A Rare Case of Disseminated Entomophthoromycosis in an Adolescent Boy Presenting as Mediastinal Mass

To the Editors: Entomophthoromycosis (EM) is an uncommon but emerging fungal infection in the pediatric age group, affecting even immunocompetent hosts. We hereby report a healthy adolescent boy with respiratory and gastrointestinal symptoms who poses a significant challenge in diagnosis and management. A 15-year-old boy presented with fever, breathlessness and abdominal pain for 2 months. There was associated chest pain, easy fatigability and persistent vomiting. No history of skin rash or B-symptoms was present. At admission, he was febrile, pale with tachypnea and requiring high-flow oxygen support. Systemic examination showed right-side decreased air entry and hepatosplenomegaly. The hemogram showed microcytic anemia (7.1 g/dL), leukocytosis (38,720/μL), eosinophilic predominance (3820/μL) and thrombocytopenia 58,000/μL. Renal and liver function tests and angiotensin-converting enzyme levels were normal. Chest radiograph showed mediastinal widening with right middle and lower zone consolidation. Bone marrow examination demonstrated thrombocytopenia and eosinophilia. Blood, bone marrow and pleural fluid cultures were sterile. Serum IgE was elevated (4630 IU/L). Urine for histoplasmosis antigen, Brucella serology and autoimmune workup were negative. Computed tomography revealed multifocal lung consolidation and multiple conglomerated mediastinal nodes. There were multiple lesions in the liver, spleen, adrenal gland, stomach and large bowel loops with conglomerated abdominal nodes (Fig. 1). Bronchoalveolar lavage culture was sterile. Biopsy from mediastinal station 4R node and liver revealed periodic acid-Schiff-positive, broad, pauci-septate hyphae with wide-angle branching, possibly invasive zygomycetes fungi. However, cultures were negative. The child was given liposomal amphotericin B for 2 weeks, followed by posaconazole. Genetic analysis was unremarkable.FIGURE 1.: Dual-phase contrast-enhanced computed tomography (CECT) scan. A: Axial and (B) sagittal images in the arterial phase show a large hypoenhancing lesion in the mediastinum causing significant compression of the superior vena cava (SVC, white arrow in B) and arch of azygous with the formation of multiple collaterals. Focal hepatic hot spot sign (black arrow in A and B) is seen in segment IV as increased enhancement in the arterial phase due to SVC obstruction and portosystemic shunts between SVC and left portal vein via internal mammary and paraumbilical vein collaterals. C: In coronal image of abdomen (venous phase), few left subdiaphragmatic, pericolonic (yellow arrows) necrotic lesions are seen along with significant colonic wall thickening (red arrows), ascites, right pleural effusion. D: Axial image (venous phase) depicts a peripherally enhancing centrally necrotic round lesion in segment VI of liver (purple arrow) along with significant gastric wall thickening (green arrow).Even after 3 months of posaconazole, he had progressive weight loss, abdominal pain and vomiting. Investigations revealed elevated eosinophils (3320/μL) and serum IgE (5413 IU/mL). Routine biochemical tests were within normal limits. Magnetic resonance imaging of the chest showed resolving lung and mediastinal lesions. However, the abdomen showed gastric outlet obstruction with newer lesions in jejunal and ileal loops (Figure, Supplemental Digital Content 1, https://links.lww.com/INF/G129). Histopathology of the ultrasound-guided pyloric biopsy revealed fungi with Splendore-Hoeppli phenomenon, consistent with entomophthoromycosis. He was given liposomal amphotericin B for 2 weeks, followed by a combination of itraconazole and cotrimoxazole therapy for 6 months. Repeat imaging after 6 months showed an excellent response to treatment (Figure, Supplemental Digital Content 2, https://links.lww.com/INF/G130). EM, a slow-growing fungal infection belonging to phylum Entomophthorales, includes 2 genera, Basidiobolus (subcutaneous/systemic dissemination) and Conidiobolus (rhino-facial). The incidence is sporadic; with only 460 cases reported globally. The disseminated forms are usually less than 20 years old, with a male/female ratio of 3:1. The modes of transmission include trauma, local inoculation, aero-digestive route, or insect bite.1 Systemic EM is often mislabeled for malignancy or chronic granulomatous infections/inflammation. The presence of the Splendore-Hoeppli phenomenon, characteristic fungal hyphae and absence of vascular invasion are specific to EM.2 A definitive diagnosis of EM can be made only by culture or molecular typing. However, fungal hyphae are often damaged during biopsy or processing and hence positive in only 15%–20%. Prolonged systemic antifungal therapy is the keystone in treatment. Potassium iodide is the most commonly used agent in subcutaneous form.3 Though voriconazole and posaconazole have been successfully used, itraconazole therapy for 3–6 months is the first-line agent with proven clinical efficacy.4,5 Prognosis is usually excellent, with fatality noted in immunocompromised or resistant cases.1 Our case highlights an uncommon cause of mediastinal mass, later diagnosed as EM, ultimately requiring a combination of antifungals.