A 41-year-old male patient was admitted to a tertiary public hospital in Sao Paulo city, Brazil, with a history of fever, fatigue, weight loss, disseminated skin lesions, low urine output, and mental confusion progressing over three months. The patient received outpatient treatment for thoracic herpes zoster and was diagnosed with HIV infection three weeks earlier but decided not to initiate antiretroviral therapy. At hospital admission, upon physical examination, he was afebrile and dehydrated, with a blood pressure of 109/72 mmHg, pulse rate of 130 beats/min, and oxygen saturation of 97% on room air. Mental confusion was observed (Glasgow Coma Scale - GCS = 14). The lung sounds were clear upon auscultation, the abdomen was innocent, and there was no peripheral lymphadenopathy, but diffuse maculopapular and crusty skin lesions were noticed (Figure 1A). Laboratory results showed hemoglobin = 13.9 g/dL, white blood cell count = 6,500/mm3, platelet count = 82,000/mm3, C-reactive protein = 26.1 mg/dL, creatinine level = 4.0 mg/dL, sodium concentration = 127 mg/dL, lactate dehydrogenase = 5,782 U/L, aspartate aminotransferase = 342 U/L, alanine aminotransferase = 340 U/L, total bilirubin = 3.9 mg/dL (direct bilirubin = 3.4 mg/dL), international normalized ratio = 1.71, triglycerides = 324 mg/dL, and ferritin > 100,000 ng/mL. Serologic diagnosis of HIV-1 infection was confirmed, CD4 count was 4 cells/mm3, and HIV-1 viral load was 1,749,163 copies/mL. The chest computed tomography (CT) showed unspecific findings (Figure 1B). The brain CT scan and the cerebrospinal fluid were normal. The abdominal CT scan showed no hepatosplenomegaly, but some retroperitoneal, periaortic, and interaortocaval lymph node enlargement was identified. On day 1, the sequential organ failure assessment (SOFA) score was 8, and septic shock with multiorgan dysfunction (acute renal failure, metabolic acidosis, hepatic failure, and coagulopathy) was diagnosed.
The primary care team initiated volemic expansion, and ceftriaxone was administered empirically. Yeasts suggestive of Histoplasma spp. were observed in the cytoplasm of macrophages of a routine peripheral blood smear (Figure 1C). On day 2, the patient was transferred to the ICU and required supplemental oxygen (1 L/min). Amphotericin B deoxycholate was initiated. On day 3, the SOFA score was 14 and the patient's clinical condition progressed with reduced level of consciousness (GCS 10) and refractory septic shock, requiring high doses of vasopressors, corticosteroids, mechanical ventilation, and hemodialysis. Yeasts suggestive of Histoplasma spp. also were observed in the cytoplasm of macrophages in the bone marrow and skin samples (Figure 1D) on days 3 and 7, respectively. Hemophagocytosis was not observed in the bone marrow. After four weeks of incubation, peripheral blood and bone marrow samples cultures revealed Histoplasma spp. Aerobic, anaerobic, and mycobacterial blood and bone marrow cultures were all negative. In addition, Xpert MTB/RIF Ultra assay, mycobacterial cultures, and acid-fast bacillus smear from tracheal secretion were negative. The patient stayed in the ICU for 32 days, receiving empiric broad-spectrum antibiotic therapy and frequent blood and platelet transfusions. Treatment with amphotericin B was extended to 23 days (20 days with amphotericin B deoxycholate and 3 days with liposomal amphotericin B). Antiretroviral therapy was initiated on day 10. After progressive clinical improvement and most laboratory test results returned to normal, the patient was discharged from the hospital with no need for dialysis and an early follow-up in the outpatient clinic of our hospital. Eight months after the discharge, he is fully active and able to perform all pre-hospitalization activities without restrictions. The recent laboratory results showed mild abnormality of kidney function (creatinine level = 1.3 mg/dL), CD4 count = 180 cells/mm3, and HIV-1 viral load < 40 copies/mL. In addition, the patient is maintaining regular use of darunavir/ritonavir, dolutegravir, lamivudine, prophylactic trimethoprim-sulfamethoxazole and itraconazole.