Omar, A.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is commonly seen in immunocompromised patients. Telomere biology disorder (TBD), which is a genetic disorder marked by mutations in telomere-maintenance genes, leading to shortened telomere, accelerated aging, and multi-systems effects including the pulmonary and immune systems. Idiopathic pulmonary fibrosis (IPF) is the most common pulmonary manifestation in TBD. Opportunistic infections, such as PJP, occurring de novo are rare in TBD, presenting unique diagnostic and therapeutic challenges. Case Presentation We present a female in her seventies with chronic dry cough and exertional dyspnea referred for evaluation of interstitial lung disease (ILD). Her family history revealed early-onset pulmonary fibrosis in her mother and sister. A year before the presentation, she developed acute hypoxic respiratory failure with bilateral pulmonary infiltrates. Bronchoalveolar lavage confirmed PJP despite no established immunosuppression. She received Bactrim and prednisone without clinical improvement. High-resolution chest CT revealed progressive infiltrates and fibrotic lung disease. Surgical lung biopsy showed organizing pneumonia, diffuse alveolar damage, and fibrosis, consistent with probable usual interstitial pneumonia (UIP). Ultimately, she developed rapidly progressive ILD. Further evaluation ruled out autoimmune and connective tissue disease. Telomere studies confirmed TBD, with her lymphocyte and granulocyte telomere lengths between the 1st and 10th percentiles. (figure1) Genetic testing is underway for familial pulmonary fibrosis. Discussion This case illustrates a rare presentation of PJP de novo in a patient with TBD, highlighting opportunistic infections risk in those patients without immunosuppression and before transplantation. TBD results in quantitative and qualitative T-cell immunodeficiency, reducing CD4+ T-cell count, predisposing to opportunistic infections, including PJP. TBD patients often experience a rapidly progressive course of ILD due to inherited telomere dysfunction causing limited regenerative capacity of Alveolar epithelial type 2 cells (AEC2s) exacerbated by environmental or age-related factors such as oxidative stress or smoking. Management requires a multidisciplinary approach with early genetic testing, antifibrotic therapies, and prophylactic treatments to prevent infections. This case underscores the importance of considering TBD in patients with opportunistic infections like PJP in the absence of traditional immunosuppressive risk factor and in patients with premature or progressive pulmonary fibrosis. Conclusion Telomere biology disorder can present with rapidly progressive ILD with atypical infections like PJP while on immunosuppression. To the best of our knowledge de novo PJP pneumonia in patient with TBD is unreported in the literature. High clinical suspicion, quantitative CD4 evaluation and consideration of PJP prophylaxis prevent an otherwise fatal outcome. Figure1: