Abstract Pulmonary lymphangiectasia (PL) is a rare pediatric condition with limited therapeutic options and variable clinical presentations. We report a novel case of recurrent respiratory failure with viral illnesses diagnosed with PL with a gene mutation in EGFR.A 3-year-old male presented with a history of chronic wet cough, wheeze and choking with feeds since 5-months-old. At 6 months, he was found to aspirate on video feeding swallow study (VFSS). Despite laryngeal cleft injection and repair, he was admitted to the PICU 4 times due to acute hypoxemic respiratory failure with viral infections over the next 18 months, including one intubation. He did not respond to oral steroids, short acting beta agonists, or inhaled corticosteroids. Clinical examination was significant for bilateral crackles that worsened with illness and never resolving when well. He did not have digital clubbing and never required oxygen outside of illness. Flexible and rigid bronchoscopy showed normal anatomy with copious secretions, and his bronchoavleolar lavage demonstrated 65% neutrophils, 26% macrophages, and 3% lymphocytes. Work up included a negative sweat chloride test, and normal echocardiogram and immune function. CT chest showed scattered subsegmental atelectasis, mosaic attenuation, and peribronchial thickening without evidence of bronchiectasis. Ground glass opacities on CT were never in the traditional pattern for NEHI. Invitae genetic testing panels for primary immune deficiency and neonatal respiratory distress revealed heterozygous variants of unknown significance (VUS) in COPA, NOTCH 2, ABCA3 and SH3BP2 genes. Interferon signatures performed on a research basis were negative. Lung biopsy demonstrated lymphangiectasia, including blood in lymphatics, pulmonary edema, muscularized lymphatics, and an increased presence of neuroendocrine cell bodies (Figure 1). Genetic analysis of the lung tissue identified a mutation in EGFR (c.2305GA) and VUS in BAP1, NOTCH2, and POLE. MR lymphangiogram showed normal lymphatics in the chest, abdomen, and pelvis. At 30 months, sirolimus was initiated, and he has since experienced two respiratory illnesses without requiring supplemental oxygen. Twice daily furosemide has also been used with increased crackles.PL is a rare diagnosis that relies on clinical and CT findings, lung biopsy, and genetics. His lung biopsy demonstrated PL and MR lymphangiogram lacked diffuse lymphatic disease. Genetic analysis of the lung tissue revealed a mutation in the EGFR gene, which has been linked with PL. EGFR is known to activate the mTOR pathway, promoting cell proliferation and growth, suggesting that sirolimus, an mTOR inhibitor, may reduce lymphatic tissue growth and improve long-term outcomes. This abstract is funded by: None
Saad et al. (Fri,) studied this question.