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Despite major desiccation of mucous membranes in Sjögren's syndrome (SS), fatigue is often experienced by patients as the most disabling complaint.1,2 Unfortunately, there is no proper treatment available to combat the fatigue in SS. Beside a variety of somatic and non-somatic conditions,2–,6 increased immune activity has been implicated as a cause of fatigue in autoimmune diseases.6,7 If responsible for fatigue in SS, it could serve as a treatment target. The purpose of this study was, therefore, to examine the relation between fatigue and immune variables in SS.
Thirty six consecutive patients with primary SS visiting our outpatient departments participated in this study. Two control groups were used: a group of 18 patients diagnosed with secondary SS, and a group of 34 non-medicated healthy controls. Diagnoses were based on the revised European criteria for the classification of SS.8 Control groups were matched for age and sex. Disease duration or treatment did not differ significantly between patients with primary and secondary SS. Patients with other chronic diseases were excluded from the study. The Dutch Fatigue Scale (DUFS) was used to quantify fatigue. This validated questionnaire poses nine questions about different aspects of fatigue (table 1⇓).9 Because depression is frequently observed in SS,2,5 a standardised psychiatric questionnaire (SCL-90) was used to rule out this potential confounding variable for fatigue.10 Immunological activity was evaluated by assessing rheumatoid factor, antinuclear antibodies, presence of anti-SS-A and anti-SS-B, levels of immunoglobulins (IgG, IgM, and IgA), haemoglobin levels, leucocytes, thrombocytes, erythrocyte sedimentation rate, and C reactive protein (CRP). After preliminary analysis using correlation tests, the best model to explain fatigue was calculated by using multiple regression with forward selection (SPSS version 8.0). Independent Student t tests were used to compare the studied groups.
Fatigue was equally raised in patients with both primary and secondary SS, and differed significantly from that of healthy controls. Twenty one (58%) patients with primary SS scored “high” or “very high” out of the six categories for depression according to the SCL-90 criteria. These depression scores did not significantly differ from the scores in secondary SS patients. Further analysis showed that 79% of the fatigue in patients with primary SS could be explained by depression, total level of immunoglobulins, and thrombocyte counts (p<0.001). Both depression and thrombocyte counts showed a significant positive correlation, whereas levels of immunoglobulins showed a negative correlation.
Though tempting as a treatment target, the immune and inflammatory variables failed to predict fatigue satisfactorily in primary SS. Levels of immunoglobulins showed, surprisingly, a significant negative correlation. Thrombocyte counts showed a significant positive correlation. Although increases in thrombocytes follow the acute phase reaction, no significant correlation between thrombocyte counts and CRP levels were found. A chance association between fatigue and thrombocyte counts as well as immunoglobulin levels seems thus possible. Therefore, the intriguing question whether immune or inflammatory activity is a causative factor of chronic fatigue in SS remains unravelled. Because no difference in fatigue was found between patients with primary and secondary SS, the presence of another autoimmune disease appears to have no additional effect on the amount of fatigue in SS. In agreement with findings of previous studies, a significant relation was found between the degree of fatigue and the level of depression in patients with primary SS.2,5 It is concluded that none of the laboratory variables reflecting immune activity predict fatigue satisfactorily in primary SS. Signs of depression, as present in most of the patients with primary SS, proved to be the most relevant cause of their exhausting fatigue. Therefore we recommend including a psychosomatic approach in the treatment of fatigue in primary SS.
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