Lymphoma risk in systemic lupus: effects of disease activity versus treatment.

OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. RESULTS: We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls. CONCLUSIONS: In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.

Healthcare service utilisation costs are reduced when rheumatoid arthritis patients achieve sustained remission.

OBJECTIVE: Determine healthcare service utilisation costs among patients using biological therapies for rheumatoid arthritis (RA), considering the magnitude and duration of patient response achieved. METHODS: Clinical data from the Alberta Biologics Pharmacosurveillance Program (ABioPharm) was linked with provincial physician billing claims, outpatient visits and hospitalisations. The annual mean healthcare service utilisation costs (total, RA-attributable, non-RA attributable) were estimated for patients during the best disease activity level reached during treatment. RESULTS: Of 1086 patients: 16% achieved DAS28 remission >1 year, 37% had a DAS28 remission period <1 year, 13% had a low disease activity (LDA) period <1 year and 31% had persistent moderate or high disease activity. Mean annual healthcare service utilisation cost savings for those in sustained remission was $2391 (95% CI 1437 to 3909, p<0.001) and $2104 (95% CI 838 to 3512, p<0.001) for those with non-sustained LDA, relative to the persistent disease activity group. Savings were also observed for those in sustained remission compared to non-sustained remission (annual savings $1422, 95% CI 564 to 2796, p<0.001). RA-related costs were consistent across disease activity and cost categories; the majority of costs were attributable to non-RA related hospitalisations. CONCLUSIONS: We provide evidence of economic benefits to the healthcare system when RA patients achieve persistent good disease control. Benefits from brief periods of remission and LDA are also observed. Coupled with an expected increase in productivity from improved disease control, there is societal benefit to the utilisation of biologics in RA management to achieve treatment goals.

Quantification of small joint space width, periarticular bone microstructure and erosions using high-resolution peripheral quantitative computed tomography in rheumatoid arthritis.

OBJECTIVES: This paper aims to investigate the ability of a novel imaging technique, high-resolution peripheral quantitative computed tomography (HR-pQCT), to quantify joint space width at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, and provide periarticular bone microstructure measurements (including volumetric density and morphometric indices). We also compared the sensitivity and specificity of HR-pQCT to detect erosions relative to plain radiography. METHODS: HR-pQCT imaging of the MCP and PIP joints of the dominant hand was performed in 30 rheumatoid arthritis (RA) and control subjects matched for age, sex and dominant hand use. The joint space width was calculated by determining the number of voxels between three-dimensional images of the articular surfaces. Periarticular bone microstructure was quantified for the 2nd and 3rd MCP joints using standard analysis. The presence of erosions was confirmed by viewing both two- and three-dimensional images of the joints. RESULTS: Quantitative measures of joint space width and periarticular bone microstructure were obtained with precision. Although not powered to detect differences between RA and control subjects, we identified a trend to narrowing of the 2nd MCP joints in RA (mean difference 250 µm, p=0.057). RA erosions most frequently occurred at the metacarpal head of the MCP joint, and HR-pQCT identified erosions in 24.7% more joints compared to plain radiography. CONCLUSIONS: This is the first study to exploit the quantitative capabilities of HR-pQCT to provide joint space width measurements at the MCP and PIP joints. We provide further proof that HR-pQCT improves erosion detection and yields reproducible periarticular bone microstructure measurements.

Efficacy of Allogeneic Hematopoietic Cell Transplantation for Autoimmune Diseases.

