Limited Scleroderma CREST Syndrome is associated with worse

Limited Scleroderma (CREST Syndrome) is associated with worse xerostomia and xerophthalmia in patients being evaluated for Primary Sjogren’s Syndrome Yifan Li 1, Arthur A. M. Bookman MD FRCPC 2 1. Schulich School of Medicine & Dentistry, Western University, London, ON, Canada. 2. Division of Rheumatology, University of Toronto School of Medicine, Toronto, ON, Canada. Introduction • The presence of overlapping autoimmune diseases is not uncommon in patients who are being evaluated for Primary Sjogren’s Syndrome (PSj. S). • The hallmark of PSj. S is subjective and objective evidence of xerophthalmia or xerostomia, otherwise known as sicca. • It is unknown whether the presence of Limited Scleroderma (CREST syndrome) impacts the presence or severity of sicca. Purpose • To determine if the presence of CREST syndrome affects the incidence or severity of sicca in patients being evaluated for PSj. S. Methods • Patients were pre-screened for objective evidence of abnormal serology, dry eyes or dry mouth based on Schirmers test 1 and unstimulated salivary flow (USSF)3. • 609 patients were assessed on protocol at the Sjogren’s Clinic of the Toronto Western Hospital over 22 years. • The evaluation included a visual analogue score (VAS) for severity of xerophthalmia and xerostomia, as well as Schirmer’s-1 test 1, Rose Bengal staining 2, USSF 3, minor salivary gland biopsy and serology. • PSj. S was classified according the American European Consensus Group (AECG) Criteria 4. • Patients with anti-centromere antibody (ACA) were designated as CREST Syndrome whether or not they met criteria for PSj. S. • A 2 -tailed student t-test with heterogenous variance was used to compare measures of severity. Results Conclusions • Among 609 patients: average was 53. 4 years with 91% female. 446 met the AECG criteria for PSj. S. • 34 patients (5. 6%) were ACA positive and were designated as CREST syndrome patients. All had sicca. Of these, 26 patients met the AECG criteria for PSj. S. These patients were designated as CREST syndrome overlap patients. Whether or not the CREST patients met AECG criteria made no difference with respect to either the incidence or severity of sicca symptoms (data not shown). • Of all 34 CREST patients: 91% had xerophthalmia; 100% had xerostomia; severity of xerophthalmia was 6. 6 (out of 10); severity of xerostomia 8. 5 (out of 10). CREST overlap patients (n = 26) Primary Sjogren’s Syndrome patients (n = 420) P-value Clinical Differences Incidence of Raynaud’s phenomenon (%) 88% 28% p < 0. 001 Serological Markers Incidence of positive Ro/La antibodies 35% 77% p < 0. 001 Incidence of elevated serum Ig. G 24% 57% p < 0. 001 Average levels of serum Ig. G (gm/L) Xerophthalmia 12. 4 19. 4 p < 0. 001 Incidence of xerophthalmia 96% p > 0. 05 Severity of xerophthalmia (on VAS, max 10) 7. 0 6. 4 p > 0. 05 Average Rose Bengal score 5. 7 5. 6 p > 0. 05 Schirmer's-1 test (mm/5 mins) 3. 5 4. 1 p < 0. 05 100% 98% p > 0. 05 Severity of xerostomia (on VAS, max 10 ) 8. 5 6. 7 p < 0. 001 USSF (m. L/15 mins) 0. 1 0. 4 p < 0. 001 Salivary gland biopsy Focus Score ≥ 1 92% 100% p < 0. 001 Xerostomia Incidence of xerostomia Table 1. Effects of the presence of CREST Syndrome on patients who have primary Sjogren’s Syndrome. Normal serum Ig. G levels are 7 -16 gm/L in healthy patients. VAS = visual analogue score. Rose-Bengal test evaluates ocular surface epithelial damage (out of 9). Schirmer's test measures lacrimal gland production. USSF (unstimulated salivary flow; normal USSF ≥ 1. 5 mm/15 min). Salivary gland biopsy positive result: ≥ 1 focus per 4 mm 2. Statistically significant p-values are in bold. • CREST syndrome overlap patients had subjectively and objectively worse xerostomia than PSj. S patients without overlap. • CREST syndrome overlap patients had more severe objective xerophthalmia than PSj. S patients. A significant difference in ocular symptoms could not be detected. • CREST patients may meet AECG Criteria for PSj. S despite a less frequent anti-Ro or –La positivity. These patients have a less frequent but more profound elevation of Ig. G levels. References 1. van Bijsterveld OP. Diagnostic tests in the Sicca Syndrome. Arch. Ophthal 1969; 82: 10 – 14. 2. Prause JU, Kriegbaum NJ, Manthorpe R, Oxholm P. Rose bengalscore--a possible key parameter when evaluating disease level and progression in primary Sjögren's syndrome. J Autoimmun. 1989 Aug; 2(4): 501 -7. 3. Speight PM, Kaul A, Melsom RD. Measurement of whole unstimulated salivary flow in the diagnosis of Sjögren's syndrome. Ann Rheum Dis. 1992 Apr; 51(4): 499 -502. 4. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH; European Study Group on Classification Criteria for Sjögren's Syndrome. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American. European Consensus Group. Ann Rheum Dis. 2002 Jun; 61(6): 554 -8. Review. Acknowledgements This project was made possible with the support of the Sjogren’s Society of Canada summer student research grant.