Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

Osteoporosis in Africa-where are we now.

Africa is experiencing an exponential increase in the number of older persons. The number of persons surviving with human immunodeficiency virus is simultaneously increasing due to improved availability of anti-retroviral therapy. The burden of non-communicable diseases, in particular, osteoporosis and its consequent fragility fractures, is also predicted to increase. Osteoporosis, however, remains a neglected disease and there are no age-standardized reference data available to accurately screen and diagnose individuals with osteoporosis. Epidemiological studies reporting the incidence of hip fracture or vertebral fractures are limited from Africa, especially Sub-Saharan Africa. The studies are usually limited as they are based on a retrospective data and small study numbers and often from a single study site. However, compared with early initial studies, the more recent studies show that osteoporosis and fractures are increasing across the continent. The overall incidence rates for osteoporosis and fractures still vary greatly between different regions in Africa and ethnic groups. Predisposing factors are similar with those in developed countries, but awareness of osteoporosis is sorely lacking. There is a lack of awareness among the population as well as health authorities, making it extremely difficult to quantify the burden of disease. There is great potential for research into the need and availability of preventive strategies. The FRAX® tool needs to be developed for African populations and may circumvent the shortage of bone densitometry.

Ethnic and gender-specific incidence rates for hip fractures in South Africa: A multi-centre study.

BACKGROUND: Limited data exist on the incidence of hip fractures in South Africa (SA). We report gender and ethnic specific incidence rates of hip fractures in SA. METHODS: In a multicentre prospective study, conducted in geographically defined municipalities of three provinces in SA, a structured questionnaire was administered to all subjects aged 40 years and over, presenting with a new atraumatic hip fracture, from 1 April 2017 to 31 March 2018. Gender and ethnic specific incidence rates (IR) of hip fractures were calculated using population statistics from Statistics SA. FINDINGS: Of the 2767 subjects enrolled, 1914 (69·2%) were women and 853 (30·8%) were men. The majority of subjects were from the White population (40·9%) followed by those from the African (26·4%), Coloured (18·7%) and Indian (13·9%) populations. Men with hip fractures were significantly younger than women in the total group (69 [IQR 59-79] versus 77 years [IQR 68-84], p < 0·001) and in each ethnic group. White subjects were significantly older (p < 0·0001) and Africans significantly younger (p < 0·0001) than the other ethnic groups. In women, the highest IR was noted in the White population (176·0 per 100,000), followed by that in the Indian (147·7 per 100,000), Coloured (73·2 per 100,000) and African populations (43·6 per 100,000). A similar pattern was seen in men albeit at lower rates, with the highest rate in White men at 76·5 per 100,000. In the total study population and the African population, the IR was higher in men compared to women in subjects under 60 years. In the White population, the IR was higher in men compared to women in the 40-44 years age group. While in the Coloured and Indian populations the IR was higher in men compared to women in the 40-49 years and 45-54 years age groups, respectively. There was an increase in the relative risk ratios with age in the total study population, and in all ethnic groups in both women and men. INTERPRETATION: Hip fractures occur in all ethnic groups in South Africa with higher IRs in the White and Indian populations compared to the Coloured and African populations. Consistent with the published literature, the overall hip fracture IR was higher in women than in men, except in the younger age groups, and increased with age. FUNDING: South African Medical Research Council and the University of KwaZulu-Natal Competitive Research Grant.

Polyarteritis nodosa presenting as a bladder outlet obstruction.

Polyarteritis nodosa (PAN) of the urinary tract is rare. An unusual case of systemic PAN involving the bladder neck is described. A 27-year-old man, with known diastolic hypertension diagnosed 2 years earlier, was admitted with chronic urinary obstruction complicated by hydronephrosis. He had symptoms of myalgia and weight loss, was afebrile but had an elevated erythrocyte sedimentation rate and acute-on-chronic renal impairment. All virological and serological tests including hepatitis B and anti-neutrophil cytoplasmic antibody were negative. A computed tomography scan of the brain revealed small-vessel disease. A bladder neck mass was visualised on cystoscopy. Histological examination of this demonstrated a medium-sized necrotising vasculitis with small-vessel fibrinoid necrosis suggestive of PAN. At least six of the American College of Rheumatology criteria for PAN were met. The patient was treated with pulses of intravenous cyclophosphamide and oral corticosteroids with a good clinical response.

Approach to lower back pain.

