A 53-year-old female kidney transplant recipient from Southeast Pennsylvania was transferred to our institution after, 2 weeks of care in another hospital with pneumonia. She had received 3 kidney transplants (the last 25 years before this presentation) because of end-stage renal disease secondary to post-streptococcal glomerulonephritis. Her immunosuppressive regimen consisted of prednisone (alternating 5 mg and 10 mg orally every other day) and azathioprine (25 mg orally daily).
Three months before her presentation, she developed painful palpable erythematous skin lesions on the anterior surface of her lower extremities. At the time, she was being evaluated for continuous ambulatory peritoneal dialysis because of chronic allograft failure and the lesions were initially thought to be a result of calciphylaxis. An interferon-gamma release assay (IGRA) for tuberculosis (TB) (Quantiferon-TB Gold InTube; Cellestis, Inc, Valencia, California, USA) performed as part of a pre-dialysis workup was positive; therefore, treatment with isoniazid was initiated for presumed latent TB infection (LTBI). The treatment was stopped prematurely after 1 month because of pruritus. At that time, an incisional skin biopsy was performed on a left thigh lesion and reported as consistent with EN. Special stains, including Grocott's methenamine silver (GMS), were unrevealing. EN was assumed to be associated with her recent LTBI diagnosis. She was treated with oral super-saturated potassium iodide and later on with systemic corticosteroids (intramuscular betamethasone). Despite receipt of EN-directed therapies, new skin lesions appeared.
She was eventually admitted to her hospital with a subacute history of fatigue, dyspnea, and dry cough, in addition to newly appearing skin lesions. She was febrile (39.4 C) and hypoxemic at presentation. A computed tomography scan of the thorax revealed bibasilar peribronchial thickening with patchy infiltrates. A bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy were performed. Microscopic examination of BAL fluid revealed yeast cells on GMS stain that were not compatible with Pneumocystis jirovecii and thought to be colonizing Candida species. Other stains and cultures were negative, including those for mycobacteria and cytomegalovirus. Transbronchial biopsy showed nonspecific chronic inflammation. A bone marrow biopsy was also performed and failed to identify any organisms on special stains. A punch skin biopsy from a lesion on the right thigh demonstrated panniculitis with numerous small budding yeasts. Her condition deteriorated despite broad-spectrum antimicrobial therapy (including caspofungin) and she required intubation and administration of vasopressors.
After 2 weeks of hospitalization, the decision was made to transfer the patient to our hospital. Upon admission in our intensive care unit, she was alert and appropriately responsive despite endotracheal intubation and intermittent vasopressor requirement. Erythematous tender plaques of 3-6 cm were noted on the extensor surface of upper and lower extremities. The abdomen was soft and non-tender. One febrile episode was observed at 38.4 C on day 2. Pertinent laboratory and microbiological data are presented in Table 1. A chest and abdomen computed tomography showed multifocal ground-glass opacities in the lungs, a hypodense lesion in the liver and heterogeneous enhancement of the spleen and transplanted kidney. Treatment was initially adjusted to piperacillin-tazobactam (2.25 g intravenously [IV] every 6 h) and azithromycin (500 mg IV daily). A serum Aspergillus galactomannan antigen (GMA) enzyme immunoassay (EIA) (Platelia  Aspergillus EIA, Bio-Rad Laboratories Inc., Hercules, California USA) was positive on day 2, with an optical density index of 2.7, which led to addition of voriconazole (350 mg IV every 12 h) for suspected invasive pulmonary aspergillosis. An infectious disease consultation was requested and based on her clinical presentation, small yeast forms in BAL and skin, and positive serum GMA EIA, a presumptive diagnosis of disseminated histoplasmosis was made and voriconazole was changed to liposomal amphotericin B (5 mg/kg IV daily) on day 3.
Despite aggressive supportive therapy, the patient died of multiorgan failure on day 7. Serum and urine were tested for Histoplasma antigen (collected on day 2) and found to be positive at >39 and 11.57 ng/L, respectively (MVista  Histoplasma Quantitative EIA, MiraVista Diagnostics, Indianapolis, Indiana USA). Eventually, the peritoneal fluid, the BAL fluid, and the second skin biopsy grew H. capsulatum after 2, 3, and 4 weeks of incubation, respectively. Bone marrow and blood cultures were sterile.
The initial biopsy (left thigh) was reviewed and revealed necrotizing granulomatous panniculitis with septal accentuation; GMS stains did not elucidate any organisms. The subsequent biopsy (right thigh) revealed numerous GMS-positive small budding yeasts without pseudohyphae in a background of panniculitis. Few macrophages appeared to contain organisms.