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Concept: Rheumatic fever

162

Taking DMARDs as prescribed is an essential part of self-management for patients with Rheumatoid Arthritis. To date, the Compliance Questionnaire for Rheumatology (CQR) is the only self-report adherence measure created specifically for and validated in rheumatic diseases. However, the factor structure of the CQR has not been reported and it can be considered lengthy at 19 items. The aim of this study was to test the factor structure of the CQR and reduce the number of items whilst retaining robust explanation of non-adherence to DMARDs. Such a reduction would increase the clinical utility of the scale, to identify patients with sub-optimal adherence to DMARDs in the clinic as well as for research purposes.

Concepts: Rheumatic fever, Rheumatoid arthritis, Rheumatology, Vasculitis, Psychometrics, Gout, Arthritis, Rheumatism

118

Streptococcus pyogenes is an important global pathogen, causing considerable morbidity and mortality, especially in low and middle income countries where rheumatic heart disease and invasive infections are common. There is a number of promising vaccine candidates, most notably those based on the M protein, the key virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development. Considerable effort is needed by key players to bring current vaccine candidates through phase III clinical trials and there is a clear need to develop a roadmap for future development of current and new candidates.

Concepts: Immune system, Clinical trial, Bacteria, Microbiology, Vaccination, Streptococcus pyogenes, Rheumatic fever, Streptococcus

69

Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study.

Concepts: Epidemiology, Disease, Diseases and disorders, Death, Heart, Rheumatic fever, Heart disease, Circulatory system

28

Rheumatic heart disease (RHD) is a chronic condition characterized by fibrosis and scarring of the cardiac valves and damage to the heart muscle, leading to congestive heart failure and death. This prospective cohort study was conducted to investigate the possible relation between the levels of serum adhesion molecules and acute rheumatic fever (ARF) carditis, valvular insult severity, and residual valvular lesion after improvement of rheumatic activity. Serum levels of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were assayed by enzyme-linked immunoassay (ELISA) for 50 children with ARF carditis during activity and after improvement and for 50 healthy children as control subjects. After the acute attack, patients were followed up regularly to detect residual valvular lesion. The serum levels of these adhesion molecules were significantly higher in the patients than in the control group (p < 0.001). In addition, the levels of serum adhesion molecules were significantly higher in the patients with severe carditis than in the patients with mild to moderate carditis (p < 0.001). Among the severe carditis group, the level of serum adhesion molecules was significantly higher among the patients with heart failure than among the patients without heart failure (p < 0.001). Furthermore, the pretreatment serum levels of ICAM-1 and VCAM-1 were significantly higher among the patients with residual valve lesion (p = 0.002) than among those without the lesion (p < 0.001). The cutoff values were obtained for the prediction of residual valvular lesion (ICAM-1, >1,032.3 μg/ml; VCAM-1, >3,662.3 μg/ml; E-selectin, >104.8 μg/ml). Finally, by combining the three adhesion molecules in a single prediction model, the highest area under the curve (AUC) ± standard error (SE) was obtained (0.869 ± 0.052), and the positive likelihood ratio for having a residual valvular lesion was increased (17.33). Levels of serum adhesion molecules could predict residual valvular lesions in RHD patients. The authors recommend that the serum level of adhesion molecules be measured in all cases of ARF carditis.

Concepts: Cardiology, Heart, Rheumatic fever, Cell adhesion molecule, Rheumatism, Intercellular adhesion molecule, VCAM-1, Heart valve

27

Rheumatic fever and Rheumatic heart disease continue to be an important public health problem in the developing countries. Doppler echocardiography is now widely used for early detection and recurrences of clinical evident carditis (CC) and silent (subclinical) carditis (SC). The aim of the study is to determine the frequency of silent carditis and to compare clinical and echocardiographic features of the patients with silent and clinical carditis.

