A40-22 Targeted Treatment of Erdheim Chester Disease Associated Interstitial Lung Disease

Abstract Introduction Erdheim Chester Disease (ECD) is a rare histiocytic disorder characterized by xanthomatous infiltration of tissues by CD68 positive, CD1A and S100 negative, foamy histiocytes. ECD can involve multiple organ systems with the cardinal manifestations being sclerotic lesions in long bones, perinephric inflammation, aortic sheath encasement, and central nervous system involvement. While other histiocytic neoplasms like Langerhans cell histiocytosis (LCH) are known to cause interstitial lung disease (ILD), the association with ECD is not well described and the treatment paradigm of ECD associated ILD is not well established. Case Description A 79-year-old male with past medical history of hypertension, coronary artery disease, obstructive sleep apnea, and atrial fibrillation presented with several months of progressive dyspnea on exertion. The patient did not smoke cigarettes and had no other relevant exposures to inhaled antigens. CT chest revealed diffuse nodular ground glass opacities and septal thickening. Laboratory work up was negative for autoimmune serologies. The patient underwent surgical lung biopsy which demonstrated that the lesional infiltrate was composed of plump histiocytes within a fibrotic background involving the lung in a lymphatic distribution, including subpleural regions, interlobular septae, and extending around the bronchovascular areas. Immunohistochemical studies confirmed the histiocytes to be positive for CD163, CD14, Factor 13a, cyclin D1 and negative for CD1a, Langerin, CD21, CD23, and CD35, consistent with the diagnosis of ECD. Droplet digital PCR testing of the lung tissue confirmed the presence of BRAF V600E mutation. The patient started treatment with low dose cobimetinib. Following treatment, the patient noticed substantial improvement in symptoms along with improvement on chest radiology and reduction in FDG avidity on PET scan. Discussion ECD is a monogenic inflammatory myeloid neoplasm driven by mutations causing activation of the mitogen activating protein kinase (MAPK) pathway. The discovery of these driver mutations has led to the testing and FDA approval of targeted therapies such as BRAF and MEK inhibitors to treat ECD. Our case demonstrates successful radiological and clinical response to targeted treatment with MEK inhibition in ECD associated ILD and highlights the need to maintain a high index of clinical suspicion for ECD when evaluating patients with ILD. This abstract is funded by: None