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DOI: 10.1111/j.1610-0387.2010.07453.x Academy 619 © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010/0808 JDDG | 8 ˙ 2010 (Band 8) Section Editor Prof. Dr. Jan C. Simon, Leipzig Keywords chromoblastomycosis sporotrichosis mycetoma subcutaneous mycoses treatment JDDG; 2010 8:619–628 Submitted: 6. 3. 2010 | Accepted: 17. 4. 2010 CME Subcutaneous mycoses: chromoblastomycosis, sporotrichosis and mycetoma Alexandro Bonifaz 1 , Denisse Vázquez-González 1 , Ana María Perusquía-Ortiz 2 (1) Departamento de Micología, Servicio de Dermatología, Hospital General de México, Ciudad de México (2) Department of Dermatology, University of Münster, Germany Summary Subcutaneous mycoses are common in subtropical and tropical regions of the world. They are rarely observed in Europe. These mycoses are heterogeneous, but all are caused by penetrating trauma of the skin. Most cases in Europe are observed in returning travelers, aid workers, archaeologists and immigrants. Therefore, a careful, thorough history is essential in order to reach a proper diagnosis. We provide up-to-date epidemiological, clinical, diagnostic, and ther- apeutic data on the three most important imported subcutaneous mycoses in Europe: chromoblastomycosis, sporotrichosis and mycetoma. Introduction Chromoblastomycosis, sporotrichosis and mycetoma all develop at sites of penetrat- ing injuries, but differ in epidemiology, clinical findings and treatment. Chromoblastomycosis Etiology and pathogenesis Chromoblastomycosis is caused by various pigmented or dematiaceous fungi. Two main pathogens are: Fonsecaea pedrosoi and Cladophialophora carrionii (Table 1) [1–3]. The disease occurs predominantly in tropical and subtropical regions. Fungi such as F. pedrosoi are found in hot and humid climate zones in the soil, in plants and woods, in decaying plant material, in compost. This explains dissemination in farmer and agricultural workers. Fungal infections caused by C. carrionii are found, in contrast, most frequently in semiarid zones (Cactaceae). Chromoblastomycosis has a worldwide distribution, especially in Madagascar, Brazil and Costa Rica, occasionally on the American continent in the USA, Mexico, Venezuela, the Dominican Republic and Colombia; in Asia in Japan, China and Malaysia; in Europe in Russia, the Czech Republic, Romania and in Eastern Germany [4, 5]. Infection usually occurs in adulthood between the age of 20 and 40 years [2, 4, 6]. Occurrence in childhood is exceptional [1, 6]. Men are preferentially infected (m:f 4:1), which may reflect occupational activities instead of hormonal factors [1, 2 4]. Affected individuals are generally immunocompetent. Clinical findings The disease takes a chronic course. It is practically limited to subcutaneous tissue, only rarely involves bone or spreads lymphatically [1–4]. Clinically characteristic are initially unilateral and asymmetric scaling erythematous cutaneous-subcutaneous nodules, especially on the limbs; later verrucous lesions, vegetating plaques, scaling cauliflower-like tumors, ulcers and crusts develop. The size of the lesions ranges from The two main pathogens causing chro- moblastomycosis are Fonsecaea pe- drosoi and Cladophialophora carrionii. The disease occurs predominantly in tropical and subtropical regions. Clinically characteristic are initially uni- lateral and asymmetric scaling erythem- tous cutaneous-subcutaneous nodules, especially on the limbs. Sometimes psoriasis-like erythematosquamous plaques or tumor-like lesions appear.

Subcutaneous mycoses: chromoblastomycosis, sporotrichosis and mycetoma

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Page 1: Subcutaneous mycoses: chromoblastomycosis, sporotrichosis and mycetoma

DOI: 10.1111/j.1610-0387.2010.07453.x Academy 619

© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010/0808 JDDG | 8˙2010 (Band 8)

Section EditorProf. Dr. Jan C. Simon,

Leipzig

Keywords• chromoblastomycosis• sporotrichosis• mycetoma• subcutaneous mycoses• treatment

JDDG; 2010 • 8:619–628 Submitted: 6. 3. 2010 | Accepted: 17. 4. 2010

CME

Subcutaneous mycoses: chromoblastomycosis,sporotrichosis and mycetomaAlexandro Bonifaz1, Denisse Vázquez-González1, Ana María Perusquía-Ortiz2

(1) Departamento de Micología, Servicio de Dermatología, Hospital General de México, Ciudad de México(2) Department of Dermatology, University of Münster, Germany

SummarySubcutaneous mycoses are common in subtropical and tropical regions of theworld. They are rarely observed in Europe. These mycoses are heterogeneous,but all are caused by penetrating trauma of the skin. Most cases in Europe areobserved in returning travelers, aid workers, archaeologists and immigrants.Therefore, a careful, thorough history is essential in order to reach a properdiagnosis. We provide up-to-date epidemiological, clinical, diagnostic, and ther-apeutic data on the three most important imported subcutaneous mycoses inEurope: chromoblastomycosis, sporotrichosis and mycetoma.

