IgG4-related pleural effusion with high adenosine deaminase levels: A case report and literature review

Abstract

Rationale: Levels of pleural fluid adenosine deaminase (ADA), a useful marker for the diagnosis of tuberculous pleurisy, are elevated in some reports of immunoglobulin G4 (IgG4)-related pleural effusion. We describe a patient with IgG4-related pleural effusion who exhibited a high concentration of ADA. Furthermore, we reviewed the literature to compare patients with IgG4-related pleural effusion and tuberculous pleurisy.

Patient concerns: A 75-year-old male patient had dyspnea for 1 month with a left pleural effusion that was exudative, lymphocyte dominant. The pleural fluid test results revealed a total protein (TP) concentration of 6.60 g/dl, a lactate dehydrogenase (LDH) level of 383 IU/dl, and an ADA concentration of 54.5 U/L. An interferon gamma release assay showed a negative result.

Diagnoses: Histological analysis of the thoracoscopic pleural biopsy revealed lymphoplasmacytic infiltration, with 80 IgG4-positive plasma cells/high-power field, and an IgG4/IgG ratio of approximately 40% to 50%. Other diseases were ruled out based on symptoms, negative autoimmune antigen results, and histopathologic findings. Thus, he was diagnosed with IgG4-related pleural effusion.

Interventions: He received 15 mg of prednisolone as therapy.

Outcomes: His pleural effusion and symptoms improved gradually within several months, and prednisolone was tapered to 6 mg daily.

Lessons: It is important to distinguish between IgG4-related pleural effusion and tuberculous pleurisy. Therefore, we compared 22 patients with IgG4-related pleural effusion from PubMed and the Japan Medical Abstracts Society to 40 patients with tuberculous pleurisy at Fukujuji Hospital from January 2017 to May 2019. According to thoracentesis findings, 14 of 18 patients with IgG4-related pleural effusion had high ADA more than 40 U/L. The pleural effusion of patients with IgG4-related pleural effusion showed higher TP levels (P < .001) and lower LDH (P < .001) and ADA levels (P = .002) than those with tuberculous pleurisy. Moreover, the pleural fluid ADA/TP ratio was a good predictor for differentiating IgG4-related pleural effusion and tuberculous pleurisy (area under the receiver operating characteristic curve of 0.909; 95% confidence level: 0.824-0.994).

Figure 1

A chest radiograph showing left pleural effusion.

Figure 2

A chest high-resolution computed tomography scan. Chest CT showed a moderate amount of left pleural effusion, peripheral consolidation with interlobular septal thickening in mainly the bilateral upper lobe, emphysema, and swelling of the mediastinal lymph nodes.

Figure 3

Histological findings of the thoracoscopic left pleural biopsy. The left parietal pleural biopsy specimens revealed the presence of dense collagenous fibrosis with lymphoplasmacytic and plasma cell infiltration without storiform fibrosis and obstructive phlebitis. It did not show malignancy, granuloma, or lymphoid follicles. Based on immunohistochemical staining, 80 IgG4-positive plasma cells/high-power field and an IgG4/IgG ratio of approximately 40% to 50% were obtained. A: Hematoxylin–eosin (H&E) staining × 100, B: H&E staining × 200 C: Immunohistochemical staining for IgG × 400, D: Immunohistochemical staining for IgG4 × 400.

Figure 4

The area under the receiver operating characteristic curve of the pleural fluid ADA/TP ratio for differentiating between IgG4-related pleural effusion and tuberculous pleurisy. The area under the curve was 0.909 (95% CI: 0.824–0.994). The predictive accuracy at the cut-off value was less than 15 points, with a sensitivity of 93.8%, specificity of 72.5%, and odds ratio of 36.8 (95% CI: 4.7–1702.4). CI = confidence interval.