OBJECTIVES: Given the paucity of epidemiological and clinical data representing the South African experience with the spondyloarthropathies, a study was designed to achieve a description of the spectrum of spondyloarthropathy in patients of different ethnic origin attending the Rheumatic Diseases Unit (RDU), University of Cape Town (UCT), in respect of differences in: clinical and/or radiographic expression of disease; gender HLA-B27 status, and choice of therapy and requirements for reconstructive orthopaedic surgical procedures. STUDY DESIGN: The study comprised a retrospective descriptive review of all new cases of spondyloarthropathy seen at the RDU, UCT Medical School, from 1 January 1988 to 31 December 1994, who were consecutively identified from an analysis of the clinical records. The RDU (UCT) is one of two principal referral centres for rheumatic-related diseases in the Western Cape region, and provides clinical services at Groote Schuur Hospital (GSH, Observatory) and Princess Alice Orthopaedic Hospital (PAOH, Retreat) in Cape Town for an estimated population of 3. 4 million (Western Cape), 55% (1.9 million) of whom are resident in the Cape Peninsula region (81). A minority of patients from further afield (Northern Cape and Eastern Cape) also attend the unit. Approximately 12 500 patients attend PAOH outpatient Department (OPD) annually, of which 35% are seen by the RDU staff each year (average values calculated from attendance registers for the period 1 January 1988 to 31 December 1994). New patients constitute about 6% of all patients seen by the RDU per annum (Table 2). Statistical data were not available from the OPD Arthritis Clinic (AC) at GSH, but similar proportions would be expected, since both clinics are staffed by the same complement of doctors and operate under similar circumstances at both venues.

No description available.

Systemic sclerosis (SSc) is a rare systemic, autoimmune disease characterized by vascular changes and fibrosis of the skin and internal organs. Patients with SSc more frequently than healthy controls reported upper gastrointestinal (GI) symptoms, which was more abundant in the diffuse cutaneous form (dcSSc) of the disease than in the limited (lcSSc). One-third of a population-based cohort of 79 SSc patients reported faecal incontinence, compared to 11% in 158 healthy matched controls (p<0.001), and this symptom negatively influenced general well-being and social life. Impaired rectal sensibility, rectal bleeding, irritable bowel syndrome-like symptoms, abdominal pain, the need for manual assistance at defecation, and the use of oral laxatives were more common in patients than in controls. SSc patients reported lower scores in both physical and mental scales of the SF-36 questionnaire than controls, indicating worse health-related quality of life. Gastric emptying was slower in patients than in controls, and a higher prevalence of delayed gastric emptying in patients with dcSSc indicated more severe GI tract involvement than in lcSSc. Electrogastrographic recordings did not correlate to gastric emptying results, indicating factors other than defective myoelectric signals contributed to disturbed gastric function. SSc patients with faecal incontinence had lower anal squeeze pressures than patients without this symptom. Only patients with faecal incontinence had ultrasonographic abnormalities in the internal and external anal sphincters, and absence of the rectoanal inhibitory reflex. Thus, faecal incontinence in SSc patients may depend on both neurogenic and structural mechanisms. A discrete increase in fibre density observed in a majority of SSc patients might have implications from a disease mechanistic perspective. Sera from 47% of 70 SSc patients had the capacity to induce interferon (IFN)-α, production which correlated to the presence of anti-RNP and anti-SSA autoantibodies. Increased serum levels of IFN-inducible protein were associated with vascular manifestations, and increased serum levels of IFN-α with digital ulcers. Increased serum levels of monocyte chemoattractant protein-1 or IFN-α were associated with lung fibrosis. An activated type I IFN system previously observed in several other systemic autoimmune diseases is also present in SSc and may contribute to vascular pathology and the pro-fibrotic process.

Staphylococcus aureus (S. aureus) is responsible for many human diseases including septic arthritis and sepsis shock. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in inflammation and produced mainly by macrophages and monocytes. It is believed to be involved in pathogenesis of septic arthritis. Time window of TNF-a in innate immunity against staphylococcal infection was studied in this project. Two experiments were carried out: In the first experiment mice were infected with a low dose (8x106cfu/mouse) of S. aureus to induce septic arthritis whereas in the second experiment the mice were infected with a higher dose (8x107cfu/mouse) of S. aureus to induce sepsis shock. All mice were divided into three groups. The first group was treated with anti-TNF-α 20 minutes after infection. The second group was treated with the anti-TNF-α three days after infection. The third group served as control and was injected with PBS instead of anti-TNF-α. The mice were regularly weighed and signs of arthritis and mortality were recorded. Two weeks after inoculation bacteria viable counts in different organs was done, as well as histopathological assessment of joints and measurement of cytokines in blood. We have observed that mice treated with anti-TNF-α had less severe arthritis and also less mortality. However, they had more bacteria accumulated in the kidneys and lost more weight compared to the control group. The results were mostly seen in the group early treated with TNF-α, compared to the late treated group. We conclude that anti-TNF-α might be potentially used as a therapy against septic arthritis and sepsis shock. This should be combined with antibiotics to eliminate the bacteria while the anti-TNF-α reduces the severity of the inflammation and thus reduce the risk of permanent joint destruction and mortality. We can conclude that blocking TNF-α early on is essential in order to get the best results.

No description available.

