Relationship Between Genetic Risk and Age of Diagnosis in Systemic Lupus Erythematosus.

OBJECTIVE: Specific risk alleles for childhood-onset systemic lupus erythematosus SLE (cSLE) vs adult-onset SLE (aSLE) patients have not been identified. The aims of this study were to determine if there is an association (1) between non-HLA-related genetic risk score (GRS) and age of SLE diagnosis, and (2) between HLA-related GRS and age of SLE diagnosis. METHODS: Genomic DNA was obtained from 2001 multiethnic patients and genotyped using the Immunochip. Following quality control, genetic risk counting (GRCS), weighted (GRWS), standardized counting (GRSCS), and standardized weighted (GRSWS) scores were calculated based on independent single-nucleotide polymorphisms from validated SLE loci. Scores were analyzed in a regression model and adjusted by sex and ancestral population. RESULTS: The analyzed cohort consisted of 1540 patients: 1351 females and 189 males (675 cSLE and 865 aSLE). There were significant negative associations between all non-HLA GRS and age of SLE diagnosis: P = 0.011 and r2 = 0.175 for GRWS; P = 0.008 and r2 = 0.178 for GRSCS; P = 0.002 and r2 = 0.176 for GRSWS (higher GRS correlated with lower age of diagnosis.) All HLA GRS showed significant positive associations with age of diagnosis: P = 0.049 and r2 = 0.176 for GRCS; P = 0.022 and r2 = 0.176 for GRWS; P = 0.022 and r2 = 0.176 for GRSCS; P = 0.011 and r2 = 0.177 for GRSWS (higher GRS correlated with higher age of diagnosis). CONCLUSION: Our data suggest that there is a linear relationship between genetic risk and age of SLE diagnosis and that HLA and non-HLA GRS are associated with age of diagnosis in opposite directions.

Persistent Disease Activity Remains a Burden for Patients with Systemic Lupus Erythematosus.

OBJECTIVE: Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time. METHODS: Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K. RESULTS: There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years. CONCLUSION: Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

Improving Access to Rheumatologists: Use and Benefits of an Electronic Consultation Service.

OBJECTIVE: To describe the use and benefits of an innovative eConsult service to improve access to rheumatologists. METHODS: There were 225 eConsults directed to rheumatology that were categorized by type of question and effect on face-to-face referral rates. RESULTS: The median response time by the rheumatologists was 1.9 days. Clinical questions included drug treatment (34%), diagnosis (26%), or management (14%). Osteoporosis was the most common diagnosis (22%), followed by pain in multiple joints (11%), and polyarthritis (10%). A face-to-face referral was avoided in 38% of cases. CONCLUSION: There are clinical questions that can be answered quickly by an eConsult, improving access to rheumatologists.

Influence of Education on Disease Activity and Damage in Systemic Lupus Erythematosus: Data From the 1000 Canadian Faces of Lupus.

OBJECTIVE: To determine whether socioeconomic status assessed by education is associated with disease activity and the risk of organ damage in systemic lupus erythematosus (SLE). METHODS: Data from the 1000 Canadian Faces of Lupus, a multicenter database of adult SLE patients, was used to compare education as either low (did not complete high school) or high (completed high school or further) for disease activity and damage. Education was also studied as a continuous variable. The relationships between education and SLE outcomes (any organ damage defined as a Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI] score ≥1, serious organ damage [SDI score ≥3], and end-stage renal disease) were evaluated using logistic regression analyses adjusted for age, sex, race/ethnicity, and disease duration. RESULTS: A total of 562 SLE patients met inclusion criteria (mean age 47 years, 91% female, and mean disease duration of 10 years); 81% had high education. The low education group was twice as likely to be work disabled (30%; P < 0.0001); they had higher disease activity and reduced renal function. Linear regression analysis revealed that low education was significantly associated with higher disease activity at enrollment into the 1000 Canadian Faces of Lupus database, after adjustment for age (at entry and at diagnosis), race/ethnicity, and sex (B 1.255 + 0.507 [SE], ß = 0.115, P = 0.014). In our adjusted logistic regression models we were unable to demonstrate significant associations between education and SLE damage. Results did not change when varying the education variable. CONCLUSION: In this cohort, low education was associated cross-sectionally with higher disease activity and work disability, but not damage.

