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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., The prevalence of rheumatic diseases is increasing in African countries, leading to an increased need for specialist rheumatologists and disease-modifying drugs. In this Review, the authors outline what is currently known about the state of rheumatic diseases in Africa., Key points In the past, there has been an emphasis on communicable diseases in Africa, but attention has now shifted towards non-communicable diseases such as rheumatic diseases. Common rheumatic diseases are seen in Africa and are both comparable and different from presentations seen outside of Africa. Diverse genetic and environmental factors affect the presentation of common rheumatic diseases among different African nations. A shortage of appropriately trained staff, laboratory testing capacity and effective medications exists across the whole continent. Advocacy and research are needed to increase awareness of the risk factors, presentations and management of rheumatic diseases in Africa. Specialized treatment guidelines are needed for resource-poor countries in Africa.

Takayasu arteritis (TA) is a rare large vessel vasculitis that particularly affects women of child-bearing age. Management of pregnant patients with TA is often challenging due to the cardiovascular and cerebrovascular complications of the disease. We report two new cases of pregnancy in patients with TA and review all published cases from sub-Saharan Africa. Analysis of 16 pregnancies in 15 patients (including our two cases) showed that seven patients had radiographic Type V TA disease, namely involvement of the entire length of the aorta. Four patients were newly diagnosed with TA during pregnancy and two pregnancies were unbooked at time of first presentation. Seven pregnancies were complicated by disease flares (n = 4) and/or hypertension (n = 6). Four pregnancies resulted in preterm delivery and six required caesarean sections. There was one documented case of pre-eclampsia resulting in the only maternal death. Intrauterine growth restriction was documented in two of six pregnancies in which foetal ultrasonography was performed. There were four low birth weight infants and one fresh stillbirth (associated with the maternal death). In the handful of case reports of pregnancy in TA from sub-Saharan Africa, both maternal and foetal outcomes were generally good and similar to international findings. In a substantial proportion of patients, the diagnosis of TA was made in pregnancy, reflecting challenges of access to appropriate health care in resource constrained sub-Saharan Africa.

Objective: Fertility, pregnancy, and the postpartum period can pose many challenges for patients with systemic lupus erythematosus (SLE) in sub-Saharan Africa. We explored the perceptions and exper...

Background Systemic lupus erythematosus (SLE) often has a profound negative impact on health-related quality of life (HRQoL). In the absence of any qualitative studies in sub-Saharan Africa, we undertook a study to explore living experiences, perceptions and unmet needs of South African patients with SLE. Methods Twenty-five women with SLE consented to participate in the study. They underwent individual in-depth interviews exploring their physical concerns, emotional health, sexual well-being and fertility. NVivo software was used for analysis. Results Participants were either of black ancestry or mixed racial ancestry, mainly indigent with only a quarter gainfully employed. Living with pain was the most common complaint, negatively impacting on activities of daily living (ADL), family expectations, social life, sleep and intimacy. Most participants expressed challenges of living with fatigue, and many felt their fatigue was misconstrued as being ‘simply lazy’. This pernicious fatigue had negative consequences on many facets of ADL, including caring for dependants, job sustainability and sexual well-being. All participants experienced low emotional states, often associated with suicidal ideations. Many experienced difficulties with fertility and childbearing and these were exacerbated in many instances by the pessimism of health care providers, resulting in confusion and depression. Physical disfigurements resulting from lupus-associated alopecia and rashes and corticosteroid-induced weight fluctuations were a major concern. These changes often affected self-image and libido, leading to strained personal relationships. Coping mechanisms that participants adopted included intense spiritual beliefs, ‘pushing through the difficult times’ and use of alternative therapies to relief symptoms was common. A poor understanding of SLE on the part of participant’s family and the community, coupled with the unpredictable course of the disease, exacerbated frustration and social exclusion. For most, limited income, lack of basic services, family dependencies, and comorbid diseases, such as human immune deficiency virus (HIV), exacerbated the daily negative SLE experiences. Conclusion In this study of mainly indigent South African women, SLE is associated with complex, chronic and challenging life experiences. The chronic relapsing and unpredictable nature of the disease, poor understanding and acceptance of SLE, compounded by a background of poverty, inadequate social support structures, negatively impact on a range of personal, social and vocational daily life experiences. Improved access to psychosocial services and SLE education might result in better outcomes. Trial registration (Ethics Project identification code: 275/2016 and M160633 registered 10 & 29 August 2016).

BACKGROUND Psoriasis is associated with cardiometabolic diseases (CMDs) in Caucasians, but no data is available from sub-Saharan populations on either CMD prevalence or psoriasis risk factors. Our aim was to investigate the prevalence of CMDs in a predominantly non-Caucasian cohort of South Africans with psoriasis and to determine the principal risk factors associated with psoriasis. METHODS This was a cross-sectional case-control study of adult psoriasis patients (n = 103) and controls (n = 98), comparing sociodemographic, anthropometric, clinical, and biochemical characteristics. The groups were matched for gender, ethnicity, and body mass index (BMI). RESULTS The prevalence of metabolic syndrome (MetS) (52.4% vs. 33.7%; P = 0.007), type 2 diabetes (T2D) (25.2% vs. 4.1%; P

PURPOSE: To compare botulinum neurotoxin (BNT) injections to surgery as first-line therapy in large-angle essential infantile esotropia (IE). PATIENTS AND METHODS: Children between the ages 6 months and 6 years with IE of ≥40 prism dioptres (PD) were randomised to either a maximum of three BNT injections or surgical intervention of bimedial rectus muscle recession for angles ≤60 PD and augmented with BNT injection in angles >60 PD. Time taken for each procedure was documented. Orthophoria or misalignment of ≤10 PD was regarded as a complete response (CR). Follow-up visits were done at 3, 6, 12 and 24 weeks. RESULTS: Mean (SD) age and baseline angle of esotropia were 26.9 (14.5) months and 61.9 PD (12.8), respectively, for the overall cohort. The proportion of children who achieved CR was significantly higher in the surgery arm compared to the BNT injection arm (OR = 4.01, 95% CI 1.74–9.22) but the time taken was six times longer (p 24 months achieved CR. In children with esotropia ≤60 PD, CR was achieved in 50% while those with esotropia >60 PD CR was achieved in 25%. CONCLUSION: Surgery remains the gold standard for treatment of esotropia but BNT injection is a safe and effective alternative in children ≤24 m and with smaller angles of esotropia ≤60 PD in resource-limited centres.

Systematic studies on connective tissue disorders are scarce in sub-Saharan Africa. Our aim was to analyse the published clinical data on systemic sclerosis (SSc) in sub-Saharan Africa. A systematic review was carried out in accordance with the PRISMA guidelines. We screened the Embase, PubMed and African Health Sciences databases for literature published until March 2018. Searches produced 1210 publications. After abstract and full-text screenings, 91 publications were analysed, and epidemiological information and clinical features extracted. Publications were mostly publications case reports (36%), cross-sectional studies (26%) and case series (23%) and came predominantly from South Africa (45%), Nigeria (15%) and Senegal (14%). A total of 1884 patients were reported, 66% of patients came from South Africa. The patients were between 4 and 77 years old; 83% of patients were female. Overall, 72% had diffuse SSc. Raynaud´s phenomenon was reported in 78% and skin ulcerations in 42% of patients. Focal skin hypopigmentation was common and telangiectasia not frequent. Interstitial lung involvement was reported in 50%, pulmonary hypertension in 30%, heart involvement in 28% of patients. Oesophageal reflux was observed in 70% and dysphagia in 37% of patients. Antinuclear antibodies were positive in 65% of patients. Anti-centromere autoantibodies (9.2%) and RNA polymerase 3 antibodies (7.1%) were rare and anti-fibrillarin most frequent (16.5%). SSc presentations in sub-Saharan Africa differ from those reported in Europe and America by a frequent diffuse skin involvement, focal skin hypopigmentation and a high prevalence of anti-fibrillarin autoantibodies.

