Acute Exacerbation of Interstitial Lung Disease: A Case Series and a Narrative Literature Review

Acute exacerbation of interstitial lung disease (AE-ILD) represents sudden, severe deterioration in patients with pre-existing ILD and is associated with high morbidity and mortality. Our work presents a case series of AE-ILD in patients with idiopathic pulmonary fibrosis (IPF), idiopathic non-specific interstitial pneumonia (iNSIP), and connective tissue disease-associated ILD (CTD-ILD) managed at our institution and provides a narrative review of AE-ILD. Across cases, AE-ILD manifested as rapid progression of dyspnea and extensive ground-glass opacities (GGOs) on imaging, often triggered by infections or immune-mediated processes. Despite treatment, all cases were fatal, confirming that mortality remains high in AE-ILD. In our literature review, we focus on dysregulated innate immunity, an altered microbiome, potential microaspiration, surgical procedures, and autoantibody-mediated inflammation as triggers, as well as the risk factors for and prevalence of AE-ILD. We also examine pharmacological and non-pharmacological interventions, with particular emphasis on the role of antifibrotic agents as a key protective factor. Evidence for and against corticosteroid use in AE-IPF and non-IPF AE-ILD is discussed, highlighting the radically different treatment approach for AE in melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM)-associated ILD compared to AE-IPF. Our findings underscore the heterogeneous presentation and poor prognosis of AE-ILD, emphasizing the urgent need for standardized diagnostic criteria, risk stratification, and prospective studies with larger cohorts to establish evidence-based therapeutic strategies.