Treatment Algorithms in Systemic Lupus Erythematosus.

OBJECTIVE: To establish agreement on systemic lupus erythematosus (SLE) treatment. METHODS: SLE experts (n = 69) were e-mailed scenarios and indicated preferred treatments. Algorithms were constructed and agreement determined (≥50% respondents indicating ≥70% agreement). RESULTS: Initially, 54% (n = 37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus: first-line therapy was topical agents and hydroxychloroquine and/or glucocorticoids then azathioprine and subsequently mycophenolate (mofetil); uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids ± hydroxychloroquine ± methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine and/or glucocorticoids, then methotrexate and subsequently rituximab; pericarditis: first-line therapy was nonsteroidal antiinflammatory drugs, then glucocorticoids with/without hydroxychloroquine, then azathioprine, mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a pericardial window; interstitial lung disease/alveolitis: induction was glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies, subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids and rituximab; antiphospholipid antibody syndrome: standard anticoagulation with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events; mononeuritis multiplex and central nervous system vasculitis: first-line therapy was glucocorticoids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and then rituximab, IVIG, or plasmapheresis; and serious lupus nephritis: first-line therapy was glucocorticoids and mycophenolate, then cyclophosphamide then rituximab. CONCLUSION: We established variable agreement on treatment approaches. For some treatment decisions there was good agreement between experts even if no randomized controlled trial data were available.

Transformation of meaning perspectives in clients with rheumatoid arthritis.

The purpose of this qualitative study was to examine the process of transformation of personal beliefs, values, feelings, and knowledge (meaning perspectives) underlying occupational change in a small group of clients with rheumatoid arthritis during home-based rehabilitation. A grounded theory approach used to collect and analyze data concurrently included: (1) a sample of five adult clients diagnosed with rheumatoid arthritis in occupational therapy, (2) data collection through 28 semi-directed interviews, and (3) data analysis using the constant comparison method. The study identified meaning perspectives of these clients with rheumatoid arthritis and explored the transformation of perspectives related to the modification of occupational performance. The study suggests that the exploration of meaning perspective transformation by clients and therapists could be a potential part of rehabilitation intervention.

Association of smoking with cutaneous manifestations in systemic lupus erythematosus.

OBJECTIVE: To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE). METHODS: We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data. RESULTS: In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials. CONCLUSION: Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.

Neuropsychiatric lupus: the prevalence and autoantibody associations depend on the definition: results from the 1000 faces of lupus cohort.

OBJECTIVES: The (ever) prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) can vary widely depending on the definition used. We determined the prevalence of NPSLE in 1000 Faces of Lupus, a large multicenter Canadian cohort. METHODS: Adults enrolled at 10 sites who satisfied the American College of Rheumatology (ACR) classification for systemic lupus erythematosus (SLE) were included. NPSLE was defined as (i) NPSLE by ACR classification criteria (seizures or psychosis), (ii) ACR, SLEDAI (seizure, psychosis, organic brain syndrome, cranial nerve disorder, headache, and cerebrovascular accident (CVA)), SLAM (CVA, seizure, cortical dysfunction, and headache), and SLICC (cognitive impairment, psychosis, seizures, CVA, cranial or peripheral neuropathy, and transverse myelitis) with and (iii) without minor nonspecific NPSLE manifestations (including mild depression, mild cognitive impairment, and electromyogram-negative neuropathies), and (iv) by ACR and SLEDAI neuropsychiatric (NP) indexes alone. Factors associated with NPSLE were explored using regression models. RESULTS: Cohort size was 1253, with mean disease 12 ± 10 years, mean age 41 ± 16 years, and 86% female. Subgroup size was dependent on the specific definition of NPSLE. Prevalence of NPSLE was 6.4% in group (i), n = 1253 (n = 80); 38.6% in group (ii), n = 681(n = 263); 28.7% in group (iii), n = 586 (n = 168); and 10.2% in group (iv), n = 1125 (n = 115). In univariate analysis, Aboriginals had a nearly 2-fold increase in frequency of NPSLE in all groups. Education level and income were not associated with NPSLE (P = 0.32 and 0.03, respectively). As well, number of ACR criteria, SLAM, age at diagnosis, disease duration, and gender were not associated with NPSLE. Anti-Ro was significantly associated in groups (i) and (iv) and antiphospholipid antibodies (aPL) were increased in groups (i), (ii), and (iii); however, this lost significance when thromboembolic events were excluded from SLICC, SLEDAI, and SLAM indexes. In group (iv), absence of anti-Sm was significant. In multivariate analysis, anti-Ro and aPL (i) and anti-Ro+ and lack of anti-Sm (iv) were significant. NPSLE was not increased in those with +anti-DNA, La, or ribonucleoprotein (RNP), lupus anticoagulant (LAC), or anticardiolipin (aCL) antibody. CONCLUSIONS: The prevalence and factors associated with NPSLE varied depending on the definition used, was highest in Aboriginals, and may be higher if +anti-Ro or aPL are present. SLAM and SLICC include mild subjective disease manifestations, which contributed to a 10% higher prevalence of NPSLE compared to a more strict definition. NPSLE may be less in this database than other publications as its overall prevalence may be decreasing, or because of selection bias inherent to those who enter an observational cohort. NPSLE was associated with aPL and often anti-Ro and varied by ethnicity.

