Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

Predictors of severe hemolytic anemia and its impact on major outcomes in systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

OBJECTIVE: To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. METHODS: Factors associated with time to severe AIHA (hemoglobin level ≤7 g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. RESULTS: Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111 days (IQR 43-450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02-4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01-1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91-6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. CONCLUSIONS: Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.

Factors associated with neuropsychiatric involvement in Latin American patients with systemic lupus erythematosus.

INTRODUCTION: Factors related to presentation of neuropsychiatric (NP) SLE manifestations, early in the course of the disease, and during follow up have not been clearly established. PURPOSE: To identify disease and non-disease related factors associated with NP manifestations in early SLE. METHODS: We included 1193 patients from the GLADEL inception cohort free of NP involvement at cohort entry. We evaluated the association of demographic, clinical and laboratory data with NP involvement during follow-up. STATISTICAL METHODS: Independent factors associated with NP involvement were identified using a multivariable Cox regression model. RESULTS: Factors independently associated with NP manifestations were: mestizo ethnicity (HR 1.701, 95% CI 1.282-2.258, p = 0.0002), myalgias/myositis (HR 1.832, 95% CI 1.335-2.515, p = 0.0002), pneumonitis (HR 2.476, 95% CI 1.085-5.648, p = 0.0312), shrinking lung (HR 2.428, 95% CI 1.074-5.493, p = 0.0331) and hemolytic anemia (HR 1.629, 95% CI 1.130-2.347, p = 0.0089). Longer disease duration at cohort entry (13 to 24 months) was associated with a lower risk of developing NP manifestations (HR 0.642, 95% CI 0.441-0.934, p = 0.0206). CONCLUSIONS: Patients with myalgias/myositis, pneumonitis, shrinking lung and hemolytic anemia are at higher risk of NP involvement, whereas longer disease duration at cohort entry is associated with a lower risk of developing NP involvement.

Clinical features, damage accrual, and survival in patients with familial systemic lupus erythematosus: data from a multi-ethnic, multinational Latin American lupus cohort.

OBJECTIVES: This study aimed to compare the clinical features, damage accrual, and survival of patients with familial and sporadic systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multinational Latin American SLE cohort was studied. Familial lupus was defined as patients with a first-degree SLE relative; these relatives were interviewed in person or by telephone. Clinical variables, disease activity, damage, and mortality were compared. Odds ratios (OR) and 95% confidence intervals (CI) were estimated. Hazard ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for time to damage and mortality. RESULTS: A total of 66 (5.6%) patients had familial lupus, and 1110 (94.4%) had sporadic lupus. Both groups were predominantly female, of comparable age, and of similar ethnic distribution. Discoid lupus (OR = 1.97; 95% CI 1.08-3.60) and neurologic disorder (OR = 1.65; 95% CI 1.00-2.73) were significantly associated with familial SLE; pericarditis was negatively associated (OR = 0.35; 95% CI 0.14-0.87). The SLE Disease Activity Index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) were similar in both groups, although the neuropsychiatric (45.4% vs. 33.5%; p = 0.04) and musculoskeletal (6.1% vs. 1.9%; p = 0.02) domains of the SDI were more frequent in familial lupus. They were not retained in the Cox models (by domains). Familial lupus was not significantly associated with damage accrual (HR = 0.69; 95% CI 0.30-1.55) or mortality (HR = 1.23; 95% CI 0.26-4.81). CONCLUSION: Familial SLE is not characterized by a more severe form of disease than sporadic lupus. We also observed that familial SLE has a higher frequency of discoid lupus and neurologic manifestations and a lower frequency of pericarditis.

First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR).

Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.

Remission and Low Disease Activity Status (LDAS) protect lupus patients from damage occurrence: data from a multiethnic, multinational Latin American Lupus Cohort (GLADEL).

