Clinical manifestations are variable depending on the organ system involved. Most commonly, IgG4-RD is associated with autoimmune pancreatitis; other manifestations include lymphadenopathy, biliary obstruction (may present similarly to primary sclerosing cholangitis), salivary dysfunction, lacrimal gland dysfunction, retroperitoneal fibrosis, cutaneous plaques on the head and neck, and atopy (asthma, eczema), though nearly any organ system can be affected. Symptoms typically develop over months to years, and treatment success is variable.
Diagnostic criteria, proposed by Umehara, include:
- Clinical examination shows characteristic diffuse / localized swelling or masses in single or multiple organs.
- Hematological examination shows elevated serum IgG4 concentrations (135 mg/dL).
- Histopathologic examination shows:
- (1) Marked lymphocyte and plasmacyte infiltration and fibrosis.
- (2) Infiltration of IgG4+ plasma cells: ratio of IgG4+/IgG+ cells >40% and >10 IgG4+ plasma cells per high-power field.
D80.3 – Selective deficiency of immunoglobulin G [IgG] subclasses
234549008 – Immunoglobulin G4 deficiency
- Granuloma faciale
- Sarcoidosis – Presents more frequently on the nose as red-brown papules or plaques. Diascopy reveals an "apple jelly" yellow-brown color. Biopsy reveals noncaseating granulomas.
- Adult-onset asthma and periocular xanthogranuloma (AAPOX) – A rare non-Langerhans histiocytosis. Classically, presents with infiltration of the eyelids and lymphadenopathy. Biopsy typically reveals foamy histiocytes and Touton giant cells. Plasma cell infiltration may also be noted.
- Rosai-Dorfman disease – Differentiated on histology by the presence of emperipolesis and histiocytic infiltrate and a relative paucity or absence of IgG4+ plasma cells.
- Angiolymphoid hyperplasia with eosinophilia – Classically, presents as dome-shaped vascular papules, often agminated, about the ears. Extracutaneous involvement is reported but rare, as opposed to IgG4-RD, where extracutaneous involvement is the rule. Biopsy reveals dermal or subcutaneous vascular proliferation and inflammatory cells.
- Castleman disease – Shares systemic features with IgG4-RD including diffuse lymphadenopathy; however, differs in cutaneous findings. Rarely, it can be associated with xanthelasma and plane xanthomas which present as yellowish plaques about the eyes or elsewhere.