Cutaneous vasculopathy associated with cocaine use.

OBJECTIVE: Cocaine is known to cause thrombotic complications. Its use has also been associated with a variety of rheumatologic manifestations, most notably cutaneous vasculopathy. We report clinical features and laboratory findings of cocaine-related cutaneous vasculopathy. METHODS: Here we describe 8 patients with cocaine-related cutaneous vasculopathy. RESULTS: Our patients most commonly presented with purpuric lesions and ulcers with areas of skin necrosis. Extracutaneous features included fatigue and arthritis in most patients, as well as weight loss in 3 patients, pneumonia in 3, diffuse reactive lymphadenopathy in 1, and acute upper airway obstruction in 2. Laboratory abnormalities included elevated inflammatory markers and positive perinuclear antineutrophil cytoplasmic antibodies (ANCAs) in all patients, and antimyeloperoxidase antibodies in 7 of 8 patients. Cytoplasmic ANCA was positive in 5 of 8, equivocal in 2 of 8, and negative in 1 of 8 patients. Anti-proteinase 3 antibodies were found in 6 of 8 patients. Six of 8 patients had positive antinuclear antibodies and 5 of 8 had positive anti-double-stranded DNA antibodies (4 of 5 were at low titers). Two patients previously thought to have systemic lupus erythematosus had low complement levels. Lupus anticoagulant was positive in 3 of 8 and equivocal in 5 of 8. Anticardiolipin IgG was positive in 1 of 8 and IgM was positive in 6 of 8; ß(2) -glycoprotein I IgM was positive in 2 of 8. Cold agglutinins were strongly positive in 6 of 6 patients in whom they were measured. Skin disease improved in 3 patients who appeared to have stopped using cocaine. It was chronic and progressive in 4 patients who continued to use cocaine, 2 of whom died presumably due to multidrug overdose. CONCLUSION: This report outlines clinical features and distinctive laboratory findings that, when present in the right clinical setting, should prompt consideration of cocaine-related cutaneous vasculopathy.

Medication use in systemic lupus erythematosus.

OBJECTIVE: To evaluate factors affecting therapeutic approaches used in clinical practice for the management of systemic lupus erythematosus (SLE), in a multicenter cohort. METHODS: We combined data from 10 clinical adult SLE cohort registries in Canada. We used multivariate generalized estimating equation methods to model dichotomized outcomes, running separate regressions where the outcome was current exposure of the patient to specific medications. Potential predictors of medication use included demographic (baseline age, sex, residence, race/ethnicity) and clinical factors (disease duration, time-dependent damage index scores, and adjusted mean SLE Disease Activity Index-2K scores). The models also adjusted for clustering by center. RESULTS: Higher disease activity and damage scores were each independent predictors of exposure to nonsteroid immunosuppressive agents, and for exposure to prednisone. This was not definitely demonstrated for antimalarial agents. Older age at diagnosis was independently and inversely associated with exposure to any of the agents studied (immunosuppressive agents, prednisone, and antimalarial agents). An additional independent predictor of prednisone exposure was black race/ethnicity (adjusted RR 1.46, 95% CI 1.18, 1.81). For immunosuppressive exposure, an additional independent predictor was race/ethnicity, with greater exposure among Asians (RR 1.39, 95% CI 1.02, 1.89) and persons identifying themselves as First Nations/Inuit (2.09, 95% CI 1.43, 3.04) than among whites. All of these findings were reproduced when adjustment for disease activity was limited to renal involvement. CONCLUSION: Ours is the first portrayal of determinants of clinical practice patterns in SLE, and offers interesting real-world insights. Further work, including efforts to determine how differing clinical approaches may influence outcome, is in progress.