Allogeneic hematopoietic cell transplantation (HCT) may be efficacious for autoimmune diseases (AIDs), but its efficacy for individual AIDs is unknown. Factors influencing the likelihood of relapse for each AID are also unknown. This study aimed to determine the likelihood of relapse for each common AID and to generate hypotheses about factors influencing the likelihood of relapse. We reviewed charts of adult patients with nonhematologic AIDs who had undergone HCT in Alberta (n = 21) and patients described in the literature (n = 67). We used stringent inclusion criteria to minimize the inclusion of patients whose AID may have been cured before transplantation. We also used stringent definitions of AID relapse and remission. AID relapsed in 2 of 9 patients (22%) with lupus, in 4 of 12 (33%) with rheumatoid arthritis (RA), in 0 of 4 (0%) with systemic sclerosis (SSc), in 3 of 16 (19%) with psoriasis, in 1 of 12 (8%) with Behçet's disease (BD), in 1 of 15 (7%) with Crohn's disease (CD), in 0 of 5 (0%) with ulcerative colitis (UC), in 4 of 8 (50%) with multiple sclerosis (MS), and in 3 of 3 (100%) with type 1 diabetes mellitus (T1DM). Among highly informative patients (followed for >1 year after discontinuation of immunosuppressive therapy if no relapse, or donor AID status known if relapse), relapse occurred in 0 of 3 patients with lupus, in 2 of 7 with RA, in 0 of 2 with SSc, in 3 of 6 with psoriasis, in 0 of 3 with BD, in 0 of 10 with CD, in 0 of 3 with UC, in 2 of 3 with MS, and in 2 of 2 with T1DM. There appeared to be no associations between AID relapse and low intensity of pretransplantation chemoradiotherapy, multiple lines of AID therapy (surrogate for AID refractoriness) except perhaps for lupus, absence of serotherapy for graft-versus-host disease (GVHD) prophylaxis, lack of GVHD except perhaps for lupus, or incomplete donor chimerism. Even though remission commonly occurs after HCT in lupus, RA, SSc, psoriasis, BD, CD, and UC, HCT is efficacious for only a subset of patients. The efficacy appears to be unrelated to pretransplantation therapy, GVHD, or chimerism. Large studies are needed to determine the characteristics of patients likely to benefit from HCT for each AID.

The global burden of SLE: prevalence, health disparities and socioeconomic impact.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can potentially lead to serious organ complications and even death. Its global burden - in terms of incidence and prevalence, differential impact on populations, economic costs and capacity to compromise health-related quality of life - remains incompletely understood. The reported worldwide incidence and prevalence of SLE vary considerably; this variation is probably attributable to a variety of factors, including ethnic and geographic differences in the populations being studied, the definition of SLE applied, and the methods of case identification. Despite the heterogeneous nature of the disease, distinct patterns of disease presentation, severity and course can often be related to differences in ethnicity, income level, education, health insurance status, level of social support and medication compliance, as well as environmental and occupational factors. Given the potential for the disease to cause such severe and widespread organ damage, not only are the attendant direct costs high, but these costs are sometimes exceeded by indirect costs owing to loss of economic productivity. As an intangible cost, patients with SLE are, not surprisingly, likely to endure considerably reduced health-related quality of life.

Improving Appropriate Access to Care With Central Referral and Triage in Rheumatology.

OBJECTIVE: To evaluate the short-term and long-term impact of a centralized system for the intake and triage of rheumatology referrals on access to care and referral quality. METHODS: An innovative central referral process, the Central Referral and Triage in Rheumatology (CReATe Rheum) program, was implemented in 2006, serving a referral base of 2 million people. Referrals are received in a central office, triaged by trained nurses, and assigned to the next available appointment on a prioritized basis. To evaluate the short-term impact, we compared wait times, duplicate referrals, and no-shows from a pre-implementation practice audit to a 2-year post-implementation evaluation (January 2007 to December 2008). Rheumatologists also assessed the quality and completeness of the referral information and accuracy of the urgency category assigned during triage. We evaluated the long-term impact by tracking referral volume, wait times, and rheumatologist manpower each year until December, 2013. RESULTS: During the first 2 years, wait-time variability between rheumatologists decreased, and wait times were reduced for moderate and urgent referrals. CReATe Rheum improved the quality of referral information and eliminated duplicate referrals. The urgency of the referral was assigned correctly in 90% of referrals. Over the long term, CReATe Rheum maintained short wait times for more urgent patients despite a growing number of referrals and a stable number of rheumatologists. CONCLUSION: A centralized system for the intake and triage of rheumatology referrals improved referral quality, reduced system inefficiencies, and effectively managed wait times on a prioritized basis for a large referral population.