Background Uveitis is a known cause of blindness in the developed world, where non-infectious diseases dominate the spectrum of underlying aetiologies. However, data from sub-Saharan Africa is lacking. Here we aim to describe the diseases associated with non-infectious uveitis and the impact of currently available treatment in this setting. Methods A retrospective observational analysis of children with non-infectious uveitis from January 2010 to December 2017, attending the tertiary paediatric rheumatology and ophthalmology referral units in Cape Town was conducted. Statistical analysis utilising STATA13 software was performed with p < 0.05 considered significant. Results Twenty-nine children were identified with a median age at first visit of 74 months (IQR 49–86 months), female to male ratio of 0.9:1, predominantly of mixed race (72.4%). Juvenile idiopathic arthritis associated uveitis (JIAU) (48.3%) was the most frequent diagnosis. All children with JIAU had chronic anterior uveitis and 3 (21.4%) presented with uveitis before arthritis. There were no differences between children with uveitis and those with arthritis only, for gender (p = 0.68) and race (p = 0.58) but significantly, children with uveitis presented at an overall younger age (p = 0.008), with antinuclear antibody positive (p < 0.001) oligo-articular JIA (p = 0.01) and older age appeared to be protective (p = 0.01 OR1.0 CI 0.6-1.7). Children with idiopathic uveitis (41.4%) were predominantly male (66.6%), of mixed race (75%), with chronic anterior uveitis (41.7%) and presented with cataracts (100%). Less commonly, sarcoidosis (6.9%) and Behcet's disease (3.5%) were diagnosed. 55.2% had complications at presentation, predominantly cataracts (87.5%). 19 children (65.5%) had inactive disease at 12 months from diagnosis and remission as assessed at the last clinical visit, was achieved in 58.6% on standard initial therapy and in 75% of those on tumour necrosis factor inhibitors. Surgery was needed in 41.4%, primarily in the idiopathic group. Visual acuity improved or was maintained on treatment. Conclusion The spectrum and characteristics of immune mediated non-infectious uveitis are comparable to that reported in developed countries. Current practice detects children with potentially sight-threatening disease and access to tumour necrosis factor inhibitors has improved outcomes in refractory cases.

Study rationale: Juvenile dermatomyositis (JDM) is a rare idiopathic inflammatory myopathy of childhood with an incidence of 1.9-3.2 per million. The aetiology of JDM is uncertain but may result from immune dysregulation triggered by environmental factors in genetically susceptible children. The demographic and clinical characteristics of JDM may thus differ by race and geographic regions. Few studies have described the characteristics of JDM patients from Africa. There is need for further studies for better understanding of the epidemiology, clinical characteristics and outcome of patients with JDM from the continent. Methods: We conducted a retrospective observational study to determine clinical characteristics and outcomes of patients satisfying the Bohan and Peter criteria for probable JDM seen between 2004-2013 in Red Cross, Groote Schuur and Tygerberg hospitals in Cape Town. Data was analyzed using R version 3.1.0 (2014-04-10). Results: Twenty-five cases were identified: 16 female and 9 male. Thirteen (52%) of the cases were of indigenous African, eleven (44%) mixed and one (4%) European ancestry. The median ages at disease onset and diagnosis were 6.75 (range 2.0-9.7) and 7.9 (range 3.4-9.75) years respectively. Muscle weakness and characteristic cutaneous manifestations occurred in all the 25 patients while 24 had elevated muscle enzymes. All the patients received corticosteroids, seventeen (73.9%) received methotrexate and four received rituximab. Eleven patients had calcinosis during the disease course [median follow up period of 50 (range 0.5-159) months]. The mortality was 2/25 (8%) while only 40% of the patients had clinically inactive disease by PRINTO criteria. There was no difference in racial distribution (p-value = 1), age at disease onset (p-value = 0.87) and disease duration prior to treatment initiation (p -value = 0.75) between patients who had clinically active and inactive disease. Discussion: The demographic characteristics of children with JDM were similar to that from most other regions of the world with female predominance and similar age at onset. The median delay in diagnosis (4 months) was not longer than that reported in most other studies. However, some children had prolonged delay of up to 7 years due to misdiagnosis that denied them appropriate treatment in a timely manner. Majority (60%) of the patients also remained with clinically active disease, which put them at risk of further disease complications including calcinosis. Even though the mortality rate was low (8%) this was still more than double that reported in most recent large studies especially from the resource rich countries. Conclusions: Long-term follow up of JDM patients is advisable since majority of patients seem to have clinically active disease many years after disease onset despite treatment. Formulation and use of appropriate treatment guidelines and protocols may aid in the early diagnosis and appropriate management for optimum outcomes.

No description available.

The major histocompatibility complex (MHC) class I molecule, Human Leukocyte Antigen B27 (HLA-B27) is a strong genetic risk factor for Ankylosing Spondylitis (AS). However, the mechanism linking HLA-B27 and the development of AS is unknown. Recent studies have shown that monoclonal antibodies targeting interleukin 17A (IL-17A) are an effective therapy for many patients with AS suggesting that IL-17A secreting lymphocytes mediate the disease. Published experimental evidence suggests further a potential role for 4 specific killer cell immunoglobulin-like receptors (KIRs) in the pathogenesis of AS, namely KIR3DL1, KIR3DL2, KIR2DL5, and KIR3DS1. KIRs are immunomodulatory receptors for MHC class I molecules that are expressed by a variety of lymphocyte subsets. We hypothesize that the expression of these AS-associated KIRs differentially modulates the expression of IL-17A in HLA-B27 positive vs. negative individuals thereby affecting susceptibility to AS. To begin to address this hypothesis, the experiments described in thesis were performed to develop a set of multi-color flow cytometry panels that permit the analysis of expression of KIR3DL1, KIR3DL2, KIR2DL5, KIR3DS1 and of IL-17A by major classical and unconventional lymphocytes subsets. These panels will be used in future studies to analyze peripheral blood samples from genotyped HLA-B27 positive and negative healthy individuals as well as from AS patients and controls.

No description available.