Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis.

OBJECTIVE: To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America. METHODS: Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history. RESULTS: Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (pBonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (pBonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment. CONCLUSION: Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.

Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis.

OBJECTIVE: To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). METHODS: GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. RESULTS: Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema. CONCLUSION: We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.

Comprehensive treatment of dactylitis in psoriatic arthritis.

Dactylitis, a hallmark clinical feature of psoriatic arthritis (PsA) and other spondyloarthropathies, may also be a severity marker for PsA and psoriasis. Traditionally, clinicians have used nonsteroidal antiinflammatory drugs and local corticosteroid injections to treat dactylitis, although conventional disease-modifying antirheumatic drugs are also used. We performed a systematic literature review to determine the most efficacious current treatment options for dactylitis in PsA. Effect sizes were greatest for the biologic agents ustekinumab, certolizumab, and infliximab, suggesting that therapy with one of these agents should be initiated in patients with dactylitis. However, the limited data highlight the need for randomized, placebo-controlled trials, with dactylitis as a primary outcome, to determine a valid, reliable, and responsive clinical outcome measure for PsA patients with dactylitis.

Diffuse idiopathic skeletal hyperostosis in psoriatic arthritis.

OBJECTIVE: To determine the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in patients with psoriatic arthritis (PsA) and to identify the features associated with its occurrence. METHODS: Patients were recruited from the University of Toronto PsA observational cohort initiated in 1978. All patients fulfilled the CASPAR criteria. Radiographs of peripheral joints and spine were obtained every 2 years. DISH was defined as flowing bony bridges in at least 4 contiguous thoracic vertebrae. Each PsA patient with DISH was matched by sex to 3 PsA patients without DISH. Demographics, disease characteristics, and radiographic features were compared using McNemar test, Fisher's exact test, chi-square test, and paired t test as appropriate. Logistic regression analyses models with stepwise regression were conducted. RESULTS: DISH was observed in 78 (8.3%) of 938 patients with PsA. Patients with DISH were older and had longer disease duration, higher body mass index (BMI), and higher uric acid levels. Diabetes and hypertension were more prevalent in patients with DISH than in those without. The severity of radiographic damage to peripheral joints was also greater in patients with DISH. The presence of inflammatory back pain, HLA-B*27 allele, and sacroiliitis was similar in both groups. Patients with DISH had more syndesmophytes and calcaneal spurs. Older age, higher BMI, and the presence of radiographic damage to peripheral joints were associated with DISH in multivariate analysis. CONCLUSION: The diagnosis of DISH is possible in the presence of axial PsA. DISH was associated with known DISH-related factors including older age and high BMI, as well as the presence of radiographic damage to peripheral joints.

Psoriasis and psoriatic arthritis in Peruvian aborigines: a report from the GRAPPA 2011 annual meeting.

OBJECTIVE: To determine the presence of psoriasis and psoriatic arthritis (PsA) in aboriginal people living in the Andean Mountains of Peru. METHODS: Consecutive patients with psoriasis and PsA attending an arthritis clinic in Juliaca, Puno, Peru, located 3824 m above sea level were examined. The CASPAR (ClASsification of Psoriatic ARthritis) criteria were used for classification of PsA. Diagnosis of psoriasis was confirmed by a dermatologist. RESULTS: Seventeen patients [11 (65%) men and 6 (35%) women] fulfilled classification criteria for PsA; one patient was of European ancestry and is not included in this report. Of the 16 aboriginal patients in this report, 5 were natives of Quechua ancestry and one was native Aymara. At the time of their first clinic visit, no native patient with PsA had a family history of psoriasis or PsA, and all patients exhibited an established disease of long duration and severity. Methotrexate was the drug of choice for all patients; 2 patients are currently receiving biological therapy. CONCLUSION: Contrary to what has been reported in the literature, both psoriasis and PsA are present in aboriginal people from the Andean Mountains of Peru. More studies are needed to further define the phenotype of these disorders, as well as the pathogenetic role of genetic and environmental factors.

Global partnering opportunities and challenges of psoriasis and psoriatic arthritis in Latin America: a report from the GRAPPA 2010 annual meeting.