The effect of different remission definitions on identification of predictors of both point and sustained remission in rheumatoid arthritis treated with anti-TNF therapy.

OBJECTIVE: Predictors of remission in rheumatoid arthritis (RA) have been defined in cross-sectional analyses using the 28-joint Disease Activity Score (DAS28), but not with newer composite disease activity measures or using the more clinically relevant state of sustained remission. We have evaluated predictors of remission using cross-sectional and longitudinal durations of disease state, and by applying additional definitions of remission [American College of Rheumatology/European League Against Rheumatism Boolean, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI)]. METHODS: Individuals in the Alberta Biologics Pharmacosurveillance Program were classified for the presence of remission (point and/or sustained > 1 yr) by each of the 4 definitions. Multivariate models were constructed including all available variables in the dataset and refined to optimize model fit and predictive ability to calculate OR for remission. RESULTS: Nonsmoking status independently predicted point remission by all definitions (OR range 1.20-2.71). Minority ethnicity decreased odds of remission by DAS28 (OR 0.13) and CDAI (OR 0.09) definitions. Male sex was associated with DAS28 remission (OR 2.85), whereas higher baseline physician global (OR 0.67) and erythrocyte sedimentation rate values (OR 0.98) decreased odds of DAS28 remission. Higher baseline patient global score (OR 0.77) and swollen joint counts (OR 0.93) were negative predictors for CDAI remission. Higher baseline Health Assessment Questionnaire (OR 0.62) reduced odds for remission by the SDAI definition, and educational attainment increased these odds (OR 2.13). Sustained remission was negatively predicted by baseline physician global for the DAS28 (OR 0.80), and higher tender joint count (OR 0.96) for the CDAI. CONCLUSION: We demonstrate the influence of duration of remission state and remission definition on defining independent predictors for remission in RA requiring anti-tumor necrosis factor therapy. These predictors offer improved applicability for modern rheumatology practice.

Effect of remission definition on healthcare cost savings estimates for patients with rheumatoid arthritis treated with biologic therapies.

OBJECTIVE: Sustained remission in rheumatoid arthritis (RA) results in healthcare utilization cost savings. We evaluated the variation in estimates of savings when different definitions of remission [2011 American College of Rheumatology/European League Against Rheumatism Boolean Definition, Simplified Disease Activity Index (SDAI) ≤ 3.3, Clinical Disease Activity Index (CDAI) ≤ 2.8, and Disease Activity Score-28 (DAS28) ≤ 2.6] are applied. METHODS: The annual mean healthcare service utilization costs were estimated from provincial physician billing claims, outpatient visits, and hospitalizations, with linkage to clinical data from the Alberta Biologics Pharmacosurveillance Program (ABioPharm). Cost savings in patients who had a 1-year continuous period of remission were compared to those who did not, using 4 definitions of remission. RESULTS: In 1086 patients, sustained remission rates were 16.1% for DAS28, 8.8% for Boolean, 5.5% for CDAI, and 4.2% for SDAI. The estimated mean annual healthcare cost savings per patient achieving remission (relative to not) were SDAI $1928 (95% CI 592, 3264), DAS28 $1676 (95% CI 987, 2365), and Boolean $1259 (95% CI 417, 2100). The annual savings by CDAI remission per patient were not significant at $423 (95% CI -1757, 2602). For patients in DAS28, Boolean, and SDAI remission, savings were seen both in costs directly related to RA and its comorbidities, and in costs for non-RA-related conditions. CONCLUSION: The magnitude of the healthcare cost savings varies according to the remission definition used in classifying patient disease status. The highest point estimate for cost savings was observed in patients attaining SDAI remission and the least with the CDAI; confidence intervals for these estimates do overlap. Future pharmacoeconomic analyses should employ all response definitions in assessing the influence of treatment.

Clinical and serological features of patients referred through a rheumatology triage system because of positive antinuclear antibodies.

