Anti-MDA5-associated rapidly progressive interstitial lung disease in clinically amyopathic dermatomyositis with secondary invasive pulmonary Aspergillus flavus infection after aggressive immunosuppressive therapy: a case report

Abstract

Anti-melanoma differentiation-associated gene 5 (MDA5) positive rapidly progressive interstitial lung disease (RP-ILD) with clinically amyopathic dermatomyositis (CADM) is a life-threatening condition. Prompt initiation of immunosuppressive therapy is crucial for improving outcomes. However, such treatment strategies substantially increase the risk of opportunistic infections, including invasive pulmonary aspergillosis (IPA), even in patients without typical risk factors. A 59-year-old previously healthy woman reported a four-month history of progressive dyspnea, dry cough, and hoarseness, initially treated as pneumonia without clinical improvement. On admission, the patient presented with tachypnea, hypoxemia, bilateral crackles, and Gottron papules but no muscle weakness. High-resolution computed tomography (HRCT) suggested organizing pneumonia, and serological testing revealed strongly positive anti-MDA5 antibodies, raising suspicion for RP-ILD associated with CADM. Bronchoalveolar lavage fluid culture grew Aspergillus flavus , which was considered colonization due to non-specific imaging and absence of typical risk factors. From day 7 to day 9 after admission, the patient’s condition deteriorated rapidly, with progressive respiratory failure accompanied by a marked hyperinflammatory state. Follow-up HRCT demonstrated worsening ground-glass opacities, consolidations, and traction bronchiectasis. A diagnosis of RP-ILD associated with CADM and positive anti-MDA5 antibodies was established. Aggressive triple immunosuppressive therapy was promptly initiated, including pulse methylprednisolone, cyclophosphamide, and mycophenolate mofetil. Subsequently, the patient developed fever and a positive serum galactomannan assay, raising a strong suspicion of IPA. Combination antifungal therapy with amphotericin B lipid complex and voriconazole was administered. Despite these interventions, respiratory failure continued to worsen, necessitating mechanical ventilation. The patient died on day 17 of hospitalization due to acute respiratory distress syndrome and septic shock. This case highlights the dual challenge of managing anti-MDA5-associated RP-ILD and recognizing opportunistic infections during intensive immunosuppression. IPA may occur as a life-threatening complication caused by A. flavus , even in the absence of classical risk factors or typical radiological features, leading to delayed diagnosis. Routine screening for IPA using serum or bronchoalveolar lavage galactomannan should be considered in patients undergoing potent immunosuppressive therapy.