OBJECTIVE: To evaluate disease activity statuses' (DAS') impact on systemic lupus erythematosus (SLE) outcomes. MATERIALS AND METHODS: Four DAS were defined: remission off-therapy: SLE Disease Activity Index (SLEDAI)=0, no prednisone or immunosuppressive drugs (IS); remission on-therapy: SLEDAI=0, prednisone ≤5 mg/day and/or IS (maintenance); low (L) DAS: SLEDAI ≤4, prednisone ≤7.5 mg/day and/or IS (maintenance); non-optimally controlled: SLEDAI >4 and/or prednisone >7.5 mg/day and/or IS (induction). Antimalarials were allowed in all. Predefined outcomes were mortality, new damage (increase of at least one Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI) point) and severe new damage (increase of at least 3 SDI points). Univariable and multivariable Cox regression models were performed to define the impact of DAS, as time-dependent variable, on these outcomes. RESULTS: 1350 patients were included, 79 died during follow-up, 606 presented new and 177 severe new damage. In multivariable analyses, remission (on/off-therapy) was associated with a lower risk of new (HR 0.60; 95% CI 0.43 to 0.85), and of severe new damage (HR 0.32; 95% CI 0.15 to 0.68); low disease activity status (LDAS) was associated with a lower risk of new damage (HR 0.66; 95% CI 0.48 to 0.93) compared with non-optimally controlled. No significant effect on mortality was observed. CONCLUSIONS: Remission was associated with a lower risk of new and severe new damage; LDAS with a lower risk of new damage after adjusting for other damage confounders.

ANCA-associated pauci-immune glomerulonephritis: always pauci-immune?

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is considered "pauci-immune" with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement. However, it is not unusual to see some immune deposits (ID) within glomeruli on immunofluorescence (IF). We determined to evaluate the prevalence and clinical significance of immune deposits in ANCA-associated GN. METHODS: We included all patients with ANCA associated vasculitis with renal biopsies between January 2002 and May 2014: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal limited vasculitis. Patients were divided into Group A: biopsy without ID (≤2+ intensity of immunostaining) and Group B: biopsy with ID (>2+ intensity of immunostaining). Serum creatinine, estimated glomerular filtration rate (eGFR) at time of the biopsy, amount of proteinuria and hematuria, requirement of dialysis and extra renal involvement were recorded. RESULTS: Fifty-three patients (75.4% females) were included. Mean age at biopsy was 66.3 years. Typical pauci-immune GN was found in 39 patients (73.5%, group A). In 14 patients (26.4%, group B) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in group B (mean 1.6/24 h (SD: 10.7) vs. 0.8/24 h (SD: 7.6), p=0.0036). CONCLUSIONS: In ANCA GN at least a quarter of patients were not "pauci-immune" (26.4%). In this subgroup, immune deposits were only associated with a significantly higher proteinuria. Further basic and clinical research is needed to elucidate the significance of immune deposition in ANCA GN.

Does a Simplified 6-Joint Ultrasound Index Correlate Well Enough With the 28-Joint Disease Activity Score to Be Used in Clinical Practice?

OBJECTIVE: Ultrasound (US) has become an important tool in the management of rheumatoid arthritis (RA) but it is time consuming in clinical practice. We compared 3 US indices (with different numbers of joints) with disease activity measured by the 28-Joint Disease Activity Score (DAS28) in order to find the most parsimonious index still useful in clinical practice. METHODS: Sixty consecutive RA patients were included. The DAS28 score was calculated by the attending rheumatologist, and later in the day, they underwent US examination by another rheumatologist trained in US (bilateral gray-scale and power Doppler examination of the wrist and metacarpophalangeal and proximal interphalangeal joints). Three different US indices were constructed: index A (22 joints), index B (10 joints), and index C (6 joints). RESULTS: All 3 US indices were significantly higher in patients with active disease versus inactive disease (P < 0.05 for all 3). Ultrasound index C showed the best correlation with DAS28 (rho = 0.5020, P < 0.0001) and a very good discriminative value for moderate to high disease activity (DAS28 >3.2) and for absence of remission (DAS28 >2.6) (areas under receiver operating characteristic curve = 0.75 and 0.80, respectively). A cutoff value of 3 in US index C showed sensitivity of 88.89% and specificity of 66.67% for absence of remission. Correlation between the 3 US indices was excellent. CONCLUSIONS: A US index of 6 joints (both wrists and second and third metacarpophalangeal joints bilaterally) correlated well with disease activity measured by DAS28 and may be used to evaluate RA patients in daily practice.

Rheumatoid arthritis in Latin Americans enriched for Amerindian ancestry is associated with loci in chromosomes 1, 12, and 13, and the HLA class II region.

