction in 4 patients and local infection in 1 patient treated with imiquimod and they were minimal and most of them were treated by non–steroidal anti-inflammatory drugs (NSAID), topical steroid and topical antibiotic.

DISCuSSIon

Although CL is a self-healing disease, it is recommended for patients with ACL to receive treatment because of the prolonged course, potential scar formation and role of infected humans as reservoir 19.

Unfortunately, no ideal therapy for CL is available, and its treatment has been remained a challenge. Pentavalent antimonials remain the mainstay of treatment 5. However, a high rate of adverse events, length of treatment, and relapses in up to 25 percent of cases highlight the limitations of these drugs 3.

In this clinical trial, combined imiquimod and cryotherapy was compared with intralesional MA in the treatment of dry type CL.

Imiquimod is an immune response modifier that increases local cytokine production, with a subsequent activation of both the innate (rapid, nonspecific) and adaptive (specific, cellular and

humoral) immune systems 20.In this study, we did not observe significant

difference in clinical response between two therapeutic methods (65/5% in group A vs. 83.3% in group B).

In previous study in Iran (Kerman), ninety-nine patients with biopsy-confirmed CL were enrolled in an open label study. After 40 days of treatment, there was a response rate in 23%, 35% and 37% in weekly intralesional MA (n=35), imiquimod (n=29), and combination treatment group of imiquimod 5% cream and intralesional meglumine antimoniate (n= 35), respectively, indicating a better response in patients with combination of intralesional MA plus imiquimod cream compared with patients treated with MA 21. In contrast to this study, clinical response in our imiquimod group was higher, 65.5% versus 35%, which this difference may be due to cryotherapy combined with imiquimod.

Miranda et al, recruited 40 patients with clinical resistance to antimony in Peru. All patients received MA (20mg/kg/d intramuscular or intravenous) and were randomized to receive either topical 5% imiquimod cream or placebo as control every other day for 20 days. Lesions resolved more rapidly in the imiquimod group. The cure rate in the imiquimod- treated group was 50% at one month (vs. 15% in the placebo group), 61% at 2 months (vs. 25%), and 72% at 3 months (vs. 35%) (P<0/05 at all time points) 17. This study was performed in some parts of Peru, that were endemic for the new world CL, but our study was conducted in an endemic area of old world CL caused by L. tropica. All patients in the Miranda study, previously has been treated with MA (intramuscular or intravenous), but none of the patients in our study were treated previously with MA.

In a study in Mashhad (Iran), Firooz et al treated 59 patients with Imiquimod and intramuscular MA (20 mg/kg of pentavalent antimony daily for 2 weeks) and the control group was treated with placebo and intramuscular MA. This study revealed no beneficial effect of combining a 4 week course of treatment with 5% imiquimod cream and a standard course of treatment with MA in patients with CL in an endemic area of L. tropica 19.

In Firooz et al study, patients were treated with combined MA (intramuscular) and imiquimod, but in our study patients were treated with imiquimod and cryotherapy and in control group patients

Figure 2. Variation of the size of lesion in 12 weeks of treatment



received MA intralesionally. This may be explained the diversity of responses between two studies.

Our results thus demonstrated that topical application of imiquimod with cryotherapy has the less significant effect in comparison with MA alone for the treatment of Old World CL. This therapy may have particular advantages for cases with facial lesions and for children, because intralesional injection with pentavalent antimony is a relatively painful procedure which needs to be performed regularly every 1-2 weeks, but imiquimod is well tolerated.

Clinical trials for CL are usually confronted due to differences in the design, duration of treatment, sample size, end point definition, causative organisms, etc. It seems that combination therapy has important place for treatment of CL. Imiquimod can be one of this combination because of immunomodifying effect in regard to pathogenesis of CL. Further studies are needed to evaluate this effect.

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9. Smith PAJ. Long incubation period in leishmaniasis. BMJ 1955; 2: 1143.

10. Blum J, Desjeux P, Schwartz E, Beck B, Hatz C.Treatment of cutaneous leishmaniasis among travellers. J Antimicrob Chemother 2004;53:158-66.

11. Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Microbiol Rev 2006; 19:111-26.

12. Minodier PH, Parola PH. Cutaneous leishmaniasis treatment. Travel Med Infect Dis 2007;5:150-8.

13. Imbertson LM, Beaurline JM, Couture AM, Gibson SJ, Smith RM, Miller RL, et al. Cytokine induction in hairless mouse and rat skin after topical application on the immune response modification. J Invest Dermatol 1998;110:734-9.

14. Buates S, Matlashewski G. Treatment of experimental leishmaniasis with the Immunomodalutors imiquimod and S-28463: efficacy and mode of action. J Infect Dis 1999; 179: 1485-94.

15. Beutner KR, Tyring SK, Trofatter KF Jr, Douglas JM Jr, Spruance S, Owens ML, et al. Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts. Antimicrob Agents Chemother 1998;42:789-94.

16. Arevalo I, Ward B, Miller R, Meng TC, Najar E, Alvarez E, et al. Successful treatment of drug – resistant cutaneous leishmaniasis in humans by use of imiquimod, an immunomodulator. Clin Infect Dis 2001; 33: 1847-51.

17. Miranda-Verástegui C, Llanos-Cuentas A, Arévalo I, Ward BJ, Matlashewski G.Randomized, double-blind clinical trial of topical imiquimod 5% with parenteral meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru. Clin Infect Dis 2005; 40:1395 -403.

18. Sharifi I, Zarezadeh M, Fekri AR. Identification of cutaneous leishmaniasis species by immunoflurescence examination using monoclonal antibodies in Kerman and Rafsanjan cities, south – eastern Iran. Hamdard Med 2001: 44: 103-6.

19. Firooz A, Khamesipour A, Ghoorchi MH, Nassiri-Kashani M, Eskandari SE, Khatami A, et al. Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis. Arch Dermatol 2006; 142: 1575-9.

20. Najarian DJ,English JC. Imiquimod Cream: A new multipurpose topical therapy for dermatology. P&T 2003; 28: 122-6.

21. Crawford R, Holmes D, Meymandi S. Comparative study of the efficacy of combined imiquimod 5% cream and intralesional meglumine antimoniate versus imiquimod 5% cream and intalesional meglumine antimoniate alone for the treatment of cutaneous leishmaniasis. J Am Acad Dermatol.2005; 52 (suppl 1): S 118.

48

Original article


The effect of different concentrations of topical podophyllin on cutaneous leishmaniasis

Introduction: Cutaneous Leishmaniasis (CL) is a parasitic disease caused by Leishmania species. Currently accessible treatments remain insufficient, and there is pressure to develop suitable and effectual options. In this study, we used different concentrations of podophyllin in vitro on leishmania parasites and then on leishmaniasis lesions in mice and compared their efficacy.

Method: We used podophyllin (14.3 μg/ml) in vitro against leishmania major parasites, then in experimental animals in different concentrations.

Results: Podophyllin (14.3 μg/ml) that used in vitro eradicated leishmania major parasites, but, in mice after four weeks was not effective and the diameter of the lesions increase with use of topical podophyllin.

Conclusion: Despite the lethal effect on leishmania in vitro, treatment with different doses of podophyllin could not accelerate the healing process of the leishmaniasis lesions of the experimental rats.

Keywords: leishmaniasis, podophyllin, treatment, in vitro

Nasrin Hamidizadeh, PhD1

Behrooz Barikbin, MD1

Maryam Yousefi, MD1

Abbas Sahraei, MD1

Ali Khamesipour, PhD2

Shima Younespour, MSc1

Hanif Sadeghitehrani, MD3

1. Skin Research Center, Shohada-e-Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2. Center for Research and Training in Skin Disease and Leprosy, Tehran University of Medical Sciences, Tehran, Iran

3. Biomedical Radiation Science Center, Department of Oncology, Radiology and Clinical immunology, Faculty of Medicine, Uppsala University, Sweden

Corresponding Author:Maryam Yousefi, MDAssistant professor of dermatology, Skin Research Center, Shohada-e-Tajrish Hospital, Tajrish, Tehran, IranE-mail:[email protected]


InTRoDuCTIon

Leishmaniasis is an infectious disease 1 commonly caused by different kinds of leishmania like leishmania tropica (in urban areas) and leishmania major (in rural areas) in the old world. The phlebotomine insect vector bite transmits leishmaniasis to humans 2.

Leishmaniasis is characterized by a clinical, immunological and histopathological range that is associated with immunological capability of the host, the species and virulence of the parasite and inadequately defined environmental factors. Clinical

manifestations of leishmaniasis are cutaneous, mucosal and visceral lesions. A rare form is diffuse cutaneous leishmaniasis (DCL) that is related to the imperfect cell-mediated immune response to the leishmania parasite 3.

The first line treatment for Leishmaniasis is still pentavalent antimonials, but other drugs such as amphotericin B, paromomycin, imidazoquinoline derivatives, and miltefosine have been studied in other reviews for treatment of leishmaniasis 4,5.

Although many treatment modalities are present, there is no perfect therapy for leishmaniasis.


Received: December 3, 2010Accepted: May 24, 2011

The effect of topical podophyllin on cutaneous leishmaniasis


Some treatments such as glucantime are painful and costly 4,5, other treatments have side effects such as headache, vomiting, skin reaction and abdominal pain 5. As a result, development of more efficient and easily tolerated medications that can be suitably administered are of important advantages. Podophyllin is a plant alkaloid used for the treatment of genital warts. It interferes with cell replication, crosses cell membranes and works as a keratolytic that causes arrest of cell mitosis in metaphase 6.

In this study, we postulated podophyllin could eradicate leishmania parasite by arresting cell mitosis; therefore, we used different concentrations of podopoyllin in vitro on leishmania parasites and then on leishmaniasis lesions in mice and compared their efficacy.

MATERIAl AnD METhoDS:

Cell culture

L e i s h m a n i a m a j o r ( M R H O / I R / 7 5 / E R ) promastigotes were cultured at 26ºC in RPMI 1640 containing 10% fetal calf serum (FCS) and antibiotics. The log-phase promastigotes were washed in phosphate-buffered saline (PBS), adjusted to a concentration of 1 × 106 cell/ml into 98 wells plate in a fresh medium. Podophyllin was added to the promastigotes (14.3 μg /ml). After incubation at 26ºC for 1h, 2h and 24 h at 5% CO2, the promastigotes were counted and checked for viability using a light microscope.

Mouse infection

Fifty four BALB/c mice (4- to 6-week-old female) were purchased from Pasteur Institute, Karaj, Iran. The animal experiments were carried out according to Ethical Committee Acts of the Shahid Beheshti and Tehran University of Medical Sciences. Mice were inoculated subcutaneously at the base with amastigote forms obtained from the spleen and the liver of mice infected with leishmania major (MRHO/IR/75/ER). Four groups were tested by podophyllin 5%, podophyllin 10%, podophyllin 20% and control group (infected but untreated mice). Podophyllin was applied using a sterile tip directly onto the skin to form a thin layer once weekly for 4 weeks. The treated area was then left open without

dressing. Images were taken at baseline and then weekly. The lesion size measurement (mm) was done weekly with a caliper. Ethical committee of the Skin Research Center of Shahid Beheshti Medical University approved the study protocol in March 2009 (Certificate number: 1112MTB).


The Kruskal-Wallis test was used to compare groups at similar sessions and in case of any dif ference, the Mann-Whitney-U-test with Bonferroni correction was applied for pair-wise comparisons. For each group, Friedman test was used to evaluate the differences of lesions’ diameters among the five time-points (baseline, and after 1, 2, 3 and 4 weeks) and if there were any differences, the Wilcoxon tests with Bonferroni corrections were conducted to compare the lesions’ diameters at each week with the previous week and baseline. Statistical analysis was performed using the statistical software SPSS 16 (SPSS Inc. Chicago, IL, U.S.A.). P values less than 0.05 were considered significant.

RESulT

Podophyllin, 14.3 μg /ml used in vitro, eradicated leishmania major parasites.The first group (13 mice), second group (13 mice) and third group (12 mice) were treated with podophyllin 5%, 10% and 20% respectively. The control group (13 mice) did not receive any treatment.

The four groups were compared according to lesions’ diameters at similar sessions. There were no statistical significant differences in lesions’ diameter among the groups at baseline (p=0.105).

At first week, a significant difference in lesions’ diameter was observed in all groups (p=0.004) and pair-wise comparisons showed a significant difference between podophyllin 10% and the control group, and between podophyllin 20% and the control group (p=0.006 and p<0.001, respectively). Mean lesions’ diameter of the podophyllin 10% and 20% groups were more than control group one week after beginning of the treatment (Table 1).