Concepts: Epidemiology, Diseases and disorders, Medical terms, Cardiology, Doppler echocardiography, Echocardiography, Medical ultrasound, Rheumatic fever

27

TREM-1 (triggering receptor expressed on myeloid cells) is a surface molecule expressed on neutrophils and macrophages which has been implicated in the amplification of inflammatory responses triggered during infection. In the present study, we have investigated the clinical significance of TREM-1 in Streptococcus pyogenes-induced severe sepsis in both experimentally infected mice as well as in patients with streptococcal toxic shock. We found that S. pyogenes induced a dose-dependent upregulation of TREM-1 in in vitro cultured phagocytic cells and in the organs of S. pyogenes-infected mice. Furthermore, we reported a positive correlation between serum levels of soluble TREM-1 (sTREM-1) and disease severity in infected patients as well as in experimentally infected mice. Hence, sTREM-1 may represent a useful surrogate marker for streptococcal sepsis. We found that modulation of TREM-1 by administration of the TREM-1 decoy receptor rTREM-1/Fc substantially attenuated the synthesis of inflammatory cytokines. More importantly, treatment of S. pyogenes-infected septic mice with rTREM-1/Fc or the synthetically produced conserved extracellular domain LP17 significantly improved disease outcome. In summary, our data suggest that TREM-1 may not only represent a valuable marker for S. pyogenes infection severity but it may also be an attractive target for the treatment of streptococcal sepsis.

Concepts: Inflammation, Bacteria, Streptococcus pyogenes, Rheumatic fever, Streptococcus, Septic shock, Sepsis, Group A streptococcal infection

27

Acute pharyngitis is a non-specific symptom that can result from a number of viral and bacterial infections. For most eitiologies, symptoms are self-limited and resolve without lasting effects; however, pharyngitis resulting from infection with Streptococcus pyogenes (group A Streptococcus, GAS) can be associated with serious sequelae including acute rheumatic fever and acute glomerulonephritis. Rapid accurate detection of GAS in pharyngeal specimens from individuals suffering pharyngitis aids in management and selection of antibiotic therapy in these patients. A total of 796 pharyngeal swabs were collected at three separate clinical centers. Each specimen was analysed using the illumigene Group A Strep DNA amplification assay (Meridian, Cincinnati, OH). Results were compared to direct and extracted culture methods using Gram-stain and GAS-specific latex agglutination test to confirm GAS identification. Discrepant results were resolved using an alternative nucleic acid amplification test. The culture-based prevalence of GAS in this study was 12.8% (102/796). The illumigene assay detected GAS in 74/74 (100% sensitivity) direct culture positive and 100/102 (98.0% sensitivity) extracted culture positive specimens. GAS was detected by illumigene in an additional 42 (94.2% specificity) specimens that were direct culture negative and 16 specimens that were extracted culture negative (97.7% specificity). Discrepant analysis using an alternative molecular assay detected GAS nucleic acid in 13/16 (81.3%) “false positive” specimens and ½ “false negative” specimens, resulting in a final sensitivity of 99.0% and specificity of 99.6% for detection of GAS in pharyngeal swabs using the illumigene assay.

Concepts: DNA, Bacteria, Streptococcus pyogenes, Rheumatic fever, Streptococcus, Type I and type II errors, Glomerulonephritis, Group A streptococcal infection

27

Background: Streptococcus salivarius K12 has been shown to inhibit the growth of Streptococcus pyogenes due to bacteriocins release. Because of its ability to colonize the oral cavity, we have tested the strain K12 for its efficacy in preventing streptococcal pharyngitis and/or tonsillitis in adults. Methods: Forty adults with a diagnosis of recurrent oral streptococcal pharyngitis were enrolled in the study. Twenty of these subjects took for 90 days a tablet containing Streptococcus salivarius K12 (Bactoblis®). The other 20 subjects served as untreated controls. A 6-month follow-up was included to evaluate any persistent protective role. Results: The 20 adults who completed the 90-day course of Bactoblis® showed a reduction in their episodes of streptococcal pharyngeal infection (about 80%). The 90 days treatment was also associated with an approximately 60% reduction in the incidence of reported pharyngitis in the 6-month period following use of the product. The product was well tolerated by the subjects with no treatment-related side effects or drop-outs reported. Conclusion: Prophylactic administration of Streptococcus salivarius K12 to adults having a history of recurrent oral streptococcal pathology reduced the number of episodes of streptococcal pharyngeal infections and/or tonsillitis.

