First Department of Internal Medicine, Sapporo Medical University, School of Medicine and 1 Sapporo Medical University, Sapporo, Hokkaido, Japan
Correspondence to: M. Yamamoto, First Department of Internal Medicine, Sapporo Medical University, School of Medicine, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, Japan. E-mail: mocha{at}cocoa.plala.or.jp
SIR, Mikulicz's disease (MD) represents a unique condition involving symmetrical enlargement of the lacrimal and salivary glands, the cause of which is unknown. It has been included within the diagnostic criteria for primary Sjögren's syndrome (SS) due to their histological resemblance [1]. However, it is clear that the pathogenesis of MD differs from that of SS because an elevated serum IgG4 concentration and infiltration of abundant plasmacytes with IgG4 into the lacrimal and salivary glands are seen in MD patients [2]. Clinically, MD exhibits good responsiveness to glucocorticoids, showing improvements in not only lacrimal and salivary gland swelling but also secretion. We attempted to objectively document this phenomenon and to serologically evaluate steroid efficacy.
Analyses were performed in eight MD patients (two men, six women) who consulted doctors at Sapporo Medical University between April 1997 and January 2005. MD was diagnosed according to the following criteria: (i) persistent (more than 3 months) symmetrical swelling of more than two lacrimal and major salivary glands; (ii) prominent mononuclear infiltration of lacrimal and salivary glands; and (iii) exclusion of other diseases that exhibit glandular swelling, such as sarcoidosis or lymphoproliferative disease [2]. Lacrimal gland function was evaluated by Schirmer's test, and salivary gland function was examined by Saxon's test. IgG subclass was measured by nephelometry. These tests were performed before and after treatment. MannWhitney's U-test was used for data comparison, and values of P<0.05 were considered statistically significant.
After prescription of 3040 mg prednisolone/day, lacrimal secretion increased from 6.90±0.77 to 15.70±11.56 mm/5 min (P<0.05), and salivary secretion improved from 1.98±1.86 to 3.66±0.77 g/2 min after treatment (P<0.05). Serum IgG concentration decreased from 4270.0±2098.0 to 1440.1±424.7 mg/dl (P<0.005). Serum levels of each IgG subclass decreased as follows: IgG1, from 1632.9±781.1 to 681.0±227.5 mg/dl (P<0.005); IgG4, from 1556.4±937.1 to 234.7±75.3 mg/dl (P<0.005). IgG subclass/total IgG ratio also changed, as follows: IgG1, from 38.26±3.92 to 46.83±3.98% (P<0.01); IgG4, from 34.85±7.87 to 16.67±5.88% (P<0.005) (Fig. 1).
|
The present analysis proves that different approaches to secretory function are necessary for MD and SS. In SS, cevimeline hydrochloride stimulates the remaining gland function and promotes secretion; however, active steroid treatment is of particular value in MD because glandular destruction has not occurred.
One of the serological characteristics of MD is an elevated concentration of IgG4. In addition, the ratio of serum IgG4 to total IgG is 34.85%, while in healthy controls the ratio is about 4%. It is known that the ratio does not vary with race, sex or age after adulthood. We found that the serum IgG4/total IgG ratio decreased significantly in MD patients after steroid therapy, although it is expected that steroids would decrease IgG4 concentration as a result of immune suppression. This phenomenon may be related to disease activity and the subsequent improvement in symptoms. However, in our MD cases the serum IgG4/total IgG ratio failed to normalize, and increased after tapering or interrupting the steroid dose (<5 mg prednisolone/day). We believe that 57.5 mg prednisolone/day is necessary to maintain disease suppression.
The authors have declared no conflicts of interest.
References
|