At second week, there was a significant difference in lesions’ size among four groups (p<0.001) and with pair-wise comparisons, significant differences between podophyllin 10% and the

Hamidizadeh et al


control group, podophyllin 20% and the control group, and between podophyllin 5% and 10% groups were demonstrated (p=001, p=005 and p=0.002, respectively). According to Table 1, the mean lesions’ diameter at the second week after beginning of the treatment in podophyllin 10% group was more than podophyllin 5% and the control group.

At weeks 3 and 4, no significant difference was observed among four groups (Table 1). There were significant increases in lesions’ diameters of control group at second week in comparison to first week and at third and fourth weeks in comparison to baseline (p=0.005,p=0.001 and p=0.002, respectively) (Figure 1).

In the podophyllin 5% group, there were significant increases in lesions’ diameter at the second and fourth week in comparison with the baseline and also at fourth week in comparison with the third week (p=0.004, p=0.002 and p=0.002, respectively) (Figure 1).

Significant increases in lesions’ diameters of second, third and fourth weeks in comparison with baseline and of second week in comparison to first week were observed in podophyllin 10% group (p-values at most 0.004) (Figure 1).

Finally, there were significant increases in lesions’ diameter of the podophyllin 20% group at the first, second, third and fourth weeks in comparison

with baseline, and the fourth week compared to the third week (p-values at most 0.005) (Figure 1).

DISCuSSIon

Leishmaniasis has a big range of clinico-pathological forms and therefore needs different treatments. The most common type of cutaneous leishmaniasis (CL) treatment is antimonials. Intralesional injection of antimonials can prevent side-effects resulting from systemic administration 7 and numerous studies have confirmed their efficacy in the treatment of CL 8-12. Various other drugs have also been used but all have limitations concerning ease of use and financial aspects 4,5. Podophyllin is a plant alkaloid 6, commonly used in topical forms such as a chemotherapeutic agent 13. It interferes with cell replication, crosses cell membranes and works as a keratolytic that causes arrest of cell mitosis in metaphase 6. Podophyllin has been applied in many disease e.g oral hairy leukoplakia 14-16, measles and herpes simplex virus type I infection 17, condyloma acuminatum 18,19, cytomegalovirus and Sindbis virus infections 20. Also, it has an anti-tumor and anti-rheumatoid arthritis activity 21 and has been traditionally used for the treatment of genital warts 6.

Despite the evident beneficial effects of podophyllin, no study has been conducted to assess its effects on leishmaniasis. In this regard, in the present study, the efficacy of podophyllin was investigated on leishmaniasis. The present survey postulated that podophyllin could eradicate leishmania parasite by arresting cell mitosis. Therefore, we used different concentrations of podopoyllin in vitro on leishmania parasites and then on leishmaniasis lesions in mice and compared their efficacy.

Our study demonstrated that podophyllin could eradicate leishmania parasite in vitro although in mice, after four weeks of treatment, the mean lesion size increased significantly in podophyllin groups with different concentrations and also in the Figure 1. Mean diameters of lesions by groups over time.

Group baseline 1th week 2th week 3th week 4th weekPodophyllin 5% 4.74 (1.87) 6.19 (1.93) 7.64 (1.73) 7.04 (3.29) 10.10 (2.57)Podophyllin 10% 4.65 (0.98) 6.78 (1.58) 10.57 (3.02) 8.03 (3.10) 9.42 (3.73)Podophyllin 20% 4.56 (1.79) 7.15 (1.34) 8.92 (1.32) 9.28 (1.79) 11.01 (2.26)Control 5.72 (2.46) 5.21 (1.06) 6.96 (1.84) 8.80 (2.13) 10.08 (2.27)

Table 1. Mean (standard deviation) diameters of lesions by groups over time.

The effect of topical podophyllin on cutaneous leishmaniasis


7. Mujtaba G, Khalid M. Weekly vs. fortnightly intralesional meglumine antimoniate in cutaneous leishmaniasis. Int J Dermatol 1999; 20: 607-9.

8. Kellum RE.Treatment of cutaneous leishmaniasis with an intralesional antimonial drug (Pentostam). J Am Acad Dermatol 1986; 15: 620–2.

9. Faris RM, Jarallah JS, Khoja TA, Al-Yamani MJ. Intralesional treatment of cutaneous leishmaniasis with sodium stibogluconate. Int J Dermatol 1993;32:610–2.

10. Sharquie KE, Al-Talib KK, Chu AC. Intralesional therapy of cutaneous leishmaniasis with sodium stibogluconate. Br J Dermatol 1988;119: 53-7.

11. Sharque KE, Najim RA, Farjou IB. A comparative controlled trial of intralesionally administered zinc sulfate, hypertonic sodium chloride and pentavalent antimony compound against acute cutaneous leishmaniasis. Clin Exp Dermatol 1997; 22: 169-73.

12. Tallab TM, Bahamdam KA, Mirdad S, Johargi H, Mourad MM, Ibrahim K, el Sherbini AH, et al. Cutaneous leishmaniasis schedule for intralesional treatment with sodium stibogluconate. Int J Dermatol 1996; 35:594-7.

13. Gowdey G, Lee RK, Carpenter WM. Treatment of HIV-related hairy leukoplakia with podophyllum resin 25% solution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:64-7.

14. Sanchez M, Spielman T, Epstein W, Moy J. Treatment of oral hairy leukoplakia with podophyllin. Arch Dermatol 1992; 128:1659.

15. Arendorf TM, Bredekamp B, Cloete CAC, Sauer G. Oral manifestations of HIV infection in South African patients. J Oral Pathol Med 1998; 27:176-9.

16. Lozada-Nur F, Costa C. Retrospective findings of the clinical benefits of podophyllum resin 25% sol on hairy leukoplakia. Oral Surg Oral Med Oral Pathol 1992; 73:555-8.

17. Hammonds TR, Denyer SP, Jackson DE, Irving WL. Studies to show that with podophyllotoxin the early replicative stages of herpes simplex virus type 1 depend upon functional cytoplasmic microtubules. J Med Microb 1996; 45:167–72.

18. Wilson J. Treatment of genital warts—what’s the evidence? Int J STD AIDS 2002;13:216-20; quiz 221-2.

19. Beutner KR. Podophyllotoxin in the treatment of genital warts. Curr Probl Dermatol 1996; 24: 227–32.

20. MacRae WD, Hudson JB, Towers GH. The antiviral action of lignans. Planta Med 1989;55: 531-5.

21. Subrahmanyam D, Renuka B, Kumar GS, Vandana V, Deevi DS. 9-deoxopodophyllotoxin derivatives as anti-cancer agents. Bioorg Med Chem Lett 1999; 9:2131-4.

control group over time. Our findings suggested that podophyllin was not an appropriate drug for the treatment of CL. A possible explanation could be the anti mitotic effect of podophyllin, which prevents the proliferation of cells near the lesion thus resulting in the expansion of the wound. This effect was more prominent especially when we used podophyllin 20%.

The reason we did not achieve proper results from our study may refer to the fact that the dose of podophyllin was not adjusted appropriately according to the weight of the mice, which led to disorganization in cellular proliferation. Another limitation of our study was that we did not check the parasite burden by smear from the lesions, and podophyllin might have been injected into a non-healing ulcer without any parasites in some cases. In conclusion, treatment with different doses of podophyllin could not accelerate the healing process of leishmaniasis lesions. However, furthur structured studies could be more beneficial to elucidate the possible role of podophyllin in the treatment of cutaneous leishmaniasis.

REFEREnCES

1. Convit J, Ulrich M. Antigen-specific immunodeficiency and its relation to the spectrum of American cutaneous leishmaniasis. Biol Res 1993; 26:159–66.

2. Alrajhi AA.Cutaneous leishmaniasis of the Old World. Skin Therapy Lett 2003; 8:1-4.

3. Alvar J, Croft S, Olliaro P. Chemotherapy in the treatment and control of leishmaniasis. Adv Parasitol 2006;61: 224–61.

4. Sundar S, More DK, Singh MK, Singh VP, Sharma S, Makharia A, et al. Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis 2000;31:1104–7.

5. Ouellette M, Drummelsmith J, Papadopoulou B. Leishmaniasis: drugs in the clinic, resistance and new developments. Drug Resist Update 2004;7: 257–66.

6. Türkmen M, Ertam I, Unal I, Dereli T. Facial angiofibromas of tuberous sclerosis: successful treatment with podophyllin. J Eur Acad Dermatol Venereol 2009;23: 713-4.

52

Original article


Clinical efficacy and tolerability of valacyclovir versus acyclovir in treatment of herpes zoster

Background: Acyclovir, a specific and selective inhibitor of replication of herpesviridae family, has well documented efficacy for speedy rash healing and decreasing pain of herpes zoster. Limited oral bioavailability of acyclovir requires frequent dosing. Valacyclovir is rapidly and almost completely converted to acyclovir in vivo and gives three to fivefold increase in acyclovir bioavailability. The aim of this study was to assess the clinical efficacy, safety and tolerability of oral valacyclovir versus standard oral acyclovir in the treatment of herpes zoster.

Methods: A blind randomized prospective study was performed during May 2007 to August 2007 in Midnapore Medical College. Immunocompetent patients, aged ≥40yrs presenting with herpes zoster within 72 hours after onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg of valacyclovir thrice daily for 7 days or acyclovir 800 mg 5 times daily for 7 days. A total of 60 patients were included and randomized to receive either valacyclovir (n=30) or acyclovir (n=30) and they were evaluated at 8 days, 15 days and 29 days, respectively.

Results: A statistically significant reduction of skin lesion and zoster associated pain were noticed in valacyclovir compared to acyclovir group. However, presence of post herpetic neuralgia on the 29th day was less in acyclovir compared to valacyclovir group (70.0% vs. 83.3%, P>0.05). Only one patient on valacyclovir and two patients on acyclovir complained of nausea and mild abdominal pain.

Conclusion: We conclude that for the management of herpes zoster, valacyclovir might be superior to acyclovir in respect to reduction of skin lesions and pain.

Keywords: acyclovir, herpes zoster, treatment, valacyclovir

Arun Achar, MD1

Partha Pratim Chakraborty, MD2

Tarapada Ghosh, MD3

Biswanath Naskar, MD1

Tapobrata Guharay, MD 4

Samiran Bisai, PhD5

1. Department of Dermatology, Midnapore Medical College, Midnapore.

2. Department of Medicine, Midnapore Medical College, Midnapore.

3. Department of Pediatrics, Midnapore Medical College, Midnapore.

4. Department of Community Medicine, Midnapore Medical College, Midnapore.

5. Department of Anthropology, North Eastern Hill University, Shillong and Department of Anthropology, Vidyasagar University, Midnapore.

Correspondence Author:Samiran Bisai, PhDDepartment of Anthropology, Vidyasagar University, Midnapore – 721 102, West Bengal, India.E-mail: [email protected]


InTRoDuCTIon

Herpes zoster remains an important medical problem throughout the world. It may occur at any age in the otherwise immunocompetent individuals. The reported incidence in the general population ranges from 0.8 to 4.8 per 1000 persons 1. The characteristic rash and associated pain may occur

when varicella zoster, which becomes dormant in sensory ganglia following primary varicella zoster virus infection, is reactivated, often in association with declining cellular immunity associated with advancing age 2. Post herpetic neuralgia is one of the most common complications of herpes zoster. The incidence of post herpetic neuralgia varies with age. It is rare under 40 years but about 50%


Received: April 7, 2011Accepted: May 24, 2011

Efficacy and tolerability of valacyclovir in treatment of herpes zoster


of patients over 60 years may be affected 3.Acute herpes zoster presents with skin rashes

distributed over one or more dermatomes that usually resolve within 4 weeks; however, in an untreated patient, the associated pain and post herpetic neuralgia, may persist for several months to even years and can be a serious disabling condition, particularly in the elderly 4-6. Replication of varicella zoster virus in the ganglion of involved nerve results in destructive inflammation and / or nerve dysfunction. This may partly explain the pain, although the full pathogenesis of the syndrome is not clear 6.

Oral Acyclovir (800mg five times daily) is widely used for the treatment of acute herpes zoster. It speeds rash healing and decreases the severity of acute pain 7,8. In some studies, acyclovir also appears to reduce the prevalence, severity and duration of chronic pain 6-9. The limited oral bioavailability of acyclovir, however, necessitates frequent dosing to achieve a better therapeutic concentration in plasma for the treatment of acute herpes zoster 4,7.