IntroductionChromoblastomycosis, sporotrichosis and mycetoma all develop at sites of penetrat-ing injuries, but differ in epidemiology, clinical findings and treatment.

ChromoblastomycosisEtiology and pathogenesis Chromoblastomycosis is caused by various pigmented or dematiaceous fungi. Two mainpathogens are: Fonsecaea pedrosoi and Cladophialophora carrionii (Table 1) [1–3]. Thedisease occurs predominantly in tropical and subtropical regions.Fungi such as F. pedrosoi are found in hot and humid climate zones in the soil, inplants and woods, in decaying plant material, in compost. This explains disseminationin farmer and agricultural workers. Fungal infections caused by C. carrionii are found,in contrast, most frequently in semiarid zones (Cactaceae). Chromoblastomycosis hasa worldwide distribution, especially in Madagascar, Brazil and Costa Rica, occasionallyon the American continent in the USA, Mexico, Venezuela, the Dominican Republicand Colombia; in Asia in Japan, China and Malaysia; in Europe in Russia, the CzechRepublic, Romania and in Eastern Germany [4, 5]. Infection usually occurs in adulthood between the age of 20 and 40 years [2, 4, 6]. Occurrence in childhood isexceptional [1, 6]. Men are preferentially infected (m:f 4:1), which may reflect occupational activities instead of hormonal factors [1, 2 4]. Affected individuals aregenerally immunocompetent.

Clinical findingsThe disease takes a chronic course. It is practically limited to subcutaneous tissue,only rarely involves bone or spreads lymphatically [1–4]. Clinically characteristic areinitially unilateral and asymmetric scaling erythematous cutaneous-subcutaneousnodules, especially on the limbs; later verrucous lesions, vegetating plaques, scalingcauliflower-like tumors, ulcers and crusts develop. The size of the lesions ranges from

The two main pathogens causing chro-moblastomycosis are Fonsecaea pe-drosoi and Cladophialophora carrionii.The disease occurs predominantly intropical and subtropical regions.

Clinically characteristic are initially uni-lateral and asymmetric scaling erythem-tous cutaneous-subcutaneous nodules,especially on the limbs. Sometimes psoriasis-like erythematosquamousplaques or tumor-like lesions appear.

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a few millimeters up to several centimeters. Sometimes psoriasis-like erythematosqua-mous plaques or tumor-like lesions appear (Figure 1a) [2–4]. Complications of thechronic inflammation are particularly fibrosis and lymphedema. Lymphedema alsofacilitates bacterial superinfection. Occasionally chronic disease with alternating ulcer-ation and scarring leads to squamous cell carcinomas [1, 3–6].

Diagnostic approach Laboratory diagnosis is made on the basis of mycological and histological criteria. Indirect microscopy (KOH examination) “fumagoid” cells are seen. These are coffee-colored, thick-walled cells with a double membrane and central septum (“like coffeebeans”). Cultures on Sabouraud dextrose and Sabouraud yeast agar as routine detec-tion test confirm the species: slowly growing pigmented dematiaceous fungi that canbe identified micromorphologically and by genetic sequencing (Figure 1b, c) [1, 4]. Histology: The epidermis often displays pseudoepitheliomatous hyperplasia. In thepapillary and reticular dermis lymphohistocytic infiltrates and tuberculoid granulo-mas with epitheloid cells, giant cells of the Langerhans and foreign body type areobserved. “Fumagoid” cells can readily be differentiated in routine hematoxylin-eosin staining (HE) in the stratum corneum, in granulation tissue or giant cells[2–4]. As these can often be found in the stratum corneum the mycological diagno-sis is often made by direct microscopy using a tape stripping technic.

TherapyThe treatment of chromoblastomycosis depends on the pathogens, the severity andextent of lesions (fibrosis, impaired lymphatic drainage) and the choice of medica-tion [7, 8]. Treatment results are often unsatisfactory. The recurrence rate is high par-ticularly in long-lasting and extensive involvement. Physical methods, chemo- andcombination therapy are employed (Table 2) [2]. Physical methods: 1. Cryosurgery has shown the best results. Here open spray or con-tact probes, together with measure of tissue temperature, are employed, especially forsmall lesions. 2. Local hyperthermia with heating of the skin surface to a mean tem-perature of 43 °C. The results are variable. 3. Surgical excision or curettage and elec-trodesiccation for small and sharply well-delineated lesions [2, 4, 6]. Chemotherapy: A multitude of substances have been tried with variable success: cal-ciferol, potassium iodide, 5-fluorocytosine, ketoconazole, fluconazole, ampho-tericin B. The best results were observed with intraconazole and terbinafine with atreatment duration between 6 and 12 months [2–4, 6].For itraconazole high doses of 200–400 mg daily are recommended. With this com-plete cure was observed in 42 % of cases after an average of 7.2 months. This drug

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Table 1: Principal etiologic agentsof chromoblastomycosis [2, 4].

