A 69-year-old Japanese woman was referred from a local hospital for left pleural effusion noted on a chest radiograph during a routine hospital visit. The patient had mild dyspnea and normal oxygenation without any other symptoms. She had smoked 10 cigarettes per day for 29 years but denied any occupational exposure to dust. She reported no history of allergy, tuberculous infection, or pancreatic or autoimmune disease.
On physical examination, she exhibited normal vital signs and peripheral oxygen saturation at room air. However, the left lung had decreased lung sounds on auscultation. Laboratory testing (Table 1) revealed a white blood cell count of 3800/muL with 65.5% polymorphonuclear leukocytes and 5.0% eosinophils. Chest radiography revealed moderate left pleural effusion (Fig. 1). The pleural fluid was drained via thoracentesis. It exhibited findings consistent with lymphocyte-dominant exudative pleural effusion, and the ADA level was elevated to 69.7 U/L (Table 2). Tuberculous pleurisy was suspected; however, the pleural fluid bacterial cultures and polymerase chain reaction (PCR) tests for tuberculosis and nontuberculous mycobacteria, and the interferon-gamma release test yielded negative findings. In addition, the rheumatoid factor, anti-cyclic citrullinated peptide antibodies, antinuclear antibody, and the analysis for tumor markers were negative. We excluded rheumatoid pleuritis, systemic lupus erythematosus, and carcinomatous pleurisy based on the clinical findings. Fluorodeoxyglucose (FDG) positron emission tomography imaging revealed FDG accumulation in the mediastinal and cervical lymph nodes (Fig. 2). Neither lymphadenopathy nor pleural thickening was detected on contrast-enhanced computed tomography of the neck to the pelvis (Fig. 3).
The culture positivity rate of the pleural fluid in tuberculous pleurisy is low. Based on the clinical findings, IgG4-RD and tuberculous pleurisy were suspected. However, distinguishing between IgG4-RD and tuberculous pleurisy is challenging since both the diseases are characterized by pleural effusion and high ADA levels. We ascertained that tissue diagnosis for definitive diagnosis was warranted for both tuberculous pleurisy and IgG4-related pleurisy; thus, thoracoscopy was conducted. The histological analysis revealed dense lymphocytic infiltrates and mild eosinophilic infiltrates with no malignancy or granuloma (Fig. 4A). Additional blood tests revealed a serum immunoglobulin G (IgG) level of 3065 mg/dL, IgG4 of 724 mg/dL, and serum immunoglobulin E level of 5309 mg/dL. Immunohistochemical staining revealed 286 IgG4-positive plasma cells/high-power field in the pleural membranes (Fig. 4B); the ratio of IgG4-to IgG-positive plasma cells (IgG4/IgG) was 46% (Fig. 4B and C), which met the diagnostic criteria for IgG4-RD. Hence, the patient was diagnosed with IgG4-related pleural effusion.
She was treated with prednisolone (PSL) at 40 mg/day (0.6 mg/kg/day), which achieved complete resolution of the pleural effusion. The responsiveness to PSL further supported the diagnosis of pleurisy secondary to IgG4-RD.