Silent Acute Rheumatic Fever Unmasked by Using Handheld Echocardiography for Febrile Children Presenting in a Rheumatic Heart Disease-Endemic Area.

OBJECTIVE: To understand the burden of acute rheumatic fever (ARF) among children living in low-income countries who present to the hospital with febrile illness and to determine the role of handheld echocardiography (HHE) in uncovering subclinical carditis as a major manifestation of ARF. STUDY DESIGN: This was a cross-sectional study carried at the Pediatric Hospital in Al Obeid, North Kordofan, Sudan, from September 2022 to January 2023 and including febrile children 3 through 18 years of age with or without clinical features of ARF and without another cause for their fever (not excluding malaria). History, examination, blood investigations, and HHE were done. ARF was diagnosed according to the Jones criteria. Clinical ARF was diagnosed if there was a major clinical Jones criterion and silent ARF if the only major Jones criteria was subclinical carditis. RESULTS: The study cohort included 400 children with a mean age of 9 years. Clinical ARF was diagnosed in 95 patients (95/400, 24%), most of whom presented with a joint major manifestation (88/95, 93%). Among the 281 children who did not present with a clinical manifestation of ARF, HHE revealed rheumatic heart disease (RHD) in 44 patients (44/281, 16%); 31 of them fulfilled criteria for silent ARF (31/281, 11%). HHE increased the detection of ARF by 24%. HHE revealed mild RHD in 41 of 66 (62%) and moderate or severe RHD in 25 of 66 (38%) patients. Both sensitivity and specificity of HHE compared with standard echocardiography were 88%. CONCLUSIONS: There is a significant burden of ARF among febrile children in Sudan. HHE increased the sensitivity of diagnosis, with 11% of children having subclinical carditis as their only major manifestation (ie, silent ARF). RHD-prevention policies need to prioritize decentralization of echocardiography to improve ARF detection.

Long-term antibiotic prophylaxis for prevention of rheumatic fever recurrence and progression to rheumatic heart disease.

