Grand Rounds

Histoplasmosis in an Immunocompromised Child- How to Diagnose and Treat?

Dhruv Gandhi, Aditi Gupta, Ira Shah
Department of Pediatric Infectious Diseases, BJ Wadia Hospital for Children, Mumbai, India

Address for Correspondence: Dhruv Gandhi, 5B/13 Shyam Niwas, Breach Candy, Mumbai-400026, Maharashtra, India. Email: dhruvgandhi2610@gmail.com

Keywords: histoplasma, endemic mycoses, pediatric fungal infection, antifungal agents, azoles, voriconazole

Clinical Problem:
A 12-year-old boy, diagnosed with acute myeloid leukemia(AML) in February 2024, and on venetoclax and azacytidine therapy, presented to us in April 2024 with high-grade fever, wet cough, and loss of weight and appetite for 2 months. Non-contrast computerized tomography(NCCT) chest in February 2024 showed consolidation along the right mediastinal pleura, adjacent ground-glass opacities in the right upper lobe and two small nodules in the right lung, suggestive of fungal pneumonia. At our centre, he was initially admitted to the pediatric intensive care unit for the management of compensated septic shock and septic cardiomyopathy requiring inotropic support. He received intravenous antibiotics and voriconazole. During admission, he had an episode of violent coughing followed by blood-streaked sputum. Contrast-enhanced CT with angiography of the thorax showed an ill-defined and heterogeneously-enhancing mediastinal mass in the right paratracheal region. The mass was biopsied and the histopathological examination revealed an abscess with granulation tissue but no granulomas. Bacterial and fungal cultures of the biopsied tissue did not grow any organism. Xpert MTB/RIF of the biopsied tissue and serum interferon-gamma release assays were negative. Urinary histoplasma antigen was positive and serum ß-D-glucan levels were high (Table 1). He was started on liposomal amphotericin-B(L-AMB)(3mg/kg/day) for 2 weeks followed by oral voriconazole(Table 1). Urinary histoplasma antigen levels decreased in May 2024. NCCT thorax in May 2024 showed almost complete regression of the previously seen right paratracheal mass with subtle foci of fibroatelectatic changes.

Table 1. Investigations of the patient.

Investigations	March 2024	April 2024	May 2024	Reference Range
Hemoglobin (gm/dL)	-	9.9	11.6	11.5-15.5
White blood cell count (cells/cumm)	-	11210	12700	5000-13,000
Platelet count (106cells/cumm)	-	4.43	3.23	1.50-4.50
Voriconazole trough levels (µg/mL)	4.43	0.94	1.02	1-5.5
Urine histoplasma galactomannan (ng/mL)	-	1.3	1.06	<0.9

How to diagnose and treat histoplasmosis in an immunocompromised child?