Valacyclovir, 2-[2-amino-1, 6-dihydro-6-oxo-9H-purin-9-yl-methoxy] ethyl valinate hydrochloride, is the L-valine ester of acyclovir. It was developed to provide increased oral bioavailability of acyclovir 10. Valacyclovir is better absorbed than acyclovir due to an active stereoselective transporter in intestinal brush border membrane. Valacyclovir is converted rapidly and virtually to acyclovir after oral administration in healthy adults by intestinal and hepatic first pass metabolism through hydrolysis. Thus, the mechanism of action and spectrum of activity of valacyclovir are the same as that of acyclovir. Unlike acyclovir, valacyclovir is a substrate for intestinal and renal peptide transporters. Therefore, the proportion of bioavailability of acyclovir increases 3-5 times greater to approximately 70% following valacyclovir administration 11. The comparatively better oral bioavailability of valacyclovir contributes to the need for less frequent administration. Apart from the differences in bioavailability, the mechanism, clinical spectrum and adverse effects are similar 12.

This randomized prospect ive study was conducted in Midnapore Medical College and Hospital to assess the clinical efficacy, safety and tolerability of oral valacyclovir versus standard oral acyclovir in the treatment of herpes zoster.

PATIEnTS AnD METhoDS

T h i s r a n d o m i z e d p r o s p e c t i v e s t u d y o f valacyclovir versus acyclovir for the treatment of acute herpes zoster was carried out in Midnapore Medical College and Hospital between March 2007 and August 2007.

Patients

Non-pregnant patients who were 40 years of age or older, were immunocompetent and were not on any immunosuppressive medication and presented within 72 hours after the onset of rash were enrolled in the study. The clinical diagnosis of herpes zoster was based on the presence of unilateral dermatomal rash. The ethics committee of Midnapore Medical College and Hospital approved the study protocol. A written informed consent was obtained from each patient prior to enrollment. Routine hematological examination, liver function test and renal function test (urea and creatinine) were done before the treatment and after completion of valacyclovir/acyclovir therapy.

Drug administration

A total of sixty patients were included in the study. Out of them, 30 patients were treated with valacyclovir and remaining 30 patients with acyclovir. The patients were selected randomly, those with even number were put on valacyclovir and the odd ones were given acyclovir. Thus, the patients were randomized to receive either 1000 mg valacyclovir three times daily from the day of presentation for 7 days or oral acyclovir 800 mg five times daily for the same period.

Efficacy assessment

At the time of presentation, the patients were evaluated for zoster rashes including the proportion of the total lesion area consisting of macules/papules, vesicles, crusts and healed rashes, the distribution of rash (trigeminal, cervical, thoracic and lumbosacral) and prodromal symptoms. The patients were reviewed after 1 week (8th day), 2 weeks (15th day) and 4 weeks (29th day) to assess response to treatment in both groups. The responses were evaluated by the percentage of improvement

Achar et al


in skin lesion and zoster associated pain in each visit and the appearance of post herpetic neuralgia after the 4th week.

The impact of pain on daily activities was determined using a numerical scale with six levels as follows 13.No Pain 0 = no pain and discomfort

Just noticeable 1 = Pain can easily be ignored

Mild 2 = Pain does not interfere with daily activities

Moderate 3 = pain interfered with concentration or sleep

Severe 4 = Pain interfered with all but basic needs

Very Severe 5 = Pain required rest or bed rest

All adverse effects were recorded during the follow-up period.


Student t-test, odds ratio (OR) and 95% confidence interval (CI) was calculated following standard statistical method. The differences in the severity of zoster associated pain, skin rash and presence of post herpetic neuralgia between the two treatment groups was compared using chi-square test. All statistical tests were done using EPI6 statistical package. A p-value less than 0.05 was considered significant.

RESulT

A total of 60 patients with herpes zoster were enrolled in the study. They were randomized into two groups- valacyclovir (n = 30) and acyclovir (n = 30). All the patients completed the 4-week study period and were reviewed after one week,

two weeks and four weeks. None of these patients withdrew because of serious adverse events. Only one patient on valacyclovir and two patients on acyclovir complained of nausea and mild abdominal pain, but they continued the treatment. More importantly, no abnormalities were detected during the routine hematological, liver or renal function tests either before or after treatment.

Of 60 patients, 40 (66.7%) were male and 20 (33.3%) were female. The mean age of the patients was 51.9 ± 8.9 years; no significant difference was observed between two treatment groups. Moreover, there were no significant differences between two groups in other basic characteristics. There were four types of herpes zoster patients in this study; among them thoracic type is the commonest (56.6%). Other types are cervical (28.3%), trigeminal (10%) and lumbosacral (5%). Most of the patients (60.0%) complained of prodromal symptoms (Table 1).

During the 1st review period (i.e. the 8th day), we noticed that most of the patients improved partially. We accepted the 75% skin lesion improvement as the significant improvement on the 8th day of treatment. By the 15th day, most of the patients showed complete healing of the skin lesions. Hence, on the 15th day, we accepted 100% improvement as the significant improvement (Figure 1,2).

The changes in skin lesions following the treatment are presented in Table 2. Faster resolution of skin lesions was noted in the valacyclovir group compared to acyclovir group during the 1st review (the 8th day) (90.0% vs. 20.0%) and the 2nd review (15th day) (93.3% vs. 30%) and the comparison was statistically significant (p<0.001). After the 4th week, skin lesions healed completely in all the patients of both groups.

Table 3 presents the rate of zoster-associated pain after treatment. At 8th day, zoster associated

Characteristics of patients Total patients Acyclovir Valacyclovir p-valueAge (year) Mean ± SD 51.9 ± 8.9 50.7 ± 8.7 53.2 ± 8.9 0.276Sex

Male 40 (66.6%) 19 (63.3%) 21 (70.0 %) 0.782Female 20 (33.4%) 11 (36.7%) 9 (30.0%) 0.782

Type Thoracic 34 (56.6 %) 17 (56.7 %) 17 (56.7 %) 0.794Cervical 17 (28.3%) 9 (30 %) 8 (26.7 %) 0.998Trigeminal 6 (10.0 %) 2 (6.7%) 4 (13.3%) 0.673Lumbosacral 3 (5.0%) 2 (6.7%) 1 (3.3%) 0.991Presence of Prodromal symptom 36 (60.0%) 19 (63.3%) 17 (56.7 %) 0.796

Table 1. Demographic characteristics of patients



both treatment groups as evaluated after 28 days. It was observed that the presence of post herpetic neuralgia was more common in the valacyclovir group than the acyclovir group but with no significant difference (83.3 % vs 70.0%, p>0.05).

DISCuSSIon

The 4-week randomized parallel and controlled study demonstrated that treatment with valacyclovir three times daily was effective in treating patients with herpes zoster. Overall, women may have a slightly greater risk of developing zoster when compared to men; but in the present study, we observed that men were more frequently affected than women (66.6% vs. 33.4%) 15. This study showed that the commonest type of herpes zoster

pain was less in the valacyclovir group compared to the acyclovir group (56.7% vs. 36.7%) but the differences was not statistically significant. However, at 15th day, 83.3% of the patients in the valacyclovir group reported no pain compared to 40.0% of patients in the acyclovir group, and the differences was highly significant (P<0.001). Table 4 shows the incidence of post herpetic neuralgia in

Figure 2. (a) Herpes zoster lesion before treatment with valacyclovir.(b) Clinical improvement after 7 days of treatment with valacyclovir.

Figure 1. (a) Herpes zoster lesion before treatment with acyclovir. (b) Clinical improvement after 7 days of treatment with acyclovir.

Days In Acyclovir Group (n =30)

In Valacyclovir Group (n =30) p-value

8th day (75% reduction)

6 (20.0%) 27 (90.0%) <0.001

15th Day (100% reduction)

9 (30.0%) 28 (93.3%) <0.001

Table 2. Comparison of skin changes of herpes zoster in patients treated with acyclovir versus valacyclovir

Achar et al


was thoracic (56.6%) as mentioned in previous studies 15. The prodromal symptoms commonly preceded the herpes zoster eruption (60%) similar to other studies 13.

Skin lesions improved faster in patients on valacyclovir compared to acyclovir (93.3% vs. 30.0%) and the difference was statistically significant. An earlier study also noticed the faster resolution of skin lesion in valacyclovir group but their findings were not statistically significant 4. Pain is the most common debilitating feature of herpes zoster 13. The majority of the patients experience pain immediately before and during the acute rash phase. However, a more important clinical concern is to prevent or reduce the possibility of persistent pain. A significant improvement in zoster - associated pain was noticed in the present study in patients on valacyclovir compared to acyclovir (83.3% vs. 40.0%) unlike other studies 4,13.

Post herpetic neuralgia was more frequently seen in patients who were on valacyclovir rather than acyclovir (83.3% vs. 70.0%) but the difference was not statistically significant. However, a large multicentre study found that the treatment with valacyclovir for 7 days significantly reduced the incidence of the post herpetic neuralgia compared to acyclovir 4.

A recent review documented that valacyclovir significantly decreased the incidence and severity of post herpetic neuralgia. Valacyclovir recipients had a mean duration of 40 days of pain after lesion resolution compared to 60 days of pain after lesion resolution for acyclovir recipients. In terms of zoster related discomfort, it is estimated that valacyclovir provides a 25% benefit over acyclovir 12. In our study, we also found that skin lesions and zoster associated pain improved significantly faster in the valacyclovir group while we noted no significant reduction in post herpetic neuralgia. The less

frequent dosing schedule of valacyclovir is mainly due to its enhanced bioavailability of 65% compared to 15% to 20% for acyclovir which allows for more convenient dosing adjustment 7,16,17.

Safety profile of acyclovir has been carefully established during more than 18 years of clinical use. In the present study, there was no clinically significant difference in nature, frequency or severity of adverse events between the two treatment groups, as reported in earlier studies 4,13.

In conclusion, our study demonstrated that administration of valacyclovir three times daily was an effective and safe treatment for acute herpes zoster. Treatment with valacyclovir has the benefits of rapid resolution of skin lesions and zoster associated pain compared to acyclovir, but no additional benefit was noted in the incidence of post herpetic neuralgia. Valacyclovir has the convenience of a three times daily dosing, thereby ensuring better patient compliance, which makes this regimen an excellent choice for treatment of herpes zoster. However, studies on larger numbers of patients are required to assess the incidence of post herpetic neuralgia in treatment with valacyclovir and acyclovir and elucidate the cost effectiveness of valacyclovir versus acyclovir in different societies.

Acknowledgement

The authors gratefully acknowledge the patients for their co-operation during the study period. The authors are also thankful to the authority of Midnapore Medical College & Hospital for logistics support.

REFEREnCES

1. Smiley ML, Murry A. Acyclovir and its l-valyl ester, valacyclovir. Curr Prob Dermatol 1996; 24:209-18.

2. deMoragas JM, Kierland RR. The outcome of patients with herpes zoster. AMA Arch Derm 1957;75:193-6.

3. Haribhakti PB, Macwan R. Viral skin infections. In: Valia RG, Valia AR editors. IADVL Textbook and Atlas of Dermatology,2nd ed. Mumbai: Bhalani Publishing House; 2003: 285 - 322.

Days In Acyclovir Group (n =30) In Valacyclovir Group (n =30) p-value8th day (75% improvement) 11 (36.7%) 17 (56.7%) 0.19615th Day (No pain) 12 (40.0%) 25 (83.3%) <0.001

Table 3. Comparative efficacy in improving zoster associated pain.

Days In Acyclovir Group (n =30)

In Valacyclovir Group (n =30) p-value

29th day 21 (70.0%) 25 (83.3%) 0.222

Table 4. Incidence of post herpetic neuralgia.



4. Beutner KR, Friedman DJ, Forszpaniak C, Andersen PL, Wood MJ. Valacyclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother 1995;39:1546-53.

5. Davies L, Cossins L, Bowsher D, Drummond M. The cost of treatment for post-herpetic neuralgia in the UK. Pharmacoeconomics 1994;6:142-8.

6. Crooks RJ, Jones DA, Fiddian AP. Zoster- associated chronic pain: an overview of clinical trials with acyclovir. Scand J Infect Dis Suppl 1991;80:62-8.

7. Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. N Z Med J 1989; 102: 93-5.

8. Whitley RJ. Therapeutic approaches to varicella - zoster virus infections. J Infect Dis 1992; 166 (Suppl 1): S 51-7.

9. Harding SP, Porter SM. Oral acyclovir in herpes zoster ophthalmicus. Curr Eye Res 1991;10:177-82.

10. Hay CM, Reichman RC. Antiviral Drugs. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ, editors. Fitzpatrick`s dermatology in general medicine. 7 th ed. New York: McGraw-Hill; 2008: 2203-11.

