Chromomycosis - A Case Series Over a 10-year Period from the National Skin Centre

BULLETIN FOR MEDICAL PRACTITIONERS

Dr Ariana A, Visiting Fellow
Assoc Prof Giam Yoke Chin, Senior Consultant Dermatologist & Deputy Medical Director, National Skin Centre

Introduction
Chromomycosis or chromoblastomycosis is a chronic localized invasive fungal infection of skin and subcutaneous tissue, characterized by the presence of slowly progressive verrucous lesions. The lower limbs or feet are usually affected. The infection is caused by pigmented (dematiceous) fungi, which produce thick-walled, single or multi-celled clusters (sclerotic or muriform bodies) within the tissue.[1-3] There are several dematiceous chromomycosis fungi: Fonsecaeae pedrosoi (most common), Fonsecaeae compacta, Phialophora verrucosa, Cladosporium carionii, Rhinocladiella aquaspersa, Botryomyces caespitosus.[3,4,5] The fungi can be found in soil, wood, and rotting vegetation and infection usually results from trauma, such as a puncture from a splinter of wood.[1,3] Age of onset is 20 to 60-years, and the disease is seen mainly in the tropical and subtropical region, affecting individuals who are exposed to the soil, e.g. agricultural and mine workers.[1,3] We report on the cases of chromomycosis seen at National Skin Centre over a 10-year period from 1992 to 2002 and describe their clinical features, investigative findings and clinical outcome with systemic antifungal therapy.

Case series
A total of 2 patients with histological proven diagnosis of chromomycosis were seen at National Skin Centre from 1992 to 2002. Both were Chinese. One was a male aged 47 years and the other a female aged 44 years. The male patient presented with several irregular verrucous plaques, with scaly erythematous borders on the left back for duration of 5 years (Fig. 1). The female patient had a single erythematous nodule with an irregular border and central ulceration on the left leg for a duration of 6 months (Fig. 2). There was no underlying medical illness in both patients. None were involved with agricultural works.

The biopsies taken from both the patients showed granulomatous inflammation and abscess formation in the upper dermis. The granulomas composed of epitheloid histiocytes, foreign body-type giant cells in the areas of abscess formation. Brownish, pigmented, rounded fungal bodies or round brown spores within giant cells were present.

The culture from the biopsy specimen from the male patient grew Fonsecaece compacta. However, result of mycological culture of the female patient was negative. Both patients received systemic treatment with itraconazole 200mg/day. Serial liver function tests before and during treatment were performed and were normal. No other adverse drug reactions were recorded.

The male patient showed clinical improvement after 11 months and female patient after 3 months of therapy. Repeat biopsies at the end of treatment confirmed the absence of fungal elements and established cure. No clinical relapse was recorded.

Discussion
Clinically, chromomycosis is hallmarked by the presence of verrucous nodules at sites of fungal implantation. There are five different clinical forms of chromomycosis: verrucous, vegetative, fistulous, granulomatous and squamous.[6,7] Often, they are misdiagnosed as lupus erythematosus or squamous cell carcinoma. Histological examination shows pseudoepitheliomatous hyperplasia, hyperkeratosis, intraepidermal abscesses containing inflammatory cells, and medlar bodies or muriform or sclerotic bodies. Sclerotic body is the small brown fungal form, which are round with thick bilaminate walls 4-6 µm in diameter, which occur singly or in clusters. The dense suppurative and granulomatous dermis shows histiocytes, giant cells, plasma cells, eosinophils, abscess formation. Older lesions show dense fibrosis in and around granulomas.[1,4] Lymphatic and brain metastases are rare.

The etiological agent can be isolated and identified through culture. The result of smear of pus from lesions will show medlar bodies on 10-20% KOH preparation as black dots. Hyphal forms can be seen in crusts, pus, and exudates. The culture of organism in Sabourauds glucose agar shows velvety green to black, restricted, slow-growing colonies. The fungus grows very slowly, requiring 4-6 weeks for identification.[1]

The chances of chromomycosis being treated successfully are minimal. A wide variety of therapies have been used through the years with varying results, but, so far, as treatment of choice has not been found. Modes of therapy may be divided into simple or combined drug regimens that include systemic anti mycotic agents, thiabendazole, potassium iodide, calciferol, and 5-fluorocytosine (5-Fc). Ketoconazole is ineffective. Other therapies include physical methods such as conventional surgery, laser surgery, thermotherapy, and cryotherapy.[3,5,6,8,9]