BACKGROUND: The referral of patients with positive anti-nuclear antibody (ANA) tests has been criticized as an inappropriate use of medical resources. The utility of a positive ANA test in a central triage (CT) system was studied by determining the autoantibody profiles and clinical diagnoses of patients referred to rheumatologists through a CT system because of a positive ANA test. METHODS: Patients that met three criteria were included: (1) referred to Rheumatology CT over a three year interval; (2) reason for referral was a "positive ANA"; (3) were evaluated by a certified rheumatologist. The CT clinical database was used to obtain demographic and clinical information and a serological database was used to retrieve specific ANA and/or extractable nuclear antigen (ENA) test results. Clinical information was extracted from the consulting rheumatologist's report. RESULTS: 15,357 patients were referred through the CT system; 643 (4.1%) of these because of a positive ANA and of these 263 (40.9%) were evaluated by a certified rheumatologist. In 63/263 (24%) of ANA positive patients, the specialist provided a diagnosis of an ANA associated rheumatic disease (AARD) while 69 (26.2%) had no evidence of any disease; 102 (38.8%) had other rheumatologic diagnoses and 29 (11%) had conditions that did not meet AARD classification criteria. Of ANA positive archived sera, 15.1% were anti-DFS70 positive and 91.2% of these did not have an AARD. CONCLUSIONS: This is the first study to evaluate the serological and clinical features of patients referred through a CT system because of a positive ANA. The spectrum of autoantibody specificities was wide with anti-Ro52/TRIM21 being the most common autoantibody detected. Approximately 15% of referrals had only antibodies to DFS70, the vast majority of which did not have clinical evidence for an AARD. These findings provide insight into the utility of autoantibody testing in a CT system.

Canadian estimates of health care utilization costs for rheumatoid arthritis patients with and without therapy with biologic agents.

OBJECTIVE: To provide Canadian estimates of health care utilization costs associated with rheumatoid arthritis (RA)-related and non-RA-related care within 4 treatment strategies and in different physical functioning categories. METHODS: In the Alberta Rheumatoid Arthritis Biologics Pharmacosurveillance Program, clinical data were linked with provincial health care administrative databases to estimate health care costs. A propensity score matching technique was used to evaluate annual costs across 4 treatment strategies: 1) remaining on disease-modifying antirheumatic drugs and not progressing to therapy with a biologic agent (n = 75), 2) progressing to biologic agents (n = 68), 3) initiation and stabilization on a first anti-tumor necrosis factor agent (n = 731), or 4) requiring a switch to another biologic agent (n = 212). Costs were examined across levels of function and by cost attribution category (directly related to RA or not). RESULTS: Of 1,222 patients, 1,086 had at least 3 months of administrative data. The mean annual total cost per patient was $5,531 (median $2,568), and $2,349 (median $0) was accounted for by hospitalizations, $1,716 (median $1,358) by physician visits, and $1,465 (median $949) by emergency room and other outpatient visits. Of these costs, 41% was directly related to RA itself or associated comorbidities. The importance of physical function as a determinant of health care utilization was evident, with the annual mean cost for those with low functional disability as measured by a Health Assessment Questionnaire (HAQ) score <0.5 was $4,157 compared to $14,225 for those with a HAQ score >2.0 indicating high disability. CONCLUSION: Health care costs for RA can be minimized by aiming for better disease control and maintaining physical function.

Reproducible metacarpal joint space width measurements using 3D analysis of images acquired with high-resolution peripheral quantitative computed tomography.

