Differences in the diagnosis and management of systemic lupus erythematosus by primary care and specialist providers in the American Indian/Alaska Native population

Objectives The objective of this study is to investigate differences in the diagnosis and management of systemic lupus erythematosus (SLE) by primary care and specialist physicians in a population-based registry. Methods This study includes individuals from the 2009 Indian Health Service lupus registry population with a diagnosis of SLE documented by either a primary care provider or specialist. SLE classification criteria, laboratory testing, and medication use at any time during the course of disease were determined by medical record abstraction. Results Of the 320 individuals with a diagnosis of SLE, 249 had the diagnosis documented by a specialist, with 71 documented by primary care. Individuals with a specialist diagnosis of SLE were more likely to have medical record documentation of meeting criteria for SLE by all criteria sets (American College of Rheumatology, 79% vs 22%; Boston Weighted, 82% vs 32%; and Systemic Lupus International Collaborating Clinics, 83% vs 35%; p &lt; 0.001 for all comparisons). In addition, specialist diagnosis was associated with documentation of ever having been tested for anti-double-stranded DNA antibody and complement 3 and complement 4 ( p &lt; 0.001). Documentation of ever receiving hydroxychloroquine was also more common with specialist diagnosis (86% vs 64%, p &lt; 0.001). Conclusions Within the population studied, specialist diagnosis of SLE was associated with a higher likelihood of having SLE classification criteria documented, being tested for biomarkers of disease, and ever receiving treatment with hydroxychloroquine. These data support efforts both to increase specialist access for patients with suspected SLE and to provide lupus education to primary care providers. </jats:sec

Molecular basis for increased susceptibility of Indigenous North Americans to seropositive rheumatoid arthritis

Objective The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk HLA-DRB1 alleles are known to share a common motif, the ‘shared susceptibility epitope (SE)’. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13β stratifies with ACPA-positive RA, while His13βSer polymorphisms stratify with ACPA-negative RA and RA protection. Indigenous North American (INA) populations have high risk of early-onset ACPA-positive RA, whereby HLA-DRB1*04:04 and HLA-DRB1*14:02 are implicated as risk factors for RA in INA. However, HLA-DRB1*14:02 has a His13βSer polymorphism. Therefore, we aimed to verify this association and determine its molecular mechanism. Methods HLA genotype was compared in 344 INA patients with RA and 352 controls. Structures of HLA-DRB1*1402-class II loaded with vimentin-64Arg59-71, vimentin-64Cit59-71 and fibrinogen β−74Cit69-81 were solved using X-ray crystallography. Vimentin-64Cit59-71-specific and vimentin59-71-specific CD4+ T cells were characterised by flow cytometry using peptide-histocompatibility leukocyte antigen (pHLA) tetramers. After sorting of antigen-specific T cells, TCRα and β-chains were analysed using multiplex, nested PCR and sequencing. Results ACPA+ RA in INA was independently associated with HLA-DRB1*14:02. Consequent to the His13βSer polymorphism and altered P4 pocket of HLA-DRB1*14:02, both citrulline and arginine were accommodated in opposite orientations. Oligoclonal autoreactive CD4+ effector T cells reactive with both citrulline and arginine forms of vimentin59-71 were observed in patients with HLA-DRB1*14:02+ RA and at-risk ACPA- first-degree relatives. HLA-DRB1*14:02-vimentin59-71-specific and HLA-DRB1*14:02-vimentin-64Cit59-71-specific CD4+ memory T cells were phenotypically distinct populations. Conclusion HLA-DRB1*14:02 broadens the capacity for citrullinated and native self-peptide presentation and T cell expansion, increasing risk of ACPA+ RA

An assessment of cardiovascular disease hospitalizations and disparities by race in patients with rheumatic disease hospitalizations in Alaska, 2015–2018

Abstract Background There is an increased risk of cardiovascular disease in people with many rheumatic diseases. The primary objective of this study was to evaluate cardiovascular disease hospitalizations in Alaska for people with and without a rheumatic disease diagnosis and assess disparities by race, with a focus on Alaska Native and American Indian people. Methods This study used the Alaska Health Facilities Data Reporting Program data on inpatient hospitalizations from 2015 to 2018. We identified people with a rheumatic disease diagnosis based on any hospitalization with a set of rheumatic disease diagnoses and compared them to people hospitalized but without a rheumatic disease diagnosis. We determined the odds of cardiovascular disease hospitalization by rheumatic disease diagnosis and assessed the influence of race and other factors, using univariate analyses and multivariable models. Results People with a rheumatic disease diagnosis other than osteoarthritis had higher odds of cardiovascular disease hospitalization. The odds ratio was highest in people with gout compared to other rheumatic diseases. In multivariable models, there was an interaction between race and rheumatic disease status. Specifically, having gout increased the odds of cardiovascular disease hospitalization for people of all races, while having a rheumatic disease other than gout or osteoarthritis increased the odds of cardiovascular disease hospitalization in Alaska Native/American Indian people but not in people of other races. Conclusions The association between rheumatic disease status and cardiovascular disease hospitalization in Alaska varied by type of rheumatic disease and race. This adds substantially to the literature on associations between rheumatic disease and cardiovascular disease in Indigenous North American populations

