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.

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.

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.

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.

Challenges in the management of rheumatoid arthritis in developing countries.

Rheumatoid arthritis (RA) is a systemic autoimmune disease which is characterized by chronic inflammation of the joints. Patients experience chronic pain and suffering, and increasing disability; without treatment, life expectancy is reduced. It is imperative to identify patients early so that control of inflammation can prevent joint destruction and disability. Although great advances have been made in the developed nations, early diagnosis remains a great challenge for developing countries during the Bone and Joint Decade (2000-2010) and beyond. Developing countries face important and competitive social, economic, health- and poverty-related issues, and this frequently results in chronic diseases such as RA being forgotten in health priorities when urgent health needs are considered in an environment with poor education and scarce resources. Epidemiological studies in developing countries show a lower but still important prevalence in different regions when compared to that in Caucasians. It seems that the severity of RA varies among different ethnic groups, and probably starts at a younger age in developing countries. Practising rheumatologists in these regions need to take into account several important problems that include suboptimal undergraduate education, inadequate diagnosis, late referrals, lack of human and technical resources, poor access to rheumatologists, and some deficiencies in drug availability. Infections are very important in RA, and special care is needed in developing countries as some endemic infections include tuberculosis, human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. These infections should be carefully taken into account when medications are prescribed and monitored. This chapter presents published information covering the main challenges faced in these environments, and suggests strategies to overcome these important problems in RA management.

Prevention of musculoskeletal conditions in the developing world.

Musculoskeletal conditions are an increasingly common problem across the globe due to increased longevity and increased exposure to risk factors such as obesity and lack of physical activity. The increase is predicted to be greatest in developing countries, and there is thus an urgent need for the implementation of strategies and policies that will prevent and control these conditions. The ideal is modification of the risk factors in the whole community, and this will have wide-ranging health benefits as these risk factors are common to other major conditions. Changing people's behaviour is a challenge; targeting those at highest risk is potentially more effective, providing that there are both affordable ways of identifying those at risk and affordable interventions. Early intervention in those with a condition such as rheumatoid arthritis is probably the most cost-effective approach, but requires diagnostic capacity--in clinical skills and/or technology--as well as access to care. There is now much evidence for what can be achieved, but the challenge is how to implement these different strategies in developing countries where there are competing priorities for limited resources. The key strategy is to raise awareness among the public, health professionals, and policy makers of the importance of musculoskeletal health, of what can be achieved by prevention and treatment, and to ensure that policies reflect this. It is also necessary to educate the public to know when to seek care, and health-care workers to recognize the early signs of musculoskeletal conditions.

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.

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.

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.

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 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.

Articular manifestations of human immunodeficiency virus infection.

Prospective studies of HIV-positive and HIV-negative individuals, longitudinal prospective studies of HIV-positive patients and the African experience with spondyloarthropathies have provided support for a direct role of HIV infection in producing a variety of articular manifestations. The most common manifestations are arthralgia and the spectrum of spondyloarthropathies, but distinct entities such as HIV-associated arthritis and the painful articular syndrome have also been reported. Although initial reports described patients with mainly asymmetric oligoarthritis, a polyarticular presentation is now seen frequently. In Caucasians, HIV-associated reactive arthritis resembles reactive arthritis in non-HIV-infected persons. Reactive arthritis, psoriatic arthritis and undifferentiated spondyloarthropathy were uncommon in Africa and are now detected more often with the HIV epidemic. Although early reports in Western communities reported asymmetrical oligoarthritis as the usual pattern, polyarticular involvement is now seen frequently. Intravenous drug abuse is the most likely risk factor for septic arthritis, even in HIV-infected persons in Western communities, while HIV infection itself may be more important in developing countries where most patients do not receive highly active antiretroviral therapy (HAART). Recent reports have drawn attention to the development of avascular necrosis of the bone in HIV-positive patients and the risk factors include HAART itself, complications of HAART, HIV infection per se or concomitant conventional risk factors. Many patients respond to conventional symptomatic therapy, and disease-modifying drug therapy is necessary for patients who have persistent and progressive arthritis. The use of HAART can modify the prevalence or expression of the articular syndromes.

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.