IgG4-Related Lung Disease Presenting as Chronic Cough

Introduction: IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory process characterized by infiltration of plasma cells with IgG4 in target organs and involvement of adaptive and innate immune systems. Here, we report the case of IgG4-related lung disease (IgG4-RLD) in a patient complaining of eighteen months of chronic cough. Case: A 67-year-old female non-smoker with a past medical history of atrial fibrillation, Systemic Lupus Erythematosus, and triple-negative left breast invasive ductal carcinoma (status post lumpectomy and chemoradiation therapy (CRT)) presented to a pulmonologist eighteen months prior for chronic cough. She reported worse symptoms with forward bending and recumbent positions. She was not on chemotherapy-induced pulmonary fibrosis agents or angiotensin-converting enzyme inhibitors. The cough began before CRT and she denied any history of recurrent respiratory and sinus infections. ENT evaluation revealed mild laryngopharyngeal reflux with suggestion of upper airway cough syndrome. She was started on empiric pantoprazole, nasal ipratropium and steroids, but without relief. Rheumatological workup showed speckled ANA antibody 1:80, positive beta-2 glycoprotein IgA/IgM antibody, negative p-ANCA and c-ANCA, and mildly elevated erythrocyte sedimentation rate. A pulmonary function test was performed and did not reveal an obstructive pattern. She also received a CT chest study that remarkably showed a 23x11 mm right lower lobe (RLL) nodule (Figure 1A), which was followed by a CT-guided lung biopsy with results suspicious for low-grade epithelial neoplasm, favoring sclerosing pneumocytoma. She then underwent a video-assisted thoracoscopic surgery procedure of the RLL consistent with nodular IgG4-RLD with 58% IgG4/IgG ratio of plasma cells and 6 IgG4+ cells/high powered field (Figure 1B-D). Discussion: IgG4- RD is an autoimmune disorder with histological manifestations presenting as lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis and variable tissue eosinophilia. About 75% of cases are reported in elderly males, however, the actual prevalence is unknown due to recent recognition and lack of awareness. While clinicians commonly refer to IgG4-RLD guidelines as summarized in Figure 1E, no specific diagnostic test exists, thereby making it important to exclude other etiologies (malignancy, Multicentric Castleman's disease, Rosai-Dorfman disease, Granulomatosis with polyangiitis, and Microscopic polyangiitis). Characteristic lung involvement includes nodules, ground glass opacities, alveolar and interstitial lung disease, and bronchovascular bundle thickening. The mainstay of IgG4-RLD treatment is with corticosteroids, however, bortezomib and cyclosporine have been used for recurrent disease along with rituximab as a steroid alternative. This case uniquely highlights a female patient with a single identified lung nodule as IgG4-RLD after cautiously ruling out other etiologies.