11. Hayden FG. Antiviral agents (Non-Retroviral). In: Bruton LL, Lazo JS, Parker KL, eds. Goodman and Gilmans- the pharmacological basis of therapeutics, 11th ed. New York; McGraw-Hill Medical Publishing Division; 2006: 1243-71.

12. Rajalakshmi R, Kumari R, Thappa DM. Acyclovir versus valacyclovir. Indian J Dermatol Venereol Leprol; 2010; 76:439-44.

13. James WD, Berger TG, Elston DM, editors. Andrews’ diseases of the skin clinical dermatology. Tenth edition. Philadelphia:Saunders Elsevier;2006:379-84.

14. Sterling J. Viral infections. In: Burns T, Breathnach S, Cox N, Griffiths C, eds. Rook’s textbook of dermatology, 8th ed. Oxford: Blackwell science; 2010:25.1-83.

15. Lin WR, Lin HH, Lee SSJ, Tsai HC, Huang CK, Wann SR,et al. Comparative study of the efficacy and safety of valacyclovir versus acyclovir in the treatment of herpes zoster. J Microbiol Immunol Infect 2001;34:138-42.

16. Purifoy DJ, Beauchamp LM, de Miranda P, Ertl P, Lacey S, Roberts G, et al. Review of research leading to new anti-herpesvirus agents in clinical development: valacyclovir hydrochloride (256 U, the l-valyl ester of acyclovir) and 882C, a specific agent for varicella zoster virus. J Med Virol 1993; 41 (suppl 1):139-45.

17. Soul-Lawton J, Seaber E, On N, Wootton R, Rolan P, Posner J. Absolute bioavailability and metabolic disposition of valacyclovir, the l-valyl ester of acyclovir, following oral administration to humans. Antimicrob Agents Chemother 1995; 39:2759-64.

58

Original article


308-nm excimer laser plus topical calcipotriol in the treatment of vitiligo; A single blind randomized clinical study

Background: There is a large variety of therapeutic agents for the treatment of vitiligo, but it still remains a challenge. Narrow-band UVB phototherapy and 308-nm excimer laser have been shown to be safe and effective for the treatment of vitiligo. Topical calcipotriol has recently been reported to enhance the efficacy of phototherapy, especially 8-methoxypsoralen plus UVA (PUVA). The goal of this study was to evaluate whether the addition of topical calcipotriol enhances the efficacy of 308-nm excimer laser in the treatment of vitiligo.

Methods: The patients with symmetrical vitiliginous lesions received 308-nm excimer laser plus Calcipotriol ointment 0.005% (Daivonex®) as the intervention group and 308 nm excimer laser plus vaselin as the control group on the lesions of the right side. All patients in the two groups applied vaselin on the lesions of the left side. The evaluation of the patients was performed at baseline and at 12th week (the last laser session). SPSS version 15.0 package software was used for statistical analysis. P-values< 0.05 were accepted as statistically significant.

Results: Seventy out of 83 patients completed the study. The diameter of the right side lesions (308nm excimer laser + calcipotriol) changed from 27.21 cm2 to 15.82 cm2 in the intervention group and from 27.86 cm2 to 16.02 cm2 in the control group; This difference was not statistically significant (p-value=0.74).

Conclusion: Our findings showed that 308-nm excimer laser was effective and safe in the treatment of vitiligo, and that topical calcipotriol had no additive or synergistic effect.

Keywords: 308-nm excimer laser, topical calcipotriol, phototherapy, vitiligo

Hassan Seirafi, MD1

Maryam Daneshpazhouh, MD1

Somayeh Khezri, MD1

Pardis Kiani, MD1

Sara Sabouri Rad, MD1

khadijeh Moghadam, MD1

Farzaneh Khezri, MD2

1. Department of Dermatology, Razi skin hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2. Department of Dermatology, Mayo Clinic, Rochester, Minnesota, United States of America

Corresonding Author:Somayeh Khezri, MDDepartment of Dermatology, Razi skin hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranEmail: [email protected]

Irct registration number: IRCT138812213543N1

Conflict of interest: none to declare

InTRoDuCTIon

Vitiligo is a worldwide disease with a prevalence of about 1-3%. There is a large variety of therapeutic agents, but its treatment still remains a challenge 1-4. There is no consensus regarding its etiology, but there are different hypotheses for its pathogenesis such as cellular autoimmunity, oxidative stress, melanocytorrhagy, heredity and neural factors. Based on the supposed etiologies, different

treatment options have been tried and approved, meaning that molecular and cellular mechanisms hold the key for various therapeutic agents used. A better understanding of vitiligo repigmentation provides new alternatives and enhances the efficacy of current treatments 5.

Phototherapy including PUVA, broad band UVB, narrow band UVB (the preferred form of phototherapy for the treatment of vitiligo) and 308-nm excimer laser (emit focused wavelength


Received: March 3, 2011Accepted: May 1, 2011

Excimer laser plus topical calcipotriol in the treatment of vitiligo


adjacent to NBUVB 311-nm) are immunomedulator agents and stimulators of the melanocyte precursors; therefore, they are proper options for the treatment of vitiligo 6. Based on the etiopathomechanisms of vitiligo, adjunctive agents combined with phototherapy, with the purpose of efficacy enhancement and minimizing their long-term side effects such as carcinogenecity, have been suggested. Calcipotriol, which is a synthetic analog of vitamin D3, is one of them. It causes proliferation, activation and migration of melanocytes as well as modifying T-cell activation. At the molecular level, combination of calcipotriol with different forms of phototherapy and 308-nm excimer laser can decrease lesion progression in vitiligo by immunosuppression, and possibly induce repigmentation by activating melanocyte precursors and melanogenic pathways synergistically. There are some studies which have shown enhancement of PUVA and NBUVB efficacy when calcipotriol was added, but no improvement has been reported in outcomes in other studies 7-11. To our knowledge, there is only one report in the literature; this report failed to show the synergistic effect of the combination of calcipotriol and 308 nm excimer laser in the treatment of vitiligo 5. To date, it has been impossible to explain the contrast between the convincing results of molecular research and the results of such clinical studies, thus, the necessity of precise clinical studies is felt to explain such differences and find more efficient therapies. Therefore, we decided to determine whether calcipotriol could enhance the efficacy of 308nm excimer laser in the treatment of vitiligo in a randomized clinical trial.

PATIEnTSS AnD METhoDS

Patients

This randomized, controlled, prospective, right/left comparative and single blinded clinical trial study was done in the laser clinic of Behsima Center, Tehran, Iran, between May 2007 and May 2009.

Inclusion criteria were generalized vitiligo for at least one year or stable vitiligo in all skin color phenotypes. Exclusion criterion were pregnancy, lactation, allergy to calcipotriol, renal insufficiency, abnormality of bone or calcium metabolism, light-sensitive dermatoses, photodermatoses, phototoxic systemic or topical medication(s), previous history

of arsenic exposure, excessive exposure to UV light and previous history of skin cancer.

The study was approved by the Ethics Committee under the supervision of vice-chancellor for Research of Tehran University of Medical Sciences. Treatment approach, duration of treatment and possible complications were explained to the patients. All patients signed the informed consent form.

Treatment protocol

Included patients with symmetrical vitiliginous lesions were randomized into 2 groups. The intervention group received 308-nm excimer laser plus Calcipotriol ointment 0.005% (Daivonex®) on the lesions of the right side of the body and the control group received 308 nm excimer laser plus vaselin on the lesions of the right side.

All patients in both groups administered vaselin on the lesions of the left side. Excimer laser was used two times weekly for 12 weeks. The average initial dose was 50 mJ/cm2.The incremental dose was 50 mJ/cm2 at each exposure. If there were moderate to severe erythema, irritation or itching, therapy was suspended until the complication was resolved; then, the dose of the laser decreased by 20% of the last session dose. If severe and non resolving complications happened, that patient left the study and received proper treatment prescribed by a dermatologist. Calcipotriol ointment 0.005% (Daivonex®) and vaselin were used 2 times daily.

Efficacy assessments

The evaluation of the patients was performed at baseline and at 12th week (the last laser session). At each evaluation, all lesions were photographed and visual scale software was used for comparing the diameter of the lesions before and after treatment in each group. Also, response rate (percentage of repigmentation) was scored (Table 1).

Repigmentation Rate %(RR) Response interpretation Score

RR ≤1 No response 01< RR ≤25 Mild response 125< RR≤ 50 Moderate response 250< RR≤75 Good response 375< RR≤100 Excellent response 4

Table 1. Repigmentation rate and response score

Seirafi et al


The score of repigmentation and the side effects in each evaluation were documented in pre-designed forms for each patient.


SPSS version 15.0 package software was used for statistical analysis. Outcomes of groups were compared with T test. P-values< 0.05 were considered statistically significant.

RESulTS

A total of 83 patients (42 females and 41 males) with bilateral symmetrical vitiliginous lesions were included in this study in a period of 2 years, from May 2007 to May 2009. Among them, 13 patients did not complete the study for unknown reasons. Seventy patients, 36 females (51.43 %)

and 34 males (48.57%), completed the study. All patients were divided into 2 groups, intervention group (35 patients) and control group (35 patients) through blocked randomization (Figure 1). Baseline demographic and clinical characteristics of each group are detailed in Table 2.

The number of the patients with the response rate scores of 0 (no response), 1 (mild), 2 (moderate), 3 (good) and 4 (excellent) was 1 (2.8%), 3 (8.5%), 19 (54.2%), 10 (28.5%) and 2 (5.7%) in the intervention group and 3 (8.5%), 4 (11%), 16 (45.7%), 9 (25.7%) and 3 (8.5%) in the control group (right side lesions), respectively (Figure 2).

In other words, 31 patients in the intervention group (308 nm excimer laser + calcipotriol) and 28 patients in the control group (308 nm excimer laser + vaselin) were clinical responders (scores 2,3,4). The details of the clinical response rates of right side lesions of each group, considering sex,

Figure 1. Consort Flow Diagram



changed from 27.86 cm2 to 16.02 cm2 and from 27.21 cm2 to 15.82 cm2, respectively. The diameter changes were statistically significant in each group (p-value<0.001).

The adverse reactions were erythema and pruritus; all were mild. There were no significant differences in side effects between 2 groups. No patient left the study due to side effects.

For determining the main goal of this study, diameter changes of right side lesions in the intervention group (308nm excimer laser plus Calcipotriol),11.84 cm2, was compared to the control group (308nm excimer laser plus vaselin), 11.39 cm2, but the difference was not significant (p-value=0.74).

DISCuSSIon

Despite various therapeutic agents for vitiligo, its treatment still remains unsatisfactory. To date, one of the most established treatments is NBUVB. The slow response of vitiliginous lesions on one hand and worsening of their appearance initially, when treated with NBUVB due to tanning of the surrounding skin on the other, have encouraged dermatologists to use a focused and high dose light (308-nm excimer laser) on the affected skin and try different combinations to find a synergistic effect with the purpose of avoiding photodamaging of

duration of disease, skin phenotype and anatomical location, are shown in Table 3.

As Table 3 shows, sex, duration of disease, skin phenotype and anatomical location of right side lesions did not affect the number of clinical responders (scores 2,3,4) in 2 groups significantly.

Spontaneous resolving of lesions was considered as a confounding factor, and for determining its effect, diameter changes of left side lesions that only received vaselin were evaluated in both groups; the changes were from 27.28cm2 to 26.4cm2 in the intervention group and from 26.45cm2 to 26.45cm2 in the control group but the differences were not significant in each group (p-value=0.95 in the intervention group and p-value=1.00 in the control group). The diameter of the right side lesions in the intervention group (308nm excimer laser + calcipotriol) and the control group

Intervention group patient No.

Control groupPatients No.

Patients 35 35Sex

Female 11 25Male 24 10

AgeMean 34 31Range 18-46 18-42

Vitiligo duration1-2years 28 213-5years 6 10>5years 1 4

Skin phenotypeI 0 0II 8 7III 16 18IV 11 10

Previous treatmentTopical corticosteroid 10 10NBUVB 3 5PUVA 3 8Elidel 5 5Tacrolimus 0 0Excimer laser 2 3

AnatomicalHead & neck 7 13Trunk 9 12Upper limb (proximal) 4 2Upper limb (distal) 4 2 Lower limb (proximal) 8 4Lower limb (distal) 3 2

Table 2. Baseline demographic and clinical characteristics

Figure 2. Percentage of patients with different repigmentation rates in each group after 12 weeks

Seirafi et al


the unaffected skin and achieving the response more rapidly. Despite the small skin carcinogenicity risk of any UVB therapy, the real risk of excimer laser still remains unknown, so caution should be taken. Considering molecular mechanisms, different combinations with phototherapy (PUVA, NBUVB, and excimer Laser) have been tried in the treatment of vitiligo 6-11. While Sassi et al, showed the efficacy of topical hydrocortisone 17-butyrate cream in enhancing the effect of excimer laser in the treatment of vitiligo of the face and neck 12 and Kawalek et al, showed the efficacy of topical tacrolimus plus excimer laser 13, others decided to try the combination of calcipotriol with phototherapy. Goldinger et al, 2007, in a non randomized single blind study containing 10 patients, showed that calcipotriol 2 times daily did not enhance the efficacy of excimer laser (3 times weekly) in the treatment of vitiligo 14. According to our study, calcipotriol did not enhance the efficacy of excimer laser in the treatment of vitiligo. This conclusion was achieved according to diameter changes in intervention and control group lesions and removing the effects of the confounding factors, although not significant.

