Azathioprine used as treatment for chronic eosinophilic pneumonia and its implications

SESSION TITLE: Diffuse Lung Disease: The Tale of the Troublesome Eosinophil SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/09/2023 02:10 pm - 02:55 pm INTRODUCTION: Chronic eosinophilic pneumonia (CEP) is a rare disease characterized by infiltration of the lungs with eosinophils. This inflammation is likely dependent on the release of inflammatory mediators from T-cells, which regulate the movement of eosinophils, as in asthma. Traditionally, corticosteroids have been the main treatment for CEP. Azathioprine (AZA) is a purine analog that suppresses DNA synthesis and has been employed as an alternative corticosteroid for the treatment of various inflammatory diseases. While AZA has been used in other eosinophilic diseases, there is little precedent to guide therapy in patients with CEP. Because of the long-term side effects of corticosteroids, azathioprine may be an alternative to the chronic relapsing course of CEP. CASE PRESENTATION: A 42-year-old woman with history of tobacco use presented with dyspnea and sputum production after recently being prescribed steroids for similar symptoms. Symptoms recurred when tapering corticosteroids. Imaging showed bilateral ground glass opacities surrounded by crescent shape dense consolation predominately in the upper lobes, known as the atoll sign, suggestive of organizing pneumonia. She underwent bronchoscopy with transbronchial biopsy to further assess microdata which again showed organizing pneumonia with negative cytology. Given the broad differential still, she underwent video assisted thoracic surgery (VATS) to better assess the parenchyma. This VATS showed patchy airspace disease with fibrin, hyaline membranes, and granulation-like tissue with atypical pneumocytes and numerous eosinophils noted throughout. There were no signs of aspiration, vasculitis, or infection in the setting of fluctuating eosinophilic count. The pathology was interpreted to be most consistent with CEP. She was unable to tolerate the adverse effects of corticosteroids. As an alternative, azathioprine was initiated, resulting in significant remission of her symptoms and improved pulmonary function tests to normal at target dose of 100mg. She later tapered the AZA on her own and experienced a return of her symptoms. This relapse prompted re-initiation of therapy which again resolved her symptoms of dyspnea. DISCUSSION: Eosinophilic pneumonia is a complicated disease with standard- of- care that consists of long-term regimens of corticosteroids. However, current literature on eosinophilic pneumonia suggests that because of the complex nature of the pathways that are involved, many different pathways can potentially be targeted therapeutically. How AZA may work in CEP is unknown. Presumably, AZA may inhibit T-cell dependent pathways, limiting eosinophilic infiltration. Azathioprine has been used in other eosinophil-driven diseases, such as a case of eosinophilic myocarditis, with rapid improvement, along with treatment of a few cases of eosinophilic esophagitis with prolonged remission. Other avenues for decreasing the reliance upon long-term glucocorticoids include medications immunomodulators, like mepolizumab and omalizumab, targeting IL-5 and IgE respectively. Both agents have shown promising results in recorded cases. CONCLUSIONS: AZA may be effective in CEP. However, more research is needed to understand how agents such as AZA mechanistically limit pulmonary eosinophilia. Our experience, and the experience of others (Sathiyamoorthy, G. et al., 2017) in treating CEP with AZA may provide a strong rationale for routine use of agents such as AZA as an alternative to corticosteroids in CEP. REFERENCE #1: Jones, J., Hostler, D. and Hostler, J. (2019) "Beyond steroids: Mepolizumab for chronic eosinophilic pneumonia," Chest, 156(4). Available at: https://doi.org/10.1016/j.chest.2019.08.165. REFERENCE #2: Kaya, H. et al. (2012) "Omalizumab as a steroid-sparing agent in chronic eosinophilic pneumonia," Chest, 142(2), pp. 513–516. Available at: https://doi.org/10.1378/chest.11-1881. REFERENCE #3: Sathiyamoorthy, G. et al. (2017) "Steroid Dependent Chronic Eosinophilic Pneumonia Treated Successfully With Azathioprine; A Novel Therapy Reported On Two Patients". B42 Interstitial Lung Disease: A Potpourri of Cases: Thematic Poster Session. Am J Respir Crit Care Med 2017;195:A3444. www.atsjournals.org. DISCLOSURES: No relevant relationships by Rao Afzal No relevant relationships by Marvi Bukhari No relevant relationships by Daniel Kass No relevant relationships by Chelsea Meyer No relevant relationships by Chris Musgrove No relevant relationships by Salahuddin Nasir