Clinical, neuroimaging and immunological phenotype of South African neuropsychiatric systemic lupus erythematosus patients.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an important cause of morbidity and mortality. We undertook this observational retrospective study of patients with NPSLE who had brain magnetic resonance imaging (MRI) to determine the indications for MRI and the correlation of clinical and laboratory findings with MRI. We identified 83 NPSLE patients (84.3% women) seen at Inkosi Albert Luthuli Central Hospital in Durban, South Africa, between June 2003 and May 2017. The mean age at SLE diagnosis was 26.24 ± 12.81 years and the median interval to NPSLE was 11.0 (interquartile range, 4.0-39.0) months. The most common indications for MRI were seizures (45.8%), psychosis (18.1%) and cerebrovascular disease (18.1%). The MRI was abnormal in 68 (81.9%) with small-vessel disease in 65 (78.3%) and large-vessel disease in eight (9.6%). The small-vessel abnormalities were white-matter hyperintensities (WMH) (59.0%), atrophy (55.4%) and lacunae (4.6%). Our patients had high disease activity at NPSLE. Cerebrovascular disease was associated with an abnormal MRI ( p = 0.018) and large-vessel disease ( p = 0.014) on MRI. Our NPSLE patients were younger and had high disease activity, and seizures were more common compared with other studies. The most common MRI abnormalities were WMH and cortical atrophy, in agreement with other studies.

The clinical manifestations and response to treatment in South Africans with lupus nephritis.

There are varying observations on the influence of ethnicity on the clinical spectrum and response to treatment in lupus nephritis (LN). We studied a multiethnic South African LN cohort to determine the clinical manifestations, histological involvement and response to therapy. We reviewed the records of LN patients at Inkosi Albert Luthuli Central Hospital in Durban. There were 105 patients, 92.5% females and they comprised 49.1% Indians and 45.3% African Blacks. The mean age was 31.3 ± 12.5 years, and 41.5% had LN at first presentation of lupus. The most common histological classes were Class V alone in 34.9%, Class IV (± Class V) in 25.5% and Class III (±Class V) in 22.6%. The estimated glomerular filtration rate was reduced (<30 ml/min) at presentation in 15 (14.2%). Eighty-seven patients received therapy for LN. A response to induction therapy was noted in 81.6% and maintenance therapy (12 months) in 73.6%. Response to mycophenolate mofetil (MMF) was 80.4% and 68.4% during induction and maintenance therapy, respectively. There was no ethnic difference in the histological class or response to MMF but African Blacks had more severe renal disease at presentation. In conclusion, our multiethnic LN cohort shows a high prevalence of membranous LN and good response to treatment.

Comparison of ethnicity, gender, age of onset and outcome in South Africans with systemic lupus erythematosus.

Ethnicity, gender and age of onset are reported to influence the expression and outcome of systemic lupus erythematosus. We studied a multi-ethnic cohort of 408 South Africans (91.2% females) comprising 237 (58.1%) Indians, 137 (33.6%) African Blacks, 17 (4.2%) Mixed ethnicity and 17 (4.2%) Whites. The most common manifestations were arthritis (80.6%), photosensitivity (67.2%), oral ulcers (50.0%), malar rash (49.0%) and renal (39.2%). The common laboratory findings were positive anti-nuclear factor (96.8%), haematological (74.8%) and anti-dsDNA antibodies (45.3%). Serositis ( p = 0.002), nephritis ( p = 0.039), leucopaenia ( p = 0.001), haemolytic anaemia ( p = 0.026), anti-dsDNA antibodies ( p = 0.028) and anti-Sm antibodies ( p = 0.050) were more common in African Blacks compared to Indians. Males had increased prevalence of discoid rash ( p = 0.006) and anti-Sm antibodies ( p = 0.016). Discoid rash ( p = 0.018), renal involvement ( p < 0.001), psychosis ( p = 0.028), seizures ( p = 0.020), anti-dsDNA antibodies ( p = 0.009), leucopaenia ( p = 0.006), haemolytic anaemia ( p = 0.017) and thrombocytopaenia ( p = 0.023) were more common with early-onset systemic lupus erythematosus. On multivariate analysis, the independent predictors of death were renal involvement, anti-dsDNA antibodies and seizures. There were 53 (13%) deaths and the five- and 10-year survival was 90.8% and 85.7% respectively, with no differences related to ethnicity or age of onset. In conclusion, we report on the spectrum and outcome of systemic lupus erythematosus in a large South African multi-ethnic cohort.