OBJECTIVE: To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry. METHODS: Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software. RESULTS: A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA-DQB1- DQA2 (P = 7.6 × 10(-10) ), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10(-6) ), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10(-7) ). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10(-6) ). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti-cyclic citrullinated peptide antibodies. CONCLUSION: Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.

Validation in Spanish of a screening questionnaire for the detection of psoriatic arthritis in patients with psoriasis.

OBJECTIVE: A patient self-administered questionnaire [PsA Screening and Evaluation (PASE)] has been developed and validated in English, but has not been tried in Spanish speaking populations. This study aimed to adapt and validate PASE in Spanish to screen Spanish speaking psoriasis patients for signs and symptoms of inflammatory arthritis. METHODS: Initial translation from English to Spanish (forward translation) was performed by two independent translators and the resulting versions were synthesized during a consensus meeting. The questionnaire was tried in a pilot study and resulted in a change in the agreement scale for a frequency scale with wording adaptation [Spanish PASE (PASE-S)]. RESULTS: One hundred and eleven patients were screened with PASE-S; 25 with PsA (without previous treatments), 23 with psoriasis, 22 with psoriasis and OA and 41 with OA without psoriasis. The diagnosis of psoriasis was performed by a dermatologist, and a rheumatologist determined the diagnosis of PsA or OA. Patients with PsA had statistically significant higher symptoms, function and total PASE-S scores compared with those without PsA. Receiver operator curves showed an area under the curve of 0.79 (95% CI 0.69, 0.89) for the total score. A cut-off value ≥34 showed sensitivity of 76%, and specificity of 74.4% for the diagnosis of PsA. CONCLUSION: The validated PASE questionnaire is a self-administered tool that can be used to screen for PsA among patients with psoriasis in a Spanish speaking population. PASE was able to distinguish between symptoms of PsA and OA.

Incidence and prevalence of psoriatic arthritis in Buenos Aires, Argentina: a 6-year health management organization-based study.

OBJECTIVES: Studies regarding epidemiology of PsA are lacking in Latin America. We estimated the incidence and prevalence of PsA in a University Hospital-based Health Management Organization in Buenos Aires [Hospital Italiano Medical Care Program (HIMCP)]. POPULATION: for incidence calculation, the population at risk was all adult members of the HIMCP, with continuous affiliation for at least 1 year from January 2000 to January 2006. Each person was followed until he/she voluntarily left the HIMCP, death or finalization of the study (final dates) contributing time at risk since January 2000 or enrolment date (whichever occurred later) to that final date. Case ascertainment: medical records of all patients with the problem psoriasis and/or PsA in the HIMCP problem-oriented computer-based patient record system, or registered in rheumatologists and/or dermatologists databases, were revised. Patients fulfilling CASPAR criteria were included. STATISTICAL ANALYSIS: incidence rate (IR) was calculated with 95% CIs. Cumulative prevalence was estimated on 1 January 2006 (denominator population ==88,112). RESULTS: In the study period, 138,288 persons contributed a total of 558,878 person-years, of whom 35 developed PsA (IR 6.26; 95% CI 4.2, 8.3 cases per 100,000 person-years). There were 12 females: IR 3.64 (95% CI 1.6, 5.7) cases per 100,000 person-years; and 23 males: IR 10.02 (95% CI 5.9, 14.1) cases per 100,000 person-years. On 1 January 2006, 65 prevalent cases were identified: prevalence 74 (95% CI 57, 94) cases per 100,000 members. CONCLUSIONS: The incidence and prevalence of PsA in this Latin American country was similar to that reported in other studies from Europe and the USA.

Incidence and prevalence of systemic sclerosis in a healthcare plan in Buenos Aires.

