Tuberculosis remains a major burden in systemic lupus erythematosus patients in Durban, South Africa.

Objective: Infections are common in systemic lupus erythematosus (SLE), with tuberculosis (TB) being important in an endemic environment. We studied the prevalence and spectrum of TB in SLE in Durban, South Africa. Methods: A medical records review of SLE patients seen over 13-year period, and the demographic data, clinical manifestations, laboratory findings, treatment and outcome were noted. Results: There were 512 SLE patients and 72 (14.1%) had TB. Thirty (41.7%) had pulmonary TB (PTB) and 42 (58.3%) had extra-pulmonary TB (EPTB). The prevalence of TB among the different ethnic groups was 36/282 (12.8%) for Indian people, 29/184 (15.8%) Black African people, 7/26 (26.9%) admixed African people and none among the 18 White people. Comparison of the 72 SLE-TB patients with 72 SLE controls showed no difference in gender, age at SLE diagnosis and disease duration. The SLE-TB patients had a significant increase in the clinical and laboratory features of disease activity (arthritis, mucocutaneous lesions, renal involvement, vasculitis, low complement, raised ds-DNA antibodies), and cumulative prednisone use over the preceding 3 months.Compared to PTB, the EPTB patients were significantly younger, developed TB earlier after SLE diagnosis, and had higher disease activity. The EPTB patients also had increase in features of disease activity (renal, thrombocytopenia, ds-DNA antibodies), and increase in ever use of intravenous methylprednisolone (IV-MP) and mycophenolate mofetil (MMF). On multivariate analysis, the independent risk factors for EPTB were ever use of MMF (p = 0.003) and IV-MP (p = 0.027). Analysis of the cumulative SLE criteria showed renal involvement was an independent risk factor for EPTB. The outcome was similar in both groups. Conclusion: We show an increased prevalence of TB (14.1%) and EPTB (58.3%) in SLE in an endemic area and confirm that features of disease activity and use of immunosuppressive therapy are the major risk factors. Renal involvement (as a cumulative criterion) is an independent risk factor for EPTB.

Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.

Rheumatic diseases in Africa.

Historically, rheumatic diseases have not received much attention in Africa, particularly in sub-Saharan Africa, possibly owing to a focus on the overwhelming incidence of infectious diseases and the decreased life span of the general population in this region. Global attention and support, together with better health policies and planning, have improved outcomes for many infectious diseases; thus, increasing attention is being turned to chronic non-communicable diseases. Rheumatic diseases were previously considered to be rare among Africans but there is now a growing interest in these conditions, particularly as the number of rheumatologists on the continent increases. This interest has resulted in a growing number of publications from Africa on the more commonly encountered rheumatic diseases, as well as case reports of rare diseases. Despite the limited amount of available data, some aspects of the epidemiology, genetics and clinical and laboratory features of rheumatic diseases in African populations are known, as is some detail on the use of therapeutics. Similarities and differences in these conditions can be seen across the multi-ethnic and genetically diverse African continent, and it is hoped that increased awareness of rheumatic diseases in Africa will lead to earlier diagnosis and better outcomes for patients.

Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis.

OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries. It is unknown whether they are relevant globally. We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs). METHODS: Electronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. Reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for study quality assessment. Similarities and discrepancies of recommendations are reported. RESULTS: After deduplication, 1693 unique citations were found; 25 full texts were screened and 12 included in the narrative synthesis. Average scores for the AGREE II domains ranged from 33.3 to 83.3%. Recommendations targeted rheumatologists and health care providers involved in RA care. Most covered some but not all of the following areas: baseline "pre-MTX" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). Recommendations agreed on baseline tests prior to starting MTX, monitoring, and need for folic acid supplementation. These aspects can serve as the foundation for the development of MTX recommendations relevant to LDCs. Recommendations disagreed on the MTX starting dose, optimal route, titration, and intervals to monitor toxicity. CONCLUSION: Existing recommendations do not uniformly address all aspects related to the use of MTX and disagree in relevant aspects of MTX use. Adaptations to these recommendations are needed to facilitate their implementation in LDCs. Key Points • This paper summarizes current recommendations on the use of methotrexate for the treatment of rheumatoid arthritis. • Areas of agreement between recommendations include the following: pre-methotrexate patient assessment, need for folic acid supplementation, and toxicity monitoring. • Areas of disagreement relate to methotrexate starting and maximal dose, titration, and frequency of assessments.

