IgG4-related disease

Lore & Background

IgG4-related disease was formerly known as IgG4-related systemic disease. It is a chronic inflammatory condition marked by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, various degrees of fibrosis, and a usually prompt response to oral steroids.

In approximately 51–70% of people, serum IgG4 concentrations are elevated during an acute phase. The disease is relapsing-remitting and tends to form mass-like, tissue-destructive lesions in multiple sites, with a characteristic histopathological appearance wherever involved. Inflammation and connective tissue deposition can lead to organ dysfunction, organ failure, or death if not treated.

Reader's Guide

IgG4-related disease is significant because it unifies several previously distinct conditions—such as type 1 autoimmune pancreatitis, Mikulicz's disease, Küttner's tumor, and retroperitoneal fibrosis—under a single diagnostic framework. Its hallmark histopathological features include a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Diagnosis requires tissue biopsy, comprehensive history, and physical examination. Serum IgG4 levels above 135 mg/dL are an evolving diagnostic criterion but are not always elevated.

Treatment with glucocorticoids often produces rapid improvement, though relapses are common. Steroid-sparing agents like rituximab, azathioprine, methotrexate, and cyclophosphamide are used, but evidence for their efficacy beyond glucocorticoids is limited. Early detection is crucial to prevent irreversible organ damage.

Did You Know?

• IgG4-RD can involve any site in the body, including the heart, esophagus, adrenal gland, ovary, and synovium.
• Relapses are common, and higher baseline serum IgG4, IgE, and blood eosinophil counts are independently predictive of relapse risk after rituximab treatment.