Lower back pain is one of the most common symptoms­and the most common musculoskeletal problem­seen by general practitioners. Iti s also a common cause of disability and an expensive condition in terms of economic impact because of absenteeism. This article discusses an approach to this common symptom and how to distinguish the benign, mechanical type of back pain from the more sinister, but less frequently encountered, inflammatory back pain.

A risk-benefit assessment of slow-acting antirheumatic drugs in rheumatoid arthritis.

There is no ideal slow-acting antirheumatic drug. Therapy of rheumatoid arthritis (RA) is currently being modified, with strong recommendations to abandon the traditional pyramidal approach. The call is for a more aggressive, earlier approach to suppress inflammation. Combination therapy rather than the use of a single agent is advocated by some. Improved methods for assessing disease activity as well as measurement of outcome have been developed. Markers of poor prognosis have helped to define patients for earlier treatment. Comparison of toxicity among such a diverse group of drugs is probably best achieved with a toxicity index measuring the number of episodes expressed in terms of patient-years of exposure. Toxicity remains the commonest reason for discontinuing an agent, while remission beyond 36 months on therapy is uncommon, except with methotrexate. The profile of toxicity is clearly defined for individual agents, but combination therapy may reveal an entirely different set of toxic manifestations. There is an urgent need to develop a set of risk factors to predict toxicity in an individual patient. Juvenile chronic arthritis behaves differently from adult RA. Drug toxicity profiles are similar, but less common. Outcome is more difficult to measure, with the major impact of disease and therapy being on growth retardation.

Extensive botryomycosis in a patient with diabetes and chronic active hepatitis.

Extensive botryomycosis was diagnosed in a patient with diabetes mellitus with chronic active hepatitis. Peptostreptococcus organisms and Staphylococcus aureus grew from the sulfur granule cultures. The patient's neutrophils showed notable inhibition of chemotaxis toward endotoxin-activated normal serum. The patient's serum also had an inhibitor to neutrophil chemotaxis, This inhibiting substance was probably antistreptolysin O. Results of other tests of neutrophil function and skin tests to evaluate cell-mediated immunity were normal.

Coexistence of myasthenia gravis and seropositive juvenile chronic arthritis.

The development of myasthenia gravis (MG) in a patient with juvenile chronic arthritis (JCA) is a rare occurrence. This report concerns a patient with seropositive JCA who developed MG during her second pregnancy.

Prevalence of metacarpal osteopenia in young rheumatoid arthritis patients.

The aim of this study was to assess the prevalence of and diagnostic role of metacarpal osteopenia in rheumatoid arthritis (RA) and to evaluate its detectability using receiver operating characteristic (ROC) analysis. Metacarpal bone mineral density was measured in 98 patients with classical RA using a computer-assisted measure of 6 metacarpal diameters (radiogrammetry) in patients aged less than 50 years. Sensitivity and specificity of the technique in discriminating the RA patients from 85 normal controls and osteopenic RA subjects from their normopenic counterparts, was determined by standard statistical techniques. Clinical, laboratory and radiological variables were compared in their ability to explain the variance of metacarpal bone density. The prevalence of metacarpal osteopenia in RA was 55%. Prolonged disease and reduced function significantly differentiated osteopenic from non-osteopenic RA patients. Discriminant analysis of RA and control groups showed that measurement of 6 metacarpals was more accurate than the 2nd metacarpal measurement alone in predicting the RA patients. The sum of 6 metacarpal combined cortical width (CCW) had a sensitivity of 61% and specificity of 68% in discriminating the RA patients from the controls. Receiver operating characteristics curves showed, not surprisingly, that objective measurement of bone diameters was superior to clinical or laboratory measures of disease activity in correctly classifying a randomly chosen RA patient as osteopenic or not. Metacarpal osteopenia is common in RA and it may be a useful measure of the disease in young patients.

Metacarpal bone mass in systemic lupus erythematosus.

We report the prevalence of metacarpal cortical thinning in systemic lupus erythematosus (SLE). Fifty-eight ambulant female patients attending a lupus clinic (mean age 32.4 years), were found to have significant thinning of metacarpal cortices (p < 0.05) when compared with 63 normal females (mean age 34.1 years). However, metacarpal bone mass was within the normal range. Measurements were made at 6 metacarpals of the 2 hands using a computer-aided technique (digitized radiogrammetry). Femoral cortical width and Singh index at the left femur, as well as the vertebral index at L3 were also recorded. The trabecular indices were in the range of normality, but the SLE group had more patients in the immediately pre-osteopenic range. Metacarpal bone loss was not related to disease duration or corticosteroid therapy. The prevalence of osteopenia in SLE is probably underestimated and the pathogenesis is likely to be multifactorial.

