A42-21 Beyond Tobacco: Inhaled Heroin as a Possible Cofactor in the Pathogenesis of Pulmonary Langerhans Cell Histiocytosis

Abstract Introduction Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung disease characterized by cystic and nodular changes due to accumulation of CD1a- and S100-positive Langerhans cells in the small airways and lung parenchyma. These cells are monoclonal and often harbor the BRAF V600E mutation, indicating features of a myeloid neoplasm. The disease primarily affects smokers, where inhaled toxins initiate airway inflammation and cytokine-driven immune activation. Alveolar macrophages and epithelial cells release TNF-α and GM-CSF, which promote Langerhans cell recruitment and proliferation in peribronchiolar regions. The ensuing cellular infiltrate and immune response cause tissue destruction, cyst formation, and fibrosis. Although tobacco exposure is the most established trigger, similar mechanisms may be induced by other inhaled substances. We report a case of biopsy-confirmed PLCH in a woman with a history of inhaled heroin use, suggesting heroin vapor or its adulterants as possible cofactors in disease pathogenesis. Case Report A 47-year-old woman with type 2 diabetes, hypertension, and prior heroin use disorder presented with three days of sharp left-sided chest pain and new-onset leg pain. She reported exertional dyspnea but denied cough or hemoptysis. Chest imaging revealed bilateral interstitial opacities with upper-lobe-predominant cystic and fibrotic changes, mild hilar lymphadenopathy, and a small left pneumothorax. Bone scintigraphy demonstrated focal uptake in the right fourth rib. Bronchoscopy was unremarkable. Surgical lung biopsy showed histiocytes, hemosiderin-laden macrophages, rare eosinophils, and fibrosis. Immunohistochemistry was positive for CD68, S100, CD1a, and cyclin D1, confirming PLCH. She was treated with a prednisone taper and trimethoprim-sulfamethoxazole prophylaxis, with symptomatic improvement despite continued tobacco use. Discussion PLCH represents a molecularly driven inflammatory disorder in which inhaled agents activate alveolar macrophages and epithelial cells, inducing cytokine release and subsequent Langerhans cell proliferation. These monoclonal cells, often bearing BRAF V600E mutations, contribute to airway remodeling and parenchymal damage. While cigarette smoke remains the primary etiologic factor, heroin vapor may provoke comparable oxidative and inflammatory stress responses. Adulterants mixed with heroin could act as antigens or chemical irritants, amplifying macrophage-mediated cytokine cascades and promoting peribronchiolar injury. Though evidence is limited to isolated case reports, this association highlights a plausible molecular link between heroin inhalation and PLCH. Smoking cessation remains the cornerstone of management, but recognition and elimination of all inhaled exposures, including illicit substances, are crucial for disease stabilization and improved outcomes. This abstract is funded by: None