ObjectivesTo identify the changes in rheumatology service delivery across the five regions of Africa from the impact of the COVID-19 pandemic.MethodsThe COVID-19 African Rheumatology Study Group created an online survey consisting of 40 questions relating to the current practices and experiences of rheumatologists across Africa. The CHERRIES checklist for reporting results of internet e-surveys was adhered to.ResultsA total of 554 completed responses were received from 20 countries, which include six in Northern Africa, six in West Africa, four in Southern Africa, three in East Africa and one in Central Africa. Consultant grade rheumatologists constituted 436 (78.7%) of respondents with a mean of 14.5 ± 10.3 years of experience. A total of 77 (13.9%) rheumatologists avoided starting a new biologic. Face-to-face clinics with the use of some personal protective equipment continued to be held in only 293 (52.9%) rheumatologists’ practices. Teleconsultation modalities found usage as follows: telephone in 335 (60.5%), WhatsApp in 241 (43.5%), emails in 90 (16.3%) and video calls in 53 (9.6%). Physical examinations were mostly reduced in 295 (53.3%) or done with personal protective equipment in 128 (23.1%) practices. Only 316 (57.0%) reported that the national rheumatology society in their country had produced any recommendation around COVID-19 while only 73 (13.2%) confirmed the availability of a national rheumatology COVID-19 registry in their country.ConclusionCOVID-19 has shifted daily rheumatology practices across Africa to more virtual consultations and regional disparities are more apparent in the availability of local protocols and registries.

ObjectivesTo develop recommendations for the management of rheumatic and musculoskeletal diseases (RMDs) during the COVID-19 pandemic.MethodA task force comprising of 25 rheumatologists from the 5 regions of the continent was formed and operated through a hub-and-spoke model with a central working committee (CWC) and 4 subgroups. The subgroups championed separate scopes of the clinical questions and formulated preliminary statements of recommendations which were processed centrally in the CWC. The CWC and each subgroup met by several virtual meetings, and two rounds of voting were conducted on the drafted statements of recommendations. Votes were online-delivered and recommendations were pruned down according to predefined criteria. Each statement was rated between 1 and 9 with 1–3, 4–6 and 7–9 representing disagreement, uncertainty and agreement, respectively. The levels of agreement on the statements were stratified as low, moderate or high according to the spread of votes. A statement was retired if it had a mean vote below 7 or a ‘low’ level of agreement.ResultsA total of 126 initial statements of recommendations were drafted, and these were reduced to 22 after the two rounds of voting.ConclusionsThe preliminary statements of recommendations will serve to guide the clinical practice of rheumatology across Africa amidst the changing practices and uncertainties in the current era of COVID-19. It is recognized that further updates to the recommendations will be needed as more evidence emerges.Key Points• AFLAR has developed preliminary recommendations for the management of RMDs in the face of the COVID-19 pandemic.• COVID-19 is an unprecedented experience which has brought new concerns regarding the use of some disease-modifying anti-rheumatic drugs (DMARDs), and these recommendations seek to provide guidelines to the African rheumatologists.• Hydroxychloroquine shortage has become rampart across Africa as the drug is being used as prophylaxis against COVID-19 and this may necessitate a review of treatment plan for some patients with RMDs.• Breastfeeding should continue for as long as possible if a woman is positive for SARS-CoV-2 as there is currently no evidence that the infection can be transmitted through breast milk.

The onset of the COVID-19 pandemic has led to far-reaching changes in the delivery of healthcare services across Africa. A number of drugs used in the management of rheumatic diseases have been touted to have roles to play in the treatment and/or exacerbation of COVID-19 symptoms and this has resulted in significant changes in the practice of rheumatology. The global rheumatology community has risen to this challenge by demonstrating collaborative partnership, resulting in the establishment of the global rheumatology registry to collect data on rheumatic patients infected with COVID-19.1 In view of the study by Gianfrancesco et al ,2 an online survey consisting of 40 practice and experience questions ((online supplementary file 1) and (online supplementary file 2)) was created by the COVID-19 African Rheumatology Study Group which was formed through the network of the African League of Associations for Rheumatology (AFLAR). The aim of the study was to identify the changes in rheumatology practice and patient behaviour, as well as to highlight key concerns of rheumatologists across Africa resulting from the ongoing COVID-19 pandemic.### Supplementary data [annrheumdis-2020-218273supp001.pdf] ### Supplementary data [annrheumdis-2020-218273supp002.pdf] A total of 554 completed responses were received from 20 African countries. There were 431 (77.8%) responses from Northern Africa, 43 (7.8%) from West Africa, 6 (1%) from Central Africa, 20 (3.6%) from East Africa and 54 (9.8%) from Southern Africa. The scope of practice was adult only in 296 (53.4%), paediatric only in 15 (2.7%) and both in 243 (43.9%). A total of 288 (52.9%) of the respondents practised in academic institutions, while 162 (29.2%) practised primarily in a private setting. Forty-four (7.9%) were using hydroxychloroquine (HCQ) more than before, 19 (3.4%) admitted to have prescribed HCQ to prevent severe COVID-19 disease, 92 (16.6%) …

Psoriasis has been shown to increase the risk of cardiovascular disease. Studies indicate that the presence of abdominal aortic calcification (AAC) is a strong predictor of future cardiovascular events and all-cause mortality. Multi-detector computed tomography provides a reliable and accurate method for the detection of abdominal aortic calcification. The aim of this study was to investigate the prevalence of AAC in patients with psoriasis. Adult psoriasis patients (n=69) and controls (n=80) were recruited from the Dermatology and Rheumatology clinics at 3 academic hospitals in Johannesburg, South Africa. Controls were matched for gender, ethnicity and body mass index (BMI). Non-contrast abdominal CT imaging was performed on patients and controls. The images were then assessed for presence and location (supra-coeliac, supramesenteric, supra-renal, proximal infra-renal, aortic bifurcation) of AAC. Patients had a mean age and disease duration of 53.3 ± 14.5 years and 18.9 ± 13.3 years, respectively. There was a significantly higher prevalence of smoking, hypertension and type 2 diabetes in patients compared to controls (56.5% vs 25.0%, P