OBJECTIVE: Joint space narrowing is an important feature of progressive joint damage and functional impairment in rheumatoid arthritis (RA). Methods to provide a continuous measurement of joint space width have not been adopted in research or clinical settings. High-resolution peripheral quantitative computed tomography (HR-pQCT) (Scanco Medical AG, Brüttisellen, Switzerland) accurately and reproducibly images bone microstructure at a nominal isotropic voxel dimension of 82 µm. Given the ability of HR-pQCT to detect bone margins with high precision, we developed methodology to measure a three-dimensional (3D) metacarpophalangeal (MCP) joint space width and tested the reproducibility of the scan protocol with hand repositioning. MATERIALS AND METHODS: Consecutive HR-pQCT scans of the 2nd and 3rd MCP joints of ten subjects with early RA (70% female, mean age 45 years), with repositioning between scans, were obtained. The periosteal edges of the metacarpal head and proximal phalanx base were detected using the µCT Evaluation Program V6.0 (Scanco Medical AG). Using the method of 'fitting maximal spheres', the joint space width and distribution of joint space thickness was estimated. RESULTS: The mean minimum joint space width of the 2nd MCP was 1.82 mm (SD 0.20) and of the 3rd MCP 1.84 mm (SD 0.23). Reproducibility with repositioning was reliable, with overlapping filtered histograms and a root square mean coefficient of variance of 4.8%. CONCLUSIONS: We provide reproducible methodology for evaluating the joint space width of the MCP joints. When combined with the assessment of erosions and periarticular bone density, HR-pQCT may be the ideal technology to assess disease activity and progression in RA.

Infliximab therapy efficacy and persistence at a Canadian academic centre despite a change in access procedure.

Patients treated with infliximab at our centre through a special access programme (initiation group) had long-standing, treatment-resistant rheumatoid arthritis. The clinical experience for these patients may be different than that of patients initiating treatment after provincial government approval and cost coverage for all anti-tumour necrosis factor (anti-TNF) therapies became effective (contemporary group). We compared adverse events, drug survival and reasons for discontinuation in these two groups. A prospective cohort of patients treated with an anti-TNF therapy was assembled following the availability of infliximab in 2000. By protocol, patients are assessed for treatment response, discontinuation or switching of biologic agents and occurrence of adverse events. We report on 231 patients treated with infliximab therapy (680 patient-years). Both groups had similar drug survival (median 2.2 years) and rates of serious adverse events including infusion reactions (6.8 per 100 patient-years) and serious infections (3.4 per 100 patient-years). More patients in the initiation group discontinued infliximab for adverse events [39/139 (28%) vs. 15/92 (16%), p = 0.04] and developed drug-induced lupus [8/139 (6%) vs. 0%, p = 0.02]. Subsequent biologics were discontinued for the same reason as infliximab in only 12% (15/123) of cases. Patients treated with infliximab through a special access programme have comparable drug survival compared to a contemporary group, despite experiencing more adverse events. Only a minority of patients discontinuing infliximab due to the lack of effect or adverse events experience the same fate with subsequent anti-TNF agents.

Prevalence of systemic lupus erythematosus and systemic sclerosis in the First Nations population of Alberta, Canada.

OBJECTIVE: To estimate the population-based prevalence of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in Alberta, Canada, stratified by First Nations status. METHODS: Physician billing claims and hospitalization data for the province of Alberta (1994-2007) were used to ascertain cases of SLE and SSc using 3 case definitions. A latent class Bayesian hierarchical regression model was employed to account for the imperfect sensitivity and specificity of billing and hospitalization data in case ascertainment. We accounted for demographic factors, estimating prevalence rates for the First Nations and non-First Nations populations by sex, age group, and location of residence (urban/rural). RESULTS: Our model estimated the prevalence of SLE in Alberta to be 27.3 cases per 10,000 females (95% credible interval [95% CrI] 25.9-28.8) and 3.2 cases per 10,000 males (95% CrI 2.6-3.8). The overall prevalence of SSc in Alberta was 5.8 cases per 10,000 females (95% CrI 5.1-6.5) and 1.0 case per 10,000 males (95% CrI 0.7-1.4). First Nations females over 45 years of age had twice the prevalence of either SLE or SSc relative to non-First Nations females. There was also a trend toward higher overall SLE prevalence in urban dwellers, and higher overall SSc prevalence in rural residents. CONCLUSION: First Nations females older than 45 years of age have an increased prevalence of either SLE or SSc. This may reflect a true predominance of autoimmune rheumatic diseases in this demographic, or may indicate systematic differences in health care delivery.

Prevalence of autoimmune inflammatory myopathy in the first nations population of Alberta, Canada.

