A previously healthy 11-year-old girl presented with 8 days of fever, night sweats, and subjective weight loss. Her fevers occurred every 12 hours and reached a maximum of 39.4 C. Additional symptoms included headaches, dizziness, nausea, intermittent right-sided abdominal pain, and anorexia. The patient also reported an intermittently pruritic rash on her arms. She had no respiratory symptoms, emesis, or diarrhea.
Past medical history was significant for multiple episodes of bronchiolitis requiring hospitalization before age 2, varicella with severe mucosal involvement requiring hospitalization for nasogastric feeding at age 4, and hepatitis A at age 7. Growth and neurologic development were normal. The patient was born in Central America and immigrated to the U.S. 4 years prior. Exposure history was significant for consumption of unpasteurized cow milk while in Central America. A maternal uncle had been recently diagnosed with tuberculosis, but the patient had not had contact with him for more than 4 years. There was no other significant family history.
Physical exam revealed a thin female (weight 33.1 kg, 22% for age; body mass index 15.5 kg/m2, 16%) with enlarged, mobile, nontender cervical lymph nodes bilaterally but no palpable axillary or inguinal lymph nodes. There were small erythematous papules on the flexor surface of her left antecubital fossa and right first metacarpophalangeal joint. She had mild abdominal tenderness most significant in the right upper quadrant, but no hepatosplenomegaly or mass.
Laboratory values at admission on day of illness (DOI) 9 were notable for leukopenia, anemia, and mildly elevated C-reactive protein (CRP) (Figure 1). The erythrocyte sedimentation rate was greater than 145 mm/hr. Aspartate and alanine aminotransferase were elevated. Cerebrospinal fluid (CSF) analysis showed no leukocytes and normal protein and glucose. A fourth-generation antigen-antibody test was positive for antibodies to HIV-1. HIV RNA PCR demonstrated 294,000 copies/mL in peripheral blood and 504 copies/mL in CSF; initial CD4 T-lymphocyte count was 52 cells/mm3.
Computed tomography scan demonstrated innumerable small nodules throughout the bilateral lungs and lymphadenopathy in the cervical, axillary, hilar, mediastinal, and retroperitoneal regions. The largest nodal conglomerate in the retroperitoneum measured 4.4 cm (Figure 2). Pathology of a bone marrow biopsy demonstrated hypocellularity and noncaseating granulomas. Lymph node biopsy revealed plasmacytosis and increased histiocytes with no evidence of malignancy. Acid-fast bacillus, Fite, and methenamine silver stains were negative in both tissues. Bronchoscopy revealed no significant airway edema or erythema, and no secretions. Evaluation for tuberculosis (TB) and non-TB mycobacterial infections was negative, including QuantiFERON-TB Gold, mycobacterial cultures, and/or TB PCR from sputum, bronchoalveolar lavage (BAL) fluid, lymph node tissue, blood, stool, and/or CSF. Serum antibodies to Toxoplasma gondii, Treponema pallidum, Brucella species, Coccidioides immitis, and Histoplasma capsulatum were negative. However, urine and serum H. capsulatum antigens were positive with values greater than the upper limits of quantification. Ultimately, H. capsulatum grew in fungal cultures from blood, BAL fluid, and lymph node tissue.
Treatment was initiated with liposomal amphotericin B (5 mg/kg/day) on DOI 24. ART consisting of dolutegravir and emtricitabine-tenofovir alafenamide was begun on DOI 26. The patient began to feel subjectively better and appetite improved, but spiking fevers up to 42 C persisted until DOI 37. Hospital course was complicated by pancytopenia thought to be secondary to disseminated fungal infection, acute kidney injury attributed to liposomal amphotericin B, and liver enzyme elevation that was likely multifactorial. Per hospital protocol, the acute kidney injury was monitored with daily weights, serum creatinine measurements, and strict documentation of intakes and outputs. Oral itraconazole (10 mg/kg/day) was initiated on DOI 36 given improving fevers and decreasing CRP and serum H. capsulatum antigen. Liposomal amphotericin B was discontinued on DOI 46. Throughout the course of treatment, serum itraconazole and dolutegravir were monitored to ensure therapeutic levels were obtained. At discharge on DOI 47, the patient's CD4 T-cell count had improved to 215 cells/mm3 and HIV RNA PCR had decreased to 127 copies/mL.