Concepts: Streptococcus pyogenes, Rheumatic fever, Streptococcus, Gram positive bacteria, Streptococcaceae, Group A streptococcal infection, Streptococcus thermophilus, Streptococcus salivarius

26

Objectives: Insulin-like growth factor-1 may serve some regulatory function in the immune system. Rheumatic mitral stenosis is related to autoimmune heart valve damage after streptococcal infection. The aim of this study was to assess the level of insulin-like growth factor-1 and its correlation with the Wilkins score in patients with rheumatic mitral stenosis. Methods: A total of 65 patients with rheumatic mitral stenosis and 62 age- and sex-matched control subjects were enrolled in this study. All subjects underwent transthoracic echocardiography. The mitral valve area and Wilkins score were evaluated for all patients. Biochemical parameters and serum insulin-like growth factor-1 levels were measured. Results: Demographic data were similar in the rheumatic mitral stenosis and control groups. The mean mitral valve area was 1.6±0.4 cm2 in the rheumatic mitral stenosis group. The level of insulin-like growth factor-1 was significantly higher in the rheumatic mitral stenosis group than in the control group (104 (55.6-267) versus 79.1 (23.0-244.0) ng/ml; p=0.039). There was a significant moderate positive correlation between insulin-like growth factor-1 and thickening of leaflets score of Wilkins (r=0.541, p<0.001). Conclusions: The present study demonstrated that serum insulin-like growth factor-1 levels were significantly higher in the rheumatic mitral stenosis group compared with control subjects and that insulin-like growth factor-1 level was also correlated with the Wilkins score. It can be suggested that there may be a link between insulin-like growth factor-1 level and immune pathogenesis of rheumatic mitral stenosis.

Concepts: Immune system, Bacteria, Rheumatic fever, Immunology, Insulin-like growth factor 1, Growth hormone, Mitral valve prolapse, Mitral stenosis

22

We retrospectively analyzed electronic medical records of patients with Ehlers-Danlos Syndrome hypermobility type (HEDS), including demographic information, workup, rheumatological diagnoses in order to determine its association with rheumatological conditions. HEDS Patients were stratified according to level of workup received (no additional work (physical exam only) = NWU, limited workup = LWU, comprehensive workup = CWU)). HEDS patients were predominantly female (21:4, F:M). The percentage of patients with at least one rheumatological condition was significantly correlated with level of workup (NWU, 9.2%; LWU, 33.3%, CWU, 67.1%; p-value < 0.0001). The HLA-B27 antigen was more prevalent (p-value < 2.2 × 10(-8)) in the CWU HEDS patients (23.9%) than in the general population of the United States (6.1%). HEDS with CWU were associated with more rheumatological conditions (i.e. psoriasis, ankylosing spondylitis, rheumatoid arthritis, fibromyalgia) than those with NWU or LWU. In conclusion, HEDS is associated with complicated rheumatological conditions, which are uncovered by comprehensive workup. These conditions require different clinical management strategies than HEDS, and left untreated could contribute to the pain or even physical disability (i.e. joint erosions) in HEDS patients. While the mechanisms underlying these associations are unknown, it is important that all HEDS patients receive adequate workup to ensure a complete clinical understanding for the best care strategy possible.

Concepts: Rheumatic fever, Rheumatoid arthritis, Rheumatology, Syndromes, Arthritis, Rheumatism, Ankylosing spondylitis, Psoriatic arthritis