Documenting the disease burden of psoriasis and psoriatic arthritis (PsA) in Central and South America is difficult. The most conclusive data have come from the Iberoamerican Registry of Spondyloarthritis (RESPONDIA), which registered patients with a diagnosis of spondyloarthritis in a multinational, multicenter (Argentina, Brazil, Costa Rica, Chile, Mexico, Peru, Uruguay, Venezuela, Spain, and Portugal) cross-sectional study conducted between 2006 and 2007. Compared with elsewhere in the Western world, patients with PsA from RESPONDIA were older at study visit, at onset of symptoms, and at diagnosis of spondyloarthritis (SpA); had longer mean disease duration from onset of symptoms to diagnosis; and were more likely to have dactylitis, nail involvement, enthesitis, and peripheral arthritis in lower and upper extremities. It is critical to understand the biologic basis, estimate the disease burden, and determine the clinical treatment of PsA in Latin America. The Group for Research and Assessment of Psoriasis and PsA (GRAPPA) has an increasing number of members from this region. In a coordinated effort, GRAPPA, the Latin American Psoriasis and PsA Society (LAPPAS), and the Pan American League of Associations for Rheumatology (PANLAR) are supporting clinician researchers with educational initiatives in Latin America to understand these conditions.

International multicenter psoriasis and psoriatic arthritis reliability trial for the assessment of skin, joints, nails, and dactylitis.

OBJECTIVE: Clinical trials in psoriasis and psoriatic arthritis (PsA) involve assessment of the skin and joints. This study aimed to determine whether assessment of the skin and joints in patients with PsA by rheumatologists and dermatologists is reproducible. METHODS: Ten rheumatologists and 9 dermatologists from 7 countries met for a combined physical examination exercise to assess 20 PsA patients (11 men, mean age 51 years, mean PsA duration 11 years). Each physician assessed 10 patients according to a modified Latin square design that enabled the assessment of patient, assessor, and order effect. Tender joint count (TJC), swollen joint count (SJC), dactylitis, physician's global assessment (PGA) of PsA disease activity (PGA-PsA), psoriasis body surface area (BSA), Psoriasis Area and Severity Index (PASI), Lattice System Physician's Global Assessment of psoriasis (LS-PGA), National Psoriasis Foundation Psoriasis Score (NPF-PS), modified Nail Psoriasis Severity Index (mNAPSI), number of fingernails with nail changes (NN), and PGA of psoriasis activity (PGA-Ps) were assessed. Variance components analyses were carried out to estimate the intraclass correlation coefficient (ICC), adjusted for the order of measurements. RESULTS: There is excellent agreement (ICC >/=0.80) on the mNAPSI, substantial agreement (0.6 >/= ICC < 0.80) on the TJC, PASI, and NN, moderate agreement (0.4 >/= ICC < 0.60) on the PGA-Ps, LS-PGA, NPF-PS, and BSA, and fair agreement (0.2 >/= ICC < 0.40) on the SJC, dactylitis, and PGA-PsA. The only measure that showed a significant difference between dermatologists and rheumatologists was dactylitis (P = 0.0005). CONCLUSION: There is substantial to excellent agreement on the TJC, PASI, NN, and mNAPSI among rheumatologists and dermatologists.

Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries.

OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study.

INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients.

OBJECTIVE: Venous thrombosis is a relatively frequent and serious complication in systemic lupus erythematosus (SLE) that has been associated with the presence of antiphospholipid antibodies (aPL). However, venous thrombotic events can also be seen in patients without aPL, and only a few patients with aPL develop venous thrombosis. This study was carried out to ascertain other factors contributing to the development of venous thrombosis in SLE. METHODS: Patients with SLE, ages > or = 16 years with < or = 5 years disease duration and of Hispanic, African American, or Caucasian ethnicity, from LUMINA (LUpus in MInorities, NAture versus nurture), a multiethnic, longitudinal study of outcome, were studied. Selected socioeconomic/demographic, clinical, laboratory, and treatment-exposure variables were compared between patients who developed and those who did not develop venous thrombotic events. Significant and clinically relevant variables were then entered into different multivariable models (Cox proportional hazards and unconditional stepwise logistic regression) to identify independent risk factors associated with the primary outcome. In another model, only patients who developed an event after enrollment (time 0) in the cohort were included. RESULTS: Of 570 LUMINA patients, 51 developed at least 1 venous thrombotic event after SLE diagnosis. In univariable analyses, smoking (P = 0.020), shorter disease duration at time 0 (P = 0.017), serum levels of total cholesterol, low-density lipoprotein, and triglycerides (all P < 0.0001), and presence of lupus anticoagulant (LAC) (P = 0.045) were associated with venous thrombotic events. Survival analyses showed a time-dependent significant association of the primary outcome with smoking (P = 0.008) and a borderline significant association with the presence of LAC (P = 0.070). Multivariable models showed an independent association with smoking, age at time 0, disease activity over time, LAC, mean dose of glucocorticoids, and shorter disease duration at time 0. CONCLUSION: Venous thrombotic events occur early in the course of SLE. Our data confirm the association between LAC and venous thrombotic events. Smoking, shorter disease duration, older age, disease activity over time, and higher mean daily glucocorticoid dose were identified as additional risk factors for the development of this vascular complication. These findings may have implications for the management of patients with SLE.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXIII. Baseline predictors of vascular events.