Acute presentation of thrombocytopaenia in systemic lupus erythematosus is associated with a high mortality in South Africa.

The objective of this study was to determine the pattern of presentation, response to treatment, and outcome in patients with systemic lupus erythematosus (SLE) and thrombocytopaenia (TCP). A retrospective review of the records of patients with SLE and TCP and a matched control group of SLE patients without TCP, seen in the rheumatology department in Durban, South Africa, was performed. The demographic data, clinical findings, laboratory findings, treatment and outcome were recorded. There were 54 patients and an equal number of controls. They comprised 30 Indians and 24 African Blacks, median age of 33 years and female to male ratio 5.8:1. A group of eight patients who initially presented with idiopathic thrombocytopaenic purpura (ITP) and subsequently developed SLE were analysed separately. An acute presentation was noted in 31 patients (57%). Patients with an acute presentation had an increased prevalence of renal disease (77% vs 43.5%; p=0.01) and an increased number of deaths (38.7% vs 4.4%; p=0.004). The majority of patients responded to corticosteroids (68.5%) and splenectomy. There was an increased prevalence of renal disease (p=0.03) and deaths (p=0.004) among patients with TCP. The majority of deaths had an acute presentation ((12/13; 92.3%) (p=0.004)), and were due to infection and active lupus. TCP with an acute presentation is associated with a high mortality and predicts survival in SLE.

International league of associations for rheumatology recommendations for the management of psoriatic arthritis in resource-poor settings.

BACKGROUND: Psoriatic arthritis (PsA) is a challenging heterogeneous disease. The European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) last published their respective recommendations for the management of PsA in 2015. However, these guidelines are primarily based on studies conducted in resource replete countries and may not be applicable in countries in the Americas (except Canada and USA) and Africa. We sought to adapt the existing recommendations for these regions under the auspices of the International League of Associations for Rheumatology (ILAR). PROCESS: The ADAPTE Collaboration (2009) process for guideline adaptation was followed to adapt the EULAR and GRAPPA PsA treatment recommendations for the Americas and Africa. The process was conducted in three recommended phases: set-up phase; adaptation phase (defining health questions, assessing source recommendations, drafting report), and finalization phase (external review, aftercare planning, and final production). RESULT: ILAR recommendations have been derived principally by adapting the GRAPPA recommendations, additionally, EULAR recommendations where appropriate and supplemented by expert opinion and literature from these regions. A paucity of data relevant to resource-poor settings was found in PsA management literature. CONCLUSION: The ILAR Treatment Recommendations for PsA intends to serve as reference for the management of PsA in the Americas and Africa. This paper illustrates the experience of an international working group in adapting existing recommendations to a resource-poor setting. It highlights the need to conduct research on the management of PsA in these regions as data are currently lacking.Key Points• The paper presents adapted recommendations for the management of psoriatic arthritis in resource-poor settings.• The ADAPTE process was used to adapt existing GRAPPA and EULAR recommendations by collaboration with practicing clinicians from the Americas and Africa.• The evidence from resource-poor settings to answer clinically relevant questions was scant or non-existent; hence, a research agenda is proposed.

Keratoconjunctivitis sicca in rheumatoid arthritis.

The prevalence of keratoconjunctivitis sicca (KCS) was studied in a randomly selected group of 104 patients with rheumatoid arthritis (RA). Symptoms of KCS were noted in 33 patients (31.7%) and they were studied further. After rose bengal staining, 22 of these patients were found to have KCS which was diagnosed by the presence of corneal or conjunctival desiccation. The overall prevalence of KCS was 21.2%. Although an abnormal Schirmer's test was noted in 21 of the 22 patients with KCS, only 8 patients had values of 5 mm or less while the remainder had a mild abnormality ranging from 6 to 15 mm. A reduced marginal tear film was noted in 15 patients (68.2%) with KCS and 13 patients (59%) had a reduced tear break-up time. The Schirmer's test alone is inadequate to make a definite diagnosis of KCS and it is essential to perform slit lamp examination to detect epithelial staining with rose bengal.

Experience with azathioprine in systemic sclerosis associated with interstitial lung disease.

