University of Alabama at Birmingham

Gorgas Case 2017-03

Universidad Peruana Cayetano Heredia
The following patient was seen in the outpatient department of the Tropical Medical Institute:
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History: 80-year-old male with a 16-year history of slowly progressive crusted lesions around the right knee. Patient initially presented with painless pruritic papules on the medial aspect of the knee. Papules spread gradually to the leg and to the thigh over approximately 6-months and then all became crusted and pruritic. No history of trauma elicited. No drainage at any time. Since then, the lesions have extended very slowly and no other skin lesions have been present anywhere else. No fever or constitutional symptoms. Significant difficulty in extending the knee has developed over the last 5 years with the development of subcutaneous fibrosis of the posterior aspect of the knee. He has not had medical evaluation during his illness and initially presented to our leishmania clinic.

Epidemiology: Lives and grew up in a rural city of the highlands of Huamalies, Huanuco. Works as a farmer harvesting corn, and potato, with exposure to animals including cattle, horses, guinea pigs and chickens. No HIV risk factors.

Physical Examination: Afebrile; normal vital signs. No lymphadenopathy. Extensive involvement of the entire right knee with plaques over the anterior and posterior aspects (Image A). Individual plaques had raised and erythematous borders with areas of central scarring and atrophy. Isolated new lesions on the thigh appeared rounded with erythematous crusted borders with sparing of central areas (Image B). Significant bridging on the lateral aspect of the knee (Image C). No lymphedema, no suppuration. Chest: clear. Abdomen: no hepatosplenomegaly. Neurological: normal.

Laboratory Examination (on admission): Hb: 12.6; WBC: 7800 (58 neutrophils; no eos). Normal biochemistry and urine. Normal chest x-ray and normal plain films of both legs and knees. Negative serological tests for HBV, HTLV-1 and HIV.

UPCH Case Editors: Carlos Seas, Clinical Course Coordinator/Sofia Zavala, Associate Coordinator
UAB Case Editor: David O. Freedman, Course Director Emeritus
Diagnosis: Chromoblastomycosis.
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Discussion: A 10% KOH preparation of a skin scraping of a crusted lesion (Image D) showed pigmented thick walled multi-celled structures called sclerotic bodies, medlar bodies, or muriform bodies which are diagnostic of chromoblastomycosis. Morphologically, muriform cells constitute an aggregation of 2 to 4 fungal cells with transverse and longitudinal septation. These are double-walled brown structures with a diameter of 4 to 10 μm that resemble copper pennies. Sometimes, thick and dark hyphae are identified. Cultures can be performed on Sabouraud agar or Sabouraud with antibiotics at 25° to 28ºC. The causative organisms grow slowly (25-30 days). Culture and pathology are pending.

Implantation or subcutaneous mycoses are a heterogeneous group of diseases and organisms that share the characteristic that they develop at the site of skin penetrating trauma. Etiologic agents of subcutaneous mycoses are divided into several clinical groups:

• The eumycetomas typically cause locally invasive purulent and destructive disease that will eventually destroy underlying soft tissue and bone while sparing nerve and vasculature. Sinus tracts with granule production is common. Madura foot and related lesions are caused by Madurella mycetomatis (by far the most common cause of Madura foot in Peru; produces dark granules), Exophilia sp. and Pyrenochaeta sp., as well as Fusarium and Acremonium (produce pale granules).

Phaeohyphomycosis is caused by dematiaceous (pigmented) fungi but is not limited to skin or subcutaneous tissue and is associated with a wide range of inflammatory responses mainly in the sinuses, lungs, and brain. Disseminated disease beyond skin is usually in compromised hosts. Most frequent causes are Exophilia jeanselmi, Wangiella dermatidis, and Bipolaria species. Hyphae are typically seen histologically.

• Chromoblastomycosis is characterized by papular lesions with chronic onset that progress (often over many years) to nodules or plaques most often with a hyperkeratotic verrucous surface. Feet, knees, lower legs, and hands are the most common sites of infection. Sclerotic bodies are typically seen histologically, and invasion or spread beyond the local subcutaneous tissue does not occur. The most common etiologic agents are Fonsecaea pedrosoi (moist environment) and Cladophialophora carrionii (dry environment), with Phialophora verrucosa, and Rhinocladiella aquaspersa being less common while a few cases due to the Exophiala genus have been reported. A recent review of 123 cases from Brazil confirmed that F. pedrosoi accounted for 80% of the isolates [PLoS NTD 10(11):e0005102].

Chromoblastomycosis occurs worldwide, including in the USA, but 70% of cases are estimated to occur in tropical areas due to the moist weather conditions. Most cases in Latin America are from the Amazon rainforest of Brazil, from Mexico, and from Costa Rica, but cases are reported from Colombia, Ecuador, Venezuela, Argentina, the Dominican Republic, and Cuba. Many cases are also reported from Madagascar and South Africa. Up to 90% of cases occur in males likely due to occupational factors. Chromoblastomycosis is most often an occupational disease that is strongly associated with agricultural activities.

Chromoblastomycosis lesions are clinically polymorphic and have a large differential diagnosis. Other considerations for a life-long subcutaneous indolent infection like this includes: sporotrichosis [Gorgas Case 2008-1], eumycetoma [Gorgas Case 2002-4] (no drainage with grains were reported in this case), lobomycosis (lacaziosis) [Gorgas Case 2005-3], subcutaneous zygomycosis, subcutaneous phaeohyphomycosis, botryomycosis [Gorgas Case 2003-4], leishmaniasis [Gorgas Case 2004-1], nocardiosis [Gorgas Case 2011-1], and cutaneous tuberculosis. Squamous cell carcinoma, leprosy and leishmaniasis are less likely.

Our patient is classified in the moderate group of illness based on an old classification system that takes into account 4 criteria: total area of involvement, number of lesions, complications and lack of response to prior treatment. Long-term complications include superinfections, ulceration and lymphedema.

Treatment of chromoblastomycosis is often difficult and is based on case report and case series; there are no controlled trials. Surgery is the best physical method for the treatment of chromoblastomycosis and excisional surgery is strongly recommended for all initial small and well-delimited cutaneous lesions. Surgery may also be used in conjunction with ITZ or terbinafine treatment. Cryotherapy, heat therapy, and laser therapy are also described. For medical therapy studies suggest that both Fonsecaea and Cladophialophora species are highly susceptible in vitro to several triazole compounds, including ITZ, voriconazole, posaconazole, and isavuconazole, but not to fluconazole, 5-flucytosine (5-FC), amphotericin B or echinocandins. Terbinafine also shows in vitro activity against Fonsecaea and other etiological agents [Clin Microbiol Rev 30: 233–276–276].

Itraconazole is uniformly considered the treatment of choice with terbinafine as second line. With very chronic infections like this one, itraconazole may induce significant scarring /fibrosis that impairs functionality of the extremity. Duration of treatment is no less than 1 year starting at 200mg tid for 3 days, then 200mg bid. Measurement of serum drug levels is recommended to improve outcomes. Response is observed after 3-4 months of therapy, sustained response is not always observed due to its fungistatic nature.