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

The histopathology patterns characteristic of C neoformans infection fall into either a paucireactive pattern with myriads of densely packed organisms with mucoid gelatinous capsules that cause minimal tissue reaction or a mixed suppurative and granulomatous reaction with varying degrees of necrosis.⁴ The granulomatous form can affect histiocytes, giant cells, lymphocytes, and fibroblasts. These findings along with the characteristic carminophilic capsule of C neoformans allows for a prompt diagnosis. However, the C neoformans spore somewhat characteristically measures 3 to 20 mm in diameter and stains well with periodic acid–Schiff stain and GMS.^4,5 Therefore, the lack of capsule broadened our early differential to include Histoplasma capsulatum, S schenckii, Paracoccidioides brasiliensis, and even Blastomyces dermatitidis.

Neuville et al¹ proposed the following criteria for the diagnosis of PCC: the absence of dissemination and predominantly a solitary skin lesion on unclothed areas presenting as a whitlow or phlegmon, a history of skin injury or damage leading to direct inoculation, participation in outdoor activities, exposure to bird droppings, and isolation of C neoformans serotype D. Other factors that strongly support PCC diagnosis over squamous cell carcinoma (based on a review of the literature) are rural residential environment, older age, equal prevalence among men and women, and lack of underlying disease. Presence of these factors seem to favor PCC over squamous cell carcinoma, as some still consider the existence of PCC in general to be controversial because skin manifestations represent a sentinel finding indicative of disseminated disease.^1,3

The fungus can be found worldwide as an ubiquitous saprophyte of soil, especially if the soil is enriched with pigeon droppings. A link between C neoformans and pigeons has been suggested, with dried avian excreta allowing the yeast to abundantly grow because of its high nitrogen content.^5,6 Other possible sites include decaying wood, fruits, vegetables, and dust.¹ There are 4 main serotypes and 3 varieties of C neoformans: C neoformans var grubii (serotype A; worldwide distribution), C neoformans var gattii (serotypes B and C; more circumscribed diffusion and distribution including subtropical regions of Australia, Central Africa, South Asia, and California), and C neoformans var neoformans (serotype D; worldwide distribution).^3,7 A literature review indicated that known cases of serotype D (global incidence, 9%) tended to produce cutaneous lesions without systemic involvement.⁷ Microscopically, the most important characteristic feature found in all serotypes is the polysaccharide capsule, which normally acts as an important virulence factor.⁶ This capsule as well as detection of the budding yeast can be visualized with india ink (cerebrospinal fluid), methylene blue, or mucicarmine staining. The latex agglutination test for cryptococcal antigen has been used as a serologic test for cerebrospinal fluid, blood, and urine with a sensitivity of 86% to 95%.⁸

Treatment of cryptococcal disease depends on location and severity of lesions. Many cases of PCC spontaneously resolve, but it is a recommended practice to treat the lesions via incision, local irrigation and debridement, and anti-inflammatory and antifungal agents.⁹ Antifungal therapy with amphotericin B with or without flucytosine was the standard of therapy. The newer oral azole compounds (eg, ketoconazole, fluconazole, itraconazole) are effective against Cryptococcus, making them the probable treatment in immunocompetent patients because of fewer side effects. Nonetheless, these drugs should be maintained for several weeks or even months to achieve complete resolution of PCC.¹⁰

Our patient’s clinical presentation, physical findings, and treatment response seemed to fit well with a diagnosis of PCC, particularly the solitary skin lesions on unclothed areas of the skin; history of skin injury, participation in farming, or exposure to bird droppings (eg, contaminated soil, manure); isolation of C neoformans; and lack of evidence of disseminated disease. Once a diagnosis of PCC is made, however, evaluation of a patient’s immune system and other systemic involvement must be performed, as solitary skin lesions can be the only symptom and an early marker of disseminated disease. Inclusion of a lumbar puncture in the absence of localizing signs is not required in the workup of PCC, with the emergence of more cases of PCC being required before conclusive recommendations can be made. A strong history and physical examination, including pertinent details such as local trauma and exposure to bird droppings, along with the criteria provided by Neuville et al¹ and laboratory information may be sufficient to diagnose PCC; close monitoring should be continued.¹ Luckily, of the reported cases of PCC in immunocompetent individuals, oral antifungal therapy usually has been curative.^2,3 The fact that our patient did not develop generalized disease could be explained by the presence of the possible serotype D, low virulence of the capsule-deficient strain, or perhaps some other immunologic mechanism of defense.