However, we may have reached this conclusion because we used 308 nm excimer laser plus calcipotriol schedule, our timing or our preparation; therefore, different types of regimen schedules

should be tried to determine the real effect of vitamin D derivatives on enhancing excimer laser efficacy in the treatment of vitiligo. To our knowledge, this was the first phase 2 randomized clinical trials done to investigate whether topical calcipotriol enhances 308-nm excimer laser efficacy in the treatment of vitiligo. In conclusion, our study showed that combination of excimer Laser with calcipotriol did not produce a superior result in the treatment of vitiligo than did excimer laser alone.

REFEREnCES

1. Ortonne JP. Vitiligo and other disorders of hypopigmentation. In: Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. 2nd ed. Spain: Mosby Elsevier; 2008: 913-20.

2. Bleehen SS, Anstey AV. Disorders of skin colour. In: Burns T, Breathnach S, Cox N, Griffiths c. Rook’s textbook of dermatology. 7th ed. Oxford: Blackwell Science Publication; 2004: 39.53-7.

3. James WD, Berger TG, Elston DM. Disturbances of pigmentation. In: Andrew’s disease of the skin. 10th ed. Philadelphia: Saunders Elsevier; 2006: 859-62.

4. Hadi SM, Spencer JM. Vitiligo. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I. Treatment of skin disease. 3rd ed. Philadelphia: Saunders Elsevier; 2010: 776-80.

5. Birlea SA, Costin G-E, Norris DA. New insights on therapy with vitamin D analogs targeting the intracellular pathways that control repigmentation in human vitiligo. Med Res Rev 2009;29:514-46.

Intervention group* Control group* P-valueSex

Female 9/11 (81.8%) 21/25 (84%)0.11

Male 22/24 (91.6%) 7/10 (70%)Duration of disease

1-2 years 27/28 (96.4%) 18/21 (85.7%)0.783-5 years 4/6 (66.6%) 8/10 (80%)

>5 years 0/1 (0%) 2/4 (50%)Skin phenotype

I 0/0 (0%) 0 (0%)

0.20II 7/8 (87.5%) 6/7 (85.7%)III 15/16 (93.7%) 16/18 (88.8%)IV 9/11 (81.8%) 6/10 (60%)

Anatomical locationHead & neck 7/7 (100%) 12/13 (92.3%)

0.55

Trunk 9/9 (100%) 11/12 (91.6%)Upper limb (proximal) 3/4 (75%) 1/2 (50%)Upper limb (distal) 3/4 (75%) 1/2 (50%)Lower limb (proximal) 6/8 (75%) 2/4 (50%)Lower limb (distal) 2/3 (66.6%) 1/2 (50%)

Table 3. Treatment outcome

*Clinical responders No. (score2, 3, 4)



6. Hadi SM, Spencer JM, Lebwohl M. The use of the 308-nm excimer laser for the treatment of vitiligo. Dermatol Surg 2004;30:983-6.

7. Ostovari N, Passeron T, Zakaria W, Fontas E, Larouy JC, Blot JF, et al. Treatment of vitiligo by 308-nm excimer laser: An evaluation of variables affecting treatment response. Lasers Surg Med 2004;35:152-6.

8. Lotti T, Buggiani G, Troiano M, Assad GB, Delescluse J, De Giorgi V, et al. Targeted and combination treatments for vitiligo. Comparative evaluation of different current modalities in 458 subjects. Dermatol Ther 2008;21:S20-6.

9. Ermis O, Alpsoy E, Cetin L, Yilmaz E. Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study. Br J Dermatol 2001;145:472-5.

10. Hartmann A, Lurz C, Hamm H, Bröcker E-B, Hofmann UB. Narrow-band UVB311 nm vs. broad-band UVB therapy in combination with topical calcipotriol vs. placebo in vitiligo. Int J Dermatol 2005;44:736-42.

11. Arca E, TaŞTan HB, Erbil AH, Sezer E, KoÇ E, Kurumlu Z. Narrow-band ultraviolet B as monotherapy and in combination with topical calcipotriol in the treatment of vitiligo. J Dermatol 2006;33:338-43.

12. Sassi F, Cazzaniga S, Tessari G, Chatenoud L, Reseghetti A, Marchesi L, et al. Randomized controlled trial comparing the effectiveness of 308-nm excimer laser alone or in combination with topical hydrocortisone 17-butyrate cream in the treatment of vitiligo of the face and neck. Br J Dermatol 2008;159:1186-91.

13. Kawalek AZ, Spencer JM, Phelps RG. Combined excimer laser and topical tacrolimus for the treatment of vitiligo: a pilot study. Dermatol Surg 2004; 30:130-5.

14. Goldinger SM, Dummer R, Schmid P, Burg G, Seifert B, Lauchli S. Combination of 308-nm xenon chloride excimer laser and topical calcipotriol in vitiligo. J Eur Acad Dermatol Venereol 2007;21:504-8.

64

Original article


Erythroderma in Khuzestan province, southwest of Iran

Bachground: Erythroderma is a rare but serious skin disorder that may result from different causes. There are many publications on this subject, with a different incidence rate for each etiology. The aim of this study was to determine the frequency of erythroderma, and describe the incidence of each etiologic cause in patients indigenous to Khuzestan.

Methods: In a retrospective study, we reviewed the files of patients diagnosed with erythroderma who were admitted to the dermatology ward of Sina Hospital, affiliated to Jondishapour Medical University of Ahvaz, southwest of Iran, in a period of 9 years from 1980 to 1989. We studied the clinical and pathology reports of patients and the final etiologic diagnosis.

Results: Total admission was 6210 patients and the total number of erythrodermic patients was 85. The frequency of erythroderma in our dermatology department was 1.37%. The most common causes in order of frequency were eczema (32.94%), drug reaction (23.52%), psoriasis (21/18%), and malignancy (8.23%). Previous history of skin disease was found in 44 of 85 patients (51.76%) and 28 (32.9%) of them were suffering from eczema. The mean age of our patients was 49.11 years and the male-female ratio was 1.6:1.

Conclusion: Erythroderma is a rare condition. The most common causes in our study were eczema and drug reactions; the high incidence of drug reactions in our patients compared to studies in other countries may be due to more administration of drugs in Iran, especially in Khuzestan

Keywords: drug reaction, erythroderma, etiology, eczema, frequency, inpatient

Mohammad Ali Mapar, MDAmir Hosein Roozbeh, MDMohammad Bagher Mohammad Hasani

Department of Dermatology, Ahvaz Jondishapour Medical sciences, Ahvaz, Iran

Corresponding Author:Mohammad Ali Mapar,MDDepartment of Dermatology, Ahvaz Jundishapour Medical sciences, Ahvaz, IranEmail: [email protected]


InTRoDuCTIon

Erythroderma, also known of exfoliative dermatitis and first described by Herba in 1868 1, is a reaction pattern characterized by generalized or nearly generalized and confluent erythema affecting more than 90% of the body surface and accompanied by a variable degree of scaling. Due to the large areas of the affected skin and the advanced age of most patients, erythroderma imposes an important risk to the life of the patients 2. A variety of diseases and other exogenous factors may cause

this condition. Therefore, it is important to identify and treat any underlying disease whenever possible and to remove any contributing external factors 3. The aim of our study was to assess the frequency of different etiologies, the sex ratio and the age of the patients at the onset of erythroderma.

PATIEnTS AnD METhoDS

Because erythroderma imposes an important risk to the life of the patients, we generally treat them as inpatients. In a retrospective study, we


Received: December 12, 2010Accepted: May 8, 2011



reviewed the files of 85 patients diagnosed with erythroderma out of 6210 patients who were admitted to the dermatology ward of Sina Hospital affiliated to Jundishapur Medical University of Ahvaz in a period of about 9 years from 1980 to 1989. We studied the medical records of all erythrodermic patients by checking the data of clinical and pathologic reports and the final etiologic diagnosis. All data were tabulated for further analysis.

RESulTS

In the above-mentioned period, the total number of admissions was 6210 patients of whom 85 patients were erythrodermic. The frequency of erythroderma in our dermatology department was 1.37%. Regarding the 3.5 million population of Khuzestan province and the 9-year period of this study, the incidence of erythroderma in Khuzestan province was estimated about 0.27 per 100,000 inhabitants per year. The sex ratio (male/female) was 1.6:1. The mean age of our patients was 49.11 years with the youngest patient being 4 days old and the oldest being 92 years old (Table 1). Previous history of skin disease was positive in 44 patients (51.76%) and 28 of them were suffering from eczema. The most common diseases in order of frequency were eczema 32.94%, drug reaction 23.52%, psoriasis 21/18% and malignancy 8.23% (Table 2). According to our findings, the second most common cause of erythroderma was drugs among which carbamazepin and penicillins were the two most common (Table 3). Malignancies associated with erythroderma are presented in Table 4.

DISCuSSIon

Erythroderma is defined as diffuse erythematous dermatitis involving all or almost the entire skin. The skin becomes red, dry and scaly. A burning sensation and pruritus are usually present. Erythroderma is a rare but severe and life-threatening disorder with many different underlying causes. Because both the clinical manifestations and histopathologic findings of erythroderma are usually non-specific, it is impossible to detect the precise underlying causes in many cases. The condition usually affects older people and some of its etiologies are lethal, so it is necessary to establish its etiology as soon as possible in order to facilitate its precise and immediate management. Awareness of the most frequent causes of erythrodema can help us to develop an efficient diagnostic strategy and often results in appropriate management of the disease 1-3.

To our knowledge, this study is the first report of the incidence and causes of erythroderma from Khuzestan Province in the southwest of Iran. The incidence of erythroderma in our study was about 0.27 per 100,000 people per year, which is much lower than other studies in other parts of the world. The annual incidence of erythroderma in the Netherlands is 0.9 patients per 100,000 4 and in Finland is 1-2 per 100,000 5 but Sehgal and Srivastava from India reported an incidence of 35 per 100, 000 6. The mean age of our patients was 49.11 years that is similar to the study of Akhyani et al from Tehran-Iran 7 reporting a mean age of 46.2 years but was higher than the 41.6 years reported from Pakistan 8 and lower than 61 years reported from Finland 5. The male to female ratio in our study was 1.6, similar to the 1.85 reported by Akhyani et al from Tehran 7. This ratio was

Age Number Male Female Percentage0-9 7 4 3 8.2310-19 9 5 4 10.5920-29 3 - 3 3.5330-39 11 7 4 12.9440-49 9 4 5 10.5950-59 12 7 5 17.1260-69 16 12 4 18.8270-79 11 6 5 12.9480-89 5 5 - 5.8890-99 2 2 - 2.35Total 85 52 33 100

Table 1. Age and sex of the patients

Etiology Number PercentageEczema 28 32.94Drugs 20 23.52Psoriasis 18 21.17Malignancy 7 8.23Ichthyosis 2 2.35Dermatomyositis 1 1.17Pemphogus foliceous 1 1.17Lichen planus 1 1.17Unknown 7 8.23Total 85 100%

Table 2. Dermatoses as the causative factor of erythroderma

Mapar et al


1.85 in Pakistan and 1.94 in Finland but 2.25 in Thailand 2. Previous history of skin disease was found in 44 patients (51.76%) and 28 (32.9%) of them were suffering from eczema. The most common disease was eczema (32.94%), followed by drug reaction (23.52%); these findings are different from a report from Finland that showed 42% and 10% respectively; in addition, 12% developed erythroderma due to contact reaction to topical drugs 5. In Thailand, pre-existing dermatoses were seen in 38% and drugs reactions were seen in 23% of the patients 2. These results in Pakistan were 74.4% and 5.5% respectively 8 which are much different from our study. Regardless of the causes of erythroderma, the pathology reports are usually suggestive of eczema but the exact diagnosis should not only be based on the pathology repot. The large differences between our study and Pakistan’s may be due to the method of diagnosis in their study or other unknown factors. It should be noted that the percentage of eczema in Pakistan’s study is much higher than other reports.