Nutritional status in rheumatoid arthritis. Effects of disease activity, corticosteroid therapy and functional impairment.

Sixty-five patients with rheumatoid arthritis (RA) (mean age 37.2 years) were compared with 71 controls (mean age 33.8 years). Anthropometric measurements included body diameters and skin-fold thickness at multiple sites, while biochemical markers of nutritional status included serum albumin, thyroxine-binding pre-albumin and retinol-binding globulin levels. None of the RA subjects was outside the range that extended 2 standard deviations above and below the normal control values for lean body mass. Discriminant analysis showed that corticosteroid therapy did not significantly influence skinfold thickness in RA. A combination of bi-acromial and bi-ankle diameters had a sensitivity of 70% and a specificity of 72% in differentiating the RA group, in whom disease activity had a greater effect on body diameters than corticosteroid therapy did. Differences related to functional impairment were a manifestation of disease activity rather than a direct effect on skinfold thickness or body diameters. According to anthropometric measurements in ambulant patients, RA does not result in malnutrition in young individuals.

Early treatment of avascular necrosis in systemic lupus erythematosus.

Avascular necrosis (AVN) of the hips is associated with significant disability, and the majority of established cases require major surgery. In a retrospective analysis of 185 patients with systemic lupus erythematosus (SLE) 13 (7%) were found to have AVN. Of these, six had Raynaud's phenomenon, all had been on corticosteroids, and one had digital vasculitis. The mean duration of corticosteroid therapy was two years (range four months to five years). Five patients developed AVN two to 10 years after discontinuing steroids. The mean duration of disease at the onset of AVN was 6.85 years (range 1-19 years), and the mean age at onset of AVN was 31 years. Ten patients had severe multisystem involvement. None of the patients abused alcohol. Surgery was performed on 11 hips. Three had total hip replacement for stages 3 and 4 and seven had core decompression for stages 1 and 2. AVN progressed in two (28%) of these patients. In another patient core decompression failed for technical reasons. She subsequently required total hip replacement. The early detection of AVN to avoid the need for major surgery is stressed.

Assessment of age-related bone loss in normal South African women by means of the Hologic QDR 1000 system.

The aim of this study was to evaluate age-related changes in cortical and trabecular bone mineral density (BMD) in South African subjects, and to develop a local reference database for dual energy X-ray absorptiometry with the QDR 1000 densitometer. A questionnaire was used to recruit volunteers. Age, years since menopause, use of medications and medical diseases were recorded. Men were excluded. Only whites and coloureds were studied. Three hundred and eleven women had single measurements over a 2-year period. Seven sets of subjects were defined according to age (18-44; 45-49; 50-54; 55-59; 60-64; 65-69; > 70 years) (N = 163; 32; 35; 23; 25; 16; 17 respectively). Height and weight did not change significantly with age. There were significant differences in lumbar and femoral BMD (Ward's) compared with those of American subjects in the different age categories. Both the lumbar and total femoral BMD began to fall significantly between the ages of 60 and 65 years (P < 0.01). Ward's triangle showed a significant fall in BMD between 45 and 50 years of age (P < 0.01). Ward's BMD predicted 36% of the variation in lumbar BMD at 45 years but 10% at 70 years. Ward's triangle is a useful predictor of femoral bone loss in later years. The fracture threshold at the lumbar vertebrae was 0.822 g/cm2; at Ward's triangle it was 0.443 g/cm2. This gave a 16% prevalence of osteopenia in the lumbar region and a prevalence of 24% at Ward's area.

Ethnicity and patterns of spondyloarthritis in South Africa--analysis of 100 patients.

OBJECTIVE: To determine the spectrum and ethnic differences of spondyloarthritis disease patterns in patients attending the Rheumatic Diseases Unit, University of Cape Town, South Africa. METHODS: A retrospective survey of case records of 100 patients with spondyloarthritis seen between January 1988 and January 1995. RESULTS: Of these 100 patients, 71 were male, 53 were Colored [mixed race descendants of Khoisan (Hottentot and Bushmen), Whites, Malays and Black Africans], 40 White, 5 Black and 2 Indian (descendants of immigrants from the Indian subcontinent). Our results show that the prevalence and disease patterns of spondyloarthritis in this South African cohort are comparable to those seen in Europe and North America with respect to clinical and radiological features, as well as therapeutic and orthopedic surgical requirements. No major ethnic differences in disease patterns were observed in White and Colored patients studied. CONCLUSION: The spectrum of spondyloarthritis in South Africa is similar to that seen elsewhere in the world. Our study confirmed the rarity of these conditions in Black South Africans.