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

Background:In SSc, ILD is a major cause of morbidity and mortality. High resolution computed tomography (HRCT) is the gold standard for the diagnosis. Predictors of ILD onset are eagerly awaited to improve SSc-ILD management. Pulmonary function test (PFTs) are routinely performed to measure lung function changes.Objectives:Our aim was to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) in predicting the development of SSc-ILD.Methods:The longitudinal data of DLCO, FVC and ILD on HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0), after 12 (±4) (t1) and 24 (±4) (t2) months. Patients with negative HRCT for any sign of ILD both at t0 and t1 were included. Patients who presented or developed pulmonary hypertension during the study period were excluded. At baseline, demographic data, disease duration from Raynaud’s onset, disease subsets, autoantibodies and other laboratory and instrumental data were recorded.Results:474/17805 patients were eligible for the study (403 females, 71 males): 26.0% dcSSc, 58.3% lcSSc, 220 (48.0%) patients with positive anticentromere antibodies (ACA) and 117 (25.4%) with positive antitopoisomerase I antibodies (Topo-I abs). Among all enrolled patients, 46 (9.7%) developed HRCT signs of ILD at t2. Patients with Topo-I abs showed an association with ILD development at t2 (16.7% vs 7.8%, p=0.0031), contrarily ACA positive patients were negatively associated with ILD appearance after 2 years of follow-up (4.4% vs 14.4%, p=0.0001). Positive t2 HRCT patients had a significant lower value of DLCO and FVC at all three assessments when compared to patients with a negative HRCT at t2 (Table 1) and both t0 DLCO and FVC values negatively correlated with ILD development (Table 1). The mean t0 to t1 change (Δ) of DLCO in patients with negative t2 HRTC and positive t2 HRCT were -0.5 (±12.6) and -1.0 (±15.1), respectively. The mean t0 to t1 ΔFVC in patients with negative t2 HRTC and positive t2 HRCT were -0.2 (±10.6) and 0.1 (±11.5), respectively. None of them predicted the appearance of ILD at t2 (ΔDLCO: OR (IC) 0.997 (0.97-1.02), p=0.8024; ΔFVC OR (IC) 1.002 (0.97-1.03), p=0.8664). The data showed an association between t0 DLCO value0 FVC value0 DLCOConclusion:Our data suggest that an impaired baseline DLCO (Table 1.DLCO and FVC values at t0, t1 and t2 values in patients with positive or negative HRCT for ILD at t2 and their statistical differences.Patients without ILD at t2 (mean±SD)Patients with ILD at t2 (mean±SD)OR (95%CL)p-valueDLCO at t079.0 ± 16.669.9 ± 17.40.97 (0.95 - 0.99)0.0006DLCO at t178.4 ± 16.868.9 ± 18.60.97 (0.95 - 0.98)0.0005DLCO at t278.0 ± 17.065.1 ± 19.10.95 (0.93 - 0.97)FVC at t0102.2 ± 17.394.6 ± 16.20.97 (0.96 - 0.99)0.0052FVC at t1101.9 ± 17.994.7 ± 16.50.98 (0.96 - 0.99)0.0092FVC at t2101.6 ± 17.694.5 ± 20.00.98 (0.96 - 1)0.0126Disclosure of Interests:Gemma Lepri: None declared, Cosimo Bruni Speakers bureau: CB reports personal fees from Actelion, personal fees from Eli Lilly, Grant/research support from: CB reports personal fees from Actelion, personal fees from Eli Lilly, grants from European Scleroderma Trial and Research (EUSTAR) group, grants from New Horizon Fellowship, grants from Foundation for Research in Rheumatology (FOREUM), grants from Fondazione Italiana per la Ricerca sull’Artrite (FIRA), outside the submitted work, Lorenzo Tofani: None declared, Alberto Moggi Pignone: None declared, Martina Orlandi: None declared, Tomasetti Sara Speakers bureau: Speaker’s fees for Roche and Boehringer Ingelheim, Mike Hughes: None declared, Francesco Del Galdo: None declared, Rosaria Irace: None declared, Oliver Distler Grant/research support from: OD (last three years) has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Valeria Riccieri: None declared, Yannick Allanore Speakers bureau: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Grant/research support from: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Ana Maria Gheorghiu: None declared, Elise Siegert: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla: None declared, Mohammed Tikly: None declared, Nemanja Damjanov: None declared, Francois Spertini: None declared, Luc Mouthon: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Consultant of: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Grant/research support from: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Armando Gabrielli: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Speakers bureau: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Grant/research support from: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Daniel Furst: None declared, Silvia Bellando Randone: None declared

ObjectiveTo compare the cost implications of botulinum neurotoxin (BNT) injection to surgery in infantile esotropia (IE) in a public/government funded hospital.Methods and analysisA simple costing comparison was undertaken for a randomised clinical trial in IE. Patients were randomised to receive either BNT or standard surgery. The participants in the BNT arm were further subdivided into subgroups based on their age in months and degree of esotropia in prism dioptres (PD) at presentation: G1 ≤60 PD/24 months, G2 ≤24 months/>60 PD, G3 >24 months/≤60 PD, G4 >24 months/>60 PD. The costs were calculated for each arm from primary treatment to eventual satisfactory outcome defined as orthophoria or microtropia (≤10 PD). A bottom-up costing analysis was done for single and multiple procedures for each arm. Comprehensive variable costs as well as fixed costs were calculated at each point of intervention and expressed in local currency ZAR (US$1=ZAR15.00). Costing was analysed for surgery and BNT subgroups (based on clinical success)ResultsThere were 101 patients enrolled in the trial. 54 in the BNT arm and 47 in the surgery arm. Cost for single surgery and single BNT was ZAR 7743.04 and 1713.14, respectively. A favourable clinical outcome was achieved in 72% of surgery arm and 37% of BNT arm. The mean cost for eventual favourable outcome in BNT arm was ZAR9158.08 and in surgery arm ZAR9124.27 (p=0.26). Mean cost in G1 was ZAR6328.45, in G2 ZAR7197.45, in G3 ZAR11891.93 and G4 ZAR12882.44 (p=0.018).ConclusionBNT has a cost–benefit in IE and is a viable option in the primary treatment of IE in resource constrained regions. Clinical outcomes and economic benefit in smaller angle of esotropia and younger patients are comparable to surgery.

As part of a larger cross-sectional, case-control study on cardiometabolic diseases in psoriasis this study investigated the association of visceral fat and serum adipokines with psoriasis and cardiometabolic diseases. A total of 103 patients with psoriasis and 98 controls, matched for body mass index, ethnicity and sex, were recruited over 15 months. Abdominal visceral fat was measured by computerized tomo-graphy. Logistic regression analysis revealed that visceral fat was associated with psoriasis (odds ratio (95% confidence interval): 1.56 (1.15, 2.11)), hyper-triglyceridaemia (1.67 (1.22, 2.28)), low high-density lipoprotein (1.63 (1.19, 2.22)) and type 2 diabetes (1.77 (1.24, 2.54)), (p < 0.005 for all). These respective associations were linked to serum interleukin-6, adiponectin, tumour necrosis factor and insulin resistance. Psoriasis was associated with type 2 diabetes (7.94 (2.64, 23.9)), independent of visceral fat. These data suggest that visceral fat and its mediators play a key role in psoriasis-associated cardiometabolic diseases. Psoriasis itself is associated with an increased risk of type 2 diabetes.

Background Cutaneous involvement is very common in systemic lupus erythematosus. We describe the prevalence and spectrum of lupus-specific (cutaneous lupus erythematosus) and non-specific cutaneous features amongst mostly black South Africans with systemic lupus erythematosus. Patients and methods A retrospective record review of 298 South Africans (262 blacks and 36 non-blacks) with systemic lupus erythematosus was carried out. Cutaneous features were classified according to the Gilliam and Sontheimer classification of cutaneous lupus. Results Most (81.5%) patients were black African females. The mean (SD) age at diagnosis and follow-up duration were 35.0 (11.8) and 8.0 (5.9) years, respectively. Cutaneous lupus erythematosus was seen in 76.1% of patients, mainly chronic cutaneous lupus erythematosus with the discoid lupus erythematosus subtype seen in 52.1% of patients. Acute cutaneous lupus erythematosus was seen in 30.2% of patients and was more common in non-blacks than blacks (odds ratio = 3.8 (1.9–7.9)); localized acute cutaneous lupus erythematosus was more common than generalized acute cutaneous lupus erythematosus (odds ratio = 2.6 (1.6–4.4)). Non-specific cutaneous features occurred in 77.2%, with oral/nasal ulcers and Raynaud’s phenomenon each occurring in approximately 40% of patients. Diffuse melanonychia at initial diagnosis was present in 37.4% of patients and was more common in blacks than non-blacks (odds ratio = 3.1 (1.3–7.3)). Acute cutaneous lupus erythematosus was associated with renal disease (odds ratio = 2.8 (1.6–4.7)) and chronic cutaneous lupus erythematosus with arthritis (odds ratio = 2.02 (1.24–3.29)). Diffuse melanonychia was associated with less renal disease and anti-dsDNA antibody positivity (odds ratio = 0.4 (0.3–0.7) and 0.4 (0.2–0.6), respectively) and significantly lower lupus severity index scores (mean (SD) = 5.99 (1.11) vs 6.56 (1.36) in patients with no melanonychia, p Conclusion In this study of South Africans with systemic lupus erythematosus, the skin was the most commonly affected organ. In general, cutaneous lupus erythematosus was associated with less severe systemic disease. Acute cutaneous lupus erythematosus was less common in blacks, whereas discoid lupus erythematosus was more common than reported in Caucasians. Diffuse melanonychia was a distinctive finding and was associated with milder systemic disease.

