A new conceptualization for Mikulicz's disease as an IgG4-related plasmacytic disease

Abstract

Mikulicz's disease (MD) has been included within the diagnosis of primary Sjögren's syndrome (SS), but it represents a unique condition involving persistent enlargement of the lacrimal and salivary glands characterized by few autoimmune reactions and good responsiveness to glucocorticoids, leading to the recovery of gland function. Mikulicz's disease was recently reported to be associated with elevated immunoglobulin G4 (IgG4) concentrations in the serum and prominent infiltration of plasmacytes expressing IgG4 into the lacrimal and salivary glands. The following features were used for diagnosis: (1) visual confirmation of symmetrical and persistent swelling in more than two lacrimal and major salivary glands; (2) prominent mononuclear cell infiltration of lacrimal and salivary glands; and (3) exclusion of other diseases that present with glandular swelling, such as sarcoidosis and lymphoproliferative disease. These features are not observed in most SS cases. The complications of MD include autoimmune pancreatitis, retroperitoneal fibrosis, tubulointerstitial nephritis, autoimmune hypophysitis, and Riedel's thyroiditis, all of which show IgG4 involvement in their pathogenesis. Mikulicz's disease thus differs from SS and may be a systemic IgG4-related plasmacytic disease.

Fig. 1

Ratio of each IgG subclass/total IgG. The IgG4/total IgG ratio increased significantly in Mikulicz's disease, when compared with that in Sjögren syndrome

Fig. 2a,b.

Specimens of labial salivary glands in patients with Mikulicz's disease (MD) and Sjögren's syndrome (anti-IgG4 monoclonal antibody staining, magnified 1 : 200). a Mikulicz's disease, b Sjögren's syndrome. The MD specimen exhibits abundant infiltration of plasmacytes with IgG4