The evolution of invasive pulmonary aspergillosis on chest imaging in response to antifungal therapy

A 78-year-old man presented with 1-month symptoms of dyspnoea and non-productive cough. He was initially diagnosed with biopsy-confirmed ulcerative colitis on a colonoscopy about 4-month ago. He was treated with intravenous methylprednisolone without any clinical improvement and required intravenous infliximab for remission. He was eventually discharged on an oral prednisone taper regimen and scheduled infliximab infusion. His tuberculin skin test was negative before the initiation of infliximab. Laboratory workup involving complete blood count and comprehensive metabolic panel (CMP) were within normal limits. His chest imaging (figure 1A) on admission revealed diffuse, bilateral nodular lesions, with halo signs. Empirical antifungal therapy of intravenous voriconazole was initiated due to concerns of invasive pulmonary aspergillosis (IPA). Infectious workup, including serum beta-D-glucan and galactomannan, returned negative. Bronchoscopy with transbronchial biopsy was performed (figure 2) that revealed numerous slender and septate hyphae branching at acute angles with tissue invasion on H&E and Grocott methenamine silver stain consistent with IPA. His infliximab was held, and he was cautiously tapered off his oral prednisone. After 3 weeks of voriconazole therapy, he reported progressive dyspnoea and found to have elevated liver enzymes on CMP, despite voriconazole trough levels consistently maintained at a therapeutic level of 1.0-5.5 μg/mL. Repeat chest imaging (figure 1B) revealed progressive enlargement of known diffuse nodular lesions with the development of cavitary lesions and new appearing nodular lesions, concerning for failure of voriconazole therapy in the setting drug-related hepatotoxicity. A decision was made to transition to isavuconazonium sulfate therapy. Repeat chest imaging in 3 weeks (figure 1C) demonstrated the stability of multiple mass-like cavitary lesions where some have regressed in size without new appearing nodular lesions. He continued to improve clinically with serial chest imaging (figure 1D,E), showing regression of his known IPA-related lung lesions. He suffered from no drug-related adverse events and eventually transitioned to oral isavuconazonium sulfate therapy to complete a total 9-month duration of antifungal therapy as an outpatient. © 2021 BMJ Publishing Group. All rights reserved.