In direct microscopy (KOH examina-tion) “fumagoid” cells are characteris-tic. Cultures in Sabouraud dextroseand Sabouraud yeast agar as routinedetection test confirm the species.

Treatment results are often unsatis-factory.

Physical methods: Cryosurgery hasshown the best results.

Chemotherapy: best results with itra-conazole (200–400 mg daily) andterbinafine (500 mg daily) with atreatment duration between 6 and 12 months.

• Fonsecaea pedrosoi• Cladophialophora carrionii• Phialophora verrucosa• Exophiala dermatitidis• Rhinocladiella aquaspersa• Cladophialophora yegresii• Fonsecaea monophora

Figure 1: Widespread chromoblastomycosis (a). Dermatopathology: “copper bodies” (H&E, 40X)(b). Micromorphology: Fonsecaea pedrosoi (erythrosine, 60X) (c).

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can be used alone or in combination with cryosurgery [2, 4, 6]. The good results arebased on the high sensitivity of the etiologic agents to this drug, due to their lowminimum inhibitory concentrations (MICs) [2, 4]. Terbinafine is employed in doses of 250–500 mg daily. Several reports exist of suc-cessful treatment with lower doses (250 mg daily) [2, 4, 6], but 500 mg daily isviewed as more adequate. Queiroz-Tellez et al. [2] achieved clinical and mycologicalcure in 74.2 % after twelve months of treatment. Terbinafine is particularly effectiveand well-tolerated with only few drug interactions [2, 6]. Due to the high recurrence rate, chemotherapeutic agents have often been combined.Gupta et al. [7] reported good results for a combination of itraconazole withterbinafine in chronic cases where amphotericin B and various oral antifungal agentshad not been effective. They suspect synergistic effects of the two drugs on the basisof differing actions on ergosterol synthesis.

SporotrichosisEtiology and pathogenesisThis subcutaneous or deep cutaneous fungal infection with a subacute to chroniccourse is caused by dimorphous fungi of the Sporothrix schenckii complex. Primarilyskin and lymphatic vessels are involved in the form of subcutaneous nodules or gum-mata, only rarely bone, joints or internal organs [1, 4, 8]. Recently, Marimon et al.[9] have described the Sporothrix schenckii complex, which includes in addition toSporothrix schenckii sensu stricto four other species: S. albicans, S. brasiliensis,S. globosa and S. mexicana. There are current reports of epidemics in domestic ani-mals, so that sporotrichosis can be viewed as a zoonosis [4, 8]. It occurs on all continents, but most cases are seen in the Americas (Peru, Mexico,Colombia, Brazil, Uruguay, Guatemala). It has been observed in almost all ofEurope, especially in Spain, France and Germany. The pathogens of the Sporothrixschenckii complex develop in plants, wood, decaying plant materials in climates withan average temperature of 20–25 °C and humidity over 90 %. They also occur incats, dogs, birds, rodents and reptiles [4, 5, 8]. Inoculation usually occurs by injurywith contaminated splinters or animal bites. The incubation period is variable (7 to30 days). Most in danger are farmers, gardeners, livestock breeders and flower grow-ers, miners, veterinarians, packers etc. There is no sexual preference (m:f 1:1).Children are frequently infected (5 to 15 years, about 30 % of cases), especiallyyoung adults (16–35 years, 50 %) [1, 3, 8].In highly endemic regions the fungus can gain access to the airways and incite primarypulmonary forms with usually asymptomatic cavitary disease. Immunosuppression ofall kinds can facilitate spread of the disease to other organs. The differences betweenthe various Sporothrix species relate mainly to their sensitivity to different antifungalagents [4, 5, 8].

Clinical findingsSporotrichosis appears in different clinical forms:Lymphocutaneous sporotrichosis: the most common form (70 %) affects the extremi-ties and the face with erythematous-violet, often ulcerated, gumma-like, subcuta-neous, nodular lesions along lymphatic vessels up to the regional lymph nodes(Figure 2a). This is associated with slight pruritus and pain. In exceptional cases lym-phatic drainage may be impaired. In children it is located in the face uni- or bilater-ally in 40 % of cases [1, 4, 8].

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Table 2: Chromoblastomycosis: Therapy of choice [2, 4, 6].

Sporotrichosis is caused by the dimorphous fungi of the Sporothrixschenckii complex. Primarily skin andlymphatic vessels are involved in theform of subcutaneous nodules.