Chronic disease and impairment among Alaska native elders : the Alaska Education and Research Towards Health (EARTH) study

Background: Chronic diseases and impairments are prevalent among older Americans. However, prevalence data for Alaska Native (AN) elders are limited, with estimates usually extrapolated from national studies in which AN elders may not be well-represented. The aim of this study was to describe the prevalence of selected chronic diseases, impairments, and measured medical risk factors among a large community sample of AN elders. Methods: Design, setting, and participants. A community-based cross-sectional study of baseline information from 656 AN elders aged 55 years or over who participated in the Alaska Education and Research Towards Health (EARTH) Study, March 2004 to August 2006. Measurements. Self-reported lifetime prevalence of 17 doctor-diagnosed chronic diseases, and point prevalence of vision, hearing, oral, and general health impairment were estimated from data collected using audio computer-assisted self-administered questionnaires. In addition, height, weight, blood pressure, fasting blood lipids, and fasting blood glucose levels were measured.Results: The four most prevalent chronic diseases among AN elders were high blood pressure (55%), arthritis (49%), high cholesterol (42%), and adult bone fracture/break (35%). The median number of chronic diseases reported was three (inter-quartile range, 2 to 5). The prevalence of self-reported vision impairment was 15%, hearing impairment 18%, and having had all natural teeth removed 25%. Almost 50% were obese. High blood pressure (systolic &ge; 140 mm Hg and/or diastolic &ge; 90 mm Hg) was measured in 23%, high low density lipoprotein (LDL) cholesterol (&ge; 130 mg/dL) in 39%, and high fasting plasma glucose (&gt; 125 mg/dL) in 9%. Obesity was more prevalent among women than men. There were also significant regional differences in rates of obesity and high LDL cholesterol.Conclusion: These data may be useful in public health programs and health services planning

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ABSTRACT. Objective. To determine whether anti-peptidylarginine deiminase type 4 (PAD4) antibodies were present in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA) in 2 indigenous North American populations with high prevalence of RA. Methods. Participants were recruited from 2 indigenous populations in Canada and the United States, including patients with RA (probands), their unaffected FDR, and healthy unrelated controls. Sera were tested for the presence of anti-PAD4 antibodies, anticyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF). HLA-DRB1 subtyping was performed and participants were classified according to number of shared-epitope alleles present. Results. Antibodies to PAD4 were detected in 24 of 82 (29.3%) probands; 2 of 147 (1.4%) relatives; and no controls (p &lt; 0.0001). Anti-CCP was present in 39/144 (27.1%) of the relatives, and there was no overlap between positivity for anti-CCP and PAD4 in the relatives. In RA patients, anti-PAD4 antibodies were associated with disease duration (p = 0.0082) and anti-CCP antibodies (p = 0.008), but not smoking or shared-epitope alleles. Conclusion. Despite a significant prevalence of anti-CCP in FDR, anti-PAD4 antibodies were almost exclusively found in established RA. The prevalence of anti-PAD4 antibodies in RA is similar to the prevalence described in other populations and these autoantibodies are associated with disease duration an

Anti-PAD4 in RA relatives Personal non-commercial use only. The Journal of Rheumatology-CCP in RA

ABSTRACT. Objective. To determine whether anti-peptidylarginine deiminase type 4 (PAD4) antibodies were present in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA) in 2 indigenous North American populations with high prevalence of RA. Methods. Participants were recruited from 2 indigenous populations in Canada and the United States, including patients with RA (probands), their unaffected FDR, and healthy unrelated controls. Sera were tested for the presence of anti-PAD4 antibodies, anticyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF). HLA-DRB1 subtyping was performed and participants were classified according to number of shared-epitope alleles present. Results. Antibodies to PAD4 were detected in 24 of 82 (29.3%) probands; 2 of 147 (1.4%) relatives; and no controls (p &lt; 0.0001). Anti-CCP was present in 39/144 (27.1%) of the relatives, and there was no overlap between positivity for anti-CCP and PAD4 in the relatives. In RA patients, anti-PAD4 antibodies were associated with disease duration (p = 0.0082) and anti-CCP antibodies (p = 0.008), but not smoking or shared-epitope alleles. Conclusion. Despite a significant prevalence of anti-CCP in FDR, anti-PAD4 antibodies were almost exclusively found in established RA. The prevalence of anti-PAD4 antibodies in RA is similar to the prevalence described in other populations and these autoantibodies are associated with disease duration an

Azathioprine metabolite measurements are not useful for following treatment of autoimmune hepatitis in Alaska Native and other non-Caucasian people

BACKGROUND: In autoimmune hepatitis (AIH) patients treated with azathioprine, the utility of measuring thiopurine methyltransferase (TPMT) and azathioprine metabolites has been limited