Adult-Onset Telomere Biology Disorder Associated With Interstitial Lung Disease and Pneumocystis jirovecii Infection

Adult-onset telomere biology disorders (TBDs) are increasingly recognized as underdiagnosed causes of progressive pulmonary disease and immune vulnerability. This study describes the clinical presentation, diagnostic evaluation, and outcomes of patients presenting in adulthood with TBD-associated interstitial lung disease (ILD) complicated by Pneumocystis jirovecii infection. A retrospective analysis was conducted on adult patients exhibiting unexplained fibrotic ILD alongside recurrent or opportunistic infections. Telomere length assessment and genetic screening for pathogenic variants in telomere maintenance genes were performed. Patients demonstrated markedly shortened telomeres for age and carried mutations in key telomere-related genes. Clinically, individuals presented with progressive dyspnea, radiologic patterns consistent with fibrotic ILD, and increased susceptibility to P. jirovecii pneumonia, often in the absence of classical immunosuppression. The coexistence of impaired telomere maintenance and immune dysfunction appeared to exacerbate pulmonary decline and increase the risk of infection. Early recognition of TBDs in adults with atypical ILD and opportunistic infections is critical for appropriate management, including tailored immunosuppressive strategies and consideration of antifibrotic or transplant pathways. This study underscores the importance of integrating telomere biology into the diagnostic framework of complex pulmonary and infectious presentations.