Arsenic mobilization in a seawater inundated acid sulfate soil.

Tidal seawater inundation of coastal acid sulfate soils can generate Fe- and S0(4)-reducing conditions in previously oxic-acidic sediments. This creates potential for mobilization of As during the redox transition. We explore the consequences for As by investigating the hydrology, porewater geochemistry, solid-phase speciation, and mineralogical partitioning of As across two tidal fringe toposequences. Seawater inundation induced a tidally controlled redox gradient Maximum porewater As (~400 µg/L) occurred in the shallow (<1 m), intertidal, redox transition zone between Fe-oxidizing and S0(4)-reducing conditions. Primary mechanisms of As mobilization include the reduction of solid-phase As(V) to As(lll), reductive dissolution of As(V)-bearing secondary Fe(lll) minerals and competitive anion desorption. Porewater As concentrations decreased in the zone of contemporary pyrite reformation. Oscillating hydraulic gradients caused by tidal pumping promote upward advection of As and Fe(2+)-enriched porewater in the intertidal zone, leading to accumulation of As(V)-enriched Fe(lll) (hydr)oxides at the oxic sediment-water interface. While this provides a natural reactive-Fe barrier, it does not completely retard the flux of porewater As to overtopping surface waters. Furthermore, the accumulated Fe minerals may be prone to future reductive dissolution. A conceptual model describing As hydro-geochemical coupling across an intertidal fringe is presented.

Clinical and serologic factors associated with lupus pleuritis.

OBJECTIVE: Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort. METHODS: We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression. RESULTS: In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (+/- SD) was 46.8 +/- 13.5 years, and disease duration at study entry was 12.1 +/- 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p

Resident evaluations: the use of daily evaluation forms in rheumatology ambulatory care.

OBJECTIVE: The in-training evaluation report (ITER) is widely used to assess clinical skills, but has limited validity and reliability. The purpose of our study was to assess the feasibility, validity, reliability, and effect on feedback of using daily evaluation forms to evaluate residents in ambulatory rheumatology clinics. METHODS: An evaluation form was developed based on the Royal College of Physicians and Surgeons of Canada CanMEDS roles. There were 12 evaluation items including overall clinical competence. They were rated on a 5-point scale from unsatisfactory to outstanding. All internal medicine residents rotating on rheumatology were strongly encouraged to provide the form to their preceptor at the end of each clinic. A questionnaire was administered to residents and faculty. RESULTS: Seventy-three internal medicine residents completed a 1-month rotation at University of Ottawa (n=26) and McMaster University (n=47). Faculty members completed a total of 637 evaluation forms. The number of evaluation forms ranged from 2 to 16 (mean 8.73) per resident. At an average of 8.73 forms per resident the reliability was 0.71 for the composite score. Fourteen forms would be required for a reliability of 0.8. The correlation between the objective structured clinical examination scores and the forms was 0.48 (p=not significant). Faculty and residents reported increased feedback following implementation of the forms. CONCLUSION: The use of daily evaluation forms is feasible and provides very good reliability. Use of the evaluation forms increases feedback to residents on their performance. The forms were well received by faculty and residents.

The 1000 Canadian faces of lupus: determinants of disease outcome in a large multiethnic cohort.

