IgG4-RD is an uncommon immune-mediated disorder that can cause fibroinflammatory lesions in nearly any organ 7. The mean age at onset was 50.3 ± 14.9 years and the majority of patients were men (60.8%) 8. Intrathoracic lesions in patients with IgG4-RD include bronchial thickening, nodules, ground glass shadow, pleural thickening/effusion, lymphadenectasis and retromediastinal fibrosis. Yunyun Fei et al.  found that only 4/87(4.6%) patients present pleural effusion in IgG4-RD patients with intrathoracic involvement. However, Kasashima et al. has shown that pleural effusion may be the main manifestation of IgG4 related pleural lesions. They reported that 6/8 (75%) patients with IgG4-related pleural lesion had pleural effusion.
At present, the pathogenesis of IgG4-RD is not clear. Previous studies show immune-mediated mechanisms triggered by autoimmune and infectious factors may contribute to the fibroinflammatory process. Type 2 helper T cells and Tregs overexpress cytokines including interleukins (IL-4, IL-5, IL-10, and IL-13) and transforming growth factor β, promoting eosinophilia and leading to increased serum IgG4 and IgE, and progression of fibrosis 10. Eosinophilia in IgG4-RD is generally viewed as an integral part of the clinical feature. One observational study found that IgG4-pleural effusion patients have potential allergic diseases 6. This patient also had a history of chronic urticaria and present elevated serum IgE level and eosinophil counts in pleural fluid and serum. However, Zhang et al.  found that eosinophilia appeared independent of allergies in IgG4-RD. The causes of eosinophilia in IgG4-RD are not clear at present. Previous studies suggested that eosinophilia was probably induced by a process inherent to IgG4-RD immune response itself. There was homology between human carbonic anhydrase II and the α-carbonic anhydrase of Helicobacter pylori, and between the plasminogen-binding protein of H. pylori and the ubiquitin-protein ligase E3 component n-recognin 2 expressed in pancreatic acinar cells 12. These innate immune responses against microbial antigens may be associated with the eosinophilia in IgG4-RD.
This elderly patient showed unilateral EPE as the main manifestation, and was highly suspected of malignancy. However, the previous study found that malignant pleural effusion usually present lower (< or = 40%) pleural fluid eosinophil percentage 13. And there was no evidence of tumor by FDG-PET/CT and cytological examination of pleural effusion. Collagen-vascular disease related interstitial pneumonia is another usual cause of unilateral pleural effusion. The patient had no rash, arthralgia or other symptoms. Positive antinuclear antibody alone was not specific for the diagnosis of collagen vascular disease. Although IgG4-RD is an important cause of reactive or secondary eosinophilia, IgG4-related pleural effusion in previous cases was dominated by lymphocytes 14. However, the proportion of eosinophils predominated in pleural fluid in our patient. IgG4-RD should be considered in the differential diagnosis of EPE in future.
The diagnosis of IgG4-RD depends on the typical pathology features including the lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, obliterative phlebitis and increased numbers of IgG4+ plasma cells 15. However, either storiform fibrosis or obliterative phlebitis may not be a prominent feature in IgG4-related pleural lesions 16. Clinicopathological correlation is needed when pleural effusion is the only manifestation of the disease. Elevated serum IgG4 (XX135 mg/dl) was once considered to be a diagnostic marker of the disease, but serum concentrations of this immunoglobulin are normal in up to 40% of patients with biopsy-proven IgG4-related disease 15. Some researchers noticed that pleural effusion IgG4 levels were even higher than serum IgG4 levels in 5/9 patients (56%) . Murataet et al.  reported that 12 of 35 (34%) patients with unknown pleural effusions were found to have marked IgG4-positive plasma cell infiltration in the pleura and confirmed that effusion IgG4 levels were significantly higher in the IgG4+ group than in the IgG4− group (median 54 versus 27 mg/dl, P < 0.01). High effusion IgG4 concentration may be an indication of IgG4-related pleural lesions.
In summary, IgG4-RD is a rare cause of unexplained eosinophilic pleural effusion. Clinicians should be alert to the possibility of IgG4-related pleural effusion in the elderly in condition of excluding other reasons carefully.