Current and future advances in practice: IgG4-related disease

IgG4-related disease (IgG4-RD) is an increasingly recognized cause of fibroinflammatory lesions in patients of diverse racial and ethnic backgrounds and is associated with an increased risk of death. The aetiology of IgG4-RD is incompletely understood, but evidence to date suggests that B and T cells are important players in pathogenesis, both of which are key targets of ongoing drug development programmes. The diagnosis of IgG4-RD requires clinicopathological correlation because there is no highly specific or sensitive test. Glucocorticoids are highly effective, but their use is limited by toxicity, highlighting the need for studies investigating the efficacy of glucocorticoid-sparing agents. B cell-targeted therapies, particularly rituximab, have demonstrated benefit, but no randomized clinical trials have evaluated their efficacy. If untreated or under-treated, IgG4-RD can cause irreversible organ damage, hence close monitoring and consideration for long-term immunosuppression is warranted in certain cases. IgG4-related disease (IgG4-RD) can affect nearly any organ and cause masses or inflammatory lesions. Common sites of disease include the salivary glands, lacrimal glands, orbit, pancreas, biliary tract, lungs and retroperitoneum. IgG4-RD has been increasingly recognized over the last 20 years and described in patients of diverse racial and ethnic backgrounds. It is associated with an increased risk of death. The cause of IgG4-RD is unknown, but several aspects of the immune system, including B cells and T cells, are thought to contribute to the disease and might be important targets for new treatments. To diagnose IgG4-RD, one must consider the history, physical examination, laboratory results, imaging and pathology findings. Elevated IgG4 levels in the blood and significant numbers of IgG4+ plasma cells in the tissue are not specific to the diagnosis of IgG4-RD but can support a diagnosis in the right clinical setting. IgG4-RD can lead to organ damage if it is not treated, but there are effective treatments, including steroids. Given that steroids can cause significant side effects, a number of trials are evaluating the potential role of steroid-sparing drugs. The optimal approach to treatment is still being defined, and ongoing clinical trials will help to address this knowledge gap.