IgG4-RD is a recently described disorder that involves lymphoplasmacytic infiltrates causing fibrotic and tumor-like lesions that can affect multiple organ systems . IgG4 elevation in association with autoimmune pancreatitis was first recognized in 2001 . In 2003, the term systemic IgG4-related disease was proposed . Before its recognition as a unified disease, the different organ manifestations of this disorder had been presumed to be unrelated, single-organ disorders [4–7].
Despite RA not being considered an IgG4-RD, several studies have investigated the role of serum IgG4 in RA. It was found that serum IgG4 levels were higher in RA patients compared to healthy population . A few studies have demonstrated that serum IgG4 level was elevated in a subset of RA patients [9–11]. Furthermore, it was suggested that elevated serum IgG4 levels may be associated with a specific clinical phenotype of RA, which is characterized by higher disease activity, higher level of autoantibodies, and poor response to Methotrexate and Leflunomide therapy . However, there is no clear association between RA and increased risk of developing IgG4-RD.
Pulmonary involvement of IgG4-RD was first described in 2004 [13, 14]. Subsequently, several case reports have demonstrated that the lungs are a common target organ of IgG4-RD, with a highly variable clinical and radiological manifestations [15–17].
Since the clinical and radiological manifestations of IgG4-RD are highly variable and nonspecific, establishing the diagnosis of IgG4-RD requires a high index of suspicion. In most cases, tissue biopsy with histopathologic examination usually provides strong evidence for the diagnosis of IgG4-RD [18, 19]. Biopsies typically reveal lymphoplasmacytic tissue infiltration of IgG4-positive plasma call and lymphocytes, accompanied by fibrosis that has storiform features. However, histopathological findings are not diagnostic alone and must be interpreted in the context of clinical, serologic, and radiologic data. Similarly, serum IgG4 levels are a significant aid in diagnosis, but are neither sensitive nor specific for IgG4-RD. Ryu and colleagues  identified 3,300 patients who had IgG subclass testing done, less than one-fifth of these patients manifested evidence for IgG4-RD. As a result, the diagnosis of IgG4-RD cannot be predicted entirely based on a single finding and a collaborative approach between clinicians, radiologists, and pathologists is needed to arrive at a definite diagnosis.
Because of its recent recognition, international guidelines for the diagnosis, management, and treatment of IgG4-RD are limited. In 2011, Japanese experts have proposed comprehensive diagnostic criteria for this disease . The Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and proposed the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD .
In 2019, the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) formulated the 2019 ACR/EULAR IgG4-RD Classification Criteria for international use .
The optimal treatment for IgG4-RD has not been established. Majority of the literature regarding treatment of IgG4-RD is focused upon treatment modalities for type 1 autoimmune pancreatitis. The mainstay treatment for IgG4-RD is glucocorticoids. A prednisone dose of 0.6 mg/kg (or 30-40 mg) once daily has been suggested to treat active disease. Lung involvement tends to respond favorably to prednisone treatment and improvement is noticed in both symptoms as well as imaging . Immunosuppressive agents like Rituximab, Azathioprine, or Mycophenolate can be utilized in patients who do not respond to glucocorticoids monotherapy or cannot be tapered to less than 5 mg daily, and in patients with contraindications to glucocorticoids. Regarding maintenance therapy, it is unclear whether IgG4-RD patients should receive maintenance therapy. The introduction of maintenance therapy is beneficial in patients who are at increased risk for relapse (e.g., multiorgan involvement) and in patients with recurrent disease. A low-dose glucocorticoid or glucocorticoid-sparing agent can act as maintenance therapy . Additional studies are needed to define the duration of maintenance therapy.
The long-term prognosis of IgG4-RLD is uncertain. A favorable response to corticosteroid therapy is typical. However, relapses are common following discontinuation of therapy.