Subcutaneous Zygomycosis: A Report of One Case Responding Excellently to Potassium Iodide.

Subcutaneous Zygomycosis is a rare opportunistic fungal infection caused by Basidiobolus ranarum. Though this entity is endemic in South India, limited numbers of cases have been reported from this part of the country. We report a case of subcutaneous zygomycosis in a 25 year old lady who presented with a nontender, firm to hard swelling over the upper-left arm. Finger was easily inserted below the indurated edge. Histopathology revealed suppurative granuloma with aseptate hyphae. Patient responded excellently to saturated solution of potassium iodide in subsequent visits.

What was known?

Subcutaneous zygomycosis caused by Basidiobolus ranarum presents as firm, nontender swelling over the extremities or trunk of healthy individuals and responds well to potassium iodide and azoles.

Introduction

Zygomycosis is a group of fungal infections caused by a number of fungi belonging to the class zygomycetes. The class includes two orders of medical importance mucorales and entomophthorales. Mucorales are responsible for mucormycosis, more severe form of the disease, seen mainly in immunocompromised host. On the other hand, entomophthoromycosis caused by fungi of the order entomophthorales are of two types: Subcutaneous zygomycosis (B. ranarum) and rhinofacial Zygomycosis (Conidiobolus coronatus). B. ranarum are saprophytes found in soil, decaying vegetables, and gastrointestinal tract of frogs. Basidiobolomycosis clinically manifests as chronic infection of subcutaneous tissue in immunocompetent host involving trunk and extremities. Here we present a case of subcutaneous zygomycosis in a 25-year old immunocompetent lady who responded dramatically to saturated solution of potassium iodide.

Case Report

A 25-year old lady was brought to Dermatology OPD with a gradually increasing painless swelling over the upper-left arm of 8 month duration. The lesion appeared insidiously as an erythematous nodule which gradually increased in size to attain the present configuration. There was no preceding history of trauma. The patient was nondiabetic and no history suggestive of any major illness in the past especially history regarding immunosuppression could be elicited. On cutaneous examination, we revealed a well-defined, firm to hard, painless, nontender, indurated swelling of approximate 6.5 × 7.5 cm2 in size with surface ulceration and crusting at places [Figure 1]. Lesion was freely mobile over the underlying structures. The margin was well defined and indurated with positive finger insinuation test. Patient was afebrile and regional lymph nodes were not palpable. Rest of the general survey and systemic examinations were within normal limit.

Figure 1

Well-defined mass with surface crusting and ulceration and positive finger insinuation test

Routine investigations including complete hemogram, renal, and liver function tests did not reveal any abnormality. She was seronegative for HIV by ELISA. X-ray of upper-left arm showed soft tissue shadow without any bony involvement. Biopsy sample was taken and sent for histopathology and culture. On direct microscopy with 10% potassium hydroxide mount, we found broad, irregular aseptate hyphae. Histopathology from skin lesion showed dense infiltrate of eosinophils, small cluster of epithelioid cells, foci of necrosis with few broad aseptate fungal hyphae surrounded by eosinophilic material (Splendore-Hoeppli phenomenon) [Figures 2 and 3]. Culture on Sabouraud's dextrose agar demonstrated luxurious, creamy white, membranous, centrally heaped up, radially folded colony with peripheral satellite growth. Bacteriological culture yielded no growth. Lactophenol cotton blue (LPCB) test could not be performed due to lack of facility.

Figure 2

Scanner view showing eosinophilic granuloma with cluster of epithelioid cells and foci of necrosis

Figure 3

×40: Showing broad aseptate fungal hyphae surrounded by eosinophilic material (Splendore-Hoeppli phenomenon)

After confirming the diagnosis as Basidiobolomycosis with the help of microscopy and culture, the patient was put on saturated solution of potassium iodide with strict vigilance of thyroid function and signs of iodism. The patient responded remarkably within 2 months. During the first follow up after 1month, lesion reduced to a great extent [Figure 4] and on subsequent visit, it almost disappeared leaving some hyperpigmentation [Figure 5].

Figure 4

First follow-up after 1 month

Figure 5

Second follow up after 2 months

Discussion

Zygomycetes constitute a class of ubiquitous organism which causes clinically relevant fungal infection in humans. Class zygomycetes can be subdivided into two orders, mucorales, and entomophthorales. Members of the order entomophthorales such as B. ranarum are associated with chronic infection of cutaneous and subcutaneous tissue and usually do not disseminate to internal organs.[12] On the contrary, the order mucorales tend to cause invasive disease such as pulmonary, rhinocerebellar and gastrointestinal infection in immunocompromised host.[12] Few reports state mucorales as the culprit organism causing cutaneous/subcutaneous infection in immunocompetent individuals.[3]

The first case of subcutaneous zygomycosis had been reported from Indonesia in 1956.[4] Human disease with B. ranarum is prevalent in tropical countries. As far as Indian scenario is concerned, disease is more concentrated in south India.[56] The fungus is a saprophytic one and present in decaying vegetables, intestine of amphibians, reptiles, fish, and insectivorous bat.[7] Subcutaneous zygomycosis results from inoculation of fungal spore into the dermis or subcutis. Possible mode of transmission is minor trauma which may be through insect bite, intravenous catheter, or even intramuscular injection.[68] Clinically, the disease starts as hardened nodule on extremities or trunk which if untreated may spread and expand locally to form hard, painless, nontender swelling. The mass can be raised up by inserting fingers underneath its smooth and rounded edge. Although ulceration of the nodule may be a possible fate, dissemination is extremely rare. Previously, clinical isolates of basidiobolus were classified into B. ranarum, B. haptosporus, and B. meristosporus. But recent taxonomic studies using sophisticated techniques such as restriction enzyme analysis prove that B. ranarum is the sole agent causing all the human disease.

Histopathologically, subcutaneous Zygomycosis is characterized by small foci of suppurative granuloma distributed all over the dermis and subcutis. Though different types of cells including lymphocytes, histiocytes, plasma cell, and multinucleated giant cells contribute to the composition, eosinophils play the major role. Dominance of eosinophils could be attributed to the release of IL4 and IL10 which help in recruiting eosinophils to the target site.[9] The presence of eosinophilic infiltrate in the granuloma is so characteristic that it is also called eosinophilic granuloma. Degranulation of eosinophils leads to formation of eosinophilic sheath (Splendore-Hoppelli phenomenon) surrounding aseptate or infrequently septate thin walled hyphae. Though direct examination of the biopsy sample may suggest a diagnosis of this entity, culture is gold standard for confirmation.

The possibility of misdiagnosing this entity as neoplasm should be kept in mind as it is a great mimicker of soft tissue tumor, synovial sarcoma and Burkitt's lymphoma.[10] Other important differentials are mycobacterial infection, sporotrichosis, and parasitic infection such as onchocerciasis.

Most of the patients of subcutaneous zygomycosis respond excellently to potassium iodide and azoles. In our patient it was potassium iodide which effectively cured the infection.

Conclusion

In a nutshell, early diagnosis and awareness of this entity even in this part of the country is important to prevent disfigurement, misdiagnosis, and avoidance of unnecessary investigations and surgical interventions.

What is new?

Patient responded extremely well only with potassium iodide and did not develop any sign of iodism with strict compliance to therapy. Our case also denotes that this entity is not exclusive only in South India.