Physical methods Chemotherapy Combination therapy

• Excision• Cryosurgery and

curettage• Local hyperthermia

• 5-Fluorocytosine• Itraconazole• Terbinafine

• Itraconazole + cryosurgery• Terbinafine + cryosurgery• Itraconazole + terbinafine

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Fixed cutaneous sporotrichosis: This chronic form (25 % of cases) is characterized by a single vegetating or verrucous, sharply delineated plaque with an erythematous-violet border, covered by scales and crusts and usually asymptomatic (Figure 2b). It is the most limited of the clinical forms and occurs in immunocompetent patients[1, 4, 5, 8]. Disseminated cutaneous sporotrichosis: This form consists of erythematous, violet and pru-ritic plaques. It usually affects only the face, usually in immunosuppressed patients [4, 8].Hematogenous cutaneous sporotrichosis: This rarest form (1–2 %) manifests withgumma-like subcutaneous nodular lesions, ulcers and verrucous plaques with pruri-tus and pain. They appear on the skin as well as mucous membranes. They are asso-ciated with a poor prognosis and occur in immunosuppressed patients. It is thoughtthat the fungus behaves as an opportunistic pathogen.Extracutaneous sporotrichosis: In immunosuppressed patients it is caused byhematogenous dissemination in internal organs, bone, joints etc. or by primary inoc-ulation of the pathogen in the lungs [5, 8].

Diagnostic approachDiagnosis is made by isolating Sporothrix schenckii from exudate of cutaneous lesionsor sputum in common culture media (Sabouraud dextrose agar with antibiotics). Thecolonies are well-circumscribed, membranous, ray-like, beige to coffee-colored.Microscopically the pathogen produces conidia, hyphae and conidiophores (sympo-dulae) often in the form of a “daisy flower” (Figure 2c, d). Direct microscopy andstaining are of little help, as these yeasts are difficult to observe. Histology: Tuberculoid granulomas with extensive necroses. In exceptional cases“asteroid bodies” or the Splendore-Hoeppli phenomenon (antigen-antibody com-plexes and cell detritus of inflammatory cells or plasma cells, histiocytes, lymphocytesand eosinophils) can be found. To detect yeast cells and elongated blastoconidiastaining with periodic acid-Schiff (PAS) stain or methenamine silver is needed.Further useful diagnostic methods include intradermal reaction to sporotrichin, spe-cific for lymphocutaneous and fixed cutaneous sporotrichosis, as well as serological(precipitin, agglutinin, complement fixation) and molecular tests (polymerase chainreaction to chitin synthetase gen ChS1 and gen 26S rDNA) [1, 3–5, 8].

TherapySpontaneous involution has been reported occasionally. The disease usually has a benign course and responds well to various treatments. In regions where

Disseminated, hematogenous cuta-neous and extracutaneous variants ofsporotrichosis usually occur in im-munosuppressed patients.

The diagnosis is confirmed by isolat-ing Sporothrix schenckii from exudatesof cutaneous lesions or sputum inSabouraud culture media.

Sporothrichosis has a benign course andresponds well to various treatments.

Figure 2: Lymphangitic cutaneous sporotrichosis (a). Fixed cutaneous sporotrichosis (b).Macromorphology: Sporothrix schenckii (Sabouraud dextrose agar) (c). Micromorphology: Sporothrixschenckii (Cotton blue stain, 60X) (d).

The two most common clinical vari-ants of sporotrichosis are lymphocu-taneous (70 %) and fixed cutaneous(25 %).

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Sporothrix sp. are endemic, potassium iodide is favored due to good efficacy, safetyand low costs; it is administered orally (1–3 g daily in children, 3–6 g daily inadults). The duration of therapy in uncomplicated sporotrichosis (lymphocuta-neous and fixed form) is on average 4 months. Potassium iodide is usually well-tol-erated. The most frequent side effect is gastritis. Less frequent are rhinitis, bronchi-tis, urticaria, erythema nodosum. As an alternative therapy oral antifungal agentscan be administered with good results: itraconazole (5 mg/kg daily in children,200–300 mg daily in adults) or terbinafine 250–500 mg daily for 3–4 months. Insevere and disseminated cases amphotericin B (0.25–0.75 mg/kg daily) should beused [4, 8, 10].

