A40-24 When Air Leaks a Clue: Pneumothorax Revealing Vascular Ehlers-Danlos Syndrome

Abstract Introduction Vascular Ehlers-Danlos syndrome (vEDS) is a rare heritable connective tissue disorder caused by pathogenic variants in COL3A1, leading to fragility of vessels and hollow organs. Pulmonary manifestations are uncommon and often precede recognition of systemic disease. We describe an adult case of recurrent pneumothorax and cavitary parenchymal lesions ultimately diagnosed as vEDS. Case Report A 25-year-old man with no smoking or substance history initially presented with hemoptysis from Streptococcus anginosus and Haemophilus influenzae pneumonia, complicated by warm autoimmune hemolytic anemia requiring prolonged corticosteroids. After transient improvement, he developed recurrent cough and hemoptysis, and serial computed tomography (CT) scans revealed new cavitary and nodular opacities. In October 2024 he was found to have a left pneumothorax and underwent video-assisted thoracoscopic surgery (VATS) with talc pleurodesis; pathology demonstrated emphysematous bullae and prior rupture. Two months later he was readmitted with a right pneumothorax and underwent right-sided VATS with wedge resection. Histopathology showed organizing pneumonia with fibrotic scarring and features of prior intra-alveolar hemorrhage. Comprehensive autoimmune and infectious evaluations were negative, including antineutrophil cytoplasmic antibodies, α1-antitrypsin, HIV, and immunoglobulin studies. Given the disproportionate parenchymal destruction and recurrent spontaneous pneumothoraces, he was referred to medical genetics. A 92-gene connective tissue panel identified a pathogenic COL3A1 variant, confirming vascular Ehlers-Danlos syndrome. Upon further evaluation, family history revealed multiple vascular events including venous thrombosis, splenic rupture, and aneurysms in maternal relatives, supporting the diagnosis. Discussion Pulmonary complications of vEDS are rare but can mimic interstitial or vasculitic lung disease. Recurrent pneumothorax and parenchymal injury may reflect underlying vascular fragility, and recognition of this association is essential to avoid unnecessary or high-risk interventions. Early genetic diagnosis allows tailored management and counseling for potentially life-threatening vascular complications. Conclusion Recurrent pneumothoraces and organizing parenchymal lesions in a young nonsmoker should raise suspicion for vascular Ehlers-Danlos syndrome, even in the absence of classic systemic features. Awareness of this presentation may facilitate earlier genetic testing and avoidance of high-risk procedures in this fragile population. This abstract is funded by: None