Primary Capsule-Deficient Cutaneous Cryptococcosis in a Sporotrichoid Pattern in an Immunocompetent Host

Cryptococcosis is an opportunistic yeast infection caused by Cryptococcus neoformans that remains the most common systemic fungal infection in immunosuppressed patients and often presents with signs of meningitis. Cutaneous cryptococcosis occurs in 10% to 20% of systemic Cryptococcus infections and usually is secondary to hematogenous dissemination in patients with an underlying disease, particularly human immunodeficiency virus. Primary cutaneous cryptococcosis (PCC) is a more rare clinical identity that is characterized by skin lesions confined to 1 body region, often presenting as a whitlow or phlegmon with positive culture for C neoformans and no evidence of simultaneous dissemination. We report a rare case of PCC in a 73-year-old man with intact cell-mediated immunity.

Case Report

A 73-year-old man who was a beef farmer presented on primary care referral with multiple red nodules and ulcers on the right third and fourth digits and distal forearm following abrasion to the region. The patient reported that the lesions had started as painful nodules that would open and drain. He had been taking oral ciprofloxacin and oral ketoconazole for 3 days as prescribed by his primary care physician but had not begun to see results. He denied any travel or exposure to roses, fish tanks, or any sick contacts. A review of systems was negative for fever, night sweats, malaise, headache, or any other systemic symptoms. Physical examination revealed multiple 2- to 6-mm nodules and ulcers distributed in a sporotrichoid pattern on the right hand (Figure 1) and arm (Figure 2). Lymphadenopathy was absent and the rest of the examination revealed no abnormalities.

Figure 1. Ulceration of the right fourth digit and palm. Figure 2. Multiple nodules and ulcers distributed in a sporotrichoid pattern on the right arm.

Initially, 4 punch biopsies of the right hand and arm were obtained and sent for Gram staining, tissue culture (bacterial and fungal), and histopathologic review. A presumptive diagnosis of sporotrichosis was made, with change of treatment pending culture. On routine hematoxylin and eosin staining, marked acute and chronic granulomatous inflammation with microabscesses was noted. Acid-fast bacilli staining was negative. Follow-up Gomori methenamine-silver (GMS) staining showed numerous fungal spores with narrow base budding (Figure 3). Subsequent mucicarmine staining did not reveal dark red capsules characteristic of Cryptococcus (Figure 4). The pathology report indicated that the findings may represent sporotrichosis in the appropriate clinical setting, but GMS staining could not definitively classify Sporothrix schenckii or rule out other fungal infections without tissue culture. Before culture results could be obtained, the patient returned 2 weeks later for suture removal at which point the prior medications were stopped and itraconazole 200 mg once daily was initiated.

Upon receiving the culture results, a diagnosis of primary capsule-deficient cutaneous cryptococcosis was made. The lesions showed clinical improvement at 1-month follow-up, and treatment with itraconazole was continued with monthly liver function tests. After 5 months of continued improvement, the itraconazole dose was decreased to 100 mg once daily for 1 month. The patient was free of lesions and any sequelae at 6-month and 1-year follow-up.

Comment

Cryptococcosis is caused by C neoformans, an opportunistic, basidiomycetous, yeastlike fungus¹ that presents as a yeast in both the environment and tissue and normally is associated with immunocompromised host infection, especially in individuals with human immunodeficiency virus. The most common route of infection is through the lungs as respiratory droplets followed by hematogenous dissemination to the central nervous system and skin, with meningitis being the most common clinical manifestation and Cryptococcus being the most common cause of fungal meningitis worldwide.² Cutaneous involvement after hematogenous spread (secondary cutaneous cryptococcosis) is reported in 10% to 20% of systemic Cryptococcus cases, while PCC is limited to rare cases in which trauma or abrasions to the affected site are notable risk factors.^2,3

Figure 3. Numerous fungal spores with narrow base budding on Gomori methenamine-silver staining (original magnification ×100). Figure 4. Mucicarmine staining showed an absence of characteristic red Cryptococcus neoformans capsules (original magnification ×100).

Cryptococcus can produce a myriad of skin manifestations including but not limited to nodules, ulcers, plaques, pustules, vesicobullous lesions, and draining sinuses. Neuville et al¹ found that cellulitis, cutaneous ulcers, and whitlows were the most common presenting clinical features in PCC. Whitlows also have been reported as a rare presentation in secondary cutaneous cryptococcosis yielding to the much more prevalent presentation of umbilicated papules resembling molluscum contagiosum.¹ This polymorphic identity can therefore mimic not only other dermatoses and neoplasms but other infections such as bacterial cellulitis, herpes simplex virus, and molluscum contagiosum, especially in disseminated cryptococcosis, making microscopic assessment crucial for the diagnostic confirmation of cutaneous cryptococcosis. The differential diagnosis includes sporotrichosis and Mycobacterium marinum due to the lymphatic distribution of the lesions as well as squamous cell carcinoma. Our initial diagnosis of sporotrichosis was assumptive until mycological data could be obtained.