Objectives In RA, the relationship between autoantibody status and treatment response to MTX remains unclear. We investigated the association between autoantibody status and early remission in newly diagnosed RA patients treated with MTX using real-world data. Methods RA-patients initially treated with MTX were selected from an international observational database (METEOR). Patients were stratified into autoantibody-positive (RF- and/or ACPA-positive) or autoantibody negative (RF- and ACPA-negative). The effect of autoantibody status on the chance of achieving remission within 3 to 6 months was analysed using Cox-proportional hazards regression. Results Data from 1826 RA patients were available for analysis. DAS remission was achieved in 17% (318/1826). This was similar in autoantibody-positive [17% (282/1629)] and -negative patients [18% (36/197)]. Hence, autoantibody positivity was not associated with remission [hazard ratio (HR) 0.89, 95% CI 0.57, 1.38]. Similar findings were found when stratified for MTX monotherapy (HR 0.75, 95% CI 0.41, 1.37) or combination treatment (HR 0.76, 95% CI 0.37, 1.54). Good physical function (HAQ < 0.5) was achieved in 33% (530/1590) of all patients. Autoantibody-positivity was also not associated with HAQ < 0.5 (HR 1.05, 95% CI 0.71, 1.57). Conclusion Autoantibody status is not associated with early remission in newly diagnosed RA-patients receiving MTX. This indicates that MTX is effective as an initial treatment strategy regardless of autoantibody status.

To investigate the prevalence and spectrum of comorbidities in South Africans with systemic lupus erythematosus (SLE). A nested case-control study of a known alive group (AG) and deceased group (DG) of 200 and 40 patients, respectively, matched for age and sex, attending a tertiary Lupus Clinic. Comorbidities that were documented included, but not restricted to, those listed in the Charlson comorbidity index (CCI). Lupus disease severity was assessed using the lupus severity index (LSI). Patients were mainly black female (94%), and the median age (IQR) and median disease duration (IQR) were 33 (25–42) and 6 (3–11) years, respectively. Overall, 191 (79.5%) patients experienced ≥ 1 comorbidities. The median (IQR) LSI and CCI scores were significantly higher in the DG than the AG (8.5 (6.7–9.1) vs 6.3 (5.2–8.3), p

Background: In resource-constrained settings where biologic agents are not widely available, there are limited therapeutic options for patients with rheumatoid arthritis (RA) refractory to other synthetic disease modifying antirheumatic (DMARD) therapies. The aim of this study is to evaluate the effectiveness and safety of leflunomide (LEF) with methotrexate (MTX) in refractory RA. Methods: A retrospective record review of adult RA patients treated with LEF/MTX. Demographic details, adverse reactions, and the 3-variable 28 joint disease activity score (DAS28-3) were recorded at initiation of LEF/MTX therapy, and after 4 and 12 months of treatment. Results: Of 194 patients, most were middle-aged seropositive Black African females, with established disease [mean (standard deviation, SD) disease duration 9.4 (8.2) years] and time on previous DMARDs of 7.0 (5.5) years. Before adding LEF, the mean (SD) dose of MTX was 21.7 (3.5) mg/week, and 87.6% of patients used low dose oral corticosteroids. A good or moderate EULAR response was achieved by 44% and 42% of patients, and the retention rate was 71%. Major infections were seen in 6 patients: comprising 2 deaths, 3 cases of leucopaenia and septicaemia and 1 case of tuberculosis. Hepatotoxicity ( n = 3), intolerable gastrointestinal symptoms ( n = 3), and hypertension ( n = 17) were the most common problems. Predictors of remission or low disease activity at 12 months was a baseline DAS28-3 ⩽ 5.5 [odds ratio (OR) = 2.7; 95% confidence interval (CI) 1.1–5.6; p = 0.01]. Conclusions: LEF/MTX was effective in the majority of patients in this cohort of mainly Black African women who failed other combination synthetic DMARDs, particularly in those with moderate disease activity at the time of addition of LEF. Infections and hypertension were important complications. In a setting where biologic DMARDs are not readily accessible, the combination of LEF/MTX is a cost-effective approach.

This study was conceived in an attempt to explain the unexpectedly high frequency of elevated levels of serum cotinine measured retrospectively in a cohort of predominantly black South African females with rheumatoid arthritis (RA), findings that were inconsistent with the smoking histories derived from health questionnaires. The discrepant findings suggested either a greater tendency towards underreporting of smoking status in the study cohort, or possible confounding effects of the use of smokeless tobacco products. In addition to the cohort of RA patients (n = 138, of whom 115 (83 %) were female), blood samples were also taken from a second cohort consisting of 29 declared smokers, 18 (62 %) of whom where females, 29 smokeless tobacco (SLT) users (all female), and 22 non-users of any tobacco products, 18 (82 %) of whom were females. Serum cotinine levels were determined using an ELISA procedure. Cotinine levels of >10.0 ng/ml were detected in serum specimens from 43 (31 %), RA patients of whom 35 (81 %) were female, with a median value of 50.1 ng/ml and interquartile range (iqr) of 68.6. Only 18 of the 35 females indicated that they smoked. The groups of declared smokers and SLT users had equivalent median serum cotinine levels of 88.0 ng/ml (iqr = 10.8 ng/ml) and 87.0 ng/ml (iqr = 15.6 ng/ml), respectively, while cotinine was undetectable in specimens from non-tobacco product users (

Background:Rheumatoid arthritis (RA) has been described in virtually every ethnic population. Most RA patients harbor anti-modified protein antibodies (AMPAs), including anti-citrullinated protein (ACPA), anti-carbamylated protein (anti-CarP), anti-malondialdehyde acetaldehyde (anti-MAA), and anti-acetylated protein antibodies (AAPA). However, it is unclear whether differences exist in the AMPA response between different ethnic groups. Such differences could provide new clues to genetic and environmental factors contributing to autoantibody development.Objectives:To investigate the prevalence of different AMPA in four ethnically diverse RA populations, and their association with smoking.Methods:Enzyme-linked immunosorbent assays were used to measure anti-CarP IgG, anti-MAA IgG (both in-house), and anti-acetylated vimentin IgG (Orgentec) in ACPA-positive sera of Dutch (NL, n=103), Japanese (JP, n=174), Canadian First Nations People (FN, n=100), and black South Africans (SA, n=67) fulfilling the 1987 ACR classification criteria for RA. Ethnicity-matched local healthy controls were used to calculate cohort-specific cut-offs. Logistic regression was used to identify whether ever-smoking was associated with AMPA seropositivity in each cohort, corrected for age, gender, and disease duration. Random-effects meta-analysis was used to pool the resulting odds ratios (OR).Results:For all three AMPAs, median levels were higher in FN and especially SA than NL and JP patients (Figure 1). The median autoantibody levels in arbitrary units (in % of patients positive) for NL, JP, FN and SA RA patients were: anti-CarP IgG: 1157 (47%), 994 (43%), 1642 (58%) and 2336 (76%) (pConclusion:In these ACPA-positive ethnically diverse RA populations, levels and prevalence of various AMPAs differ, suggesting that ethnic background and environment may influence the development of the autoantibody response in RA. Despite these differences, our results imply smoking as a consistent risk factor for AAPA across different ethnic backgrounds.Disclosure of Interests:Emma C. de Moel: None declared, Veerle Derksen: None declared, Leendert A Trouw: None declared, Chikashi Terao: None declared, Mohammed Tikly: None declared, Hani El-Gabalawy: None declared, Holger Bang Grant/research support from: Employee of Orgentec Diagnostika, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Rene Toes: None declared, Diane van der Woude: None declared

