Abstract Introduction Childhood interstitial lung disease (ILD) is challenging and includes genetic, environmental and immune-mediated etiologies. We present a pediatric case of telomere biology disorder presenting with ILD and exacerbated by hypersensitivity pneumonitis (HP) underscoring the value of considering telomere biology disorders as an etiology for pediatric ILD and the importance of evaluation for factors that can accelerate its progression. Case Description An 11-year-old male with a two-year history of a chronic cough, dyspnea and weight loss presented with progressive respiratory symptoms unresponsive to standard asthma therapy. He appeared thin, tachypneic with suprasternal retractions, and diffuse bilateral coarse crackles. His nails were thickened and irregular, raising concern for dyskeratosis congenita; however, previous genetic testing was negative. Initial evaluation revealed elevated immunoglobulins, and a positive ANA 1:40. Positive family history of sarcoidosis but the patient’s ACE level was normal. Sweat chloride was normal (10, 11 mmol/L) with a heterozygous pathogenic CFTR variant. Echocardiogram showed mild pulmonary artery dilation without pulmonary hypertension. Rheumatologic evaluation was unremarkable for autoimmune disease.Spirometry demonstrated a severe restrictive pattern, and a six-minute walk test showed desaturations to 86% by minute 2. HP panel was positive for mold antigens and bird fancier’s testing was positive for parakeet and parrot antigens. Chest CT showed progressive interstitial and airway-centered disease with mediastinal lymphadenopathy. Bronchoscopy was negative for eosinophils and neutrophils with sterile cultures. A left lung biopsy demonstrated lymphohistiocytic and granulomatous pneumonitis with early septal fibrosis and bronchiolectasis. Findings suggestive of HP. Due to trachonychia and ILD, telomere length testing was obtained and confirmed shortened peripheral blood telomeres, consistent with a telomere biology disorder. Pulse steroid therapy initiated with clinical improvement. Discussion This case describes a telomere biology disorder presenting with childhood ILD and exacerbated by HP. Telomere shortening is seen in patients with both familial and sporadic ILD and predisposes to exaggerated or persistent fibrotic responses following antigen exposure. Recognizing the combination of shortened telomere length and environmental factors in the absence of a detectable telomere genetic abnormality with its association and progression of ILD can facilitate an earlier diagnosis and start of management. Additionally, we highlight the value of close attention to extrapulmonary features to suggest a possible telomeropathy such as nail dystrophy in our patient. Telomeropathies may adversely affect the response to immunosuppression, by increasing the risk of bone marrow suppression and infections. Future studies to better identify this relationship would guide routes of monitoring and treatment. This abstract is funded by: None
Tekeli et al. (Fri,) studied this question.