MycetomaEtiology and pathogenesisThe term encompasses two different groups of chronic inflammatory swelling withdeformity of the involved region and fistulization with granules (grains) in the fistulas.Actinomycetomas or actinomycetic mycetomas are caused by aerobic and gram-positive filamentous actinomycetes (microsiphonated). Usually three genera areresponsible: Nocardia, Actinomadura and Streptomyces. The most commonpathogens are the species Nocardia brasiliensis and Actinamadura madurae [3, 4].The cervicofacial variety of actinomycosis is always caused by a mixed infectionwith other anaerobic bacteria [4, 11].Eumycetomas or eumycetic mycetomas are caused by septated pigmented or hyalineand white filamentous fungi (macrosiphonated) from several genera including pigmented dematiaceae such as Madurella, Pyrenochaeta, Exophiala, Leptosphaeriaand Curvularia. The most common species are Madurella mycetomatis, Madurellagrisea and several white fungi such as Pseudallescheria, Acremonium and Fusarium,particularly Pseudallescheria boydii (Table 3) [1, 4, 12, 13].Mycetomas are quite frequent in an area parallel to the Tropic of Cancer, where spe-cial climatic conditions prevail: a juxtaposition of subtropical and tropical climate(“mycetoma belt”). The highest prevalence is found in Africa (Sudan, Somalia,Senegal, Nigeria, Chad and Niger), in India and America (Mexico, Venezuela,Brazil). Only scattered cases are reported in Europe and the USA [4, 12, 13]. Themicroorganisms which live in the soil, on plants, thorns, splinters etc. are inoculat-ed into the skin by small injuries or splinters. The primary lesion slowly spreads tosurrounding tissue, invades the subcutis and finally even muscles, connective tissueand bone [4, 5 13].

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In endemic regions oral potassium io-dide is therapy of choice (1–3 g dailyin children, 3–6 g daily in adults for 4 months).

As an alternative therapy itraconazole(5 mg /kg daily in children, 200–300mg daily in adults) or terbinafine250–500 mg daily for 3–4 months canbe administered.

The clinical symptom complex “myce-toma” encompasses chronic inflam-matory swelling with deformity of theinvolved region and fistulas whichdischarge granules (grains).

One must distinguished betweenactinomycetomas and eumycetomas.

Table 3: Principal etiologic agents of mycetoma [4, 12].

Mycetoma types Causative pathogens

Actinomycetoma

• Nocardia asteroides, N. brasiliensis, N. otitidiscaviarum(form yellow-white grains)

• Actinomadura madurae, A. pelletieri (form red grains)• Streptomyces somaliensis

Eumycetomaby Dematiaceaeor phaeohy-phomycetes (formblack grains)

• Madurella mycetomatis, M. grisea• Leptosphaeria senegalensis, Leptosphaeria tompkinsii• Pyrenochaeta romeroi• Curvularia lunata, Curvularia geniculata• Exophiala jeanselmei

Eumycetomaby white fungi orhyalohy-phomycetes (formwhite grains)

• Pseudallescheria boydii (Scedosporium apiospermum)• Acremonium falciforme, Acremonium recifei• Neotestudina rosatii• Fusarium moniliform (Fusarium subglutinans),

Fusarium solanii• Aspergillus nidulans

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Mycetomas are more common in men (4 : 1) which reflects occupational exposure.Actinomycetic as well as eumycetic mycetomas affect farmers, gardeners, housewivesworking in the fields and people working in very primitive conditions, which is whyyoung people and adults are more frequently infected than children [4, 5].

Clinical findingsThe lower limbs, especially feet (50 %), ankles, knees, flexures of knees and perinealregion, are affected most strongly [1, 4, 12]. Other often involved areas are the back,nape of neck and upper limbs. This chronic disorder manifests with swelling anddeformity of the involved area as well as the development of nodular lesions withfistulas secreting a viscous seropurulent or stringy exudate that contains the “para-sitic forms” or grains (microscopically similar to the genus Nocardia sp., macroscop-ically as in true fungi) (Figure 3a, c). Mycetomas can involve subcutaneous tissue,aponeurosis, muscle, periosteum and bone as well as internal organs [1, 4, 12, 13].In contrast to actinomycetomas eumycetomas generally cause less fistulization andmore fibrosis. Frequent symptoms are pruritus and pain on palpation, but manycases cause few complaints.

Diagnostic approachDiagnosis is confirmed by direct microscopy of fistula contents obtained by suctionwith a narrow-bore cannula with the addition of Lugol iodine solution or 10 %potassium hydroxide (KOH). Grains can be recognized microscopically (< 1 µm) asin the genus Nocardia or macroscopically (> 1 µm) as in A. madurae and the eumyce-tomas [4, 5, 12, 13].The pathogens can be cultured on media (Sabouraud dextrose and Sabouraud yeastagar). Some Species of the actinomycetes (A. madurae and Streptomyces somaliensis)grow only on media such as Löwenstein-Jensen culture medium. Suitable mediafor eumycetomas are Sabouraud dextrose or Sabouraud yeast agar [4, 5].Histology: Biopsy is essential for the diagnsosis. Independent of the causativepathogen, histological features are almost identical: purulent liquefying granulomas,sometimes of the foreign body type under an epidermis with pseudoepitheliomatoushyperplasia; deep in the dermis granulomatous infiltrate with polymorphonuclearmicroabscesses, macrophages, plasma cells and lymphocytes. Grains usually appearin the center of microabscesses and are gram- as well as Grocott-positive (Figure 3b,d) [1, 3–5, 13].