The aim of this study was to evaluate the safety and efficacy of azathioprine in the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SSc). The records of patients with SSc with ILD who were treated with azathioprine were reviewed. Patients were treated with azathioprine and low-dose prednisone if they had progressive pulmonary symptoms (deterioration in the dyspnea score) or poor or deteriorating lung function. Response was classified as improved if the FVC increased more than 10% from baseline, and stable if it remained within 10% of baseline. Serial dyspnea scores were recorded. Eleven patients were treated with azathioprine, three of whom received treatment for 6 months or less owing to adverse effects (nausea, leukopenia and pulmonary tuberculosis in one patient each). The remaining eight patients received at least 12 months' treatment and the results suggested an improvement in the mean percent predicted FVC from a baseline value of 54.25+/-3.53 to 63.38+/-6.15 after 12 months ( p=0.101). Overall, five patients improved and three remained stable. The mean dyspnea score ( n=8) improved from a baseline of 1.55+/-0.19 to 0.50+/-0.19 at 12 months ( p=0.011). This is the first case series of patients with SSc-associated ILD treated with azathioprine. Our results suggest that azathioprine may have a role in stabilizing lung function and improving symptoms in SSc, although this needs confirmation by a randomized controlled trial.

Lack of association of Human T-cell lymphotrophic virus type 1(HTLV-1) infection and rheumatoid arthritis in an endemic area.

In South Africa the association of HTLV-1 infection with myelopathy is well described in Kwa Zulu Natal, which is an endemic area for HTLV-1 infection. Japan also has a high background prevalence of HTLV-1 infection, and a significant association of HTLV-1 infection with rheumatoid arthritis has been reported. This study was undertaken to determine whether there was an association with HTLV-1 infection among black Africans with rheumatoid arthritis (RA) in Kwa Zulu Natal, South Africa. A randomly selected group of 110 black people with RA were studied. The age, sex and duration of disease were recorded and a rheumatoid factor test was performed. The presence of antibodies to HTLV-1 was assessed using an enzyme-linked immunosorbent assay. The integration of proviral DNA in peripheral blood monocytes was also studied using the polymerase chain reaction (PCR). Control data were available from a previously reported community-based study of 1018 subjects from the same geographical area. None of the 110 patients studied were positive for HTLV-1 infection by serology or by PCR. Although HTLV-1 infection is reported as a possible triggering agent for RA in Japan, we failed to detect any excess of HTLV-1 infection in black Africans with RA. Our findings are in agreement with observations in the USA and Europe.

DC-ART: decreased inflammatory synovitis.

As part of the proposal for drug development using the SMARD/DC-ART definitions, "decreased inflammatory synovitis" needs to be defined. We review the literature with respect to each of the indirect, clinical measures of decreased inflammatory synovitis and recommend a preliminary, testable definition based on a per patient response. It includes minimum disease activity criteria for patients entering studies and improvement in at least 5 of the following 6 criteria: greater than 20% improvement in joint swelling count; greater than 20% improvement in joint tenderness count; greater than 20% improvement in erythrocyte sedimentation rate; greater than 30% improvement in physician/assessor global assessment; greater than 30% improvement in pain. While this definition is sensible within the confines of our knowledge to date, using these criteria prospectively in several clinical trials will allow better definition of the appropriate pooled index to define decreased inflammatory synovitis.

Arthritis in association with human immunodeficiency virus infection in Black African children: causal or coincidental?

OBJECTIVES: To compare human immunodeficiency virus (HIV)-infected and HIV-uninfected children with arthritis of unknown origin to determine whether the association between HIV infection and arthritis is causal or coincidental. METHOD: Retrospective review of 132 children with arthritis who were tested for HIV infection. RESULTS: Thirty-five (27%) of the children were HIV infected and the male to female ratio was 2.5:1 (P = 0.02). Arthritis was the presenting feature of HIV infection in 78% of these children. The remaining 97 (73%) were diagnosed as having juvenile idiopathic arthritis. 'Spondyloarthropathy-like' features were found in 34% of HIV-infected children compared with 5% of uninfected children. CONCLUSION: The high prevalence of HIV infection in 27% of children, the predominance of males and the increased prevalence of 'spondyloarthropathy-like' features, supports a causal relationship between HIV infection and arthritis.

