Rheumatic chorea in northern Australia: a clinical and epidemiological study.
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To describe the epidemiology and clinical features of Sydenham's chorea in the Aboriginal population of northern Australia a review was conducted of 158 episodes in 108 people: 106 were Aborigines, 79 were female, and the mean age was 10.9 years at first episode. Chorea occurred in 28% of cases of acute rheumatic fever, carditis occurred in 25% of episodes of chorea, and arthritis in 8%. Patients with carditis or arthritis tended to have raised acute phase reactants and streptococcal serology. Two episodes lasted at least 30 months. Mean time to first recurrence of chorea was 2.1 years compared with 1.2 years to second recurrence. Established rheumatic heart disease developed in 58% of cases and was more likely in those presenting with acute carditis, although most people who developed rheumatic heart disease did not have evidence of acute carditis with chorea. Differences in the patterns of chorea and other manifestations of acute rheumatic fever in different populations may hold clues to its pathogenesis. Long term adherence to secondary prophylaxis is crucial following all episodes of acute rheumatic fever, including chorea, to prevent recurrence. (+info)
Superantigen-induced T cell responses in acute rheumatic fever and chronic rheumatic heart disease patients.
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CD4+ and CD8+ T cells from healthy donors, acute rheumatic fever (ARF) and chronic rheumatic heart disease (CRHD) patients responded variably to a superantigen from Streptococcus pyogenes--Streptococcal pyrogenic erythrogenic toxin A (SPE-A). In vitro culture of CD4+ T cells from ARF patients (CD4-ARF) with SPE-A exhibited a Th1 type of response as they produced high levels of IL-2, while CD4+ T cells from CRHD patients (CD4-RHD) secreted IL-4 and IL-10 in large amounts, i.e. Th2 type of cytokine profile. The skewing of human CD4+ T cells (in response to SPE-A stimulation) to Th1 or Th2 type reflects the role of the two subsets in a disorder with differing intensities at the two extremes of the spectrum. Moreover, the anergy induction experiments revealed that CD8-ARF and CD8-RHD undergo anergy (to different extents), whereas CD4+ T cells do not, in response to re-stimulation by SPE-A. These results initially demonstrate that both CD4+ and CD8+ T cells respond differentially to SPE-A, and hence it is an important observation with respect to the pathogenesis of ARF/CRHD. Anergy in CD8+ T cells in the presence of SPE-A in vitro goes a step further to show the clinical relevance of these cells and their possible role in suppression of the disease. (+info)
Rheumatic disease and the Australian aborigine.
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OBJECTIVE: To document the frequency and disease phenotype of various rheumatic diseases in the Australian Aborigine. METHODS: A comprehensive review was performed of the archaeological, ethnohistorical, and contemporary literature relating to rheumatic diseases in these indigenous people. RESULTS: No evidence was found to suggest that rheumatoid arthritis (RA), ankylosing spondylitis (AS), or gout occurred in Aborigines before or during the early stages of white settlement of Australia. Part of the explanation for the absence of these disorders in this indigenous group may relate to the scarcity of predisposing genetic elements, for example, shared rheumatoid epitope for RA, B27 antigen for AS. In contrast, osteoarthritis appeared to be common particularly involving the temporomandibular joint, right elbow and knees and, most probably, was related to excessive joint loading in their hunter gatherer lifestyle. Since white settlement, high frequency rates for rheumatic fever, systemic lupus erythematosus, and pyogenic arthritis have been observed and there are now scanty reports of the emergence of RA and gout in these original Australians. CONCLUSION: The occurrence and phenotype of various rheumatic disorders in Australian Aborigines is distinctive but with recent changes in diet, lifestyle, and continuing genetic admixture may be undergoing change. An examination of rheumatic diseases in Australian Aborigines and its changing phenotype may lead to a greater understanding of the aetiopathogenesis of these disorders. (+info)
Functional analysis of IgA antibodies specific for a conserved epitope within the M protein of group A streptococci from Australian Aboriginal endemic communities.