OBJECTIVE: To determine the baseline (time 0) risk factors associated with the subsequent occurrence of vascular events in a multiethnic US cohort (LUMINA [LUpus in MInorities: NAture versus nurture]) of patients with systemic lupus erythematosus (SLE). METHODS: Five hundred forty-six LUMINA patients were assessed at time 0 for traditional and nontraditional (disease-related) risk factors for vascular events. These were defined as 1) cardiovascular (myocardial infarction and/or definite or classic angina and/or the undergoing of a vascular procedure for myocardial infarction [coronary artery bypass graft]), 2) cerebrovascular (stroke), and 3) peripheral vascular (arterial claudication and/or gangrene or significant tissue loss and/or arterial thrombosis in peripheral arteries). The observation time (followup time in the cohort) was the interval between time 0 and the last visit. The unit of analysis was the patient and not each vascular event. Variables at time 0 and vascular events were examined by univariable and multivariable (logistic and Cox proportional hazards regression) analyses. Age, sex, ethnicity, followup time, and all known risk factors for the occurrence of vascular events were included in the model. RESULTS: Thirty-four patients (6.2%) developed one or more vascular event after time 0. The overall median duration of followup in the cohort was 73.8 months (range 10.8-111.3 months). Vascular events (13 cardiovascular, 18 cerebrovascular, 5 peripheral vascular) occurred in 7 Hispanics from Texas (6.5%), 1 Hispanic from Puerto Rico (1.2%), 15 African Americans (7.5%), and 11 Caucasians (7.1%). The mean total number of traditional risk factors was significantly higher in patients who developed vascular events than in those who did not (7.1 versus 5.6). Independent predictors of vascular events were older age, current smoking status, longer followup time, elevated serum levels of C-reactive protein (CRP), and the presence of any antiphospholipid antibody. The same variables were identified when time-dependent analyses were performed, although azathioprine use was also found to be a contributing factor. CONCLUSION: Smoking, previously not reported in SLE, emerged as a predictor of vascular events and should be strongly discouraged. Antiphospholipid antibodies and CRP support the role of inflammation and autoimmunity in the development of accelerated atherosclerosis in SLE. Ethnicity was not associated with vascular events in our patients.

Caracteristicas clinico-epidemiologicas de la diarrea aguda del adulto en un hospital de la ciudad de Cordoba / Clinical and epidemiologic characteristics of acute diarrhea of the adult in a hospital from Cordoba city

El objetivo de este estudio fue observar las principales características clínicas y epidemiológicas de la presentación de la diarrea aguda del adulto en un hospital público de la ciudad de Córdoba. Para su realización se incluyeron todos los pacientes mayores de 14 años que concurrieron a la Guardia Central del Hospital Nacional de Clínicas con diarrea aguda durante los períodos A(15-12-89 al 15-3-90), B(15-12-93 al 15-3-94), y C(15-12-94 al 15-3-95). El total de pacientes incluídos en los 3 períodos fue de 594: 337 mujeres (65,7 por ciento) y 257 varones; 143 consultaron en el período A, 250 en el B y 201 en el C. El promedio + DE de edad fue 34,6 + 13,3 años y de deposiciones diarias al momento de la consulta 7,3 + 4,7. El 86,1 por ciento presentó materia fecal de consistencia líquida durante el pisodio, 89,6 por ciento dolor abdominal, 44,7 por ciento vómitos y 18,8 por ciento sangre. El porcentaje de pacientes que concurrieron al hospital por diarrea aguda en relación al total de consultas aumentó del período A (2,47 por ciento) al B (3,61 por ciento), p=0,002 y disminuyó del período B al C(2,85 por ciento), p=0,01. Los promedios + DE de días transcurridos desde el inicio del cuadro hasta la consulta fueron 3,5 + 2,7 + 2,3 y 2,9 + 3,5 en los períodos A, B y C, diferencia estadísticamente significativa entre A y B, p<0,01. Presentó moco en la material fecal el 36,2 por ciento, 21.1 por ciento y 23,1 por ciento de los pacientes en los períodos A, B y C (p=0,01) y fiebre constatada el 61,1 por ciento, 48,1 por ciento y 48,5 por ciento respectivamente (p=0,04). El 27.1 por ciento de los coprocultivos resultó positivo en el período A, 17,6 por ciento en el B y 11,5 por ciento en el C; diferencia entre a y C: p=0,008. Se concluye que en un hospital público de la ciudad de Córdoba la diarrea aguda del adulto es causa frecuente de consulta, constatándose modificaciones de las características clínico-epidemiológicas en los ultimos años.