Background: In rheumatoid arthritis (RA), the relationship between autoantibody status and treatment response to methotrexate remains unclear. As methotrexate is the most widely used anti-rheumatic drug in clinical practice, it would be important to know whether the presence of autoantibodies is associated with better treatment response, since patients may benefit from treatment tailored to “autoantibody status”. Objectives: We investigated the relationship between autoantibody status and remission in newly diagnosed RA-patients treated with first-line methotrexate. Methods: RA-patients initially treated with methotrexate were selected from an international observational database (METEOR). Patients were stratified into autoantibody-positive (rheumatoid factor (RF)- and/or anti-citrullinated-protein antibodies (ACPA)-positive) or -negative (RF- and ACPA- negative). The effect of autoantibody status on the chance of achieving remission within 3 to 6 months was analysed using Cox-proportional hazards regression. Results: Data from 1826 RA-patients were available for analysis. DAS remission was achieved in 17% (318/1,826). This was similar in autoantibody-positive (17% (282/1629)) and -negative patients (18% (36/197)). Hence, autoantibody positivity was not associated with remission (HR0.89, 95%CI 0.57;1.38). Similar findings were found when stratified for methotrexate monotherapy (HR0.75, 95%CI 0.41;1.37) or combination treatment (HR0.76, 95%CI 0.37;1.54). Good physical function (HAQ Conclusions: In conclusion, we found that autoantibody status was not associated with early remission in newly diagnosed RA-patients receiving methotrexate in real-world clinical practice. These results do not support the hypothesis that treatment should be tailored to “autoantibody status” when it comes to initiating methotrexate therapy as first-line anti-rheumatic treatment. Rather, our results indicate that that methotrexate is effective as primary anchor drug regardless of autoantibody status. Disclosure of Interest: None declared

Objective: The aim of this study was to analyse differences in clinical presentation in patients with early (< 3 years’ duration) systemic sclerosis (SSc), comparing three age groups according to disease subsets. Method: Cross-sectional analysis of the prospective EULAR Scleroderma Trials and Research database (EUSTAR) was performed. Patients fulfilling preliminary American College of Rheumatology 1980 classification criteria for SSc, with < 3 years from the first non-Raynaud’s SSc symptom at first entry, were selected. Patients with < 3 years from the first SSc symptom, including Raynaud’s phenomenon, were also analysed. SSc-related variables, including antibodies, SSc subsets, and organ involvement, were examined. Age was categorized into ≤ 30, 31–59, and ≥ 60 years. We performed descriptive and bivariate analyses. Results: The study included 1027 patients: 90% Caucasian, 80% women, and 40% with diffuse disease. In early stages of SSc, younger patients had significantly more anti-Scl-70 antibodies and diffuse disease. With increasing age, we observed more elevation of estimated pulmonary systolic pressure on echocardiography (5%, 13%, and 30%, respectively, in the three age groups), cardiac conduction blocks (6%, 6%, and 15%), and left ventricular diastolic dysfunction (4%, 12%, and 27%). The results were similar for 650 patients with < 3 years from first SSc symptom, including Raynaud’s. Conclusion: In early stages of SSc, older patients showed data indicating more severe disease with greater cardiac involvement. The diffuse subset was more frequent in the younger subgroup. The identification of such differences may help in selecting appropriate management for individual patients in clinical practice. (Less)

To describe objectively measured changes in the volume and pattern of physical activity and sedentary behavior in patients undergoing total knee arthroplasty for osteoarthritis. Physical activity and sedentary behavior were measured in patients (13 males, 76 females) with a mean age of 64 years (range 55–80) and end-stage osteoarthritis of the knee, using an accelerometer (ActiGraph GT3X+) for seven consecutive days (24 h/day) prior to, 6 weeks and 6 months after total knee arthroplasty. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), University of California Los Angeles (UCLA) Activity index and range of motion (ROM) were also assessed. Proportion of time spent in sedentary behavior decreased from baseline to 6 months (mean 70.1 vs. 64.0%; p = 0.009) and the interruptions to sedentary behavior improved between baseline and 6 months after total knee arthroplasty (mean 85.0–93.0 breaks/day, p = 0.014). Proportion of time spent in light physical activity increased from baseline to 6 months after total knee arthroplasty (29.0 vs. 34.8%; p = 0.008). There was no change in time spent in moderate to vigorous physical activity after total knee arthroplasty. WOMAC (median 71.0 vs. 4.0, p

Summary Psoriasis (PsO) is a chronic immune-mediated inflammatory skin disorder associated with numerous co-morbidities. This descriptive review focuses on the cardiometabolic co-morbidities of PsO with reference to the epidemiology and pathogenetic mechanisms linking PsO and cardiometabolic disease (CMD). Registry-based studies have shown PsO to be associated with an increased risk of cardiovascular morbidity and mortality. Factors linking PsO and CMD include: chronic inflammation, obesity, classic cardiovascular risk factors, and the effects of systemic therapy used to treat PsO. Chronic inflammation is associated with PsO itself, and with obesity. Adipose tissue is responsible for the secretion of various adipokines, which together with pro-inflammatory cytokines arising from the psoriatic plaque, contribute to the proinflammatory and pro-atherogenic environment. Systemic therapy aimed at decreasing inflammation has been shown to improve CMD in PsO. Screening for and treating CMD and initiating lifestyle modifications will remain the most important interventions until further data emerge regarding the effect of systemic therapy on CMD progression.

To investigate the frequency, severity and predictors of interstitial lung disease (ILD) in a cohort of South Africans with systemic sclerosis (SSc). Retrospective record review of SSc patients attending a tertiary Connective Tissue Diseases Clinic. Patients with ILD, defined by a combination of clinical findings, imaging, and lung function tests were compared to patients without ILD in terms of demographics, clinical features and autoantibodies. The majority (86.8%) of the 151 patients included were of Black ethnicity, 40% had ILD, of whom 39% had moderate-severe lung disease. Univariate predictors of ILD included: disease duration (OR 1.08, 95% CI 1.01-1.15); cough (OR 2.93, 95% CI 1.37-6.29); dyspnoea (OR 2.44, 95% CI 1.23-4.87); bibasal crackles (OR 7.58, 95% CI 3.31-17.37); diffuse cutaneous SSc (dcSSc) (OR 4.55, 95% CI 2.10-9.86) and a speckled anti-nuclear antibody (ANA) pattern (OR 2.47, 95% CI 1.25-4.90). Conversely, limited cutaneous disease (OR 0.22, 95% CI 0.09-0.50) and anti-centromere antibody (ACA) (OR 0.12, 95% CI 0.02-0.97) were protective. Independent predictors of ILD on multivariate analysis were bibasal crackles (OR 9.43, 95% CI 3.25-27.39), disease duration (OR 1.19, 95% CI 1.09-1.30) and speckled ANA (OR 2.95, 95% CI 1.22-7.15). Almost all (86.4%) patients received immunosuppressive treatment and the leading cause of death was related to ILD itself (44.4%). In this cohort of predominantly Black South Africans, SSc ILD was common and carried a poor prognosis. ILD occurred mainly, but not exclusively, in patients with dcSSc, especially those with a speckled ANA pattern. Conversely, the presence of ACA was protective against ILD.