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The mucosa is one of the initial sites of group A streptococcal (GAS) infection and salivary IgA (sIgA) is thought to be critical to immunity. However, the target epitopes of sIgA and the function of sIgA in GAS immunity, in particular the role of accessory cells and complement, is largely unknown. We studied the aquisition and the function of sIgA specific for a conserved region epitope, p145 (sequence: LRRDLDASREAKKQVEKALE) of the M protein. Peptide 145-specific sIgA is highly prevalent within an Aboriginal population living in an area endemic for GAS and acquisition of p145-specific sIgA increases with age, consistent with a role for such antibodies in immunity to GAS. Human sIgA and IgG specific for p145 were affinity purified and shown to opsonize M5 GAS in vitro. Opsonization could be specifically inhibited by the addition of free p145 to the antibodies during assay. Opsonization of GAS was totally dependent on the presence of both complement and polymorphonuclear leukocytes, and, moreover, affinity-purified p145-specific sIgA was shown to fix complement in the presence of M5 GAS. These data show that mucosal IgA to this conserved region peptide within the M protein has an important role in human immunity against GAS and may be useful in a broad-based cross-protective anti-streptococcal vaccine. (+info)
HLA molecules, bacteria and autoimmunity.
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It has been well established that many diseases are linked to HLA antigens. Two of the most interesting HLA associations may provide some insight into the pathogenesis of rheumatic inflammatory conditions. In ankylosing spondylitis (AS), 96% of patients possess HLA-B27, whilst the frequency of this marker in the general population is c. 8%. In rheumatoid arthritis (RA), >90% of patients possess either HLA-DR1 or some subtypes of HLA-DR4, whilst the frequency of this marker in the general population is c. 35%. The association between HLA-B27 and reactive arthritis (ReA) has also been well established. Furthermore, it has been shown that ReA is triggered by infection via the gastrointestinal tract due to Yersinia, Salmonella or Campylobacter spp. and in the genitourinary tract due to chlamydia. In a similar way, microbiological and immunological studies have revealed an association between Klebsiella pneumoniae in AS and Proteus mirabilis in RA. This article reviews the possible pathological implications of the associations between HLA-B27, K. pneumoniae and AS, as well as HLA-DR1/DR4, P. mirabilis and RA. (+info)
Rheumatic fever--is it still a problem?
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The incidence of rheumatic fever has declined in industrialized countries since the 1950s and now has an annual incidence of around 0.5 cases per 100,000 children of school age. In developing countries it remains an endemic disease with annual incidences ranging from 100 to 200 per 100,000 school-aged children and is a major cause of cardiovascular mortality. Interest in the pathogenesis of rheumatic fever was rekindled by outbreaks in the USA (1985-1987) and the rare cases still seen in industrialized countries. The current concept is that the disease results from the host's poorly adapted autoimmune response to group A beta-haemolytic streptococci. The risk of developing rheumatic fever following untreated tonsillopharyngitis is 1% in the civilian population. Knowledge of virulence factors has been greatly enriched by progress in molecular biology. One of the key elements is protein M, a surface protein on the bacterial wall which carries specific epitopes. Several serotypes which lead to rheumatic fever have been recognized among more than 80 identified serotypes. However, the reason why specific strains within a given serotype have increased rheumatogenic virulence remains unknown. The causal strain adheres to the oral and pharyngeal cells and then releases its degradation products. These products present antigenic determinants which cross-react with certain human tissues, particularly in cardiac valve tissue and myocardium. Diagnosis is now difficult owing to the low incidence. Late diagnosis can have serious consequences and acute rheumatic fever is a therapeutic emergency requiring immediate antibiotic and anti-inflammatory treatment. In most of Europe there is tacit agreement that all cases of pharyngitis and tonsillitis should be treated with antibiotics without identification of the causal agent despite the fact that only about 20% of the cases are caused by group A beta-haemolytic streptococci, and could lead to rheumatic fever. (+info)
Comparison of short-course (5 day) cefuroxime axetil with a standard 10 day oral penicillin V regimen in the treatment of tonsillopharyngitis.
