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OBJECTIVE: To determine the validity of screening tests for Sjogren's syndrome (SS) in ambulatory patients with chronic diseases. METHODS: Three hundred randomly selected patients from the rheumatology and internal medicine clinics of a tertiary care center were assessed for SS according to the American-European Consensus Group criteria. During the screening phase, an interview, the European questionnaire for sicca symptoms, Schirmer-I test, and the wafer test were carried out in all patients. Patients with positive screening had confirmatory tests including fluorescein staining test, nonstimulated whole salivary flow, and autoantibody testing. Confirmatory tests were also done in 13 patients with negative screening. During the last phase, lip biopsy was proposed to patients who met preestablished criteria. RESULTS: Women made up 79% of the study population. Mean age of subjects was 42.8+/-15.7 years. Two hundred twenty patients (73%) had positive screening. The distribution of positive test results was: xerophthalmia 118 (39%), xerostomia 103 (34%), Schirmer-I test 101 (34%), and wafer test 187 (62%) patients. Forty (13%) patients met criteria for SS. All screening tests were useful for identifying patients with SS; however, the model composed of at least one positive response to the European questionnaire (EQ1), Schirmer-I test, and wafer test showed the best performance. CONCLUSION: Use of the European questionnaire, Schirmer-I test, and wafer test in parallel was useful for identifying patients with SS among ambulatory patients with chronic diseases.