CASE REPORT
A 44-year-old man with cystic fibrosis, status post bilateral
lung transplant 14 years prior, was admitted
to the hospital for progressively worsening shortness
of breath, headaches, and painful skin nodules on the
legs and buttocks of 4 months duration. He had been on a
longstanding immunosuppression regimen of tacrolimus,
mycophenolate mofetil, and prednisone. Five months prior,
his pulmonologist noted decreased pulmonary function
tests, and a chest X-ray revealed a new right mid-lung mass.
A computed tomography (CT) of the chest was recommended
for further evaluation but he did not follow up.
During this time he developed painful skin nodules on his
thighs and buttocks. An initial biopsy performed by an outside
dermatologist was read as erythema nodosum. His
shortness of breath worsened and he developed new headaches,
prompting hospital admission. He did not have fever,
chills, or night sweats. He denied sick contacts, recent travel,
and exposure to pets or birds. He had lived his entire life in
the Northeast region of the United States and was employed
as a bookkeeper at a library.
On admission, his vital signs were normal. Tender red 1 cm
to 5 cm subcutaneous nodules were scattered on both medial
thighs and buttocks (Figure 1). A CT scan of the chest
revealed a 3.8 cm x 2.0 cm cavitary mass in the superior segment
of the right lower lobe. A skin biopsy showed numerous
non-encapsulated yeast cells in the subcutaneous fat with a
gelatinous-type histologic reaction (Figure 2). A culture of skin
biopsy showed mucoid colonies of cryptococcus neoformans
on 5% sheep blood agar (Figure 3). The initial “erythema nodosumâ€
skin biopsy, from several weeks prior, was positive for
multiple yeasts with surrounding halos using a gomori methenamine
silver stain.
A lumbar puncture was performed and cerebrospinal fluid
(CSF) was positive for cryptococcal antigen at 1:1024. The
India ink stain of the CSF is shown in Figure 4. The patient
was started on intravenous amphotericin B (lipid complex)
300 mg Q12 hours along with oral flucytosine 1 g Q12 hours.
He was discharged 10 days after admission with a peripherally
inserted central catheter to continue treatment, but was
readmitted 1 week later with recalcitrant disease. Despite continued
aggressive anti-fungal therapy (including the addition
of voriconazole 230 mg Q12 hours), he died 8 months later
from complications of disseminated disease.
DISCUSSION
Cryptococcus neoformans is an opportunistic fungal infection
with significant morbidity and mortality in the immunocompromised
host. Solid organ transplant (SOT) recipients with
disseminated disease account for 30% to 60% of non-HIV patients
infected with cryptococcus, and carry a mortality rate
of 33% to 42%.1,2 The central nervous system (CNS) serves
as the most frequent site of dissemination from the primary
pulmonary disease, followed by the skin and soft tissue
(10%-20%). Cutaneous cryptococcosis in SOT recipients almost
always results from disseminated disease, and primary
cutaneous cryptococcosis (PCC) should be a diagnosis of
exclusion.3 Cellulitis is the most common cutaneous mani-
