Immunoglobulin-Related Disease (IgG4-RD) is an immune-mediated condition that can cause fibro-inflammatory lesions in nearly any organ (Wallace et al., 2019). It is a chronic, fibrotic inflammation characterized by the involvement of multiple organs. The most common manifestations of the disease include swelling of salivary and lacrimal glands, lymphadenopathy, and type 1 autoimmune pancreatitis (AIP) (Xie et al., 2020).
Other organs, such as lung, bronchi, kidney, retroperitoneum, thyroid, heart, mesenterium, meninges, and skin, can also be involved and the cause remains unknown (Xie et al., 2020). Other organs, such as lung, bronchi, kidney, retroperitoneum, thyroid, heart, mesenterium, meninges, and skin, can also be involved (Xie et al., 2020). Patients may present with involvement isolated to a single organ or with multiple organs involved at the same time. In untreated patients, manifestations in different organs may accumulate over time in a pattern that is termed “metachronous” (Wallace et al., 2019).
The diagnosis of IgG4-RD requires a careful consideration of all available data, including the history, physical examination, laboratory results, imaging findings, and pathology (Wallace et al., 2019). The patient’s medical history can also be useful when it suggests previous complications (e.g., autoimmune pancreatitis, tubulointerstitial nephritis) likely related to what was unrecognized IgG4-RD at the time (Wallace et al., 2019). Cross-sectional imaging of the chest and the abdomen/pelvis can reveal asymptomatic disease in a distribution that supports a diagnosis of IgG4-RD (Wallace et al., 2019). In the case of suspected pancreato-hepatobiliary disease, magnetic resonance cholangiopancreatography (MRCP) may be useful for diagnosing IgG4-RD and ruling out alternative etiologies (Wallace et al., 2019). Patients with significantly elevated serum IgG4 concentrations (e.g., > 3x the upper limit of normal) are more likely to have multi-organ disease and cross-sectional imaging may be higher yield in these patients (Wallace et al., 2019).
In the chest, the differential includes sarcoidosis, ANCA-associated vasculitis, Sjögren’s syndrome, lymphoma and primary/metastatic lung cancer, Erdheim-Chester Disease infections (including bacterial infections as well as atypical mycobacterial or fungal infections), and myofibroblastic tumor (Wallace et al., 2019). The most commonly used laboratory test to evaluate for IgG4-RD is the serum IgG4 concentration (Wallace et al., 2019). Other laboratory anomalies commonly observed in IgG4 are elevations of other IgG subclasses as well as elevations of IgEOther laboratory anomalies commonly observed in IgG4 are elevations of other IgG subclasses (Wallace et al., 2019).
Nearly all patients with IgG4-RD should be treated with immunosuppression to prevent accrual of additional organ involvement and damage in affected organs (Wallace et al., 2019). The goal of initial management is to achieve a complete remission (Wallace et al., 2019). Glucocorticoids have been the mainstay of treatment for IgG4-RD because of their efficacy as well as affordability and are typically used first-line with equivalent prednisone doses ranging from 20mg to 60mg/day depending on the severity of the presentation (Wallace et al., 2019). The general practice is to begin a slow taper of glucocorticoids after two to four weeks of therapy with the goal of discontinuation by three months, sometimes sooner (Wallace et al., 2019). During this period, the patient should be monitored for flares of disease which are common, especially at lower doses and following discontinuation (Wallace et al., 2019).