Isolated Renal Aspergillosis as a Breakthrough Infection After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation

To the Editors: Invasive aspergillosis (IA) in immunocompromised children most frequently involves the lungs and paranasal sinuses. Isolated renal aspergillosis is exceptionally rare and is usually described as part of disseminated disease.1–3 We report a pediatric case of primary renal aspergillosis presenting as a breakthrough invasive fungal infection during liposomal amphotericin B (L-AmB) prophylaxis after hematopoietic stem cell transplantation. A 10-year-old boy with relapsed T-cell lymphoma underwent allogeneic hematopoietic stem cell transplantation from a matched sibling donor. After transplantation, he developed relapsed acute lymphoblastic leukemia and received intensive chemotherapy. During a period of prolonged and profound neutropenia, he was receiving prophylaxis with L-AmB, ciprofloxacin and trimethoprim–sulfamethoxazole. He presented with febrile neutropenia without focal findings on physical examination. Blood and urine cultures were sterile, and cytomegalovirus polymerase chain reaction was negative. Because serum galactomannan (GM) antigen was elevated (optical density index 3.97), voriconazole therapy was initiated. Subsequently, thoracic computed tomography (CT), paranasal sinus CT and cerebral magnetic resonance imaging were performed and revealed no evidence of IA. Abdominal ultrasonography obtained during this diagnostic workup demonstrated a 15 mm × 15 mm hypoechoic lesion in the posterior middle portion of the right renal parenchyma. Fever resolved within 4 days after initiation of voriconazole. Abdominal magnetic resonance imaging showed a hypovascular lesion with diffusion restriction extending to the perirenal space, consistent with a perinephric abscess. Percutaneous drainage was performed, and histopathologic examination of sterile material revealed septated, acute-angle branching fungal hyphae compatible with Aspergillus species; cultures remained negative. Because of rising GM levels and lack of radiologic regression, amphotericin B deoxycholate was added to voriconazole. Despite combined antifungal therapy, the lesion enlarged on follow-up abdominal CT (Fig. 1A). Surgical excision was therefore performed. Intraoperatively, a 2 cm × 3 cm necrotic white mass involving the right renal parenchyma and adjacent tissues was identified (Fig. 1B). Histochemical staining with Grocott methenamine silver and periodic acid–Schiff confirmed Aspergillus spp. GM antigenemia became negative within 10 days after surgery, and antifungal therapy was continued with voriconazole alone. No recurrent renal lesions were detected on follow-up imaging.FIGURE 1.: A, Coronal contrast-enhanced computed tomography (CT) scan showing well-demarcated lesion, 27 mm × 26 mm × 24 mm in size and observed as a hypodense collection. B, Surgical specimen after excision.Although only a limited number of pediatric cases of isolated renal aspergillosis have been reported, none, to our knowledge, have been described as breakthrough infections during liposomal amphotericin B prophylaxis.4 This feature makes our case unique and clinically relevant. Additionally, while serum GM has high sensitivity in neutropenic patients with pulmonary IA, its performance in extrapulmonary disease is not well defined.2 In our patient, GM antigenemia correlated with disease activity and response to treatment. Breakthrough IA during L-AmB prophylaxis may be related to host factors and antifungal pharmacokinetics.5 Liposomal formulations reduce nephrotoxicity by lowering renal tissue concentrations of amphotericin B, which may paradoxically predispose susceptible patients to renal fungal infection.6 This case highlights that renal aspergillosis should be considered in immunocompromised children with persistent fever and positive fungal biomarkers, even in the absence of pulmonary disease.