Cutaneous Manifestations of Disseminated Cryptococcosis

A34-year-old man with HIV/AIDS presented to the emergency department with fatigue, dyspnea on exertion, headache, subjective fevers, and chills of 1 month's duration. He also had blurry vision and a pruritic facial rash of 2 weeks' duration. He admitted to being noncompliant with antiretroviral therapy for the past 18 months and was not taking other medications at the time of presentation.

Vital signs were within normal limits except for a heart rate of 105 beats per minute. Physical examination revealed multiple, scattered, umbilicated, flesh-toned papules that were 2 to 5 mm in diameter and located on the face and scalp. Most of the lesions had a central hemorrhagic crust and were tender on palpation (Figures 1 and 2). Laboratory testing revealed a CD4+ cell count of 7/?L and a Cryptococcus antigen (CRAG) titer of more than 1:4096. Lumbar puncture revealed CNS involvement with a cerebrospinal fluid (CSF) CRAG titer of 1:1024. Ophthalmoscopic examination revealed multiple yellow, round, and deep choroidal lesions.

Figure 1

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This image shows scattered, umbilicated, flesh-toned, 2- to5-mm papules on the face. The larger papules have a prominent centralhemorrhagic crust (thick black arrows). Some smaller lesions have atiny area of central hemorrhagic crust (white arrow), and others haveno hemorrhage in the center (thin black arrow).

Figure 2

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Classic lesionsof cutaneouscryptococcosis areseen here. Notethe tiny areas ofcentral hemorrhagiccrust(white arrows).Some of theselesions mayresemble thoseof molluscumcontagiosum(black arrow).

Treatment with intravenous amphotericin B was begun; this was followed by fluconazole therapy. Serial serum and CSF CRAG measurements were used to document clinical recovery. However, the skin lesions persisted despite treatment, and new lesions developed on the extremities.

Discussion
Cryptococcus neoformans is the most common cause of opportunistic fungal infection in patients with HIV/AIDS. This infection affects 6% to 13% of patients. Cutaneous lesions are found in 10% to 15% of patients with disseminated cryptococcosis. These lesions characteristically are most prominent on the face and neck, followed by the extremities and trunk. The most common morphological finding is umbilicated papules, clinically resembling molluscum contagiosum, and many of the papules have a tiny central area of hemorrhagic crust formation. Violaceous papules, plaques, and nodules also may be seen. Histologically, these lesions exhibit 2 patterns: the more common granulomatous pattern, with sheets of histiocytes phagocytizing abundant budding yeast forms surrounded by clear halos, and the less common gelatinous pattern, with free-floating fungi in pools of mucin. Diagnosis can be made by treating curetted tissue with potassium hydroxide preparation; by biopsy; or by serum CRAG testing, especially if disseminated disease is suspected.

Clinicians should be aware of the varied morphology of cutaneous manifestations of disseminated cryptococcosis in patients with HIV/AIDS because they are an early marker of disseminated disease and may be present well in advance of other signs of systemic infection.¹