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Q1: A painless pancreatic mass in an older man (2 min)
A 68-year-old man presents with painless obstructive jaundice and a diffusely enlarged, sausage-shaped pancreas on CT. Take us through your diagnostic reasoning. Cover the prototypic manifestation: type 1 (IgG4-related) autoimmune pancreatitis, the older-male phenotype, the characteristic imaging (diffuse enlargement with a capsule-like rim, rather than a discrete vascularly invasive mass), the markedly raised serum IgG4, and the tendency to other-organ involvement (submandibular sialadenitis, retroperitoneal fibrosis, renal lesions). State the cardinal rule: IgG4-RD mimics malignancy, so biopsy for histology and cytology before resection. Distinguish it from type 2 AIP (younger patients, inflammatory bowel disease association, neutrophilic duct-centric histology, IgG4-negative) and from pancreatic adenocarcinoma (discrete mass, vascular invasion, malignant cells on biopsy).
Q2: Histology and diagnostic criteria (2 min)
What is the gold-standard diagnostic test and how is the diagnosis formalised? Cover the histology trio — storiform (cartwheel) fibrosis, obliterative phlebitis (veins destroyed, arteries spared), and a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells. Reproduce the 2020 revised comprehensive diagnostic (RCD) criteria: organ enlargement/mass, serum IgG4 above 135 mg/dL, and histology with an IgG4+/IgG+ plasma-cell ratio above 40 percent and more than 10 IgG4-positive cells per high-power field — definite requires all three. Mention the parallel 2019 ACR/EULAR classification criteria (entry criterion, exclusion criteria, domain score of 20 or more). Emphasise that serum IgG4 is supportive, not diagnostic: it is normal in 30 to 40 percent of biopsy-proven cases and can rise in pancreatic cancer.
Q3: Pathophysiology — defend the mechanism (3 min)
Walk us through the immunopathology of IgG4-related disease. Cover: an aberrant immune response to an unknown allergen/antigen in a Th2-biased older host; clonally expanded CD4-positive cytotoxic T lymphocytes (CD4 CTLs) as the dominant effector, secreting IFN-gamma, IL-1beta, IL-5, IL-13 with a Th2 skew (IL-4, IL-5, IL-13, IL-10); the B-cell/plasma-cell axis with class-switched IgG4-positive plasma cells infiltrating tissue; the pivotal point that IgG4 is a 'blocking' antibody that fixes complement poorly and is a down-regulatory bystander (explaining why serum IgG4 correlates imperfectly with activity); and the profibrotic TGF-beta driving storiform fibrosis and obliterative phlebitis that produces the mass-like, duct-compressing lesions. Tie each mechanism to a clinical consequence (biliary obstruction, ureteric entrapment, aortic aneurysm).
Q4: Management and the relapse problem (2 min)
How do you treat IgG4-related disease? Cover the dramatic response to glucocorticoids — prednisolone 30 to 40 mg daily for 2 to 4 weeks then a taper over 3 to 6 months, with mass shrinkage and resolution of obstruction. Cover the principle of treating organ-threatening, symptomatic or relapsing disease while observing mild, asymptomatic, isolated disease. Cover relapse (common on withdrawal, up to about half of patients) and the preferred first-line steroid-sparing agent — rituximab (anti-CD20, B-cell depletion) for relapsing, steroid-dependent or organ-threatening disease, with conventional DMARDs (azathioprine, mycophenolate, methotrexate) as weaker alternatives. Add damage prevention (relieve obstruction early with stenting), bone protection and PJP prophylaxis for prolonged steroids, and vaccination before rituximab.
Q5: Differentials and pitfalls (1 min)
How do you distinguish IgG4-RD from its key mimics? Cover malignancy (pancreatic adenocarcinoma, cholangiocarcinoma — tissue diagnosis before resection); Sjogren syndrome versus Mikulicz/IgG4 sialadenitis (women, sicca, anti-Ro/La, lymphocytic sialadenitis versus older men, painless gland enlargement, IgG4-rich, anti-Ro/La negative); primary sclerosing cholangitis versus IgG4-related sclerosing cholangitis (younger men with IBD, beaded multifocal strictures, normal IgG4, no steroid response versus raised IgG4, other-organ involvement, dramatic steroid response); sarcoidosis (non-caseating granulomas, raised ACE, hilar nodes); and lymphoma (clonal cells on biopsy). State the two cardinal pitfalls: relying on serum IgG4 alone, and operating on a mass without biopsy.