University of Alabama at Birmingham

2012 Case #6

Universidad Peruana Cayetano Heredia
The following patient was seen in the outpatient department of the 36-bed Tropical Disease Unit at Cayetano Heredia National Hospital.

Image AB for 3/12/2012History: 69 year old with an 8 year history of a painless chronic skin lesion or the third finger of the right hand that began as a red papule at the site of a snakebite he had sustained several months earlier. The lesion progressed slowly over the years to become a verrucous plaque with some black dots on the surface. No fluctuance, discharge, pus or sinus tracts were present at any time. Irregular treatment with topical agents and oral antifungals including ketoconazole and fluconazole, first for 6 months and then for 1 year had led to no improvement.

Epidemiology: Coffee and orange farmer from the jungle. No known TB exposure. No risk factors for HIV.

Physical Examination: Afebrile. Single verrucous plaque with black dots on right finger [Images A, B]. No lymphadenopathy.

Laboratory Results: CBC and biochemistry normal.

Diagnosis: Chromoblastomycosis due to Phialophora verrucosa.
Images CDE for 3/12/2012 DiscussionDiscussion: Microscopic examination of a skin biopsy disclosed pigmented thick walled multi-celled structures called sclerotic bodies or muriform bodies [Image C]. Sclerotic bodies can usually also been seen on a simple KOH preparation from a scraping of one of the black dots. Culture of the scrapings on Saborauds agar grew Phialophora verrucosa with characteristic flask-shaped or elliptical phialides with a distinctive funnel-shape. PCR confirmation is pending [Image D].

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 groups:

  1. 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).
  2. 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.
  3. Chromoblastomycosis is characterized by papular lesions with chronic onset that progress to nodules or plaques most often with a hyperkeratotic verrcuous surface. 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 environments) and Cladophialophora carrionii (drier environments), with Phialophora verrucosa, and Rhinocladiella aquaspersa being less common.

Chromoblastomycosis occurs worldwide, including in the USA, but 70% of cases are estimated to occur in the moist tropics. Most cases in Latin America are from the humid Amazon 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 reported from Madagascar and South Africa. Up to 90% of cases occur in males likely due to occupational factors.

The differential diagnosis in our patient includes: sporotrichosis [Gorgas Case 2008-01], eumycetoma [Gorgas Case 2002-04], lobomycosis (lacaziosis) [Gorgas Case 2005-03], subcutaneous zygomycosis, subcutaneous phaeohyphomycosis, botryomycosis [Gorgas Case 2003-04], leishmaniasis [Gorgas Case 2004-01], nocardiosis [Gorgas Case 2011-01], cutaneous tuberculosis, leprosy, and benign and malignant tumors (e.g., Kaposi’s and other sarcomas).

Treatment of chromoblastomycosis is based on case report and case series; there are no controlled trials. Treatment choices include itraconazole alone or in combination with flucytsosine, terbinafine, cryosurgery, or heat. Small lesions may respond to surgery, heat, or cryotherapy alone [Curr Opin Infect Dis. 2009 Dec;22(6):559-63]. Our patient is receiving 200 mg/day of itraconazole and has had 2 cryotherapy applications so far. Image E shows his lesion after 4 weeks of itraconazole.

Of the newer azoles voriconazole has potent in vitro activity against Cladiphialophora carrionii, F. pedrosoi, and Phialophora verrucosa; posaconazole is approved in Europe for refractory chromoblastomycosis; and caspofungin has potent in vitro activity against F. pedrosoi [Med Mycol. 2011 Apr;49(3):225-36].

Acknowledgements: We thank Dr. Francisco Bravo, Gorgas Dermatology Professor and Dr. Betty Bustamante, Director of the IMT Mycology Lab.