IgG4-Related Disease
Rheumatology · Other Rheumatologic Diseases · study mode — pick an answer, then reveal.
Question · easy
Which set of histopathologic findings best characterizes IgG4-related disease on tissue biopsy?
The hallmark pathology of IgG4-RD is identical across all affected organs: a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform (basket-weave) fibrosis, and obliterative phlebitis, with mild-to-moderate eosinophilia. Noncaseating granulomas suggest sarcoidosis; prominent neutrophilia, leukocytoclasis, granulomatous inflammation, giant cells, and fibrinoid necrosis all argue AGAINST IgG4-RD.
MKSAP 19 B.6 Ch.13; Harrison's 22e Ch.380
Question · easy
Which patient demographic is most typical for IgG4-related disease?
IgG4-RD characteristically affects middle-aged to elderly men (male-to-female ratio ~2:1), which contrasts with most classic autoimmune diseases that favor young women. The male predominance is even stronger for pancreatic, renal, and retroperitoneal disease, while head-and-neck (orbital, salivary, lacrimal) disease approaches a 1:1 ratio.
Harrison's 22e Ch.380
Question · medium
A patient has strongly suggestive multiorgan IgG4-related disease, yet serum IgG4 measured by nephelometry returns normal. Which is the best interpretation and next step?
Nephelometry can produce a spuriously low (even normal) IgG4 result via the prozone effect when concentrations are extremely high — precisely the subset at greatest risk for multiorgan disease and end-organ injury. Dilution corrects it. Note also that ~30% of biopsy-proven cases are genuinely seronegative, so a normal IgG4 never excludes the diagnosis, but in a strongly suggestive multiorgan case the prozone effect must be ruled out.
Harrison's 22e Ch.380
Question · medium
What is the first-line therapy for active, organ-threatening IgG4-related disease?
Glucocorticoids are first-line, typically prednisone ~40 mg/day (or moderate-to-high dose for ~4 weeks) followed by a slow taper; the response is usually swift and striking. Rituximab is an excellent second-line for relapsing or glucocorticoid-resistant disease, azathioprine is a glucocorticoid-sparing agent, and surgery is reserved for specific complications (e.g., a mass jeopardizing an organ).
MKSAP 19 B.6 Ch.13; Harrison's 22e Ch.380
Question · hard
Which statement best describes the B-cell–targeted therapy inebilizumab in IgG4-related disease?
Inebilizumab depletes CD19+ B cells; the phase 3 MITIGATE trial showed an 87% reduction in flare risk (HR 0.13), and in April 2025 it became the first and only FDA-approved therapy for IgG4-RD. The bifunctional, non-depleting CD19/FcγRIIb mechanism describes obexelimab (INDIGO trial). Rituximab is the anti-CD20 agent, and IL-1β blockade pertains to autoinflammatory disease.
Stone, N Engl J Med 2025;392:1168-1177 (MITIGATE); Amgen FDA approval, April 2025