The patient was a 33-year-old Caucasian male with advanced AIDS (CD4+ cell count: 59 cells/mm3, HIV-1 RNA level of 308,000 copies/mL) and an extensive history of opportunistic infections including prior disseminated histoplasmosis, disseminated Mycobacterium avium complex (MAC), Pneumocystis jirovecii (PCP) pneumonia, cutaneous varicella-zoster infection, and cytomegalovirus (CMV) gastric ulcer. He had been placed on combination antiretroviral therapy (cART) with emtricitabine/tenofovir and raltegravir as well as opportunistic infection prophylaxis with itraconazole, azithromycin, trimethoprim/sulfamethoxazole (TMP/SMX), and valganciclovir, although the patient reported being poorly adherent to all prescribed medications. He presented to the hospital with a two-week history of worsening cough, shortness of breath, intermittent fever and chills, and black tarry stools. On admission, he appeared cachectic, chronically ill, and in obvious distress. Vital signs were notable for tachycardia and mild tachypnea. Physical examination revealed facial Molluscum contagiosum, ulcerations on the right lateral tongue, oropharyngeal thrush, mild diffuse abdominal pain, and moderate hepatosplenomegaly. A complete blood count was significant for pancytopenia with a leukocyte count of 2,800 cells/muL (93% neutrophils, 4% lymphocytes, and 1% monocytes), hematocrit of 20% (down from the patient's baseline of 30%), and platelet count of 28,000/mL. The results of a comprehensive metabolic panel were as follows: sodium 133 mmol/L, potassium 4.1 mmol/L, chloride 102 mmol/L, bicarbonate 22 mmol/L, blood urea nitrogen 16 mg/dL, creatinine 0.76 mg/dL, glucose 103 mg/dL, calcium 7.7 mg/dL, AST 113 units/L, ALT 25 units/L, and alkaline phosphatase 450 units/L.
On the evening of admission, the patient became febrile to 39.5 C and increasingly tachycardic, tachypneic, and hypoxic requiring supplemental oxygen, several liters of intravenous fluids, and two units of packed red blood cells. A chest radiograph was obtained which showed a diffuse miliary pattern concerning for PCP pneumonia and/or disseminated opportunistic infectious process such as tuberculosis, MAC, or fungal infection. He was started on empiric treatment with vancomycin, piperacillin/tazobactam, high dose TMP/SMX, prednisone, ethambutol, azithromycin, and liposomal amphotericin B. He responded well to broad-spectrum treatment over the next few days and subsequently underwent diagnostic bronchoscopy with bronchoalveolar lavage (BAL). BAL cultures returned positive for H. capsulatum. The patient also underwent esophagogastroduodenoscopy (EGD) given his persistent melanotic stools and progressively declining hematocrit (nadir of 18%) requiring multiple blood transfusions. EGD was significant for a well-healed scar on the greater curvature of the stomach from prior CMV gastric ulcer and new diffuse erosions throughout the second, third, and fourth segments of the duodenum (Figure 1). Multiple biopsies were taken which showed duodenal mucosa with granulomatous inflammation. Gomori's methenamine silver (GMS) stain identified macrophages with small intracellular yeasts consistent with disseminated histoplasmosis (Figure 2). Bone marrow involvement was also suspected in light of the patient's significant pancytopenia, but he had previously refused bone marrow biopsy. Urine Histoplasma antigen came back markedly elevated at >39 ng/mL (above the upper limit of detection for this particular assay) confirming the diagnosis, and the patient was treated with a two-week course of intravenous liposomal amphotericin B followed by indefinite oral itraconazole.
Following a two-week inpatient hospitalization, the patient demonstrated excellent improvement. All major presenting symptoms were resolved, including the melanotic stools, and his hematocrit was stable at his baseline. By the time of discharge, the patient had regained his prior level of functioning including full ambulatory capacity. Several weeks after discharge, sputum acid-fast culture returned positive for MAC for which he was continued on ethambutol and azithromycin.