The spectrum of idiopathic inflammatory myopathies in South Africa.

INTRODUCTION: There are many reports on idiopathic inflammatory myopathies (IIM) but little information from sub-Saharan Africa. We conducted a retrospective study of IIM in a multi-ethnic cohort seen at a single centre in Durban, South Africa. METHOD: The study included patients who fulfilled the Bohan and Peter or European League Against Rheumatism/American College of Rheumatology criteria for IIM. The information recorded included demographic data, clinical findings, results of investigations, treatment and outcome. Patients with overlap myositis (OM) had myositis and criteria for another connective tissue disease. RESULTS: There were 104 patients with IIM; 82.7% female and 70.2% African blacks. They included 41 (39.4%) with OM, 26 (25%) polymyositis (PM), 26 (25%) dermatomyositis (DM), six (5.8%) juvenile dermatomyositis and five (4.8%) cancer-associated myositis. Our patients had a younger mean age at diagnosis (36.8 ± 14.7 years) compared with 45-55 years in most other studies. Scleroderma-myositis overlap accounted for 26 (63.4%) of the patients with OM. Patients with OM were significantly younger than PM (p = 0.004) and DM (p = 0.044) and had lower, but not statistically significant, creatine kinase levels at diagnosis compared with PM (p = 0.052) and DM (p = 0.073). Interstitial lung disease was more common in OM (p = 0.001) and PM (p = 0.024) than DM. Oropharyngeal weakness was more common in DM than OM (p = 0.001) and PM (p = 0.032). African blacks were younger (p = 0.028) at diagnosis and had more cardiac abnormalities (p = 0.034) than Indians. CONCLUSION: The spectrum of IIM in our cohort of mainly African blacks is similar to other studies, with OM being the most frequent subtype. Key Points • As there is limited information on idiopathic inflammatory myopathies (IIM) in sub-Saharan Africa, this study reports the spectrum of IIM in a South African cohort of predominantly African blacks. • Our patients were younger at diagnosis, and overlap myositis was the most common phenotype. • Comparisons with other studies show similarities in the manifestations of IIM.

International Consortium for Health Outcome Measurement Set of Outcomes That Matter to People Living With Inflammatory Arthritis: Consensus From an International Working Group.

OBJECTIVE: The implementation of value-based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk-adjustment variables that is feasible to implement worldwide. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk-adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts. RESULTS: The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient-reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti-citrullinated protein antibody lab testing for RA and JIA should be collected as risk-adjustment variables. CONCLUSION: We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value-based health care framework and compare outcomes that are important to patients with inflammatory arthritis.

Periarticular calcification mimicking inflammatory polyarthritis in chronic kidney disease.

Periarticular calcification is a frequent radiographic manifestation in chronic kidney disease (CKD). However, clinical presentation as inflammatory periarthritis, tenosynovitis, and bursitis is unusual. A 34-year-old man with CKD on dialysis for three years presented with painful swollen joints. His adherence to regular dialysis, phosphate binders, Vitamin D supplements, and antihypertension therapy was poor. He had swelling of the right thumb, index, and little fingers; periarticular swelling of the left middle finger and right little toe; and extensor tenosynovitis of the wrists and right olecranon bursitis. Laboratory investigations showed the following: urea 36 mmol/L; creatinine 1764 umol/L; serum urate 0.37 mmol/L; corrected calcium 1.76 mmol/L; phosphate 4.32 mmol/L; 25-dihydroxycholecalciferol 30 ng/mL; and parathyroid hormone 104 pmol/L. Radiographs showed periarticular calcification corresponding to the sites of inflammation. The inflammation resolved with oral steroids. In our patient, deranged mineral and bone metabolism contributed to periarticular calcification at multiple sites, mimicking inflammatory polyarthritis.

Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case report.