Background Systemic sclerosis (SSc) is a prototypic systemic fibrotic disease with unclearly characterized genetic basis. Implicated genes have been associated with autoimmune dysregulation with relatively few variants associated with fibrosis [1]. We have discovered that mutations in FAM111B gene cause hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP)[2], a multisystem fibrotic condition with clinical aspects of SSc [3]. This observation has established FAM111B as a candidate gene for SSc. Objectives The objective is to investigate whether FAM111B gene mutations are present in SSc patients and further explore relationships between FAM111B mutations and clinical expression of SSc. Methods Patients with a definite diagnosis of SSc attending the Rheumatology outpatient departments at Groote Schuur Hospital, Cape Town, and Chris Hani Baragwanath Hospital, Johannesburg, were enrolled into the study. Physical examination assessing the extent of disease was done in all patients and the modified Rodnan skin score (mRSS) was used to determine the extent of the skin involvement. Blood samples were collected for DNA extraction and mutation screening using the high-resolution melt technique. Samples with abnormal electropherograms were selected for Sanger sequencing to identify mutations. Public databases were used to verify the frequency of variants in FAM111B . Results 131 patients were genotyped, 13 men and 118 women, with a mean age of 26.6 years and mean age of symptom onset at 25.3 years. The majority of patients were black (59.5%). 72% of patients had diffuse systemic sclerosis (DSSc) with a median mRSS of 11. Genetic analysis revealed seven rare genetic variants (C832G>A; C855G>T; C917A>G; C937G>A; C988C>T; C995A>C and C1006G>C) in eight patients (five patients from Johannesburg and three patients from Cape Town) [table 1]. These variants were missense mutations of unknown significance with a minor allele frequency FAM111B mutations that cause POIKMT were found in patients with SSc. Conclusions Rare genetic variants of unknown significance (GVUS) in FAM111B gene were found in patients with SSc. It is possible that the GVUS may modify the function of FAM111B , and influence the pathogenesis of SSc or are rare polymorphisms with no functional impact. References Romano, E., et al., The genetics of systemic sclerosis: an update. Clin Exp Rheumatol, 2011. 29(2 Suppl 65): p. S75–86. Mercier, S., et al., Mutations in FAM111B cause hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis. Am J Hum Genet, 2013. 93(6): p. 1100–7. Khumalo, N.P., et al., Poikiloderma, tendon contracture and pulmonary fibrosis: a new autosomal dominant syndrome? Br J Dermatol, 2006. 155(5): p. 1057–61. Disclosure of Interest None declared

ObjectivesTo determine the causes of death and risk factors in systemic sclerosis (SSc).MethodsBetween 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation.ResultsWe identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile.ConclusionCombining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.

OBJECTIVE The aim of this study was to explore the clinical utility of the clinical disease activity index (CDAI). We compared the disease control with protocolized treatment adjustment following a tight control strategy utilizing either the simplified disease activity index (SDAI) or the CDAI. METHODS In a prospective 12 month study, DMARD-naive RA patients were randomized to either a CDAI or SDAI arm and were treated with traditional DMARDs, increased on a monthly basis according to a predefined protocol to achieve low disease activity. RESULTS Of 102 patients (84 females, 96 Black Africans), the mean symptom duration was 3.0 years (s.d. 3.8) and the mean 28-joint DAS (DAS28) at baseline was 6.2 (s.d. 1.2). By 12 months, the proportion of patients in the CDAI and SDAI groups achieving low disease activity (30% and 32%) and remission (33 and 34%) were similar. There were no significant differences in the mean DAS28 or its components or in HAQ Disability Index or health-related quality of life scores. Baseline predictors of low disease activity at 12 months were shorter symptom duration (P = 0.03) and lower HAQ-DI score (P = 0.04). CONCLUSION Given that the CDAI performed as well as the SDAI, and considering the cost savings and convenience because no acute phase reactant test is necessary, we suggest the CDAI may be an appropriate tool for monthly disease activity monitoring as part of a tight control strategy in developing countries.

Osteoarthritis (OA) is a common chronic degenerative joint disorder and a major cause of pain and disability, especially in the elderly. The prevalence is steadily rising due to an increase in life expectancy and certain lifestyle factors. OA is a complex dynamic process involving all tissues of the joint organ. Multiple risk factors are associated with the occurrence and progression of OA. There is extreme variability in presentation at different joint sites and between individuals. Management of OA involves a comprehensive approach consisting of preventative measures and numerous therapeutic modalities which should be tailored to individual needs. The family practitioner plays a vital role in the diagnosis of OA, the initiation of treatment and the ongoing monitoring of the condition.

This study aimed to determine the pattern and predictors of joint damage measured by the rheumatoid arthritis articular damage (RAAD) score and to describe its relationship to functional disability in patients with established rheumatoid arthritis (RA). One hundred Black patients with RA of disease duration ≥5 years were studied cross-sectionally. Data collected included socio-demographics, disease duration, smoking, body mass index (BMI), extraarticular features, rheumatoid factor (RF), haemoglobin (Hb), disease activity (DAS28), delay in disease-modifying antirheumatic drug initiation (DMARD lag) and treatment history. As outcome measures, the RAAD score and modified Health Assessment Questionnaire (mHAQ-DI) were used to assess joint damage and disability, respectively. Data were analysed by univariate and multivariate analyses. The mean RAAD score was 28.2 ± 12.8 for a mean disease duration of 17.5 ± 8.5 years. The majority of patients still had active disease (mean DAS28 4.4) and severe disability (mean mHAQ-DI 1.9), reflected in part by a long mean DMARD lag (9 years). Wrist and ankle joints were commonly involved. Multivariate analysis revealed that longer disease duration, higher RF titres and lower BMI were significant independent predictors of a higher RAAD score. The mHAQ-DI was significantly associated with DAS28, RAAD, education and Hb. Our results provide support for aspects of validity of the RAAD score and for its use in under-resourced settings. Further longitudinal studies are needed to evaluate its sensitivity to change in monitoring joint damage. Patterns of joint involvement and the inverse relationship between BMI and joint damage also merit further investigation in Black RA patients.

