Clinical features of immunoglobulin G4 (IgG4)-related disease

Immunoglobulin G4 (IgG4)–related disease can involve one or, more commonly, multiple organs. It may be misdiagnosed as a neoplastic, inflammatory or infectious condition. Four distinct patterns of organ involvement have been identifiedWallace, 2020:

  • pancreato-hepato-biliary disease
  • retroperitoneal fibrosis with or without aortitis (arteritis affecting the aorta)
  • head- and neck-limited disease
  • Mikulicz syndrome—lacrimal and parotid gland disease and other systemic organ involvement.

The tissues most commonly affected in these 4 patterns of IgG4–related disease are outlined in Tissues commonly affected by immunoglobulin (Ig)G4-related disease and associated clinical features.

People with IgG4–related disease can have very different presentations; they may be:

  • asymptomatic, with the incidental finding of a mass on imaging (eg a renal mass resembling renal cell carcinoma, nodular lung lesions)
  • unwell, with a symptomatic mass in an affected organ (eg lymphadenopathy, orbital pseudotumour)
  • progressively unwell, with systemic features (eg weight loss, fever) and symptoms and signs reflecting the affected organ(s).
Table 1. Tissues commonly affected by immunoglobulin (Ig)G4-related disease and associated clinical featuresWallace, 2020

Affected tissue

Common clinical features

pancreato-hepato-biliary disease

pancreas

painless pancreatic mass

obstructive jaundice secondary to IgG4–related sclerosing cholangitis (bile and pancreatic duct obstruction)

diabetesLöhr, 2020

type 1 autoimmune pancreatitis

liver and biliary tree

obstructive jaundice secondary to IgG4–related sclerosing cholangitis (similar to primary sclerosing cholangitis)

symptoms and signs of acute or chronic liver failure

retroperitoneal fibrosis and aortitis

retroperitoneum

pain in the lower back, abdomen or flank

malaise, anorexia, weight loss, fever, nausea, vomiting

lower limb oedema

hydronephrosis

new-onset hypertension (secondary to kidney disease)

hydrocele, varicocele

deep vein thrombosis

aorta

aortitis—fever, back pain, aortic aneurysm

head- and neck-limited disease

orbits

orbital pseudotumour, orbital swelling, proptosis

visual loss, diplopia

meninges

cranial nerve palsies

ear

hearing loss (neurological or conductive)

bone destruction

sinuses

chronic sinusitis

thyroid

hoarseness, dyspnoea, dysphagia

Riedel’s fibrosing thyroiditis, hypothyroidism

pituitary

hypopituitarism secondary to lymphocytic hypophysitis

Mikulicz syndrome with other systemic organ involvement

lacrimal and salivary glands

sicca symptoms

lungs

pleural effusion, pleural thickening

interstitial lung disease

kidneys

interstitial kidney disease, glomerulonephritis, kidney failure

Note: IgG4 = immunoglobulin G4