BACKGROUND: Dysphagia is common in inflammatory myopathies and usually responds to corticosteroids. Severe dysphagia requiring feeding by percutaneous endoscopic gastrostomy is associated with significant morbidity and high mortality. CLINICAL CASE: A 56-year old African Black woman initially presented with systemic sclerosis (SSC) - myositis overlap and interstitial lung disease. She responded to high dose corticosteroids and cyclophosphamide followed by azathioprine, with improvement in her lung function and regression of the skin changes. Six years later she had a myositis flare with severe dysphagia. Her myositis improved after high doses of corticosteroids, azathioprine and two doses of intravenous immunoglobulin (IVIG). As her dysphagia persisted, she was fed via a percutaneous endoscopic gastrostomy (PEG) tube and given a course of rituximab. Her dysphagia gradually resolved and the PEG tube was removed within two months. She received another dose of rituximab six months later and continued low dose prednisone and azathioprine. Her muscle power improved, weight returned to normal and she remained well 20 months after hospital discharge. CONCLUSION: Our patient with SSC-myositis overlap and severe dysphagia requiring PEG feeding, improved with high dose corticosteroids, azathioprine, two courses of IVIG and rituximab, and remained in remission 20 months after hospital discharge.

Rheumatology in Africa-challenges and opportunities.

Africa faces many health challenges despite sustained growth and development over the past decade. Contributory factors are the lack of financial resources, an inadequate health professional workforce, a high burden of communicable diseases, and an increasing burden of non-communicable diseases. Rheumatology services are limited or non-existent in many parts of sub-Saharan Africa. Over the past decade, partnerships with international academic institutions have resulted in some progress in the training of rheumatologists and health professionals and development of rheumatology services in countries such as Kenya, Nigeria, and Zambia. Basic diagnostic tests, biological agents, and arthroplasty are either unavailable or not affordable by the majority of the population. Urbanization has resulted in a change in the epidemiology of rheumatic diseases with an increase in the prevalence of gout, rheumatoid arthritis, systemic lupus erythematosus, and scleroderma over the past four decades. Future growth of rheumatology services will depend on identifying committed individuals in underserved countries for training and supporting them to educate medical students, physicians, and health professionals in their home countries. There is a need to develop models of care using all categories of health workers and identify prevention strategies and cost-effective management programs for low resource settings. Africa affords an opportunity for collaborative research, including genetic and epigenetic studies, to improve our understanding of many of the rheumatic diseases.

The spectrum of posterior reversible encephalopathy in systemic lupus erythematosus.

Our aim was to compare our South African cohort of systemic lupus erythematosus (SLE) and posterior reversible encephalopathy syndrome (PRES) with other published series. We reviewed the records of 10 patients with SLE and PRES seen over a 10-year period and their demographic data, clinical manifestations, laboratory tests, imaging findings, and outcome were recorded. We identified 10 females who included six Indians, three mixed ethnicity, and one African Black. Three patients had PRES at the onset of SLE. The most common manifestations at presentation were seizures (100 %), hypertension (80 %), and altered mental state (50 %). On neuroimaging, nine patients had bilateral involvement, and the occipital (90 %), parietal (90 %), and frontal lobes (50 %) were most commonly involved. The risk factors for PRES were disease activity (90 %), renal disease (80 %) and hypertension (80 %). Ninety percent of the patients were on immunosuppressive therapy. Immunosuppressive therapy was increased in six patients (60 %), continued in two and reduced in two patients after the diagnosis of PRES. Seven patients recovered completely and three patients died from co-morbidities. A review of the larger case series of SLE and PRES showed that the presentation and neuroimaging findings were similar; most patients had active disease at the time of PRES and the majority of patients required intensification of immunosuppressive therapy. We have shown that the majority of patients with SLE have active disease at the time of PRES, and they require an increase in their immunosuppressive therapy.

Spectrum of infections and outcome among hospitalized South Africans with systemic lupus erythematosus.

