musculoskeletal and connective tissue disorders
IgG4 Related Disease
Pathophysiology of IgG4 Related Disease
The clinical manifestations of IgG4-RD are usually tumor-like masses or organ enlargement, which result from dense tissue infiltration by immune cells and expansion of the extra-cellular matrix. One or more organs are affected; the 11 organs considered typical of IgG4-RD include the pancreas, bile ducts, lacrimal glands, orbital tissues, salivary glands, lungs, kidneys, retroperitoneal tissues, aorta, meninges, and thyroid gland. Most patients have multiorgan involvement at the time of diagnosis but tend to have one dominant phenotype. One study identified approximately equal proportions of the following clinical phenotypes ( Pathophysiology reference ). Pancreatic involvement commonly manifests as autoimmune pancreatitis (type 1, IgG4-related) and may take the form of An obstructive pancreatic mass, with painless jaundice and diffuse pancreatic enlargement Acute Pancreatitis with abdominal pain and nausea Smoldering and insidious Chronic Pancreatitis with pancreatic atrophy, exocrine pancreatic insufficiency, and/or overt diabetes mellitus IgG4-related Sclerosing Cholangitis can occur, usually in patients who also have autoimmune pancreatitis. This combination is highly suggestive of IgG4-RD. IgG4-RD likely accounts for most cases of idiopathic retroperitoneal fibrosis. Fibrosis is usually circumferential around the aorta (periaortitis) or over only the anterolateral portion. Fibrosis may extend inferiorly to the iliac vessels. The main complication is ureteral compression causing hydronephrosis. IgG4-RD can also cause noninfectious Aortitis of either the thoracic or abdominal aorta, which is distinguished from retroperitoneal fibrosis by the presence of circumferential mural aortic wall thickening or enhancement on imaging studies. Lack of both fever and leukocytosis, and insidious (often incidental) rather than acute presentation, help distinguish IgG4-related aortitis from infectious aortitis. Aortitis is occasionally complicated by Major salivary (eg, parotid and/or submandibular) and lacrimal glands are commonly affected. Glands are painlessly enlarged bilaterally, but usually their function is not impaired. Elevated IgG4 levels, characteristic histopathology, and insidious tempo of disease help differentiate IgG4-RD of these organs from conditions such as Sjögren Syndrome and The orbits can be affected. IgG4-RD accounts for about 25 to 50% of cases of Inflammatory Orbital Disease (previously called orbital pseudotumor), which must be distinguished from IgG4-related Mikulicz syndrome is combined involvement of the lacrimal, parotid, and submandibular glands, typically with bilateral involvement of each set of glands. These findings, combined with a marked elevated serum IgG4 level, is essentially diagnostic of IgG4-RD; however, serum IgG4 is not always elevated in IgG4-related Mikulicz syndrome. may be involved, sometimes with hilar adenopathy and lung nodules that can resemble Sarcoidosis . Histopathology is essential for distinguishing these disorders. involvement most often manifests as Tubulointerstitial Nephritis , usually as asymptomatic impairment of kidney function, sometimes requiring dialysis; multiple renal masses and hypocomplementemia are often present. Proteinuria, sometimes in the nephrotic range, may occur, reflecting an associated glomerulopathy, but cellular casts and/or hematuria are infrequent. Many other tissues may be involved, including the skin, prostate, meninges, and sinuses. There is limited evidence of involvement of the brain, luminal gastrointestinal tract, spleen, bone marrow, or peripheral nerves. Wallace ZS, Zhang Y, Perugino CA, et al: Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts.Ann Rheum Dis78(3):406-412, 2019. doi:10.1136/annrheumdis-2018-214603 