OBJECTIVES: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. METHOD: We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. RESULTS: 9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p

Physical activity levels are decreased and sedentary behaviour levels are increased in patients with knee osteoarthritis (OA). However, previous studies have shown that following total knee arthroplasty (TKA), objectively measured physical activity levels do not change compared to before the surgery. Very few studies have objectively assessed sedentary behaviour following TKA. This study aims to assess patterns of objective habitual physical activity and sedentary behaviour in patients with knee OA and to determine whether these change following TKA. Patients diagnosed with knee osteoarthritis and scheduled for unilateral primary total knee arthroplasty will be recruited from the Orthopaedic Division at the Charlotte Maxeke Johannesburg Academic Hospital. Eligible participants will have assessments completed one week before the scheduled arthroplasty, six weeks, and six months post-operatively. The primary outcomes are habitual physical activity and sedentary behaviour which will be measured using accelerometry (Actigraph GTX3+ and activPal monitors) at the specific time points. The secondary outcomes will be improvements in osteoarthritis-specific quality of life measures using the following questionnaires: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee injury and Osteoarthritis Outcome Score (KOOS), Oxford Knee Score (OKS), Knee Society Clinical Rating System (KSS), UCLA activity index; subjective pain scores, and self reported sleep quality. The present study will contribute to the field of musculoskeletal health by providing a rich detailed description of the patterns of accumulation of physical activity and sedentary behaviour in patients with knee OA. These data will contribute to existing knowledge using an objective measurement for the assessment of functional ability after total knee arthroplasty. Although studies have used accelerometry to measure physical activity in knee OA patients, the data provided thus far have not delved into the detailed patterns of how and when physical activity is accumulated before and after TKA. Accurate assessment of physical activity is important for physical activity interventions that target special populations. NCT02675062 (4 February 2016).

UNLABELLED:Functional ability is often impaired for people with rheumatoid arthritis (RA), rendering these patients highly sedentary. Additionally, patients with RA often take medication known to negatively affect bone mass. Thus improving functional ability and bone health in this group of patients is important. The aim of this study was to investigate the effects of whole body vibration (WBV) therapy in patients with stable, established RA. Thirty one females with RA were randomly assigned to a control group (CON, n = 15) who continued with their normal activities or a WBV group (n = 16) who underwent a three month WBV therapy intervention, consisting of 15 minutes of intermittent vibration, performed twice per week. Patients were assessed at baseline, three months, and three months post intervention for functional ability using the modified Health Assessment Questionnaire; for RA disease activity using the Clinical Disease Activity Index, for quality of life using self-report fatigue and pain scores; for physical activity profiles using accelerometry, and for BMD and body composition using DXA. Patients in both groups were matched for all variables at baseline. After the intervention period, functional ability was significantly improved in the WBV group (1.22(0.19) to 0.92(0.19), p = 0.02). Hip BMD was significantly reduced in the CON group (0.97(0.05) to 0.84(0.05) g.cm(-2), p = 0.01), while no decreases were seen in the WBV group (1.01(0.05) to 0.94(0.05) g.cm(-2), p = 0.50). Despite no change in RA disease activity in either group at either follow up, fatigue levels were improved in the WBV group (4.4(0.63) to 1.1(0.65), yet remained unchanged in the CON group at both follow ups (p = 0.01). Ten minute bouts of light to moderate physical activity were significantly reduced in the CON group after the intervention (2.8(0.61) to 1.8(0.64) bouts per day, p = 0.01), and were preserved in the WBV group (3.1(0.59) to 3.0(0.61) bouts per day, p = 0.70). Intermittent WBV shows promise for sustained improvements in functional ability, for attenuating loss of bone mass at the hip, as well as for decreasing fatigue in patients with established RA. TRIAL REGISTRATION:Pan African Clinical Trials Registry PACTR201405000823418.

Ankylosing spondylitis (AS) is the prototype for spondyloarthritis primarily affecting young men. Geographic and ethnic variations exist in the prevalence and severity of AS and relate to the wide disparity in the frequency of human leukocyte antigen (HLA)-B27, a major genetic risk factor. The strength of the disease association with HLA-B27 is lower in most Arab populations (25–75 %) than in Western European populations (>90 %), and there is no association in sub-Saharan Africa, where the prevalence of HLA-B27 is

Objective. To investigate the differential expression of MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1) and hepatocyte growth factor (HGF) in clinically involved (affected) and uninvolved (unaffected) skin in patients with SSc. Methods. Punch biopsies from affected forearm and unaffected upper back skin of 16 black South Africans with dcSSc and skin samples of 15 ethnically matched healthy controls were studied. Quantitative mRNA expression of MMP-1, TIMP-1 and HGF was performed by relative reverse transcription quantitative PCR. Results. Compared with controls, TIMP-1 expression was significantly upregulated in patients, a 796- and 397-fold difference for affected and unaffected skin (P < 0.00001 for both), respectively. Conversely, MMP-1 expression was significantly decreased in patients, a 10- and 12.5-fold difference for affected and unaffected skin (P = 0.0004 for both), respectively. HGF expression was up-regulated in both affected and unaffected skin, a 14- and 18-fold difference (P = 0.004 and P = 0.002), respectively. Within the patient group, HGF expression in affected skin of patients correlated significantly with the European scleroderma disease activity score (r = 0.60, P = 0.013). Conclusion. Perturbations in gene expression of TIMP-1, MMP-1 and HGF were evident in both affected and unaffected skin of the dcSSc patients. Targeting TIMP-1, which showed the greatest dysregulation, needs to be explored as a way of reducing collagen deposition and fibrosis in dcSSc.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that affects approximately 1% of the adult population. Some 30 to 40% of patients experience work disability within five years of onset of the disease, but early aggressive medical treatment has vastly improved the long-term outcome of RA. The combination of simple clinical tools to measure disease activity, the use of traditional disease-modifying anti-rheumatic drugs (DMARDs) early in the course of the disease and the introduction of targeted biologic agents for DMARD-resistant disease has greatly reduced the risk of joint deformities, physical disability and premature death. The family practitioner, by suspecting RA early in its course and jointly monitoring efficacy and toxicity of DMARDs with the rheumatologist, plays a pivotal role in improving the care and outcome of the RA patient.

Arthritis is a common cause of pain and disability in adults. In this article, the first in a series of two articles on arthritis, a clinical approach to musculoskeletal disorders is reviewed, with emphasis on the history and examination as the basis for diagnosis of common rheumatic disorders. A simple step-by-step clinical approach is discussed and basic investigations are considered in the context of clinical findings. Some common clinical pitfalls in diagnosis are highlighted. Broad principles of management of rheumatic diseases are briefly discussed as a prelude to the second article in which an in-depth approach to the management of rheumatoid arthritis is covered.

Background: Systemic lupus erythematosus (SLE) patients are at increased risk of developing tuberculosis (TB), particularly extrapulmonary TB (ExP-TB). Aim: The present study was undertaken to investigate whether SLE patients showed increased susceptibility to develop osteoarticular TB (OA-TB). Design and Methods: We retrospectively reviewed and compared the frequency of ExP-TB, in particular OA-TB, in patients with SLE at a tertiary hospital in South Africa, to a non-SLE control TB group seen at the same hospital. Results: TB was diagnosed 111 times in 97 (17%) of the 568 SLE patients. The relative frequency of ExP-TB in the SLE group (25.2%) was significantly lower than in the control group (38.5%) (OR = 1.9, P = 0.006). In contrast, OA-TB was diagnosed in the SLE group in nine (8.1%) patients (seven with peripheral arthritis and two with TB spine) compared to 54 (0.4%) in the overall control group (OR = 20.8, P < 0.001) and 13 (0.2%) in the subgroup of known HIV positive patients in the control group (OR = 44.4, P < 0.001). Within the SLE group, Black ethnicity ( P = 0.003), lymphopaenia ( P = 0.001), C3/C4 hypocomplementaemia ( P = 0.05), corticosteroids [maximum dose ( P = 0.002) and duration of treatment ( P = 0.02)] and immunosuppressive agents ( P = 0.02) were risk factors for TB. Duration of corticosteroid therapy was the only risk factor for OA-TB ( P = 0.04). Conclusion: While the relative frequency of ExP-TB was lower in the SLE group compared to the control group, our findings suggest that SLE patients are at particular risk of developing OA-TB. Further prospective studies are needed to better understand the mechanisms that predispose SLE patients to OA-TB.