Our aim was to determine reasons for admission, the prevalence and spectrum of infections, and the outcomes in a multiethnic cohort of hospitalized systemic lupus erythematosus (SLE) patients in Durban, South Africa. We reviewed the records of hospitalized SLE patients seen over a 79-month period; the demographic data, clinical manifestations, laboratory findings, reasons for admission, nature of infection, and outcome were recorded. Our 167 patients, comprising 59.3% Indians, 33.5% African Blacks, 5.4% Coloreds, and 1.8% Whites, had 327 admissions. Active disease and infections accounted for 218 (66.7%) and 115 (35.2%) admissions respectively, with 58 (17.7%) due to both active disease and infection. Features of active disease were mucocutaneous 33.0%, hematological 30.3%, renal 28.9%, and vasculitis 27.1%. Overall, 83 patients (49.7%) had 155 infections; pneumonia (36.8%), cutaneous sepsis (18.1%), tuberculosis (13.5%), urinary tract infections (12.9%), and septicemia (7.1%) were the most common. The organisms commonly isolated were Staphylococcus aureus 25.4%, Escherichia coli 20.3%, and Klebsiella species and Mycobacterium tuberculosis in 13.6% each. Serositis (odds ratio (OR) = 2.7, p = 0.005) and seizures (OR = 4.8, p = 0.007) were associated with increased risk of infection. Twenty-four (14.4%) patients died from infection and active disease; the patients who died had higher SLEDAI scores (p = 0.02) and longer duration of hospitalization (p = 0.03) but no significant associations on multiple logistic regression analysis. Bacterial infections, including tuberculosis, are common in SLE, and they are a major cause of mortality.

The rarity of gonococcal arthritis in association with HIV infection.

Gonococcal urethritis is common with HIV, but gonococcal arthritis is rare. We report two HIV-positive patients with gonococcal arthritis and review previously published reports. A 27-year-old HIV-positive female presented with a pustular skin rash and acute oligoarthritis. Neisseria gonorrhoeae was cultured from the right elbow aspirate. The second patient, a 24-year-old HIV-positive female on zidovudine for one month, presented at 28 weeks gestation with acute oligoarthritis and peroneal tenosynovitis. Neisseria gonorrhoeae was cultured from the throat swab. Both patients responded to ceftriaxone. Gonococcal arthritis must be considered in HIV patients with acute arthritis.

Concomitant systemic lupus erythematosus and HIV: case series and literature review.

OBJECTIVES: To determine the effect of systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection on the course of each other and to review the published reports on concomitant SLE and HIV infection. METHODS: We performed a retrospective review of the records of patients with SLE and HIV seen in the Department of Rheumatology at the Inkosi Albert Luthuli Central Hospital, Durban, South Africa. We used the terms "systemic lupus erythematosus" and "HIV" or "AIDS" to identify patients with SLE and HIV infection reported in the English medical literature. RESULTS: We identified 13 patients with SLE and HIV infection. All the patients were females and there were 11 African blacks and 2 Indians. SLE and HIV infection were diagnosed together in 6 patients. In this group, there were 5 lupus flares in 4 patients, and 2 of the flares followed highly active anti-retroviral treatment (HAART). Five patients developed HIV after the diagnosis of SLE. The 3 patients in whom follow-up data was available had inactive SLE, one of whom was on HAART. Two HIV-positive patients developed SLE after receiving HAART for 30 and 35 mo. Seven of our patients also had tuberculosis. Our literature search identified 58 previously reported patients with HIV and SLE. CONCLUSION: Our case series and review of the literature show that there is a reduction in SLE disease activity in patients with concomitant SLE and HIV. However, when lupus flares occur in HIV-positive patients, they are unrelated to the use of HAART.

Improving musculoskeletal health: global issues.

Musculoskeletal (MSK) disorders are among the leading reasons why patients consult a family or primary health practitioner, take time off work and become disabled. Many of the MSK disorders are more common in the elderly. Thus, as the proportion of the elderly increases all over the world, MSK disorders will make a greater contribution to the global burden of disease. Epidemiological studies have shown that the spectrum of MSK disorders in developing countries is similar to that seen in industrialised countries, but the burden of disease tends to be higher due to a delay in diagnosis or lack of access to adequate health-care facilities for effective treatment. Musculoskeletal pain is very common in the community while fibromyalgia is being recognised as part of a continuum of chronic widespread pain rather than a narrowly defined entity. This will allow research to improve our understanding of pain in a variety of diffuse pain syndromes. The availability of newer more effective therapies has resulted in efforts to initiate therapy at an earlier stage of diseases. The new criteria for rheumatoid arthritis, and the diagnosis of axial and peripheral involvement in spondyloarthritis, permit an earlier diagnosis without having to wait for radiological changes. One of the major health challenges is the global shortage of health workers, and based on current training of health workers and traditional models of care for service delivery, the global situation is unlikely to change in the near future. Thus, new models of care and strategies to train community health-care workers and primary health-care practitioners to detect and initiate the management of patients with MSK disorders at an earlier stage are required. There is also a need for prevention strategies with campaigns to educate and raise awareness among the entire population. Lifestyle interventions such as maintaining an ideal body weight to prevent obesity, regular exercises, avoidance of smoking and alcohol abuse, intake of a balanced diet and nutrients to include adequate calcium and vitamin D, modification of the work environment and avoidance of certain repetitive activities will prevent or ameliorate disorders such as osteoarthritis, osteoporosis, rheumatoid arthritis, gout and MSK pain syndromes including low back pain and work-related pain syndromes. These prevention strategies also contribute to reducing the prevalence and outcome of diseases such as hypertension, cardiovascular diseases, diabetes and respiratory diseases. Thus, prevention strategies require urgent attention globally.