OBJECTIVE: To estimate the population-based prevalence of autoimmune inflammatory myopathy (AIM) in Alberta, Canada, with a specific focus on rates in the First Nations population. METHODS: Physician billing claims and hospitalization data for the province of Alberta (1994-2007) were used to estimate the probability of having AIM (i.e., polymyositis or dermatomyositis) based on 3 case definitions. A latent class Bayesian hierarchical regression model was employed to account for the imperfect sensitivity and specificity of billing and hospitalization data in case ascertainment. We accounted for demographic factors of sex, age group, and location of residence (urban or rural) in estimating the prevalence rates within the First Nations and non-First Nations populations. RESULTS: The overall prevalence of AIM was 25.0 per 100,000 persons (95% credible interval [95% CrI] 13.4-49.0) in the First Nations population and 33.8 (95% CrI 28.9-39.6) in the non-First Nations population. For both groups, prevalence was increased in women relative to men, rural women relative to urban women, and in those age >45 years. CONCLUSION: Unlike other rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, we did not detect an increased prevalence of AIM in Alberta's First Nations population relative to the non-First Nations population. Potential limitations include coding errors, underidentification of First Nations members, and recognized differences in access to care for the First Nations population.

The use and abuse of commercial kits used to detect autoantibodies.

The detection of autoantibodies in human sera is an important approach to the diagnosis and management of patients with autoimmune conditions. To meet market demands, manufacturers have developed a wide variety of easy to use and cost-effective diagnostic kits that are designed to detect a variety of human serum autoantibodies. A number of studies over the past two decades have suggested that there are limitations and concerns in the use and clinical application of test results derived from commercial kits. It is important to appreciate that there is a complex chain of users and circumstances that contributes to variations in the apparent reliability of commercial kits. The goal of this review is to identify the principal links in this chain, to identify the factors that weaken the chain and to propose a plan of resolution. It is suggested that a higher level of commitment and partnership between all of the participants is required to achieve the goal of improving the quality of patient care through the use of autoantibody testing and analysis.

Autoantibodies to tissue transglutaminase in Sjögren's syndrome and related rheumatic diseases.

OBJECTIVE: Sjögren's syndrome (SS) has been reported in up to 15% of patients with biopsy proven celiac disease (CD). The diagnosis of CD in the setting of SS and other systemic rheumatic diseases can be difficult because they are often associated with a number of gastrointestinal symptoms and diseases. Although the diagnosis of CD is often confirmed by a small bowel biopsy, marker autoantibodies directed against the endomysium of transitional epithelium (EMA) and tissue transglutaminase (tTG) are highly correlated with biopsy-proven disease and serve as a valuable screening test. We used an IgA-anti-tissue transglutaminase antibody (anti-tTG) ELISA to assess the prevalence of anti-tTG in an unselected cohort of patients with SS and other systemic rheumatic diseases. METHODS: Sera from 50 patients with SS, 50 with systemic lupus erythematosus (SLE), 50 with rheumatoid arthritis (RA), 30 with systemic sclerosis (SSc), and 50 healthy controls were tested for autoantibodies to tTG. A comparison group of 40 sera from patients with biopsy-confirmed CD was also included. IgA anti-tTG was measured by a commercially available ELISA kit (Inova, San Diego, CA) that employs purified tTG. RESULTS: Six of the 50 (12%) IgA sufficient SS patients had anti-tTG compared to 2 (4%) normal sera, 3 (6%) SLE, 2 (7%) SSc, and 1 (2%) RA. By comparison, in the CD cohort, 33 (83%) had anti-tTG. Five of 6 SS patients with anti-tTG had symptoms, signs, or small bowel biopsy findings consistent with a diagnosis of CD. IgA anti-tTG and EMA were accompanied by other IgA autoantibodies in SS sera. CONCLUSION: Anti-tTG ELISA is a reliable method to indicate a coexisting diagnosis of CD in patients with SS. Interestingly, the frequency of false positive tTG tests in any of the systemic rheumatic diseases is not significantly greater than in controls. Further, our study shows that anti-tTG is more prevalent in SS than in other systemic rheumatic diseases. The tTG ELISA may be used as a screening test to identify patients with SS who are at risk and require further evaluation for the presence of CD.