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The lower limbs are most of often affected, especially the feet (50 %).

Mycetomas can involve subcutaneoustissue, aponeurosis, muscle, perios-teum and bone as well as internal organs.

The diagnosis is confirmed by directmicroscopy of typical grains in fistulacontent.

Biopsy is essential for the diagnsosis.

Histology: pseudoepitheliomatous hy-perplasia overlying chronic purulentliquefying granulation tissue, some-times of the foreign body type; in thedermis granulomatous infiltrate withpolymorphonuclear granulocytes inmicroabscesses, macrophages, plasmacells and lymphocytes. Grains are usually found in the center of the microabscesses.

Figure 3: Actinomycetoma caused by Nocardia brasiliensis (a). Dermatopathology: grain of Nocardiasp. (H&E, 40 X) (b). Eumycetoma caused by Madurella mycetomatis (c). Dermatopathology: grain ofMadurella mycetomatis (H&E, 10X) (d).

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TherapyActinomycetomas are treated with antibacterial antibiotics and eumycetomas withantifungal agents. Mycetomas caused by Nocardia sp. (N. brasiliensis) ares usually treated according tothe following scheme: diaminodiphenylsulfone (DDS) 100–200 mg daily andtrimethroprim-sulfamethoxazole 80/400 to 160/800 mg each daily. Treatment iscontinued over a longer period of time depending on the clinical course. In myce-tomas with a complex location (back, thorax, visceral involvement) amikacin is addi-tionally administered intravenously in doses of 15 mg/kg daily in cycles of 15 to21 days each (3 to 5 cycles). After completion of the cycles DDS and/or trimetho-prim-sulfamethoxazole should be continued for a longer period of time [4, 5].Another widely employed scheme is: amoxicillin (875 mg) + clavulanic acid(125 mg) twice daily for 3–6 months [4]. Mycetomas due to A. madurae are resistant or not sensitive to most therapies; thesame holds true for cases caused by Streptomyces somaliensis and A. pelletieri. Here, thebest results are achieved with streptomycin (1 g daily) + trimethoprim-sulfamethox-azole (80/400–160/800 mg daily) or DDS (100–200 mg daily). The total dose ofstreptomycin should not exceed 50 g [4, 5, 12]. Surgical measures are consideredcontraindicated, as they can lead to spread of infection. In eumycetomas therapeutic results are variable; the cure rates are low. Infection with M. mycetomatis and M. grisea can be controlled by itraconazole in doses of200–300 mg daily or also by terbinafine 250–500 mg daily over a mean time periodof one and an half year. Griseofulvin and ketoconazole have also been employed, butare no longer used due to poor results and side effects. Amphotericin B 5–30 mgevery three days achieves not very consistent results. Depending on location eumyce-tomas can also be treated surgically, e. g. by amputation; they spread less than actin-omycetomas [1, 3–5, 13].The differential diagnoses of the three diseases are different depending on the clini-cal form; especially other cutaneous fungal infections, bacterial diseases and tumorsmust be excluded (Table 4). In Table 5 the features of the depicted fungal infectionsare summarized.

ConclusionsClinical features of chromoblastomycosis, sporotrichosis and mycetoma are highlyvariable; it is therefore often difficult to recognize and treat them early. Mostcausative pathogens respond to itraconazole and terbinafine. The infection is ofteninitiated by a penetrating injury of the skin. Protective measures such as wearing stur-dy and high boots during work with soil and plant materials reduce the danger ofinfection. <<<

Conflict of interestNone.

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Nocardia sp. are treated with diamin-odiphenylsulfone (DDS) 100–200 mgdaily and trimethoprim-sulfamethoxa-zole 80/400 to 160/800 mg each daily.

In mycetomas with a complex location(back, thorax, visceral involvement)amikacin is additionally administeredintravenously in doses of 15 mg/kgdaily in cycles of 15 to 21 days each (3to 5 cycles).

Surgical measures are considered con-traindicated in actinomycetomas, asthey can lead to spread of infection.

For eumycetomas depending on location surgical measures (e. g. ampu-tation) can be considered, as theyspread less than actinomycetomas.

Table 4: Principal differential diagnoses of subcutaneous mycoses.