Bonifaz and others[5] proposed that the best result were obtained with cryosurgery for small lesions, with itraconazole for large lesions, and in some cases with the combination of them, provides the best chances of cure. Itraconazole is highly lipophilic and thus preferentially redistributes to skin. Inhibition of cytochrome P-450, crucial for ergosterol synthesis, leads to cascade of abnormalities in membrane permeability, membrane-bound enzyme activity, co-ordination of chitin synthesis.[4]

The use of itraconazole in chromomycosis has been reported and had apparent cures. The dose recommended is 200 to 400 mg/day for a prolonged period, usually between 6 and 12 months but frequently longer.[4,5,10-13] In view of the known hepatotoxicity of this drug, liver function tests should be monitored regularly before, during, and after treatment.[10,12] Itraconazole has been used by various investigators with good response rates (approximately 60%) even in cases caused by Fonsecaece pedrosoi. Infection with Cladosporium Carionii responds rapidly (2 to 3 months), whereas those caused by Fonsecaece pedrosoi respond more slowly. However significant improvement occurs in all patients treated for 6 to 12 months at a dose of 200 mg/day.[12] Some patients may require prolonged therapy and can have prolonged remission, if not total cure. Given the low incidence of side effect compared with other available treatments, itraconazole should be considered as the main treatment in the treatment of chromomycosis.[10] However, treatment has to be eradication of the fungus, as non-eradication causes a chronic disease with significant socioeconomic implications, thereby deteriorating the quality of life and work capacity of individuals.

References

1. Hay RJ, Moore M. Mycology In: Champion RH, Burton JL, et all. Textbook of dermatology 6th ed. Oxford: Biackwell Science, Ltd, 1998;1277-1376.
2. Agafwalla A, Khanal B, Garg VK, Agrawal S, Jacob M, Rani S, Deb M. Chromoblastomycosis report two cases from Nepal. I. Dermatol, 2002;29(5):315-9.
3. Milam CP, Fenske NA. Chromoblastomycosis. Dermatol Clin, 1989; 7(2):2 19-25.
4. Smith CH, Barker JNWN, Hay RJ. A case of chromoblastomycosis responding to treatment with itraconazole. British J. Dermatol, 1993;128:436-9.
5. Bonifaz A, Martinez-Soto E, Carrasco-Gerard E, Peniche J. Treatment of chromoblastomycosis with itraconazole, cryosurgery and combination of both. Int J Dermatol, 199 7:36:542-7.
6. Minotto P, Bernardi CDV, Mallman LF, Edelweiss MIA, Scroferneker ML. Chromoblastomycosis a review of 100 cases in state of Rio Grande do sul, Brazil. J Am Acad Dermatol, 200 1;44:585-92.
7. Elgart GW. Chromoblastomycosis. Dermatol Clin, 1996:14:77-83.
8. Tanuma H, Hiramatsu M, Mukai H, Abe M, Kume H, Nishiyama 5, Katsuoka K. A case of chromoblastomycosis in Kitasato region Japan. Mycoses, 2000;43(1-2):79-83.
9. Poirriez J, Breuillard F, Francois N, Fruit J, Sendid B, Gross S, Dei-Cas E. A case of chromomycosis treated by a combination of cryotherapy, shaving, oral 5-Fluorocytosine, and oral amphotericin B. Am J Trop Med Hyg, 2000:63(1 -2):61-3.
10. Tuffanelli L, Milburn PB. Treatment of chromoblastomycosis. J Am Acad Dermatol, 1990;23:728-32.
11. Kullavanijaya P, Rojanavanich V. Successful treatment of chromoblastomycosis due to F pedrosoi by the combination of itraconazole and cryotherapy. Int J Dermatol, 1995:34:804-7.
12. Restrepo A. Treatment of tropical mycoses. J Am Acad Dermatol, 1994:31:S91-102.
13. Queiroz-Telles F, Purim KS, Fillus JN, et al. Itraconazole the treatment of chromoblastomycosis due to Fonsecaea pedrosoi. Int J Dermatol, 1992;31:805-12.

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