Onset of erythroderma due to drug reactions is typically sudden and rapid, and its resolution is typically faster than cases of erythroderma due to other causes. A notable exception occurs when erythroderma accompanies systemic drug hypersensitivity reactions due to antibiotics, anticonvulsants, and allopurinol. Hypersensitivity develops within 2 to 5 weeks after the medication is started and may persist for weeks despite discontinuation of the medication 9, but the best prognosis as clearing of erythroderma is in the drug reaction group 5. Most drugs can cause erythroderma. Drugs as an etiologic group had the second highest percentage in our series; one reason may be very low drug costs in Iran, the fact that physicians prescribe many drugs in one visit. Therefore, because patients are frequently on many

different drugs, it is often difficult to determine which drug is responsible. In an erythrodermic patient, any drug should be considered a potential factor. Generally, it is attributed to the drug most recently added. In our findings, the agents of greatest risk for inducing erythroderma were carbamazepine followed by penicillins.

Malignancy is definitively associated with erythroderma (most commonly cutaneous T- cell lymphoma (CTCL)) 3. About 8.23% of our cases were secondary to malignancy and the most common type of malignancy was Mycosis Fongoides (MF). In some studies, a much higher percentage of malignancy has been reported. For example, up to 25 - 40% of erythroderma are secondary to MF 10,11. Patients with chronic erythroderma without a defined etiology and a high index of suspicion for CTCL or other underlying malignancies must be maintained 3. Because erythroderma is occasionally associated with internal malignancies, even patients with previous history of known dermatoses whose clinicopathologic features are inconclusive should be investigated carefully to rule out malignant neoplastic causes 7. In 8.23% of our patients, no causes were found; these patients are classified as idiopathic. The percentage of idiopathic patients varies in most erythrodermic series. The diversity of the incidence of each cause of erythroderma in various studies seems to be related to the variability of investigative procedures and follow-up. In idiopathic cases, if the patients are followed up for a long time, a significant proportion of them will progress to Cutaneous T Cell Lymphoma 3. So, repeated skin biopsies are recommended as the best method for etiologic diagnosis of erythroderma.

In our study, only 52 out of 85 patients had skin biopsy records. In other patients, the diagnoses were determined based on history, course and clinical presentation of the diseases. Our patients, who had MF, all had skin biopsy records suggestive of MF. A patient with hepatocellular carcinoma had

Drugs Number PercentageCarbamazepin 8 40Penicillins 5 25Isoniazid 2 10NSAIDS 2 10Co-Trimoxazole 1 5Cephalexin 1 5Unknown 1 5Total 20 100

Table 3. Drugs associated with erythrodermaType of malignancy Number PercentageMycosis fungoides 3 42.85Lymphoma 1 14.28Hepatocellular carcinoma 1 14.28Adenocarcinoma of the prostate 1 14.28Unknown 1 14.28Total 7 100

Table 4. Malignancies associated with erythroderma



REFEREnCES

1. Holden CA, Berth-Jones J. Eczema, lichenification, prurigo and erythroderma In: Burns T, Breathnach S, Cox N, Griffiths C, eds. Rook’s textbook of dermatology,8th ed. Oxford: Blackwell science; 2010:17.1-55.

2. Chiratikarnwong K. Erythroderma:14 years study at Songklanagarind Hospital. Songkla Med J 2000; 18: 31-6.

3. Wilson DC, Jester JD, King LE Jr. Erythroderma and exfoliative dermatitis. Clin Dermatol 1993;11:67-72.

4. Sigurdsson V, Steegmans PH, van Vloten WA. The incidence of erythroderma: A survey among all dermatologists in The Netherlands. J Am Acad Dermatol 2001; 45:675-8.

5. Hasan T, Jansen CT. Erythroderma: a follow-up of fifty cases. J Am Acad Dermatol 1983; 8:836-40.

6. Sehgal VN, Srivastava G. Exfoliative dermatitis-A prospective study of 80 patients. Dermatologica 1986; 173:278-84.

7. Akhyani M, Ghodsi Z S, Toosi S, Dabbaghian H. Erythroderma: A clinical study of 97 cases. BMC Dermatol 2005;5:5.

8. Pal S, Haroon TS. Erythroderma: a clinico-etiologic study of 90 cases. Int J Dermatol 1998;37:104–7.

9. Rothe MJ, Bernstein ML, Grant-Kels JM. Life-threatening erythroderma: diagnosing and treating the "red man". Clin Dermatol 2005; 23, 206–17.

10. Nicolis GD, Helwig EB. Exfoliative dermatitis. A clinicopathologic study of 135 cases. Arch Dermatol 1973; 108:788-97.

11. Abrahams I, McCarthy J T, Saul L. Sanders SL. 101 cases of exfoliative dermatitis. Arch Dermatol 1963; 87:96-101.

non-specific skin histopathology and a patient with lymphoma had a positive lymph node and skin biopsy. All patients with unknown diagnosis had more than one skin histopathologic records with nonspecific changes. There are significant differences in the frequency of causes of erythroderma in different epidemiological studies, possibly due to differences in criteria and methods of selection of patients in these studies. Almost all studies are retrospective and patient selection is based on either initial condition at the time of admission, or in the middle and during the treatment or final diagnosis at the time of discharge. To overcome these biases and problems, it is better to design prospective studies

Erythroderma is a rare but serious skin disorder. Awareness of the most frequent causes can help us to develop an efficient strategy for diagnosis and appropriate management of the disease. The results of this study may serve as a guide to identify the causes in new erythrodermic patients, at least in Khuzestan.

68

case repOrt


Bilateral congenital nevus of Ota in association with Mongolian spot

A 2 4 - y e a r - o l d w o m a n p r e s e n t e d w i t h a s y m p t o m a t i c hyperpigmented bilateral patches on her temples, eyelids and forehead since birth. Furthermore, the patient had a congenital grey patch, compatible with Mongolian spot, on her buttock. She had no vascular or other cutaneous lesion. Histopathologic examination revealed bipolar dendritic melanocytes dispersed in a ribbon-like pattern between the collagen fibers and around the neurovascular bundles of the dermis. As far as we know, this is the first case of bilateral “congenital” nevus of Ota in association with a Mongolian spot reported in a patient.

Keywords: nevus of Ota, congenital nevus, dermal melanosis, mongolian spot, bilateral nevus.

Hoda Rahimi, MD1

Maryam Yousefi, MD1

Mina Mirnezami, MD2

Zahra Asadi-Kani, MD1

1. Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2. Dermatology Department, Arak University of Medical Sciences, Arak, Iran

Correspondence Author:Hoda Rahimi,Skin Research Center, Shahid Beheshti Medical University, Shohada-e Tajrish Hospital, Tehran, IranHaft-e –Tir Hospital, Lorestan University of Medical Sciences, Doroud, Irane-mail: [email protected]


InTRoDuCTIon

Nevus of Ota, a dermal melanocytic nevus first described in Japan 1, manifests as blue - black or gray-brown patchy/diffuse pigmentation that usually occurs unilaterally in areas innervated by the first and second branches of the trigeminal nerve 2. Bilateral involvement is an exception, especially if it is congenital, as in our case. Hereunder, we report an interesting case of association between bilateral “congenital” nevus of Ota and Mongolian spot.

CASE REPoRT

A 2 4 - y e a r - o l d w o m a n p r e s e n t e d w i t h asymptomatic hyperpigmented bilateral patches on her face since birth. The lesions progressed with age. She was born to a consanguineous

marriage. Her medical and family history were unremarkable. Physical examination revealed diffuse blue-grey hyperpigmented patches with irregular borders on her temples, eyelids and cheeks (Figure 1). Hyperpigmentation of the conjunctiva and sclera was also noticeable (Figure 2). Ophthalmologic examination was normal. No oral or nasal mucosal pigmentation was observed. Furthermore, the patient had a congenital grey patch, compatible with a Mongolian spot, on her buttock (Figure 3), which had become less prominent since birth. She had no vascular or other cutaneous lesions. Her general examination was normal. Histopathologic examination of the lesions revealed bipolar dendritic melanocytes dispersed in a ribbon-like pattern between the collagen fibers and around the neurovascular bundles of the dermis (Figure 4).


Received: January 26, 2011Accepted: April 23, 2011

Bilateral congenital nevus of Ota


DISCuSSIon

Nevus of Ota (Nevus fuscoceruleus ophthamo-maxillaris) was first described by a Japanese dermatologist in 1939 1. Ota nevus can be congenital or acquired in adolescence. It occurs almost entirely in persons of Asian descent. The clinical manifestations are usually unilateral; only 5 percent of cases are bilateral. Clinically, blue-gray macular pigmentation with irregular borders involves skin

that is innervated by the first and second branches of the trigeminal nerve. Histopathology of the affected skin shows the presence of dendritic cells containing melanin in the dermis 2.

Extracutaneous manifestations include ocular involvement of sclera, episclera, conjunctiva, cornea, retina, and the uveal tract. Similar discoloration can be observed in the oral mucosa (buccal and palatal), as well as in nasal mucosa and the tympanic

Figure 1. Hyperpigmented bilateral congenital patches on the face and sclera

Figure 3. Mongolian spot on the left buttock of patient.

Figure 2. Blue-grey hyperpigmentation of the sclera and face (closer view)

Figure 4. Histopathologic view of the facial lesion: dispersed melanocytes in a ribbon-like pattern between collagen fibers in the dermis (H&E *40)

Rahimi et al


membrane. Leptomeninges can also be affected. Open angle glaucoma and malignant melanoma involving the eyes are rare associations reported 3.

Nevus of Ota has been associated with idiopathic facial neuralgia, Sturge Weber syndrome 4, ipsilateral sensory neural hypoacusia, neurofibromatosis 5, primary retinitis pigmentosa and multiple blue nevi 6. Malignant transformation of the nevus of Ota to melanoma has been reported several times. Melanoma arising in the choroid, brain, orbit, iris, ciliary body, or optic nerve in association with a nevus of Ota has been described; therefore, careful observation is mandatory in these patients 6.

Various therapies have been successfully used. Cosmetic cover-up products can be used for camouflage. Cryosurgery and microsurgical treatments can leave disfiguring scars and are not recommended. Combined dermabrasion and the carbon dioxide snow method have produced good results 7. In recent years, use of laser therapy has been very effective and has given new hopes to patients with the nevus of Ota. The best results for the treatment of this condition are achieved with Q-switched Nd-YAG, ruby, and alexandrite lasers or a combination of them 8. Although there are some reports of bilateral nevus of Ota in literature 9,10, almost all of them are acquired. The point of this case is that it was congenital. As far as we know, this is the first reported case of bilateral “CONGENITAL” nevus of Ota in association with Mongolian spot in a patient.

REFEREnCES

1. Ota M. Nevus fuscocoerulens ophtalmomaxillaris. Tokio Med J 1939; 63: 1243-5.

2. Kishikawa T, Suzuki T, Sasakia Y, Aihara K, Hirayama T. Characterization of melanosomes and melanogenesis in cells cultured from Ota’s nevus. J Submicrosc Cytol Pathol 1997;29 339-52.

3. Mishima Y, Mevorah B. Nevus Oto and naevus Ito in American Negros. J Invest Dermatol 1961;36: 133-54.

4. Irimia A, Preda M, Ciuca CA, Gavrila CD. Sturge Weber syndrome in association with oculo-dermal melanosis. Oftalmologia 2007;51: 45-9.

5. Gupta A, Ram J, Jain IS. Nevus of Ota associated with neurofibromatosis. Ann Ophthalmol 1986;18: 154-5.

6. Rivers JK, Bhayana S, Martinka M. Dural melanoma associated with ocular melanosis and multiple blue nevi. J Cutan Med Surg 2001; 5: 381-5.

7. Hata Y, Matsuka K, Ito O, Matsuda H, Furuichi H, Ishizu N, Konstantinos A. Treatment of naevus Ota: combined skin abrasion and carbon dioxide snow method. Plast Reconstr Surg 1996; 97: 544-54.

8. Omprakash HM. Treatment of nevus of OTA by Q-switched, frequency doubled, ND:YAG laser. Indian J Dermatol Venereol Leprol 2002; 68: 94-5.

9. Kim SK, Kang HY. Centrally located acquired bilateral nevus of Ota-like macules (Hori’s nevus): is this a novel type? Eur J Dermatol 2008;18:596.

10. Ruiz-Villaverde R, Sánchez-Cano D, Villaverde-Gutiérrez C. Bilateral naevus of Ota in a pregnant white women. Clin Exp Dermatol 2009; 34: 422-4.

