Mikulicz's disease (MD) has been included within the diagnosis of primary Sjögren's syndrome (SS), but represents a unique condition involving enlargement of the lachrymal and salivary glands and characterized by few autoimmune reactions and good responsiveness to glucocorticoids. We have previously described elevated immunoglobulin (Ig) G4 in the serum of four patients with MD. In this paper, we accumulated more MD cases and undertook clinical and histopathological analysis of these patients to clarify differences between MD and SS.
We diagnosed seven patients with MD according to the following criteria: (i) visual confirmation of symmetrical and persistent swelling in more than two lachrymal and major salivary glands; (ii) prominent mononuclear infiltration of lachrymal and salivary glands; and (iii) exclusion of other diseases that present with glandular swelling, such as sarcoidosis and lymphoproliferative disease. We summarized the clinical and serological characteristics (IgG subclasses and IFN-gamma/IL-4 ratio) of seven patients with MD, compared with SS with glandular swelling (SSw) and without glandular swelling (SSo). After steroid administration, we analysed changes in IgG subclasses in MD. Labial salivary gland specimens in MD, SSw and SSo were stained with anti-IgG4 antibodies.
The concentration (+/-s.d.) of IgG4 was 1169.7 +/- 892.2 mg/dl in MD, 24.4 +/- 7.0 mg/dl in SSw (P<0.005) and 82.6 +/- 189.7 mg/dl in SSo (P<0.005). The IFN-gamma/IL-4 ratio was 0.392 +/- 0.083 (0.78 +/- 0.23/2.14 +/- 0.31 IU/pg) in MD, 0.004 +/- 0.002 (0.20 +/- 0.07/57.02 +/- 14.05 IU/pg) in SSw (P<0.05) and 0.012 +/- 0.009 (0.58 +/- 0.86/116.24 +/- 207.65 IU/pg) in SSo (P<0.05). The concentration (+/-s.d.) of IgG4 in MD decreased to 254.0 +/- 50.3 mg/dl (P<0.05) after glucocorticoid treatment. Histopathologically, only MD was associated with prominent infiltration of IgG4-positive plasmacytes into lachrymal and salivary glands.
Mikulicz's disease is quite different from SS clinically and histopathologically. MD is suggested to be an IgG4-related systemic disease.