BACKGROUND: Rheumatic fever is a non-suppurative, inflammatory sequela of group A Streptococcus pharyngitis that can occur at two to four weeks after infection. Following an episode of rheumatic fever, there is a risk of developing rheumatic heart disease (RHD) later in life that carries significant risk of morbidity and mortality. RHD remains the largest global cause of cardiovascular disease in the young (age < 25 years). The historical literature provides inconclusive evidence that antibiotic prophylaxis is beneficial in reducing the risk of recurrence of rheumatic fever and development of RHD. Antibiotics are thought to work by reducing the carriage of group A Streptococcus and thus reducing the risk of infection. This review was commissioned by the World Health Organization (WHO) for an upcoming guideline. OBJECTIVES: 1. To assess the effects of long-term antibiotics versus no antibiotics (control) for secondary prevention of rheumatic fever recurrence and associated sequelae in people with previous rheumatic fever or RHD. 2. To assess the effects of long-term intramuscular penicillin versus long-term oral antibiotics for secondary prevention of rheumatic fever recurrence and associated sequelae in people with previous rheumatic fever or RHD. SEARCH METHODS: We systematically searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science, clinical trial registers, ISRCTN.com and reference lists without restrictions on language or date up to 10 March 2024. SELECTION CRITERIA: We sought randomised controlled trials or quasi-randomised trials, described in any language, including participants with previous rheumatic fever and/or RHD of any age, based in community or hospital settings. Studies were included if they compared firstly antibiotic prophylaxis with no antibiotic prophylaxis, and, secondly, intramuscular penicillin prophylaxis versus oral antibiotic prophylaxis. DATA COLLECTION AND ANALYSIS: We used standardised methodological, Cochrane-endorsed procedures and performed meta-analyses with risk ratios (RR) and Peto odds ratios (Peto OR). Our primary outcomes were recurrence of rheumatic fever, progression or severity of RHD and cardiac complications. Our secondary outcomes were obstetric complications (maternal and foetal events), mortality, treatment adherence, adverse events and acceptability to participants. We performed comprehensive assessments of risk of bias and certainty of evidence, applying the GRADE methodology. MAIN RESULTS: We included 11 studies (seven RCTs and four quasi-randomised trials) including 3951 participants. The majority of the included studies were conducted in the USA, UK and Canada during the 1950s to 1960s. Most participants with previous rheumatic fever had been diagnosed using the modified Jones criteria (mJC) (four studies), were an average of 12.3 years of age and 50.6% male. We assessed the majority of the included studies to be at high risk of bias, predominantly relating to blinding and attrition bias. Comparison one: antibiotics versus no antibiotics Pooled meta-analysis of six RCTs provides moderate-certainty evidence that antibiotics overall (oral or intramuscular) probably reduce the risk of recurrence of rheumatic fever substantially (0.7% versus 1.7%, respectively) (risk ratio (RR) 0.39, 95% confidence interval (CI) 0.22 to 0.69; 1721 participants). People with early or mild RHD likely have the greatest capacity to benefit from intramuscular antibiotic prophylaxis (8.1%) compared to no antibiotics (0.7%) (RR 0.09, 95% CI 0.03 to 0.29; 1 study, 818 participants; moderate-certainty evidence). Antibiotics may not affect mortality in people with late-stage RHD (RR 1.23, 95% CI 0.78 to 1.94; 1 study, 994 participants; low-certainty evidence). Antibiotics may not affect the risk of anaphylaxis (Peto odds ratio (OR) 7.39, 95% CI 0.15 to 372; 1 study, 818 participants; low-certainty evidence) or sciatic nerve injury (Peto OR 7.39, 95% CI 0.15 to 372; 1 study, 818 participants; low-certainty evidence) compared with no antibiotics, but probably have an increased risk of hypersensitivity reactions (RR 137, 8.51 to 2210; 2 studies, 894 participants; moderate-certainty evidence) and local reactions (RR 29, 1.74 to 485; 1 study, 818 participants; moderate-certainty evidence). Comparison two: intramuscular antibiotics versus oral antibiotics Pooled analysis of two RCTs showed that prophylactic intramuscular benzathine benzylpenicillin likely reduces recurrence of rheumatic fever substantially when compared to oral antibiotics (0.1% versus 1%, respectively) (RR 0.07, 95% CI 0.02 to 0.26; 395 participants; moderate-certainty evidence). Furthermore, it is unclear whether intramuscular benzyl penicillin is superior to oral antibiotics in reducing the risk of mortality in the context of RHD (Peto OR 0.22, 95% CI 0.01 to 4.12; 1 study, 431 participants; very low-certainty evidence). There were no data available on progression of latent RHD or adverse events including anaphylaxis, sciatic nerve injury, delayed hypersensitivity/allergic reactions and local reactions to injection. AUTHORS' CONCLUSIONS: This review provides evidence that antibiotic prophylaxis likely reduces the risk of recurrence of rheumatic fever compared to no antibiotics, and that intramuscular benzathine benzylpenicillin is probably superior to oral antibiotics (approximately 10 times better). Moreover, intramuscular benzathine benzylpenicillin likely reduces the risk of progression of latent RHD. Evidence is scarce, but antibiotics compared with no antibiotics may not affect the risk of anaphylaxis or sciatic nerve injury, but probably carry an increased risk of hypersensitivity reactions and local reactions. Antibiotics may not affect all-cause mortality in late-stage RHD compared to no antibiotics. There is no evidence available to comment on the effect of intramuscular penicillin over oral antibiotics for progression of latent RHD and adverse events, and little evidence for all-cause mortality. It is important to interpret these findings in the context of major limitations, including the following: the vast majority of the included studies were conducted more than 50 years ago, many before contemporary echocardiographic studies; methodology was often at high risk of bias; outdated treatments were used; only one study was in latent RHD; and there are concerns regarding generalisability to low socioeconomic regions. This underlines the need for ongoing research to understand who benefits most from prophylaxis.

Acute rheumatic fever and Takayasu arteritis - A synchronous co-occurrence.

ABSTRACT: Acute rheumatic fever and Takayasu arteritis are examples of autoimmune diseases that commonly affect the cardiovascular system. We report an infrequent co-occurrence of both these diseases in an adolescent male. It may appear that in some individuals, the rheumatic fever may act as a trigger for the development of large vessel vasculitis. This possibility should be considered in patients on follow-up if they develop fresh features of cardiovascular compromise despite appropriate medical, interventional, or surgical therapy for rheumatic heart disease.

Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Group A Streptococcus Infections.

Group A Streptococcus causes a variety of clinical manifestations, including pharyngitis and skin and soft tissue infections as well as more invasive disease. There are also multiple nonsuppurative complications of group A Streptococcus infection, including acute rheumatic fever and poststreptococcal glomerulonephritis. Pediatricians should be able to diagnose and treat the various presentations of the infection.