Initiation but no execution - modulation of peripheral blood lymphocyte apoptosis in rheumatoid arthritis - a potential role for heat shock protein 70.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which causes synovial damage. Persistence of lymphocyte infiltrates in the rheumatoid synovium has been attributed to abnormal apoptosis. While not comprehensively investigated, perturbations in peripheral blood lymphocyte (PBL) apoptosis may also be involved in perpetuation of autoimmune processes in RA. METHODS: We investigated total, CD4+ and CD19+ PBL apoptosis in our study cohort by monitoring the translocation of phosphatidylserine using the Annexin-V assay. To examine the role of death receptor mediated apoptosis as well as activation-induced-cell-death (AICD), PBLs were labeled with CD95/Fas and CD69 markers and enumerated by flow cytometry. Proteolytic activity of initiator and executioner caspases was determined by luminometry. DNA fragmentation assays were used to examine whether apoptotic signals were transduced to the nucleus. Quantitative PCR arrays were used to investigate apoptotic pathways associated with RA-PBLs. Since heat-shock-protein-70 (HSP70) is an inducible protein which modulates apoptotic signals, we determined HSP70 levels by intra-cellular flow cytometry and western blots. RESULTS: The RA-PBLs showed signs of elevated apoptosis whilst in circulation. These include increases in the loss of plasma membrane asymmetry, indicated by increased externalization of phosphatidylserine (especially in B-lymphocytes). RA-PBLs showed a bias to CD95/Fas mediated apoptotic pathways, but low levels of the CD69 marker suggested that this was not associated with immune activation. Although downstream markers of apoptosis such as caspase-3/7 activity, were increased, no DNA fragmentation was observed in RA-PBLs. Interestingly, elevated levels of apoptosis did not correlate with absolute lymphocyte counts in RA patients. Levels of HSP70 were highly elevated in RA-PBLs compared to controls. CONCLUSION: The results suggest that while apoptosis may be initiated in RA-PBLs, they may lack commitment to fully executing the apoptotic program. This may be related to inhibition on apoptotic transduction by HSP70. This study provides evidence that abnormalities in RA-PBLs apoptosis may occur whilst still in circulation and may contribute to pathogenesis of the disease.

Functional analysis of the p53 codon 72 polymorphism in black South Africans with rheumatoid arthritis--a pilot study.

The p53 tumor-suppressor protein plays an integral role in apoptosis. Perturbations in peripheral lymphocyte (PL) apoptosis may be associated with rheumatoid arthritis (RA). Polymorphisms at codon 72 of p53 (arginine (Arg72) to proline transition) confers differences in mitochondrial translocation and apoptosis inducing capabilities of p53 in vitro. We examined associations of this polymorphism with PL apoptosis, mitochondrial depolarization, and clinical markers of disease activity in a cohort of black South African RA patients. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. PL apoptosis was measured using the annexin-V assay and mitochondrial membrane potential with the JC-1 assay. Clinical and laboratory parameters were recorded for all patients. Statistical differences in these parameters were investigated according to genotype. Genotype distribution did not differ significantly between RA patients and controls (Arg/Arg, Arg/Pro, Pro/Pro: 12%, 46%, and 42% versus 3%, 34%, and 63%), despite significantly higher frequency of the Arg72 allele in patients (p = 0.0406). There was no significant difference in PL apoptosis and mitochondrial depolarization based on p53 codon 72 genotype. In addition, clinical markers of disease activity were not significantly different between genotypes. We conclude that p53 codon 72 genotype does not influence PL apoptosis or mitochondrial depolarization and is not associated with clinical markers of disease in RA.