1. Limited Scleroderma (CREST Syndrome) is associated with worse
xerostomia and xerophthalmia in patients being evaluated for Primary Sjogren’s Syndrome
Yifan Li1, Arthur A.M. Bookman MD FRCPC2
Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
Division of Rheumatology, University of Toronto School of Medicine, Toronto, ON, Canada.
Introduction
Results
Conclusions
The presence of overlapping autoimmune diseases is not uncommon in patients who are being evaluated for Primary Sjogren’s Syndrome (PSjS).
The hallmark of PSjS 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.
Among 609 patients: average age was 53.4 years with 91% female. 446 met the AECG criteria for PSjS.
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 PSjS. 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 syndrome overlap patients had subjectively and objectively worse xerostomia than PSjS patients without overlap.
CREST syndrome overlap patients had more severe objective xerophthalmia than PSjS patients. A significant difference in ocular symptoms could not be detected.
CREST patients may meet AECG Criteria for PSjS despite a less frequent anti-Ro or –La positivity. These patients have a less frequent but more profound elevation of IgG levels.
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%
Incidence of elevated serum IgG
24%
57%
Average levels of serum IgG (gm/L)
12.4
19.4
Xerophthalmia
Incidence of xerophthalmia
96%
p > 0.05
Severity of xerophthalmia (on VAS, max 10)
7.0
6.4
Average Rose Bengal score
5.7
5.6
Schirmer's-1 test (mm/5 mins)
3.5
4.1
p < 0.05
Xerostomia
Incidence of xerostomia
100%
98%
Severity of xerostomia (on VAS, max 10 )
8.5
6.7
USSF (mL/15 mins)
0.1
0.4
Salivary gland biopsy Focus Score ≥ 1
92%
Purpose
References
To determine if the presence of CREST syndrome affects the incidence or severity of sicca in patients being evaluated for PSjS.
1. van Bijsterveld OP. Diagnostic tests in the Sicca Syndrome. ArchOphthal 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 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 Apr;51(4):
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 Jun;61(6): Review. 
Methods
Patients were pre-screened for objective evidence of abnormal serology, dry eyes or dry mouth based on Schirmers test1 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 test1, Rose Bengal staining2, USSF3, minor salivary gland biopsy and serology.
PSjS was classified according the American European Consensus Group (AECG) Criteria4.
Patients with anti-centromere antibody (ACA) were designated as CREST Syndrome whether or not they met criteria for PSjS.
A 2-tailed student t-test with heterogenous variance was used to compare measures of severity.
Acknowledgements
This project was made possible with the support of the Sjogren’s Society of Canada summer student research grant.
Table 1. Effects of the presence of CREST Syndrome on patients who have primary Sjogren’s Syndrome. Normal serum IgG 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 ≥1.5mm/15 min). Salivary gland biopsy positive result: ≥1 focus per 4mm2. Statistically significant p-values are in bold.