IgG4-related disease

Immunoglobulin G4-related disease is a rare immune-mediated systemic fibro-inflammatory condition characterised by a mass and/or thickening of the involved organ systems. The diagnosis remains challenging and requires a combination of clinical findings, serology, imaging and histological evaluation with cross-speciality input. Classification criteria have been developed with a high specificity to distinguish IgG4-related disease from disease mimics, which are essential for clinical trial design. Disease associations include occupational exposures and atopic/allergic history. Treatment dampens inflammation and shrinks masses/thickening, although relapse remains common on tapering or discontinuation of immunosuppression. Progressive fibrosclerotic disease with organ damage and failure, and an increased risk of malignancy are recognized outcomes. Our knowledge and understanding of the disease pathogenesis has expanded rapidly, leading to the discovery of circulating biomarkers that correlate with disease activity and relapse. A number of novel targeted agents are in the clinical pipeline to allow a precision medicine approach and top-down therapy.