Validation of the ACR-EULAR criteria for primary Sjögren's syndrome in a Dutch prospective diagnostic cohort.

Objectives: To validate the ACR-EULAR classification criteria for primary SS (pSS), and compare them to the American-European Consensus Group (AECG) and ACR criteria in a Dutch prospective diagnostic cohort. Methods: Consecutive patients (n = 129) referred for suspicion of pSS underwent a multidisciplinary evaluation, including a labial and/or parotid gland biopsy. Patients with an incomplete work-up (n = 8) or associated systemic auto-immune disease (n = 7) were excluded. The ACR-EULAR classification was compared with expert classification, AECG and ACR classification. Additionally, the accuracy of individual ACR-EULAR items in discriminating pSS from non-pSS was evaluated. The validity of criteria sets was described separately using parotid or labial gland biopsy results for classification. Results: Of the 114 evaluated patients, the expert panel classified 34 (30%) as pSS and 80 (70%) as non-pSS. Using labial gland biopsy results, ACR-EULAR classification showed 87% absolute agreement (κ = 0.73) with expert classification, with a sensitivity of 97% and specificity of 83%. Using the parotid gland biopsy results, the ACR-EULAR criteria performed excellently as well. Focus score, anti-SSA titre and ocular staining score showed good to excellent accuracy, whereas unstimulated whole saliva and Schirmer's test had poor accuracy. The ACR-EULAR and AECG criteria had equal validity. Compared with ACR classification, ACR-EULAR classification showed higher sensitivity but lower specificity. Conclusion: The ACR-EULAR criteria showed good agreement with expert classification, but some patients may be misclassified as pSS. Unstimulated whole saliva and Schirmer's test showed poor discriminative value. The ACR-EULAR criteria performed equally to the AECG criteria, and had higher sensitivity but lower specificity than the ACR criteria.

Predictors of Discordance between Symptoms and Signs in Dry Eye Disease.

PURPOSE: To investigate predictors of discordance between symptoms and signs in dry eye disease (DED). DESIGN: Cross-sectional association study. PARTICIPANTS: A total of 648 patients with dry eye from the Groningen LOngitudinal Sicca StudY (GLOSSY), a tertiary dry eye clinic patient cohort from the Netherlands. METHODS: Patient symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Dry eye signs were assessed by tear osmolarity, Schirmer test, tear breakup time, corneal and conjunctival staining, and meibomian gland dysfunction, all in both eyes, and a composite dry eye signs severity score was calculated from these 6 tests for each patient. Linear regression analysis was used to test the association of discordance between symptoms and signs with a wide range of independent variables (demographic and environmental variables, systemic diseases, ocular traits, and medications). MAIN OUTCOME MEASURES: Predictors of discordance between symptoms and signs in DED, defined by the difference between the rank score of the OSDI and the rank score of the dry eye signs severity score. RESULTS: Of the 648 subjects in this cohort, 536 (82.7%) were female and the mean age was 55.8 years (standard deviation, 15.6 years). Significant predictors of greater symptoms than signs were the presence of a chronic pain syndrome, atopic diseases, a known allergy, the use of antihistamines (all P < 0.001), depression (P = 0.003), osteoarthritis (P = 0.008), and the use of antidepressants (P = 0.02). Predictors of lesser symptoms than signs were increased age (P < 0.001) and the presence of Sjögren's disease (P < 0.001) (primary Sjögren's disease, P < 0.001) more than secondary Sjögren's disease (P = 0.08), and graft-versus-host disease (P = 0.04). Furthermore, greater symptoms compared with signs were highly associated with lower self-perceived health (P < 0.001). CONCLUSIONS: This large clinical study has shown that discordance between symptoms and signs in DED is an indicator of self-perceived health. The study found important predictors of greater symptoms to signs but also predictors of lesser symptoms to signs. Awareness of these predictors is helpful in assessing patients with dry eye in clinical practice.

Sex differences in clinical characteristics of dry eye disease.

PURPOSE: To investigate the role of sex on the symptomatology of DED and on the associations between symptoms and signs. METHODS: A cross-sectional study was used including 755 dry eye patients from the Groningen Longitudinal Sicca Study (GLOSSY cohort). Patient symptoms were assessed by the Ocular Surface Disease Index (OSDI) questionnaire and dry eye signs by the six most commonly used tests. Patients were divided in groups based on overall severity of signs and within these groups total and specific symptoms were compared by sex. Sex differences in Spearman correlation between symptoms and signs were calculated. RESULTS: Women had higher total symptom scores than men in both the mild (33.8 vs 24.7, P = .01) and moderate signs groups (38.3 vs 28.0, P < .005), but this difference was less apparent in the severe signs group (40.4 vs 37.2, P = .33). Independent of severity of signs, women consistently reported more light sensitivity than men (P < .01 in all groups). The correlation between symptoms and overall severity of signs score was significantly lower in women (ρ = 0.11 vs ρ = 0.33 in men, P = .01), with clearest differences between women and men in correlations with Schirmer (ρ = 0.01 vs ρ = -0.21, P = .03) and TFBUT (ρ = -0.08 vs ρ = -0.30, P = .02). CONCLUSIONS: This large clinical study has shown that sex has a large influence on the symptomatology of DED, with significantly higher symptom scores and lower correlation between symptoms and signs in women compared to men. These findings are of importance in clinical practice and in conducting research into DED.

Clinical Characteristics of Dry Eye Patients With Chronic Pain Syndromes.

PURPOSE: To investigate clinical characteristics of dry eye disease (DED) patients with a chronic pain syndrome. DESIGN: Cross-sectional study. METHODS: Four hundred twenty-five patients of a tertiary care DED patient cohort in the Netherlands were included. Chronic pain syndromes irritable bowel syndrome, chronic pelvic pain, and fibromyalgia were assessed by questionnaires. Outcome variables were the Ocular Surface Disease Index (OSDI) symptom questionnaire, tear osmolarity, Schirmer test, tear breakup time, conjunctival hyperemia, staining of the cornea and conjunctiva, and amount of mucus. Outcomes were cross-sectionally compared between DED patients with a chronic pain syndrome and those without. RESULTS: A total of 74 out of 425 DED patients (17%) had at least 1 chronic pain syndrome. The total symptom score was significantly higher in DED patients with a chronic pain syndrome than in those without (45.8 vs 33.8, P < .0005). Moreover, patients with a chronic pain syndrome scored higher on every single subscale of the 12-item OSDI symptom questionnaire. However, ocular signs were similar or even less severe in these patients. Similarly, in 64 DED patients from the population-based cohort TwinsUK, patients with a chronic pain syndrome (n = 24, 38%) had higher subscale and total (34.1 vs 14.4, P = .001) symptom scores. CONCLUSION: In DED patients, chronic pain syndromes are common and are associated with increased severity of DED symptoms across all domains of the OSDI, even though objective ocular surface signs are no worse. In clinical practice, more awareness of chronic pain syndromes might help in understanding the discrepancy between signs and symptoms in DED.