Chromoblastomycosis Sporotrichosis Mycetoma

• Tuberculosis cutis verrucosa• Sporotrichosis• Leishmaniasis• Paracoccidioidomycosis• Coccidioidomycosis• Blastomycosis• Syphilis III• Squamous cell carcinoma• Psoriasis• Bowen disease

• Tuberculosis cutis colliquativa and verrucosa• Leishmaniasis • Mycetoma• Tularemia• Chromoblastomycosis• Atypical mycobacterioses• Squamous cell carcinoma• Orf (ecthyma contagiosum)

• Osteomyelitis• Tuberculosis colliquativa• Sporotrichosis• Coccidioidomycosis• Actinomycosis • Hidrosadenitis• Furuncle

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Alexandro Bonifaz

Correspondence to Ana María Perusquía Ortiz, M. D. Center for Innovative Dermatology (ZiD)Department of DermatologyUniversity of MünsterVon-Esmarch-Straße 58D-48149 Münster, GermanyTel.: +49-251-83-56558Fax: +49-251-83-57296E-mail: [email protected]

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Table 5: Principal features of subcutaneous mycoses.

Chromoblastomycosis Sporotrichosis Mycetoma

Most frequent causative pathogens

Fonsecaea pedrosoi,Cladophialophora carrionii

Sporothrix schenckii complex

Eumycetoma: black and white filamentous fungiActinomycetoma: aerobic actinomycetes

Causative pathogen types

Dematiaceae Dimorphous fungi

Eumycetoma: black and hyaline filamentous fungi Actinomycetoma: aerobic gram-positive actinomycetes

Clinical features Verrucous plaques Gumma-like, nodular subcutaneous lesions and verrucous plaques

Swelling, deformity and fistulization

Involved body sites Lower and upper limbs Lower and upper limbs Back and lower limbs

Parasitic form “Fumagoid” cells “Asteroid bodies” and elongated yeast cells

Filamentous grains (micro- and macrosiphonated)

HistologyTuberculoid granulomawith “fumagoid” cells

Purulent chronic granuloma,rarely with “asteroid bodies”

Purulent granuloma with grains

Treatment Itraconazole, terbinafine,cryosurgery

Potassium iodide, itraconazole, terbinafine

Eumycetoma: itraconazole, terbinafineActinomycetoma: trimethoprim-sulfamethoxazole, diaminodiphenyl-sulfone, amikacin, amoxicillin +clavulanic acid

Response to treatment

Satisfactory Very good Eumycetoma: satisfactoryActinomycetoma: good

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References1 Hay JH. Cutaneus and subcutaneous mycoses. In: Anaissie EJ, McGinnis MR, Pfaller

MA: Clinical Mycology. Philadelphia PA: Churchill Livingstone, 2003: 456–73.2 Queiroz-Telles F, Esterre P, Perez-Blanco M, Vitale RG, Salgado CG, Bonifaz A. Chro-

moblastomycosis: an overview of clinical manifestations, diagnosis and treatment. MedMycol 2009; 47: 3–15.

3 Arenas R. Micología médica ilustrada. 3ª edición, McGraw-Hill, México D.F., 2008.4 Bonifaz A. Micología médica básica. 3ª edición, McGraw-Hill, México D.F., 2009.5 Dismukes WE, Pappas PG, Sobel JD. Clinical mycology. Oxford University press,

New York, 2003.6 Bonifaz A, Carrasco-Gerard E, Saúl A. Chromoblastomycosis: a clinical and mycolog-

ical experience of 51 cases. Mycoses 2001; 44: 1–7.7 Gupta AK, Taborda PR, Sanzovo AD. Alternate week and combination itraconazole

and terbinafine therapy for chromoblastomycosis caused by Fonsecaea pedrosoi inBrazil. Med Mycol 2002; 40: 529–34.

8 Arenas R. Sporotrichosis. In: Merz WG, Hay R, Eds: Topley & Wilsongs Microbiologyand Microbial infections. 10th ed. London: Hodder-Arnold, 2005: 367–84.

9 Marimon R, Cano J, Gené J, Sutton DA, Kawasaki M, Guarro J. Sporothrix brasiliensis,S. globosa, and S. mexicana, three new Sporothrix species of clinical interest. J Clin Microbiol 2007; 45: 3198–206.

10 Kauffman CA, Hajjeh R, Chapman SW. Practice guidelines for the management of pa-tients with sporotrichosis. For the Mycoses Study Group. Infectious Diseases Society ofAmerica. Clin Infect Dis 2000; 30: 684–7.

11 Stein E, Schaal KP. Die Aktinomykosen. In: Hornstein OP, Hundeiker M, Schönfeld J(Hrsg.): Neue Entwicklungen in der Dermatologie, Bd. 2. Berlin, Heidelberg, NewYork: Springer Verlag, 1987: 137–41.