BACKGROUND: Systemic sclerosis (scleroderma) is an infrequent disease. Data on incidence and prevalence are scarce and conflictive. There are no such data in Latin America or in Argentina in particular. OBJECTIVES: We undertook to examine the incidence and prevalence of systemic sclerosis in the prepaid health maintenance organization of our hospital, in the city of Buenos Aires. METHODS: Members of the plan between 1999 and 2004 were followed up for incident cases, and prevalence was calculated at the end of the period. RESULTS: A total of 98,642 persons were followed up for a total of 32,9534 person-years. Density of incidence overall was 21.2 per million person-years (95% confidence interval [CI], 5.4-37). Density of incidence for diffuse disease was 6.1 per million person-years (95% CI, 2.3-14.5), and for limited disease, it was 15.2 per million person-years (95% CI, 2-28). Prevalence was 296 per million people (95% CI, 193-434); females, 477 per million people (95% CI, 309-704); and males, 28 per million people (95% CI, 7-157). Prevalence for diffuse disease was 57 per million people (95% CI, 18-133), and for limited disease, it was 240 per million people (95% CI, 148-365). CONCLUSIONS: Despite potential biases, these data are in agreement with others from different parts of the world and the first obtained in Argentina and, to our knowledge, in Latin America.

Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL).

AIM: A decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria. METHODS: We included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed. RESULTS: Five hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence. CONCLUSIONS: Early response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.

[Insipid diabetes as initial presentation of Wegener's granulomatosis]. / Diabetes Insípida como forma de presentación de Granulomatosis de Wegener.

Wegener's granulomatosis is a granulomatous necrotizing vasculitis which predominantly affects the respiratory tract, kidney, and less frequently other organs such as the nervous system. The latter may occur in up to 54% of cases and when it does it is more frequently of the peripheral nerves. We present a 19 year old woman who commenced her disease with involvement of respiratory sinuses, lungs and kidney and who developed central insipid diabetes (CID) at onset. The CID persisted in spite of adequate response of the other organs and systems with immunosuppresor treatment. The development of CID in the context of vasculitis should suggest this as a possible mechanism.

Predictors of Remission and Low Disease Activity State in Systemic Lupus Erythematosus: Data from a Multiethnic, Multinational Latin American Cohort.

OBJECTIVE: To determine the predictors of remission and low disease activity state (LDAS) in patients with systemic lupus erythematosus (SLE). METHODS: Three disease activity states were defined: Remission = SLE Disease Activity Index (SLEDAI) = 0 and prednisone ≤ 5 mg/day and/or immunosuppressants (maintenance dose); LDAS = SLEDAI ≤ 4, prednisone ≤ 7.5 mg/day and/or immunosuppressants (maintenance dose); and non-optimally controlled state = SLEDAI > 4 and/or prednisone > 7.5 mg/day and/or immunosuppressants (induction dose). Antimalarials were allowed in all groups. Patients with at least 2 SLEDAI reported and not optimally controlled at entry were included in these analyses. Outcomes were remission and LDAS. Multivariable Cox regression models (stepwise selection procedure) were performed for remission and for LDAS. RESULTS: Of 1480 patients, 902 were non-optimally controlled at entry; among them, 196 patients achieved remission (21.7%) and 314 achieved LDAS (34.8%). Variables predictive of a higher probability of remission were the absence of mucocutaneous manifestations (HR 1.571, 95% CI 1.064-2.320), absence of renal involvement (HR 1.487, 95% CI 1.067-2.073), and absence of hematologic involvement (HR 1.354, 95% CI 1.005-1.825); the use of immunosuppressive drugs before the baseline visit (HR 1.468, 95% CI 1.025-2.105); and a lower SLEDAI score at entry (HR 1.028, 95% CI 1.006-1.051 per 1-unit decrease). These variables were predictive of LDAS: older age at entry, per 5-year increase (HR 1.050, 95% CI 1.004-1.098); absence of mucocutaneous manifestations (HR 1.401, 95% CI 1.016-1.930) and renal involvement (HR 1.344, 95% CI 1.049-1.721); and lower SLEDAI score at entry (HR 1.025, 95% CI 1.009-1.042). CONCLUSION: Absence of mucocutaneous, renal, and hematologic involvement, use of immunosuppressive drugs, and lower disease activity early in the course of the disease were predictive of remission in patients with SLE; older age was predictive of LDAS.

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.

Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. We undertook the present work to perform the first genome-wide association study on individuals from the Americas who are enriched for Native American heritage. METHODS: We analyzed 3,710 individuals from the US and 4 countries of Latin America who were diagnosed as having SLE, and healthy controls. Samples were genotyped with HumanOmni1 BeadChip. Data on out-of-study controls genotyped with HumanOmni2.5 were also included. Statistical analyses were performed using SNPtest and SNPGWA. Data were adjusted for genomic control and false discovery rate. Imputation was performed using Impute2 and, for classic HLA alleles, HiBag. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The IRF5-TNPO3 region showed the strongest association and largest OR for SLE (rs10488631: genomic control-adjusted P [Pgcadj ] = 2.61 × 10(-29), OR 2.12 [95% CI 1.88-2.39]), followed by HLA class II on the DQA2-DQB1 loci (rs9275572: Pgcadj = 1.11 × 10(-16), OR 1.62 [95% CI 1.46-1.80] and rs9271366: Pgcadj = 6.46 × 10(-12), OR 2.06 [95% CI 1.71-2.50]). Other known SLE loci found to be associated in this population were ITGAM, STAT4, TNIP1, NCF2, and IRAK1. We identified a novel locus on 10q24.33 (rs4917385: Pgcadj = 1.39 × 10(-8)) with an expression quantitative trait locus (eQTL) effect (Peqtl = 8.0 × 10(-37) at USMG5/miR1307), and several new suggestive loci. SLE risk loci previously identified in Europeans and Asians were corroborated. Local ancestry estimation showed that the HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection against development of SLE. CONCLUSION: Our results demonstrate that studying admixed populations provides new insights in the delineation of the genetic architecture that underlies autoimmune and complex diseases.

The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among "Hispanics".

Clinical and laboratory manifestations and outcome of systemic lupus erythematosus (SLE) may vary in different populations. A prospective multinational inception cohort should prove useful in identifying the influence of ethnicity on the clinical characteristics of SLE. We therefore analyzed clinical, laboratory, and prognostic variables in Latin American SLE patients with disease of recent onset who were entered into a prospective cohort, and compared these variables in the cohort's 3 major ethnic groups. Thirty-four centers from 9 Latin American countries participated by randomly incorporating SLE patients within 2 years of diagnosis into a standardized database. Participating centers were selected for their expertise in diagnosing and managing SLE. We were then able to evaluate prospectively socioeconomic variables, ethnicity, type of medical care, clinical and laboratory features, disease activity, damage, and mortality at each site. A coordinating center controlled the quality of the information submitted. Of the 1,214 SLE patients included in the cohort, 537 were mestizos, 507 were white, and 152 were African-Latin American (ALA). (There were also small numbers of pure Amerindian and oriental individuals.) Significant differences were found between them in socioeconomic characteristics, type of care, and level of education favoring whites. Mestizos and ALA were younger at onset. Delay to diagnosis and disease duration was shorter in ALA. Fever was more frequent in whites; discoid lesions in ALA; renal disease and lymphopenia in mestizos and ALA. Although we found differences in background variables between ethnic groups from different countries, mestizos from 2 distant countries (Argentina and Mexico) were clinically akin and showed similar differences to whites. Mortality was associated with lower education, poor medical coverage, and shorter follow-up. In an exploratory model nonwhite ethnicity was associated with renal disease and lymphopenia, damage, and cumulative American College of Rheumatology criteria. These differences in clinical, prognostic, socioeconomic, educational, and access to medical care features in Latin American lupus patients of 3 major ethnic groups from 9 different countries may have an impact on the patients' disease. "Hispanics," as they have come to be generically termed on the basis of language, actually constitute a markedly heterogeneous group of subjects.

[Polymyalgia rheumatica revisited]. / Actualización en polimialgia reumática.

Polymyalgia rheumatica is an inflammatory disorder that usually affects persons over the age of 50 causing proximal muscle pain and stiffness, and an elevated erythrocyte sedimentation rate. Although increasingly recognized in this age group, it remains a diagnosis of exclusion and although several diagnostic criteria have been proposed, none has been clearly accepted. While polymyalgia rheumatica is associated with giant cell arteritis, obtaining a temporal artery biopsy is not recommended in patients with polymyalgia rheumatica without symptoms of giant cell arteritis. Early diagnosis and low dose corticosteroid therapy improve patients' clinical features and functional status. Treatment usually lasts between 12 and 24 months and the majority of patients manage to discontinue treatment completely.