Clinical assessment of disease activity in rheumatoid arthritis: evaluation of a functional test.

A cross sectional analysis of the correlation between clinical, laboratory, and radiological markers of disease activity in 98 patients with classical rheumatoid arthritis (RA) is reported. The median age was 38 years, the median age at onset of disease 29 years, and the median duration of disease seven years. The Keitel function test (KFT) showed good correlation with the Ritchie articular index (RAI) (p less than 0.0001; r = 0.5) and the disability questionnaire (DQ) (p less than 0.0001; r = 0.6). The RAI and DQ correlated weakly with laboratory variables, while the KFT showed significant correlation with the erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and plasma viscosity (PV) (p less than 0.001; r = 0.4; 0.3; 0.4). Only the KFT showed significant correlations with bone mass measurements (p less than 0.01; r = -0.3; -0.4), and the Larsen index at the right wrist (p less than 0.0001; r = 0.4). Consensus analysis suggested that the KFT is a useful single clinical test of disease activity in RA. The hand functional index (HFI), a component of the KFT, showed significant correlation with the total KFT (r = 0.9). Prospective drug trials are needed to establish the value of the HFI in the monitoring of patients with RA.

Osteoporosis screening--radiogrammetry revisited.

Radiogrammetry remains a convenient method of bone mass measurement. It is the only objective means of quantifying metacarpal osteoporosis (OP) in rheumatoid arthritis (RA). An automated technique using a digitizer (interfaced with an IBM PC) for measurement of combined cortical width (CCW) at the mid-shaft of six metacarpals was evaluated in three groups of individuals under 50 years of age (98 normal controls, 96 RA, 63 SLE). Intra-observer, inter-observer, and inter-institution reproducibility was assessed with a 'phantom' embedded in a rectangular mould of wax. Intra-patient variation was also assessed in RA patients seen on two occasions less than a month apart. Two hundred and fifty-seven subjects were studied. The method was found to be reproducible for a single observer, among five different observers and in two separate institutions. The RA subjects seen on two occasions showed no significant differences in CCW. The technique showed significant differences of CCW in the three groups of premenopausal subjects (controls; RA; SLE) studied (p less than 0.001). The six metacarpal bone mass was calculated in less than 5 min. The technique of digitized radiogrammetry is an improvement on the Vernier caliper technique. The method is useful for epidemiological cross-sectional studies and for evaluation of long-term radiological changes in RA.

Trabecular bone density in premenopausal rheumatoid arthritis patients.

OBJECTIVE: This study was undertaken to compare trabecular bone mineral density (BMD) in premenopausal rheumatoid arthritis (RA) patients and normal age-matched controls. METHOD: A protocol was designed to record age, duration of disease, use of corticosteroids (CS) and/or slow-acting antirheumatic drug (SAARD) therapy together with duration of such therapy. BMD was measured using the Hologic QDR 1,000 dual energy X-ray absorptiometer. The first four lumbar vertebrae and the left femur were measured in 56 RA patients and 165 controls. Height and weight were measured. Comparisons were made between RA patients and controls, as well as between subgroups of RA patients based on CS therapy. RESULTS: Patients with RA had significantly lower BMD (P < 0.05) at all the sites than the normal controls. The mean duration of RA at the time of study was 60 months (standard deviation 58 months). Thirteen RA patients had used CS in doses less than 10 mg daily for 6 months or longer (mean 19 months), while 25 patients had been on SAARD for an excess of 6 months (mean 23 months). The CS-treated patients had significantly lower BMD than untreated subjects at the femoral neck and inter-trochanteric region (P < 0.05), but not at the lumbar spine. However, when compared with normal controls, the CS-treated subgroups had significantly lower BMD at the lumbar spine and all femoral areas. Trochanteric BMD was the best determinant of the RA group, with a sensitivity of 65% and specificity of 77%. The positive predictive value was 16%, while the negative predictive value was 10%. Using Bayes' theorem, the prevalence of osteopenia in RA was found to be 6%. CONCLUSION: We conclude that generalised bone loss is a systemic feature of RA and that loss at the spine and femur may be aggravated by CS therapy.