Abstract Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with a heterogeneous course, often complicated by overlapping features of other fibrotic lung diseases. In complex cases, fibrosis may be frequently attributed to a presumed exposure or comorbidity; however, ongoing disease progression despite standard therapy should prompt evaluation for alternative etiologies. We present a case of IPF ultimately linked to a telomere biology disorder, highlighting the importance of comprehensive assessment in atypical or rapidly progressive disease. Description A 61-year-old man with severe psoriasis on long-term methotrexate, type 2 diabetes, hypertension, severe obstructive sleep apnea, and cutaneous latent tuberculosis presented with one year of progressive exertional dyspnea. Initial high-resolution CT (HRCT) demonstrated subpleural fibrosis, traction bronchiectasis, ground-glass opacities, and focal honeycombing predominantly in the left upper lobe. Pulmonary function testing showed moderate restriction with reduced diffusion capacity for carbon monoxide (DLCO). Rheumatologic workup was negative, and ILD was initially attributed to chronic hypersensitivity pneumonitis from methotrexate and occupational carpentry exposure. Despite initiation of mycophenolate therapy and discontinuation of methotrexate, his lung function rapidly declined with a 13% reduction in FVC over less than two years, along with development of hypoxia that required up to 8L supplemental oxygen on exertion. During lung transplant evaluation, telomere testing prompted by early hair graying and multiple dental fractures revealed short telomere syndrome, prompting reclassification of his IPF as secondary to telomere dysfunction. Mycophenolate was discontinued, nintedanib was initiated, and he subsequently underwent a successful lung transplantation. Discussion The diagnostic landscape of fibrotic interstitial lung disease continues to evolve with the recognition of molecular and genetic contributors, including telomere biology disorders. In this patient, initial attribution to methotrexate toxicity was reasonable given his exposure history. However, the rapid decline in lung function and the presence of syndromic features, such as early hair graying and multiple dental fractures, prompted further evaluation. Telomere biology disorders, resulting from pathogenic variants in telomere maintenance genes or critically short telomere length, are now recognized as important contributors to both familial and sporadic IPF, often associated with accelerated progression, multisystem involvement, and poor prognosis. Identification of these clinical clues and incorporation of telomere testing were pivotal in shifting the diagnosis and guiding management. This case underscores the importance of maintaining diagnostic vigilance in progressive fibrotic lung disease and illustrates how thorough clinical and diagnostic assessment can uncover rare but clinically significant causes of IPF. This abstract is funded by: None
Umra et al. (Fri,) studied this question.