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Oral penicillin V given three times daily in doses of 50,000-100,000 IU daily has been the standard treatment for tonsillopharyngitis for the last few decades. These regimens, initially recommended by the American Heart Association, were extrapolated from i.v. dosing with long-acting forms of penicillin which had been shown to prevent post-streptococcal sequelae. More recently, several antibiotics, including cefuroxime axetil, have been shown to be at least as effective as penicillin G in eradicating group A beta-haemolytic streptococci (GABHS) but their influence on post-streptococcal sequelae has never been assessed in a large-scale trial. The German Society for Pediatric Infectious Diseases (DGPI) undertook a large study of culture-proven tonsillopharyngitis involving several agents and included a 1 year follow-up to establish the effect on sequelae. In one arm of this study, cefuroxime 250 mg bid was compared with 50,000 IU penicillin V given in three divided doses. Cefuroxime axetil was more effective than oral penicillin V in eradicating GABHS at the assessment 2-4 days post-treatment (441/490 (90%) patients versus 1196/1422 (84%) patients; P = 0.001). Clinically, the two agents were equivalent in efficacy, and carriage rates were similar (11.1% and 13.8%, respectively) in patients receiving cefuroxime axetil and penicillin V, 7-8 weeks post-treatment. One case of glomerular nephritis occurred in a patient given penicillin V. There were no post-streptococcal sequelae confirmed for patients treated with cefuroxime axetil. The findings confirm the previously reported efficacy of short-course (4-5 day) treatments with cefuroxime axetil and indicate that short-course treatment is comparable to the standard oral penicillin V regimen in preventing post-streptococcal sequelae. (+info)
Evaluation of the approach of primary care physicians to the management of streptococcal pharyngotonsillitis. IPROS Network.
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BACKGROUND: Streptococcal pharyngotonsillitis remains a common illness in children and can lead to serious complications if left untreated. OBJECTIVE: To evaluate the diagnostic and management approach of a sample of primary care physicians in the largest sick fund in Israel to streptococcal pharyngotonsillitis in children. METHODS: A questionnaire was mailed to all physicians who treat children and are employed by the General Health Services (Kupat Holim Klalit) in the Jerusalem District. The questionnaire included data on demographics, practice type and size, and availability of throat culture and rapid strep test; as well as a description of three hypothetical cases followed by questions relating to their diagnosis and treatment. RESULTS: Of the 188 eligible physicians, 118 (62.5%) responded, including 65 of 89 pediatricians (73%) and 53 of 99 family and general practitioners (53.5%). Fifty-six physicians (47.4%) had more than 18 years experience, and 82 (70%) completed specialization in Israel. Mean practice size was 950 patients. Fifty-three physicians (43%) worked in Kupat Holim community clinics, 25 (21%) worked independently in private clinics, and 40 (34%) did both. A total of 91 (77%) had access to laboratory facilities for daily throat culture. The time it took for the results to arrive was 48 to 72 hours. For the three clinical scenarios, 90% of the physicians accurately evaluated case A, a 1-year-old with viral pharyngotonsillitis, and 100 (85%) correctly diagnosed case C, a 7-year-old with streptococcal infection. As expected, opinions were divided on case B, a 3-year-old child with uncertain diagnosis. Accordingly, 75 (65.3%) physicians did not recommend treatment for case A, compared to 109 (92.5%) for case C. For case B, 22 (19%) said they would always treat, 43 (36%) would sometimes treat, and 35 (30%) would await the result of the throat culture. For 104 (88%) physicians the antibiotic of choice for case C was penicillin, while only 9 (7.5%) chose amoxicillin. However, the recommended dosage regimens varied from 250 to 500 mg per dose, and from two to four doses daily. For case C, 110 physicians (93%) chose a 10 day duration of treatment. CONCLUSIONS: The primary care physicians in the sample (pediatricians, general practitioners and family physicians) accurately diagnosed viral and streptococcal pharyngotonsillitis. However, there was a lack of uniformity regarding its management in general, and the dosage regimen for penicillin in particular. (+info)