71

case repOrt

Iranian Journal of Dermatology, Vol 14, No 2, Summer 2011

Localized genital bullous pemphigoid; A case report

Bullous pemphigoid (BP) is an autoimmune bullous disorder with urticarial pruritic papules and plaques and tense bullae in flexural surfaces of body. The localized form of the disease is a rare variant which can be triggered by different stimuli. Hereunder, we report a patient with the local type involving genitalia without any triggering factors.

Keywords: bullous pemphigoid, localized, genitalia

Afshar Ramezanpour, MD1

Abdolamir Feizi, MD2

1. Department of Dermatology, Zanjan University of Medical Sciences, Zanjan, Iran

2. Department of Pathology, Zanjan University of Medical Sciences, Zanjan, Iran

Corresponding Author:Afshar Ramezanpour, MDDermatology Ward, Valiasr Hospital, Zanjan Medical University, Zanjan, Iran.E-mail: [email protected]


CASE REPoRT

A 22-year-old married man was visited at Valiasr Hospital Clinic with a one-year history of erosive lesion on the ventral surface of his penis and scrotum (Figure 1). He had been treated by different antibiotics and topical therapy without any success.

Upon dermatologic examination, he was observed

to have an erosive macerated lesion on his genitalia (the ventral surface of the penis and scrotum) with no lesion or bulla in other parts of the body. His physical examination was otherwise normal. He had no drug history or trauma. In the result of his laboratory tests, potassium hydroxide smear, gram stain and culture, Tzank smear and VDRL, HCV Ab, HBS Ag and HIV serology were negative. Also, skin biopsy showed subepidermal blister (Figure 2)


Received: March 4, 2011Accepted: April 23, 2011

Figure 1. The erosive lesion on the ventral surface of the penis and scrotum.

Figure 2. Subepidermal blister with cellular infiltration (H&E*10).

Ramezanpour et al


and linear deposits of C3 and IgG were reported on direct immunofluorescence techniques (DIF). The diagnosis of bullous pemphigoid was made regarding the clinical and histopathological data. Our patient responded well to treatment with oral prednislone 50 mg/day for one month followed by gradual tapering of the dose. There was no recurrence of the disease at the time of this report.

DISCuSSIon

Some autoimmune bullous disorders such as pemphigus and linear IgA disease may be induced by trauma and PUVA therapy 1,2. Localized BP is a rare variant of BP that may also occur after trauma 3. Some scholars consider it as the result of different forms of epidermal damage (Koebner phenomenon) in predisposed patients; with the induction of antigen exposure in the context of subclinical pemphigoid followed by activation of the corresponding autoimmune process 4, but our patient had no history of trauma. Also, the local form of the disease has been reported following thermal burn, radiation, PUVA therapy, surgical wound and also at injection and colostomy sites 5-10. There are a few reports of localized genital BP in adults; in one of these reports, a 72-year-old woman had pruritic erythematuos plaques and erosions in her perineum and perianal area 11. This patient already had chronic itching due to chronic intertrigo or lichen sclerosis before suffering from BP, this factor was postulated as a trigger. In comparison, our patient was younger and had no triggering factor. In another report, a 67- year-old man had pruritic blisters on his penis and scrotum 12, but our patient had no blisters. Similar to our case, a report was found in the literature in which the patient had erosive lesions on her genitalia 13.

Although localized BP in vagina, perineum and perianal area have already been reported, sexual activity can also be considered as one of the triggering factors causing this type of the disorder.

The authors believe that sexual activity was most probably the cause in our patient as well. However, it is highly recommended that bullous disorders such as BP be considered in every patient with localized erosive dermatosis with no response to conventional therapy.

REFEREnCES

1. Ginarte M, Sánchez-Aguilar D, Pereiro-Ferreirós MM, Toribio J. Pemohigus vulgaris exhibiting koebner phenomenon. J Eur Acad Dermatol Venereol 1998;10: 90-2.

2. Salmhofer W, Soyer HP, Wolf D, Fodinger D, Hodl S, Kerl H. UV light induced Linear IgA dermatosis. J Am Acad Dermatol 2004;50:109-114.

3. Macfarlane AW, Verbov JL. Trauma induced bullous pemphigoid. Clin Exp Dermatol 1989; 14: 245-9.

4. Pardo J, Serna MR, Mercader P, Fortea JM. Localized bullous pemphigoid overlying a fistula for hemodialysis. J Am Acad Dermatol 2004; 51(2suppl): S131-2.

5. Vermeulen C, Janier M, Panse I, Daniel F. Localized bullous pemphigoid induced by thermal burn. Ann Dermatol Venereol 2000; 127: 720-2.

6. Leconte-Boulard C, Dompmartin A,Verneuli L, Thomine E, Joly P, Rogerie MJ, leory D. Localized bullous pemphigoid following radiotherapy. Ann Dermatol Venereol 2000; 127:70-2.

7. Perl S, Rappersberger K, Fodinger D, Anegg B, Honigsmann H, Ortel B. Bullous pemphigoid induced by PUVA therapy. Dermatology 1996; 193: 245-7.

8. Parslew R, Verbov JL. Bullous pemphigoid at sites of trauma. Br J Dermatol 1997; 137: 825-6.

9. Massa MC, Freeark RJ, Kang JS. Localized bullous pemphigoid occurring in a surgical wound. Dermatol Nurs 1996;8:101-2.

10. Vande M, Dominique M, Reilly JC. Bullous pemphigoid at colostomy site: report of a case. Dis Colon Rectum 1997;40:370-1.

11. Patsatsi A, Lazaridou E, Papagaryfallou I, Sotiriadis D. Bullous pemphigoid of the perineum and perianal area: A rare localized form in adults. Acta Derm Venereol 2008; 88: 401.

12. Lawrence A, Schiffman DO. Bullous pemphigoid of the penis. AOCD J 2010; 15: 10-2.

13. Haustien UF. Localized nonscarring bullous pemphigoid of the vagina. Dermatologica 1988; 176: 200-1.

73

case repOrt


Unilateral generalized morphea: A case report

Morphea is a localized form of scleroderma characterized by sclerotic plaques limited to the skin. Although its cause is unknown, genetic, infectious and autoimmune mechanisms have been suggessed in the pathogenesis of the morphea. It is more common among childen and young women. Although the prognosis is generally good, it sometimes causes significant morbidity. Morphea has five subtypes as plaque, generalized, bullosa, deep and linear. Unilateral forms of generalized morphea have rarely been reported in the literature. Our case has been presented because it is very rarely seen.

Keywords: generalized, morphea, unilateral

Perihan Ozturk, MD

Department of Dermatology, Kahramanmaras Sutcu Imam University, School of Medicine, Kahramanmaras,Turkey

Corresponding Address:Perihan Ozturk, MDDepartment of Dermatology, Kahramanmaras Sutcu Imam University, School of Medicine, Yorukselim mah. Hastane Cad. No. 32,46050, Kahramanmaras,TurkeyE-mail: [email protected]


InTRoDuCTIon

Morphea includes a group of diseases that show sclerosis of skin and subcutaneous tissue. Although it generally shows small limited lesions, it may also shows deep lesions causing functional or cosmetical deformites 1. About %75 of morphea patients are 20-50 years of age and it is 2.6 times more common in women than men. Environmental factors may play a triggering role in the onset of the illness. Thirteen percent of the patients with morphea have generalized morphea. If morphea plaques are seen in at least two of seven anatomical sites (head-neck, right upper extremity, left upper extremity, right lower extremity, left lower extremity, body,

face, trunk), the diagnosis is generalized morphea 1. “Unilateral generalized morphea” form is seen quite rarely.

CASE REPoRT

A 14 year-old male patient came to our clinic with spottling lesions starting on the left side of the body. He only complained of the stiffness of the lesions and pruritus, and had no prior history of trauma. On dermatologic examination, hard hyperpigmented indurated lesions with diameters ranging from 0.5 to 10 cm were present on the


Recived: November 26, 2010Accepted: December 26, 2010

Figure 1. Hyperpigmented indurated plaques with diameters ranging from 0.5 to 10 cm on the left thigh and left leg.

Figure 2. Hyperpigmented indurated on the extensor surface of the left arm.

Ozturk


front of the left shoulder, left arm extensor surface, the left surface of the back, left thigh, left leg and left foot (Figure 1,2). Laboratory tests including antinuclear antibody, complete blood count, sedimentation analysis, rheumatoid factor levels were normal. Initial diagnoses were lichen sclerosus et atrophicus, lupus panniculitis and morphea. Deep punch biopsy specimens were taken from one of the lesions. The histopathological examination of the samples revealed orthokeratosis with an atrophic squamous epithelium. In the dermis, diffuse fibrotic tissue was seen with mononuclear inflammatory infiltrative cells around the blood vessels. Adnexal structures were normal (Figure 3). Considering clinical and histopathological findings, the patient was diagnosed with morphea and received potent topical steroids twice daily and intra-lesional triamcinolone acetonide injection three times per month. At the end of the third month, the lesions improved significantly.

DISCuSSIon

Morphea is a localized form of scleroderma and is characterized by sclerotic plaques. The fibrotic reaction is limited to the skin and visceral involvement is uncommon 2. Morphea has five subtypes as plaque, generalized, bullous, linear and deep 3. About 75% of morphea patients are 20 to 50 year-old women and it is 2.6 times more common in women. Thirteen percent of morphea patients have generalized morphea 1. Morphea may be triggered by environmental factors including trauma, infections (measles, varicella, Epstein-Barr

virus, Borellia Burdorgferi), malignancies and radiation therapy 4. Our patient had no triggering factors. Morphea pathogenesis is similar to systemic scleroderma as endothelial cells, inflammatory cells and fibroblasts are involved 1. If morphea plaques are seen in at least two of seven anatomical sites, then the diagnosis of generalized morphea was made 1. In our patient, morphea plaques were seen on the left arm, left leg, left side of the body. ‘Diffuse morphea’ covers large areas of the body and has an insidious onset.

The chest wall involvement in patients with severe thoracic deformity may cause difficulty in breathing. Despite widespread cutaneous involvement in generalized morphea, internal organs involvement is rare. Arthralgia is seen by 9% of the patients 1. There was no systemic signs or symptoms in our patient. Circulating auto-antibodies can be detected in morphea like other autoimmune connective tissue diseases 1. Laboratory findings such as serum ANA, ssDNA antibodies, eosinophilia, antihistone antibodies and hypergammaglobulinemia are more common in linear and generalized morphea 1. Laboratory tests were normal in our patient. Histopathologic findings of morphea vary according to the stage of the disease and the biopsies taken. Biopsy should be taken to include the subcutaneous tissue. In the biopsies from the peripheral edge of an active lesion, lymphocytes, macrophages, plasma cells and mast cells can be seen; sometimes, intense inflammatory infiltrates with eosinophilia may also be seen 1. In our patients, biopsies were taken from the active margin of the lesion. Histopathologic examination was consistent with morphea. In contrast to localized morphea, generalized morphea lesions usually do not tend to regress spontaneously. The effect of strong topical corticosteroids can be increased with intralesional triamcinolone injection. Systemic glucocorticoids, antimalarials, azathioprine and phototherapy are not usually very effective 5. Although controversial results exist about inhibitory inf luence of salazopyrin (sulfasalazine) on the fibroblast proliferation, some authors have reported good results with salazopyrin (Sulfasalazine) in the treatment of generalized morphea 6. Our patient received strong effective topical steroids twice daily and intra-lesional triamcinolone acetonide injection three times per month. At the end of

Figure 3. The histopathological view: atrophic epidermis with diffuse dermal fibrosis (H&E*10).

Unilateral generalized morphea


the third month, a significant improvement was seen in the lesions.

Unilateral generalized morphea is a newly described type of generalized morphea. It has been very rarely reported in the literature. Nagayi et al, reported a 6 year-old boy with unilateral generalized morphea on the right side of his lower leg, trunk, and upper arm. The levels of antinuclear antibodies, rheumatoid factor, and anti single-stranded DNA antibody were elevated. No severe deformities or functional disabilities were noted. With topical corticosteroid therapy, the sclerotic skin became gradually softer, and no progression of sclerosis was noted for one year 7. Kraigher et al, reported a 20-year-old healthy Jewish woman of Yemenite origin who presented with a 2-year history of a linear eruption on the right shoulder and thorax, upper and lower arm, dorsal surface of the hand,

and lower leg 8. Gerçeker Turk et al, presented a case of unilateral generalized morphea that was triggered by vibration. They proposed that development of ipsilateral generalized morphoea without pulmonary involvement in a left handed marble worker indicated exposure to hand–arm vibration rather than to silica as an aetiological factor in this condition 9. Appelhans et al, reported four cases of unilateral generalized morphea 10. We decided to present this case because of the rarity of the disease and for the purpose of literature review.

