A novel concept of Mikulicz's disease as IgG4-related disease.

Since Morgan's report in 1953, Mikulicz's disease (MD) has been considered part of primary Sjögren's syndrome (SS). However, MD has a unique presentation, including persistent swelling of the lacrimal and salivary glands, and is characterized by good responsiveness to glucocorticoids, leading to recovery of gland function. Recently, it has been revealed that MD patients show elevated serum immunoglobulin G4 (IgG4) levels and prominent infiltration of IgG4-positive plasmacytes. 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. Thus, MD is a systemic "IgG4-related disease." In addition, recent analyses have revealed that Küttner's tumor (KT), a chronic sclerosing sialadenitis that presents with asymmetrical firm swelling of the submandibular glands, is also associated with prominent infiltration of IgG4-positive plasmacytes. MD and KT differ from SS and are thought to be singular systemic IgG4-related plasmacytic diseases. Here we discuss the results of recent studies and provide an overview of MD as an IgG4-related disease.

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

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.

[100 years of the Mikulicz syndrome]. / 100 Jahre Mikulicz-Syndrom.

Between 1888 and 1892, Mikulicz as well as Fuchs observed each a case of oculo-salivary glandular syndrome. Ten years later, Heerfordt described uveitis complicated by swelling of the lacrimal and salivary glands. Within 100 years, the interpretation of this disease changed repeatedly and considerably: infection of particularly exposed organs--non-avirulent tuberculosis--salivotropic virus--Boeck's disease--allergic-hyperergic reaction--diencephalic and nervous dystrophy with segmental projection--(auto)immune disease--oculo-salivary complex including Sjøgren's syndrome--all these were discussed as possible aetiologies. Short biographies of Johannes von Mikulicz-Radecki, surgeon at Austrian and Prussian universities; Ernst Fuchs, ophthalmologist of Vienna; Christian Frederik Heerfordt, a Danish ophthalmologist particularly fond of publicity.