Praxis Medical Insights

Clinical Presentation and Diagnosis

The American Gastroenterological Association recommends that IgG4-related disease (IgG4-RD) should be suspected in patients with obstructive jaundice (77% of cases in one series) and often associated with pancreatic involvement (91% of jaundice cases) 1
Elevated serum IgG4 levels are found in 50-80% of patients, but cannot be relied upon for making a definite diagnosis, according to the American College of Gastroenterology 1
An IgG4/IgG1 ratio >0.24 may improve specificity in distinguishing IgG4-SC from PSC (primary sclerosing cholangitis), as suggested by the European Association for the Study of the Liver 1
Serum IgG4 >4x upper limit of normal appears highly specific for IgG4-SC, according to the American Association for the Study of Liver Diseases 1

A pathological diagnosis should be pursued in cases of suspected IgG4-RD, as this allows distinction from disease mimics including PSC and cholangiocarcinoma, recommends the World Gastroenterology Organisation 1, 2
Key histopathological findings include >10 IgG4-positive plasma cells per high power field in affected tissues, and IgG4+/IgG+ plasma cell ratio >40%, as defined by the International Consensus Statement on IgG4-RD 1, 2
Primary sclerosing cholangitis (PSC) can be differentiated from IgG4-SC by a higher prevalence of inflammatory bowel disease in PSC (70%) vs. IgG4-SC (5.6%), according to the European Crohn’s and Colitis Organisation 3

Glucocorticoids are the first-line treatment and are usually efficacious, with a characteristic feature of IgG4-RD being prompt clinical and radiographic response to steroid treatment, unlike PSC which typically does not respond to steroids, as stated by the American College of Rheumatology 3
Relapse may occur in >40% of cases after initial response, and B-cell depletion with rituximab is effective in steroid-resistant disease or as a steroid-sparing agent for relapsing disease, according to the European League Against Rheumatism 3