REFEREnCE

1. Gungor E. Systemic versus localized scleroderma. In: Tuzun Y, Gurer MA, Serdaroglu S, Oguz O, Aksungur VL (eds): Dermatoloji. İstanbul, Nobel tıp Kitap evleri 2008:1034-54.

2. Aydin Y, Ustun I, Onder E, Gungor A. Severe generalized morphea: a devastating eventuality in the elderly. Turkish J Geriatrics 2010; 13:47-50.

3. Peterson LS, Nelson AM, Su WPD. Classification of morphea (localized scleroderma). Mayo Clin Proc 1995; 70: 1068-76.

4. Chung L, Lin J, Furst DE, Fiorentino D. Systemic and localized scleroderma. Clin Dermatol 2006; 24:374-92.

5. Ceylan N, Gurel MS, Kiremitci U, Demirkesen C. Jeneralize morfea- liken skleroatrofik birlikteliği. Turkish J Pathol 2008;24:178-82.

6. Aberer E, Klade H, Hobisch G. A clinical, histological, and immunohistochemical comparison of acrodermatitis chronica atrophicans and morphea. Am J Dermatopathol 1991; 13:334-41.

7. Nagai Y, Hattori T, Ishikawa O. Unilateral generalized morphea in childood. J Dermatol 2002;29:435-8.

8. Kraiger O, Brenner S, Tur E. Anti-double- stranded DNA- positive unilateral generalized morphea in an adult, possibily exacerbated by ibuprofen. Arch Dermatol 2009;145:844-6.

9. Gerçeker Turk B, Urkmez A, Kilinç Karaaslan I, Ertam I, Kandiloğlu G, Dereli T. Unilateral generalized morphea: could vibration be a stimuling factor? Clin Exp Dermatol 2010;35:165-6.

10. Appelhans C, Breuckmann F, Gambichler T, Brockmeyer NH, Altmeyer P, Kreuter A. Unilateral generalized morphea is a rare variant of localized scleroderma. Eur J Med Res 2006;28:152-6.

76

Quiz


Acquired hyperpigmented lesion on the foot

CASE

A 3.5-year-old girl presented with a 1-year history of a slow growing pigmented lesion on the dorsal aspect of her right foot. Physical examination revealed the presence of a pigmented patch with color distribution from pink to tan to dark brown, relatively well circumscribed and approximately 1.5 × 2cm with irregular borders, and especially a single dark central papule superimposed in the middle of it (Figure 1). The lesion had a soft consistency and the child did not have any other symptoms. During the last year, it had increased in dimensions and thickness.

The remainder of her physical examination was insignificant. Also, there was no positive family history of a particular disease or any history of trauma or drug usage. A 3 mm punch biopsy was obtained from the central dark papule and the specimen was sent for histopathologic examination.

What is your diagnosis?

Pouran Layegh, MD1

Nona Zabolinejad, MD2

Naghmeh Zabolinejad, MD1

Akram Momenzadeh, MS3

1. Department of Dermatology, Mashad University of Medical Sciences, Mashad, Iran.

2. Department of Pathology, Mashad University of Medical Sciences, Mashad, Iran.

3. Research Center for skin diseases & cutaneous Leishmaniasis, Mashad, Iran.

Correspondence author:Pouran Layegh, MDAssociate Professor of Dermatology, Qaem Hospital, Mashad University of Medical SciencesEmail: [email protected]



Received: December 17, 2010Accepted: January 3, 2011

Figure 1. A pigmented plaque with color distribution from pink to dark brown on the dorsal aspect of the left foot.

Figure 2. The histopathology view: intradermal nests of large epithelioid cells with a polygonal shape, occasional multinucleation, and a strongly eosinophilic cytoplasm (H&E × 10)

Acquired hyperpigmented lesion on the foot


DIAgnoSIS

Spitz nevus

Microscopic findings

The histopathology of the specimen revealed a well circumscribed and symmetrical lesion which was composed of intradermal nests of large epithelioid cells with polygonal shape, occasional multinucleation, and a strongly eosinophilic cytoplasm (Figure 2). The nuclei were large with smooth nuclear membranes, and prominent nucleoli (Figure 3). There was no mitosis or necrotic cell. The clinical and histopathological features were consistent with diagnosis of spitz nevus.

DISCuSSIon

The Spitz nevus, named after Sophie Spitz who first described it in 1948, is also known as benign juvenile melanoma and spindle and/or epithelioid cell nevus. The lesion was originally believed to occur largely in children, but it is now well recognized in young to early middle-aged adults 1. The prevalence of Spitz nevus has not been accurately documented in the general population. However, Spitz nevus account for approximately 1% of melanocytic lesions. Spitz nevi are mostly acquired, but congenital ones have been reported

as well 2. They are seen in all age groups but are uncommon beyond the age of 40 to 50 years. The lesions in adults are more pigmented than in children 2,3.

No particular etiologic factors have been found 2. They may be derived from the same progenitor cells that give rise to epidermal melanocytes and nevomelanocytes 3. Amplifications of chromosome 11p and H-RAS and activating mutations of H-RAS have been noted in a subset of Spitz nevi 4. Spitz nevi vary in size from 2 mm to 2 cm or more, with an average diameter of approximately 8 mm. Most commonly, they are well circumscribed, dome-shaped papules or nodules varying in color from pink to tan to dark brown. Generally, the color is homogeneous and the margins are well defined. Relatively flat polypoid and pedunculated m o r p h o l o g i e s h a v e a l s o b e e n d e s c r i b e d . Occasionally, lesions may have erosions and scale-crust. Telangiectasia is seen frequently 2. The head and neck area is probably the most common site, accounting for 42% of lesions in one series. Other parts of the body can be affected less frequently. It often has a recent onset, but a small percentage of nevi may be present for many years 2.

Atypical Spitz nevi refer to lesions demonstrating one or more (usually a constellation of) features that deviate from conventional Spitz nevi. The features may include a large size (e.g. > 1 cm in diameter), asymmetry, deep involvement of the dermis or subcutis, ulceration, easily found dermal mitoses (>2-3 mitoses/mm2), being specially deep, a significant pagetoid spread, prominent confluence and high cellular density of melanocytes in the dermis, and lack of maturation 2.

Histologically, these lesions display striking nests of large epithelioid cells, spindle cells or both, usually extending from the epidermis into the reticular dermis in an inverted-wedge configuration. The closely apposed nests of cells within a uniformly hyperplastic epidermis often contribute to a so-called ‘raining-down’ appearance. Both mononuclear and multinucleate giant epithelioid cells are frequently observed. These cells extend into the subjacent dermis as both single cells and as nests or fascicles. Occasional bizarre cytologic features, necrotic cells and mitotic figures are found within even the most banal lesions 2,5. Differentiation from a melanoma can often be very difficult and occasionally even impossible. Some

Figure 3. The nuclei were large with smooth nuclear membranes and prominent nucleoli (H&E*40)

Layegh et al


features that favor the diagnosis of Spitz nevus are a symmetric shape, sharp lateral demarcation maturation in depth, tadpole and multinucleated giant cells and lack of upward epidermal spread.

The clinical differential diagnosis of Spitz nevi is wide and includes other melanocytic nevi, particularly dermal nevi, hemangiomas, pyogenic granuloma, verrucae, molluscum contagiosum, juvenile and adult xanthogranulomas, dermato-fibroma, mastocytoma, clear cell acanthoma, insect bite reactions, seborrehic keratoses, epidermal nevus and adnexal tumor 2,3. The most important diagnostic problem is the histologic differentiation of Spitz nevus from cutaneous melanoma 2. Complete excision with margins free of tumor is recommended for all Spitz nevi. However, there are clinicians who reserve this recommendation for lesions with any atypical feature (clinically or histologically) or Spitz nevi in adults 2. Patients with atypical lesions should be evaluated every 6 to 12 months.

REFEREnCES

1. Newton Bishop JA. Lentigos, melanocytic naevi and melanoma. In: Burns T, Breathnach S, Cox N, Griffiths C, eds. Rook’s textbook of dermatology,8th ed. Oxford: Blackwell science; 2010:54.1-57.

2. Barnhill RL, Rabinovitz H. Benign Melanocytic Neoplasms. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. Mosby Elsevier; 2008.1713-44.

3. Grichnik JM, Rhodes AR, Sober AJ. Benign neoplasia and hyperplasia of melanocytes. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, eds. Fitzpatrick’s dermatology in general medicine, 7th ed. New York: Mc Graw Hill; 2008.1099-122.

4. Bastian BC, Leboit PE, Pinkel D. Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features. Am J Pathol 2000; 157:967-72.

5. Elder DE, Elenitsas R, Murphy GF, Xu X. Benign pigmented lesions and malignant melanoma. In: Elder DE,Elenitsas R, Murphy GF, Johnson BL, Xu X, eds. Lever’s histopathology of the skin. 10th ed. Philadelphia: Lippincott Williams and Wilkins; 2009: 699-789.

79

letter tO editOr


A case of contact dermatitis due to green bean

Editor,

Beans are the basic food for human beings. Allergic reaction to beans is not common. However, it is possible since there are many proteins in the beans. Here, the author would like to introduce a case of contact dermatitis due to green bean. A case of 23 year old female patient presented to the physician complaining of itching sensation at both hands. The symptom occurred after she performed hand squeezing on the green beans in distilled water. The patient gave no previous history of allergy to bean. On examination, both of the patient’s hands showed scaly erythematous plaques. The primary presumptive diagnosis is the contact dermatitis to green bean. This case was prescribed for antihistamine drug and topical steroid (0.1% Triamcinolone acetonide lotion) and the symptoms disappeared within a day. The patient performed self-trial of exposure to distilled water and there was no symptom. However, when she performed additional trial by squeezing green beans in distilled water again, she developed symptom and has to visit to the physician again. She repeatedly performed this self-trial for 3 times. Although this case did not agree for having skin biopsy or other sero-immunodiagnoses, the repeated exposure to the bean by the mean of skin rubbing provocative action for several times lead to the same dermatological presentation. Hence, this case was finally diagnosed to be a case of contact dermatitis due to green bean. Generally, green bean is seldom reported as an allergen. However, green bean as food allergen is uncommon 1.

The non-specific lipid transfer protein (Pha v 3) of green bean is identified as the main inducer of

allergic reaction 2. In some rare cases, the induction of asthma and rhinitis is reported 3. Nevertheless, the allergic dermatitis is more extremely rare 4. Hence, this case report is a very rare case to be documented.

Viroj Wiwanitkit

Wiwanitkit House, Bangkhae, Bangkok Thailand 10160

Correspondence Author:Professor Viroj WiwanitkitWiwanitkit House, Bangkhae, Bangkok Thailand 10160Email: [email protected]


Received: February 28, 2011Accepted: March 14, 2011

REFEREnCES

1. Pastorello EA, Pravettoni V, Farioli L, Primavesi L, Scibilia J, Piantanida M, et al. Green bean (Phaseolus vulgaris): a new source of IgE-binding lipid transfer protein. J Agric Food Chem 2010;58:4513-6.

2. Zoccatelli G, Pokoj S, Foetisch K, Bartra J, Valero A, Del Mar San Miguel-Moncin M, et al. Identification and characterization of the major allergen of green bean (Phaseolus vulgaris) as a non-specific lipid transfer protein (Pha v 3). Mol Immunol 2010;47:1561-8.

3. Daroca P, Crespo JF, Reaño M, James JM, Lopez-Rubio A, Rodriguez J. Asthma and rhinitis induced by exposure to raw green beans and chards. Ann Allergy Asthma Immunol 2000;85:215-8.

4. Igea JM, Fernandez M, Quirce S, de la Hoz B, Diez Gomez ML. Green bean hypersensitivity: an occupational allergy in a homemaker. J Allergy Clin Immunol 1994;94:33-5.

Iran J Dermatol 2011; 14: 79

ErratumThe author names of article “Malva Sylvestris in the treatment of hand eczema. Vol. 13, No. 54, winter 2010” is corrected as follows:

Barikbin Behrooz, Maarefat Afsaneh, Rahgoshai Rayhaneh, Moravvej Hamideh, Mohtasham Nahid, Yousefi Maryam, Ameri Simindokht

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Iranian Society of ISSN 0021 - 082X Dermatology IRANIAN ...zums.ac.ir/files/IT/pages/magiran/56333.pdf · ISSN 0021 - 082X Summer 2011 . Vol. 14, No.2 Serial No. 56 Published Quarterly