INTRODUCTION: IgG4 related sclerosing disease is an inflammatory and fibrosing disorder, characterized by lymphoplasmacytic inflammation with infiltration of various organs, including the pancreas, bile ducts, lung, kidney, and retroperitoneum. We report a case of a young woman with IgG4 related systemic sclerosing disease, who presents with dysphagia mimicking esophageal cancer and pulmonary infiltrates.
CASE PRESENTATION: A 31 year old previously healthy Dominican female was referred for further evaluation of a 3-month history of progressive dysphagia and weight loss. She was a nonsmoker and had no known tuberculosis exposure; her PPD status was unknown. Physical examination revealed a cachectic appearing young female, but was otherwise unremarkable. Barium swallow revealed mid-esophageal constriction. CT chest revealed a mid-esophageal mass below the level of carina, scattered nodular infiltrates in the right upper and right middle lobes, as well as calcified mediastinal lymph nodes. PET scan revealed FDG uptake in the esophageal mass (SUV 5.2), a dilated upper esophagus and mild FDG uptake in the pulmonary nodules (SUV ranging 2.0-4.0). Upper GI endoscopy revealed mid-esophageal constriction secondary to extrinsic compression; no endoluminal mass lesions were detected. Bronchoscopy with endobronchial ultrasound guided mediastinal lymph node biopsy was nondiagnostic. VATS lung biopsy of the right upper and right middle lobes was performed. Histopathology revealed multinodular lymphoplasmacytic infiltrates with bronchiolocentric distribution and distortion of alveolar structures by diffuse sclerosing inflammation. Prominent perivascular sclerosing inflammation was present, obliterating small to medium-sized vessels. Immunostaining revealed strong staining for IgG4 with mixed infiltrate of lymphocytes, plasma cells, histiocytes and neutrophils. PPD was negative. Urine Histoplasma antigen was negative. A complete metabolic profile and complete blood count were within normal limits. ACE level was within normal limits and a rheumatologic panel was negative. Total serum IgG was elevated (2280 mg/dl, normal 600-1500), as was the serum IgG4 level (414 mg/dl, normal 6-121), thereby confirming a diagnosis of IgG4 related sclerosing disease. Treatment with prednisone was initiated (1 mg/kg daily). After nearly two months of therapy, the patient’s dysphagia resolved. Radiographic imaging revealed a decrease in the size of the mediastinal mass, improvement in the pulmonary infiltrates and a decrease in serum IgG4 titers.
DISCUSSIONS: Originally implicated in causing autoimmune pancreatitis, IgG4 related sclerosing disease has since been implicated in inflammation involving multiple anatomic sites, including the lung, kidney, retroperitoneum, mediastinum, biliary tract, salivary and lacrimal glands (1). Solid nodules, ground glass opacities, alveolar interstitial and bronchovascular infiltration are four characteristic patterns of lung involvement, although pleural disease and mediastinal adenopathy have been observed; most patients have more than one pattern of involvement (2). Diagnosis is based on histopathologic findings of polyclonal lymphoplasmacytic infiltration along intrapulmonary connective tissue in the interstitium, interlobular septa and bronchovascular bundles, with strongly positive immunostains for IgG4. Total serum IgG and IgG4 levels are elevated. Alternative diagnoses, such as connective tissue disorders, must be excluded. In our patient, the esophageal mass was attributed to mediastinal adenopathy resulting in extrinsic esophageal compression, and the pulmonary infiltrates to IgG4 related interstitial lung disease. The disease is generally steroid-responsive, although cyclosporine has been used anecdotally in at least one case of steroid resistance.
CONCLUSION: IgG4 related sclerosing disease should be entertained in the differential diagnosis of individuals presenting with non-malignant causes of mediastinal adenopathy and/or pulmonary infiltrates, characterized by polyclonal lymphoplasmacytic inflammation.
DISCLOSURE: Pramod Krishnamurthy, No Financial Disclosure Information; No Product/Research Disclosure Information