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

Abstract

© BMJ Publishing Group Limited 2021. No commercial reuse. See rights and permissions. Published by BMJ. DESCRIPTION A 78yearold man presented with 1month symptoms of dyspnoea and nonproductive cough. He was initially diagnosed with biopsyconfirmed ulcerative colitis on a colonoscopy about 4month 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 betaDglucan 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 drugrelated hepatotoxicity. A decision was made to transition to isavuconazonium sulfate therapy. Repeat chest imaging in 3 weeks (figure 1C) demonstrated the stability of multiple masslike 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 IPArelated lung lesions. He suffered from no drugrelated adverse events and eventually transitioned to oral isavuconazonium sulfate therapy to complete a total 9month duration of antifungal therapy as an outpatient. In the early stages of IPA, radiographic imaging will display nodules, consolidations, halo signs and wedgeshaped infarcts. Halo sign is defined radiologically as areas of groundglass opacities (GGO) with surrounding nodules representing pulmonary infarct surrounded by alveolar haemorrhage from tissue invasion and occlusion of small and mediumsized pulmonary arteries by Aspergillus species on histopathology. Halo sign is commonly seen within the first 2 weeks of IPA infection in up to 61% of patients regardless of immunodeficiency status. 4 CT imaging may demonstrate GGO/consolidation surrounding the initial nodule as local inflammation