Rheumatoid arthritis and connective tissue disorders: sub-Saharan Africa.

Rheumatoid arthritis (RA) once a rarity in Africa, is now reported in large numbers from many parts of Africa. Although epidemiological surveys have shown that the prevalence in urban populations is similar to Western communities, it is less common in rural areas. Further epidemiological studies are needed to confirm these findings in other parts of Africa and identify factors contributing to this difference to provide a better understanding for the emergence of RA in Africa. Earlier reports suggested that in African blacks RA was a mild disease, severe radiographic changes were uncommon, deformities were rare and extra-articular features were unusual and only symptomatic therapy was necessary to control symptoms in most patients. Recent experience shows that severe disease with deformities and radiographic changes are seen and a wide spectrum of extra-articular features are noted although they may be less common than in Caucasians. African blacks with RA may have a younger age of onset and the genetic association with HLA DR4 has been confirmed. Systemic lupus erythematosus (SLE) is also recognized more often in African blacks who have a younger age of onset. SLE is also recognized less often in males. Features such as photosensitivity and serositis are less common while renal disease is more common. A reported short-term mortality of about 30% emphasizes the need for urgent efforts to improve the prognosis in SLE. The infrequent occurrence of localized systemic sclerosis and the absence of anti-centromere antibodies in blacks was noted in a recent large series of patients with systemic sclerosis. The other connective tissue diseases and systemic vasculitides are reported much less frequently and will probably be detected more often in future. Anti-cardiolipin antibodies are detected frequently in association with infections, including HIV infection. The spectrum of diseases associated with ANCA includes a variety of connective tissue diseases and infections such as HIV infection and invasive amoebiasis must be added.

Clinical regression of amyloid nephropathy in a patient with rheumatoid arthritis. A case report.

A 22-year-old woman with active seronegative rheumatoid arthritis responded to intramuscular gold but developed proteinuria which settled when this therapy was stopped. Proteinuria recurred after 2 weeks of penicillamine therapy but settled when this regimen was stopped. Six months later she developed a nephrotic syndrome and rectal and renal biopsies showed evidence of amyloidosis. She was treated with chlorambucil for 1 year and the disease activity was well controlled. There was regression of the nephrotic syndrome and her serum albumin and renal function are normal 6 years later.

Resorptive arthropathy in rheumatoid arthritis.

Our survey was undertaken to determine the prevalence of resorptive arthropathy in rheumatoid arthritis (RA). A group of 256 patients with classical or definite RA were studied and resorptive arthropathy was noted in 13 (5.1%). The age and sex ratio of the patients with resorptive arthropathy was similar to the remainder of the patients, but the duration of RA was significantly greater (p = 0.003). Patients with resorptive arthropathy had severe radiographic changes. There was no significant difference in the prevalence of nodules, a positive rheumatoid factor or antinuclear factor and functional classification (American Rheumatism Association) in patients with resorptive arthropathy when compared to the remainder of the patients. Our study shows that, in a hospital based study of patients with RA, resorptive arthropathy may be commoner than generally recognized, and its prevalence may be similar to the findings in psoriatic arthritis.

Rheumatologic manifestations of malignancy.

The association of rheumatic syndromes and malignancy is highlighted in this review. The prevalence of malignancy in a series of patients with unclassified rheumatic syndromes is reported. The spectrum of arthropathies associated with malignancy includes bilateral knee effusions, sacroiliitis, and adult-onset Still's disease. There are further reports on the well-recognized association between dermatomyositis and malignancy. The importance of screening for malignancy in patients with classic dermatomyositis as well as dermatomyositis sine myositis is highlighted. The association of mixed cryoglobulinemia with hepatitis C virus infection, hepatocellular carcinoma, and non-Hodgkin's lymphoma is discussed. Finally, the association of miscellaneous rheumatic features such as autoantibodies, vasculitis, carpal tunnel syndrome, and multicentric reticulohistiocytosis with malignancy is described.

Rheumatologic features of hematologic disorders.

The rheumatologic manifestations of hemophilia and the hemoglobinopathies have been previously reviewed. Recent observations on the management and complications of these disorders are presented. Although rheumatologic manifestations are well recognized in leukemias and lymphomas, most of the observations have been based on small series of patients and case reports. This review focuses on leukemias and lymphomas, and brief reference is made to the myelodysplastic syndromes.