University of Alabama at Birmingham

Gorgas Case 2020-05

Universidad Peruana Cayetano Heredia
The following patient was seen as an outpatient at Cayetano Heredia Hospital during the Gorgas Diploma Course.
Image for Case 2020-05

History: A 65-year-old man presented to the infectious disease clinic with a 6-year history of illness characterized by a cutaneous ulcer on the left forearm, for which he unsuccessfully received multiple courses of treatment at other medical providers with 1) pentavalent antimonials for suspected cutaneous leishmaniasis and 2) standard anti TB drugs after a skin biopsy showed a granulomatous reaction.

Epidemiology: Born in San Martin, lives in Ucayali, both in the low jungle of Peru. Works in agriculture. Denies contact with known TB patients. Past medical history is remarkable for type 2 diabetes mellitus, treated with metformin for the past 10 years.

Physical Examination: On the left forearm, a slightly elevated verrucous plaque with an atrophic center, peripheral desquamation and numerous black dots (Image A). The rest of the physical exam was unremarkable.

Laboratory: Hb:15.4 g/dL, Hct 46%; WBC 7.48 (bands: 0%, neutrophils: 47.1%, eosinophils: 18%, basophils: 0.4%, monocytes: 6%, lymphocytes: 27.8%); Platelets: 273 000. Glucose: 121, Urea: 27 mg/dL, Creatinine: 0.79 mg/dL, AST: 48 U/L, ALT 42 U/L, Alk phos: 164 UI/L.


UPCH Case Editors: Carlos Seas, Course  Director / Alvaro Schwalb and Paloma Carcamo, Associate Coordinators
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

 

Diagnosis: Chromoblastomycosis

Images for Case 2020-05
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Discussion: Microscopic examination of skin scraping revealed abundant muriform cells on direct examination (Image B), and a diagnosis of chromoblastomycosis was made. Skin biopsy confirmed this, showing pseudoepitheliomatous hyperplasia in the epidermis and chronic granulomatous inflammation with suppurative foci underneath, with structures resembling dematiaceous fungi. Fungal cultures for speciation are pending.

Diagnosis is best made by direct microscopy using KOH of skin scrapings taken from areas of the lesion with abundant black dots, which reveals muriform or sclerotic bodies - pathognomonic for chromoblastomycosis. Skin biopsy (which should include black dots as well) also reveals muriform bodies, along with signs of pyogranulomatous inflammation (Image C). Muriform bodies are usually seen as an aggregation of 2-4 round brownish thick-walled 4-12 μm structures with transverse and longitudinal septation. Occasionally, dematiaceous hyphae may also be seen. Fungal culture must be performed in order to identify species; oftentimes molecular biology techniques such as PCT are needed to complete work-up.

Chromoblastomycosis is a chronic subcutaneous mycosis caused by inoculation of spores from dematiaceous fungi. It is prevalent in Southern Africa and parts of Latin America, including Mexico, Brazil and Venezuela. However, it has also been reported in countries with temperate climates. In Peru, sporadic cases have been reported in Ucayali and Cusco (https://onlinelibrary.wiley.com/doi/abs/10.1111/ijd.13665).

It is typically caused by two genera of dematiaceous (also known as melanized or phaeoid) fungi: Cladophialophora and Fonsecaea, both found in tropical rainforests. About 90% of isolated species are identified as Fonsecaea pedrosoi (http://www.scielo.br/scielo.php?pid=S0365-05962018000400001&script=sci_arttext). They are typically isolated from soil and plants, thus farm workers and gardeners are at higher risk of infection.

Chromoblastomycosis presents with an initial papule with centrifugal growth that may evolve into different clinical forms. The verrucous-type lesion, as seen in our patient, is the most prevalent. These types of lesions are hyperkeratotic and warty in appearance, have a high fungal load, and ulcerate easily. Another type of lesion is the nodular type, with fibrotic, red-violet nodules with a smooth or hyperkeratotic surface. Plaque-type lesions can also be red or violet, and are usually well circumscribed although irregular in shape, with sharp, elevated edges. The tumoral-type lesions can be single or multiple and coalescent, and can be either smooth or scaly. Cicatricial-type lesions can have an annular, serpiginous, or irregular configuration, and usually grow centrifugally. Metastatic lesions may appear by contiguous spread, hematogenous or lymphatic dissemination. Lesions are more frequently found in lower limbs, but can appear anywhere on the body. All of the forms typically have a “cayenne pepper” appearance, as seen in Image A. The black dots represent transdermal elimination of fungal debris. Patients are usually oligosymptomatic, presenting only mild pruritus and sometimes local pain, and take a long time to seek medical attention. (http://www.scielo.br/scielo.php?pid=S0365-05962018000400001&script=sci_arttext)

The differential diagnosis for a verrucous plaque such as the one seen in our patient includes cutaneous tuberculosis, non-TB mycobacterial infections, sporotrichosis, leishmaniasis, leprosy and lobomycosis. Non-infectious diagnoses such as sarcoidosis or cutaneous malignancies must also be ruled out.

Treatment is difficult, with low cure and high relapse rates, and there is no high-grade evidence to support it. Therapy choice depends on disease severity. Mild disease, defined as a solitary plaque or nodule less than 5 cm in diameter, should be treated with surgical excision, which can be curative. Cryotherapy and thermotherapy may also be considered. However, since most patients seek medical care late in the course of the disease, this is not often an option. Moderate disease includes single or multiple lesions with nodular, verrucous or plaque morphology, less than 15cm in diameter, and involving up to two adjacent skin areas. Severe disease occurs when there is extensive involvement. For moderate to severe disease, extended regimens of oral antifungals are recommended. The agents with greatest proven efficacy are itraconazole and terbinafine, given for 6-12 months at high doses, with similar cure rates of 15-80% (https://www.ncbi.nlm.nih.gov/pubmed?term=27856522). In cases of resistance to standard antifungals, posaconazole has shown good clinical success rates (https://www.ncbi.nlm.nih.gov/pubmed/16553324).

Complications of chromoblastomycosis include tissue fibrosis that may lead to lymphatic blockage and stasis, bacterial superinfection, or even development of malignancy. Some cases of chromoblastomycosis-associated squamous cell carcinoma have been reported (https://www.ncbi.nlm.nih.gov/pubmed?term=25681378).

Our patient is currently in his third month of treatment with oral itraconazole, with slow improvement of the lesion.