12 Lichon V, Khachemoune A. Mycetoma: a review. Am J Clin Dermatol 2006; 7:315–21.

13 Fahal AH. Mycetoma: A thorn in the flesh. Trans R Soc Trop Med Hyg 2004; 98:3–11.

Academy 627

© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010/0808 JDDG | 8˙2010 (Band 8)

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628 Academy

JDDG | 8˙2010 (Band 8) © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010/0808

1. Die beiden wichtigsten ätiologi-schen Erreger der Chromoblastomy-kose sind:a) Fonsecaea pedrosoi und Cladophia-

lophora carrioniib) Nocardia brasiliensis und

Actinomadura maduraec) Sporothrix schenkii und Sporothrix

globosad) Madurella mycetomatis und

Nocardia brasiliensise) Madurella grisea und

Pseudallescheria boydii

2. Was beobachten Sie bei derChromoblastomykose in dem Nativpräparat mit KOH?a) vesikulöse makroskopische Drusenb) mikroskopische Drusenc) „fumagoide“ Zellend) „asteroid bodies“ und elongierte

Hefene) Blastokonidien und Pilzfilamente

3. Eines der bevorzugtenchemotherapeutischen Schematabei der Chromoblastomykose ist:a) Kaliumhydroxid 3 g/d über

3 Monateb) Itraconazol 200–400 mg/d über 7

Monatec) Ketoconazol 200 mg/d über 8

Monated) Trimethoprim-Sulfamethoxazol

800/160 mg/d über 12 Monatee) Amikacin 15 mg/kg/d, 3 Zyklen

von jeweils 21 Tagen

4. Eine klinische Variante derSporotrichose, die an denLymphbahnen entlang gummös-knotenartige Läsionen bis zum

regionalen Lymphknoten bildet, ist die:a) fixe kutane Sporotrichoseb) lymphokutane Sporotrichosec) disseminierte kutane

Sporotrichosed) lymphatische osteoartikuläre

Sporotrichosee) hämatogene kutane Sporotrichose

5. Die endgültige diagnostischeMethode bei der Sporotrichose ist:a) Nativpräparat in 10 % Kaliumhy-

droxid (KOH)b) serologische Untersuchung

(Komplementfixation)c) Nativpräparat mit Gram- und

PAS-Färbungend) Hautbiopsiee) Wachstum in Sabouraud-

Kulturmedien

6. Achtjähriger männlicher Patientmit lymphokutaner Sporotrichoseim Gesicht: Welche Behandlungwird bevorzugt?a) Diaminodiphenylsulfon 100 mg/d

über 1 Jahrb) Trimethoprim-Sulfamethoxazol

160/800 mg über 1 Jahrc) Kaliumjodid 1–3 g/d über

3–4 Monated) Kaliumjodid 6–9 g/d über

2 Monatee) Amphotericin B 0,25–0,75

mg/kg/d

7. Die bevorzugte klinische Lokalisation des Myzetoms ist im Allgemeinen:a) obere Extremitätenb) Kopf und Nacken

c) Rumpfd) untere Extremitätene) anogenitaler Bereich

8. Welche Struktur findet man imNativpräparat eines aktinomyzeti-schen Myzetoms?a) vesikulöse makroskopische Drusenb) „fumagoide“ Zellenc) mikroskopische Drusen mit

mikrosiphonierten Myzeliend) „asteroid bodies“ und elongierte

Hefene) Endosporen in Sphärulen

9. Das Therapieschema mit Amikacinin Zyklen von 21 Tagen zusammenmit Trimethoprim-Sulfamethoxazoloder Diaminodiphenylsulfon ist vorallem indiziert bei:a) Myzetom durch N. brasiliensis an

Thorax, Abdomen und Kopfb) Eumyzetom durch schwarze Pilzec) Eumyzetom durch weiße Pilzed) Actinomadura madurae, mit

Resistenz gegen konventionelleBehandlung

e) Patienten mit einer assoziiertenoberflächlichen Mykose

10. Die bevorzugte Behandlungbei Aktinomyzetom durchActinomadura madurae ist:a) Amoxicillin + Clavulansäureb) Streptomycin + Trimethoprim-

Sulfamethoxazol oder Diaminodi-phenylsulfon

c) Amikacin in 21-Tage-Zyklen +Trimethoprim-Sulfamethoxazol

d) Trimethoprim-Sulfamethoxazol +Diaminodiphenylsulfon

e) Fosfomycin + Linezolid

Fragen zur Zertifizierung durch die DDA

Liebe Leserinnen und Leser,der Einsendeschluss an die DDA für diese Ausgabe ist der 17. September 2010.Die richtige Lösung zum Thema „Systematisches Vorgehen bei Frauen mit Haarausfall“ in Heft 4 (April 2010) ist: 1c, 2d, 3e, 4d, 5b, 6e, 7a, 8a, 9d, 10d.Bitte verwenden Sie für Ihre Einsendung das aktuelle Formblatt auf der folgenden Seite oder aber geben Sie Ihre Lösung onlineunter http://jddg.akademie-dda.de ein.