OBJECTIVE: To describe disease expression and damage accrual in systemic lupus erythematosus (SLE), and determine the influence of ethnicity and socioeconomic factors on damage accrual in a large multiethnic Canadian cohort. METHODS: Adults with SLE were enrolled in a multicenter cohort. Data on sociodemographic factors, diagnostic criteria, disease activity, autoantibodies, treatment, and damage were collected using standardized tools, and results were compared across ethnic groups. We analyzed baseline data, testing for differences in sociodemographic and clinical factors, between the different ethnic groups, in univariate analyses; significant variables from univariate analyses were included in multivariate regression models examining for differences between ethnic groups, related to damage scores. RESULTS: We studied 1416 patients, including 826 Caucasians, 249 Asians, 122 Afro-Caribbeans, and 73 Aboriginals. Although the overall number of American College of Rheumatology criteria in different ethnic groups was similar, there were differences in individual manifestations and autoantibody profiles. Asian and Afro-Caribbean patients had more frequent renal involvement and more exposure to immunosuppressives. Aboriginal patients had high frequencies of antiphospholipid antibodies and high rates of comorbidity, but disease manifestations similar to Caucasians. Asian patients had the youngest age at onset and the lowest damage scores. Aboriginals had the least education and lowest incomes. The final regression model (R2=0.27) for higher damage score included older age, longer disease duration, low income, prednisone treatment, higher disease activity, and cyclophosphamide treatment. CONCLUSION: There are differences in lupus phenotypes between ethnic populations. Although ethnicity was not found to be a significant independent predictor of damage accrual, low income was.

Steroid-sparing effects of methotrexate in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To assess the potential benefits of methotrexate in patients with systemic lupus erythematosus (SLE). METHODS: A 12-month, double-blind, placebo-controlled trial of methotrexate with folic acid was conducted. Intent-to-treat analyses were performed with mixed linear models and alpha = 0.04 (96% confidence interval [96% CI]) to account for interim analysis of longitudinal data to assess the treatment effects on lupus disease activity and daily steroid dose across monthly measurements, and to test if the treatment effects depended on selected participant characteristics. RESULTS: Of 215 participants screened, 94 were excluded, 35 declined, and 86 were randomized (methotrexate = 41, placebo = 45). The groups were balanced for demographic and disease characteristics. Antimalarial use was more frequent in the placebo group, which was adjusted for in multivariable analyses. Sixty participants (27 methotrexate, 33 placebo) completed the study and 26 terminated early. Among participants who had the same baseline prednisone dose, those taking methotrexate received, on average, 1.33 mg/day less prednisone during the trial period (96% CI 0.06, 2.72 mg/day; a 22% reduction of their average-during-trial daily dose) compared with those in the placebo group. For the primary measure of disease activity (revised Systemic Lupus Activity Measure), methotrexate use was also associated with a marginally significant reduction in the mean during-trial score of 0.86 units (96% CI 0.01, 1.71; P = 0.039). A significant interaction between treatment and baseline damage was found (P = 0.001). CONCLUSION: Methotrexate conferred a significant advantage in participants with moderately active lupus by lowering daily prednisone dose and slightly decreasing lupus disease activity. As a therapeutic option in moderate SLE, methotrexate can be considered to be steroid sparing.

Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity.

INTRODUCTION: Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. METHODS: Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. RESULTS: We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. CONCLUSIONS: The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity.

Teaching the musculoskeletal examination: are patient educators as effective as rheumatology faculty?

BACKGROUND: Effective education of clinical skills is essential if doctors are to meet the needs of patients with rheumatic disease, but shrinking faculty numbers has made clinical teaching difficult. A solution to this problem is to utilize patient educators. PURPOSE: This study evaluates the teaching effectiveness of patient educators compared to rheumatology faculty using the musculoskeletal (MSK) examination. METHOD: Sixty-two 2nd-year medical students were randomized to receive instruction from patient educators or faculty. Tutorial groups received instructions during three, 3-hr sessions. Clinical skills were evaluated by a 9 station objective structured clinical examination. Students completed a tutor evaluation form to assess their level of satisfaction with the process. RESULTS: Faculty-taught students received a higher overall mark (66.5% vs. 62.1%,) and fewer failed than patient educator-taught students (5 vs. 0, p = 0.02). Students rated faculty educators higher than patient educators (4.13 vs. 3.58 on a 5-point Likert scale). CONCLUSION: Rheumatology faculty appear to be more effective teachers of the MSK physical exam than patient educators.