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.

Brief Report: Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in Patients With IgG4‐Related Disease

“…Wide variability exists in the reported frequency of elevated serum IgG4 levels (14)(15)(16)(17)(18), and the reliability of the serum IgG4 concentration as a biomarker for diagnosis and disease activity has been questioned. Although the prozone effect appears to explain a substantial number of false-negative results of serum IgG4 assays, the cumulative literature and our own experience suggest the existence of patients with biopsy-proven IgG4-RD and normal serum IgG4 concentrations.…”

Sonographic findings of immunoglobulin G4-related sclerosing sialadenitis

“…Both diseases have common clinical features including elevated serum IgG4 levels and histopathologic infiltration of IgG4-positive plasma cells. At present, these diseases are regarded as IgG4-related lesions of the salivary gland [6][7][8][9].…”

Hypophysitis Presenting With Atypical Rapid Deterioration: With Special Reference to Immunoglobulin G4-Related Disease -Case Report-

“…Recently, systemic immunoglobulin G4 (IgG4)-related plasmacytic disease (SIPD) has provoked keen interest in modern immunology, because of the relationship to autoimmune inflammation of multiple organs such as pancreatitis, sailvary glanditis, tubulointerstitial nephritis, retroperitoneal fibrosis, and hypophysitis. 8,[11][12][13][14] However, hypophysitis has been histologically confirmed as a part of SIPD in only one case, because of difficulty in confirming the pathology of the pituitary gland, 11) and IgG4-positive hypophysitis has never been found as the``primary'' hypophysitis with any other organ disorder of SIPD.…”