Antinucleosome antibodies (AnuA) are increasingly recognized as an important biomarker in the diagnosis and subset stratification of patients with systemic lupus erythematosus (SLE). The aim of the study was to determine the sensitivity, specificity, and clinico-serological correlates of AnuA in black South Africans with SLE. We performed a cross-sectional study of 86 SLE patients attending a tertiary center and 87 control subjects. AnuA were tested using a second-generation enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value of AnuA were 45.3, 94.3, 88.6, and 63.6%, respectively. The presence of AnuA were strongly associated with the co-presence of anti-dsDNA antibodies (OR = 3.4, p < 0.0005) and antihistone antibodies (OR = 15.7, p < 0.00001). Patients who were seropositive for AnuA were more likely to have skin involvement (discoid lupus and/or malar rash) and had higher SLE disease activity index (SLEDAI) scores and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage scores (p < 0.05). IgG anticardiolipin antibody (aCL) levels showed a significant correlation with AnuA ratios (p < 0.01). Our findings provide further evidence that AnuA are a sensitive and specific diagnostic biomarker in SLE. Moreover, our finding that the presence of AnuA, but not anti-dsDNA antibodies, are associated with worse SLICC/ACR damage scores suggest that AnuA may have a role in predicting disease outcome. The correlation between IgG aCL and AnuA is a novel finding that merits further studies to determine possible common peptide specificities of the antibodies.

Associations between habitual physical activity levels and bone health in rheumatoid arthritis (RA) were assessed. Twenty nine female patients with RA were assessed for bone mineral density (BMD), and classified as having low or normal hip BMD. Habitual physical activity levels were assessed using accelerometry, and disease activity was assessed using the Clinical Disease Activity Index (CDAI). Twenty one patients had normal bone mass, while 8 had low bone mass. There was no difference in age in the normal bone mass group (51(8)) compared to the low bone mass group (57(12)), p=0.19. Patients with normal bone mass spent on average 2 h less per day in sedentary activity (65(4)% vs. 73(2)%, p

Background To measure circulating anti-citrullinated peptide antibodies (ACPA) and cytokines pre- and 6 months post-therapy as a strategy to predict and optimize responses to traditional disease-modifying antirheumatic drugs (DMARDs) in early RA, which is an unmet need in developing countries. Patients and methods A cohort of 140 predominantly (88.5 %) black female South African patients with early RA was treated with synthetic DMARDs, mostly methotrexate (MTX) alone, or in combination with low-dose oral corticosteroids (CS). Circulating ACPA and a panel of circulating cytokines/chemokines/growth factors were measured at baseline and after 6 months of therapy in relation to disease activity and Shared Epitope (SE). Results Following 6 months of therapy, the median simplified disease activity index (SDAI) declined from a baseline of 41.4 to 16.0 (p = 0.0001) for the entire cohort, which was paralleled by significant falls in median serum ACPA levels (516.6 vs. 255.7 units/ml, p =

There is a paucity of data on the impact of chronic rheumatic diseases on functional disability and overall health-related quality of life (HRQOL) in Africans. Materials and methods: We compared Black South Africans (BSA) with rheumatoid arthritis (RA) (n=50) and systemic lupus erythematosus (SLE) (n=50) to geographically and ethnically matched controls cared for at a tertiary care facility. The modified health assessment questionnaire (mHAQ) and Medical Outcome Study short-form 36 (SF-36) scores and indices of disease activity and organ damage were collected from each group. Results: Compared to the controls, both the RA and SLE groups fared significantly worse in respect of all the domains and summary scales of the SF-36. Compared to the SLE group, the RA group scored significantly worse with respect to the mHAQ disability index (mHAQ-DI), physical function and bodily pain (BP) SF-36 subscales, and SF-36 summary physical component score (SF-PCS). In the RA group, both the mHAQ-DI and SF-PCS correlated strongly (p

To determine the prevalence and clinical correlates of anti-phospholipid antibodies (aPL), including anti-cardiolipin antibodies (aCL), lupus anti-coagulant (LA), anti-beta2-glycoprotein 1 (abeta2GP1), and anti-prothrombin (aPT) antibodies, in Black South African patients with systemic lupus erythematosus (SLE).A cross-sectional study of 100 SLE patients in whom clinical characteristics, including features of the anti-phospholipid syndrome (APS), disease activity, and damage were documented, and sera tested for aCL, abeta2GP, and aPT of all isotypes, and LA.Positive aCL, abeta2GPI, aPT, and LA were found in 53, 84, 20, and 2 patients, respectively. Immunoglobulin (Ig)A aCL and IgG abeta2GPI were the commonest aCL (49.1%) and abeta2GPI (47%) isotypes, respectively. IgA abeta2GPI were associated with both a history of thrombosis alone (p0.05) and a history of any clinical feature, thrombosis, and/or spontaneous abortion of the APS (p0.05); IgA aCL were associated with a history of any clinical APS event (p0.05); and abeta2GPI of any isotype were associated with a history of arthritis (p0.001).Our findings provide further evidence that screening for abeta2GPI and IgA aCL isotypes may improve the risk assessment for APS in SLE patients of African extraction. Further prospective studies are warranted to determine the clinical utility of these tests and to elucidate the genetic basis for the increased IgA aPL response in SLE patients of African extraction.

Oxidative stress appears to be important in the causation and perpetuation of tissue injury and fibrosis in systemic sclerosis or scleroderma (SSc). We conducted a case-control study to assess lipid peroxidation levels as determined by measuring fasting plasma malondialdehyde (MDA) and serum levels of the trace elements selenium, iron, zinc and copper in SSc. Plasma MDA levels were almost tenfold higher in patients than in controls (p=0.00007), and an inverse relationship between MDA levels and disease duration (r=-0.52, p=0.044) was observed. Selenium levels were lower in patients than in controls (p=0.012). Within the patient cohort, copper correlated inversely with the total skin score (r=-0.52, p=0.03). Our findings provide further evidence that lipid peroxidation is increased and antioxidant capacity is reduced in SSc. The gradual decline in MDA levels with time suggests that antioxidant therapy, if to be useful in SSc, is most likely to be effective early in the course of the disease.

Systemic lupus erythematosus (SLE) is mainly a disease of young women. The problem of coexistent human immunodeficiency virus (HIV) infection is a growing problem in sub-Saharan Africa. We describe a case of active life-threatening neuropsychiatric lupus in a patient with underlying HIV infection. The challenges of interpreting physical signs and laboratory features that are common to both conditions, and the dilemma of treating active SLE with cytotoxics in the immunocompromised patient, are discussed.

Historically, rheumatic diseases have received little attention in Africa and rheumatologists have been few and far between. Now, supported by the global rheumatology community, interest in the specialty is growing, despite the formidable challenges faced by those practicing rheumatology in Africa.

The general impression is that rheumatoid arthritis (RA) has a lower prevalence and a milder course in developing countries. Epidemiological studies from different regions show that varying prevalence is possibly related to urbanization. The data suggest that where severe disability does occur, it presents a significant health challenge because of scarce medical and social resources. Disease-modifying anti-rheumatic drugs (DMARDs) remain the mainstay of therapy to alter the natural history of the disease. New therapies are unlikely to be of general benefit in the developing world because of financial constraints and increased risk of infections, particularly tuberculosis, associated with the use of tumour necrosis factor-alpha blockers. Instead, future research in poorer communities should be directed at assessing the burden of disease, the role of early aggressive therapy with DMARDs in combination with glucocorticoids for the majority of patients with RA, and finally, sourcing targeted biological therapies through clinical trials and grants for compassionate use in patients with refractory disease.