A 72-year-old woman was referred to our hospital for evaluation of left pleural effusion of unknown origin. She had a history of bronchial asthma with noteworthy findings in her family history, including autoimmune diseases and tuberculosis. She reported never smoking or drinking. She had general fatigue for 6 months and had reported left dominant pleural effusion to her previous doctor; however, the cause of pleural effusion was unclear.
On physical examination, her temperature was 37.0  C, blood pressure was 149/92 mmHg, and pulse was 110 beats per minute. Percutaneous arterial oxygen saturation (SpO2) was 93% on room air. Her right axillary lymph node was palpable. Lung sounds were diminished in the left lung, without the presence of piping rale. Laboratory analysis showed that the erythrocyte sedimentation rate was elevated to 118 mm/h and serum IgG level was 5310 mg/dL, including IgG4 > 1500 mg/dL. Both rheumatoid factor and antinuclear antibody were negative. Analyses of tumor markers and the interferon-gamma release test revealed negative findings (Table 1). Chest radiograph showed left pleural effusion (Fig. 1a). Neck to pelvis computed tomography (CT) revealed swelling of the mediastinal and inguinal lymph nodes as well as left pleural effusion with local pleural thickness (Fig. 1b). Fluorodeoxyglucose (FDG) positron emission tomography imaging showed accumulation of FDG in the mediastinal lymph node, left inguinal lymph node, and left pleura (Fig. 1c).
Thoracentesis showed lymphocyte-dominant exudative pleural effusion with a high level of ADA. Culture and polymerase chain reaction analyses of pleural effusion were performed to assess the presence of tuberculosis and nontuberculous mycobacteria. Both tests were negative (Table 2).
We suspected the possibility of IgG4-RD based on clinical findings and the elevated level of serum IgG4. However, we needed to confirm the pathological diagnosis and exclude tuberculous pleurisy with elevated ADA in unilateral pleural effusion. Therefore, we performed surgical biopsies of the pleura and left inguinal lymph node (Fig. 2). Histological analysis of the biopsies revealed dense lymphocyte and plasmacyte infiltration accompanied by fibrosis. Immunohistochemical analysis showed that a large number of IgG4+ cells (50 cells or more per high-power field) were found in the pleural membrane and inguinal lymph node; the IgG4+/IgG+ cell ratio exceeded 40%, which met the diagnostic criteria for IgG4-RD. Thus, we diagnosed the patient with definite IgG4-RD with pleural effusion and inguinal lymph node swelling.
We then considered initiation of corticosteroid therapy; however, pleural effusion decreased without intervention, and dyspnea improved during the active surveillance period (Fig. 3a). The serum IgG/IgG4 levels gradually decreased (Fig. 3b) and the swelling of the mediastinum and inguinal lymph nodes also subsided (Fig. 3c). Therefore, we continued surveillance of the patient without administration of any drug; there has been neither obvious regrowth nor development of malignant disease for >4 years.