Electrophysiological findings in extensive macular atrophy with pseudodrusen.

PURPOSE: To present electroretinogram findings in extensive macular atrophy with pseudodrusen (EMAP) and describe associated systemic factors. DESIGN: Retrospective case series. METHODS: Data on medical history, visual symptoms, multimodal imaging findings, and visual field were collected from the medical records of patients with extensive macular atrophy with pseudodrusen who attended a visual electrophysiology laboratory. Electrophysiological tests, including full-field electroretinogram, multifocal electroretinogram and photopic negative response, were performed. RESULTS: Eighteen patients (10 [56%] females, age 49-66 years) were included. Of these, 17 (94%) had a history of rheumatic fever in childhood and/or adolescence, 7 (39%) had cardiovascular disease, 4 (22%) had autoimmune disease, and 10 (56%) had inflammatory conditions. The primary visual complaints were nyctalopia (95%), followed by visual field loss (67%) and dyschromatopsia (67%). The key retinal findings included retinal pigmented epithelium atrophy in the macular region and subretinal drusenoid deposits. Regarding electrophysiological results, 100% of patients had abnormalities on multifocal electroretinogram, 94% displayed alterations in photopic negative response, and 78% showed changes in the full-field electroretinogram. CONCLUSIONS: In this cohort, electrophysiologic evaluation demonstrated diffuse retinal dysfunction affecting all layers of the retina in patients with EMAP. The disease is associated with immune-mediated systemic conditions, chiefly rheumatic fever.

Acute rheumatic fever and rheumatic heart disease in children and adolescents in Victoria, Australia.

AIM: To describe the epidemiology and clinical profile of children and adolescents with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in Victoria, Australia. METHODS: A retrospective audit was undertaken of children and adolescents with ARF and RHD attending the Royal Children's and Monash Children's Hospitals in Victoria, Australia between 2010 and 2019. Potential cases were identified by searching multiple sources for relevant ICD-10-AM codes and keywords, then reviewed manually. For confirmed cases, we collected data on patient demographics, clinical features, comorbidities and management. RESULTS: Of 179 participants included, there were 108 Victorian residents and 71 non-Victorian residents. 126 had at least one episode of ARF during the study period and 128 were diagnosed with RHD. In the Victorian resident group, the overall incidence of ARF was 0.8 per 100 000 5-14 year olds. This incidence was higher in Victorian Aboriginal and/or Torres Strait Islander (3.8 per 100 000) and Pacific Islander (32.1 per 100 000) sub-populations. Of 83 Victorian residents who had an ARF episode, 11 (13%) had a recurrence. Most Victorian residents with RHD had mixed aortic and mitral valve pathology (69.4%) and moderate to severe disease (61.9%). Most non-Victorian residents were Aboriginal and/or Torres Strait Islander people (80.3%) and were commonly transferred for tertiary or surgical management of RHD (83.1%). CONCLUSIONS: ARF and RHD continue to affect the health of significant numbers of children and adolescents living in Victoria, including severe and recurrent disease. Specialised services and a register-based control program may help to prevent complications and premature death.

Acute Rheumatic Fever: Case Report and Literature Review.

A previously healthy 8-year-old Native American female presented with right-sided weakness and joint pain for two weeks. Following an initially unremarkable workup including negative brain and spine MRI she was noticed to have chorea and subsequently diagnosed with acute rheumatic fever (ARF). ARF is a group A streptococcus-related disease that most commonly is a sequelae of pharyngitis. The diagnosis of ARF utilizes the Jones criteria which includes heart disease, arthritis, chorea, the characteristic rash of erythema marginatum, and subcutaneous nodules. The most serious consequences of ARF include rheumatic heart disease and chorea. ARF can be treated with a combination of antibiotics and anti-inflammatories like aspirin.

Serological Profiling of Group A Streptococcus Infections in Acute Rheumatic Fever.

Rheumatic fever is a serious post-infectious sequela of group A Streptococcus (GAS). Prior GAS exposures were mapped in sera using a large panel of M-type specific peptides. Rheumatic fever patients had serological evidence of significantly more GAS exposures than matched controls suggesting immune priming by repeat infections contributes to pathogenesis.

Chorea as the presenting feature of acute rheumatic fever in childhood; case reports from a low-prevalence European setting.

BACKGROUND: Despite a notable decrease in acute rheumatic fever (ARF) incidence in the past few decades, there are still cases in our setting. Sydenham chorea (SC) may be the initial manifestation for this condition in childhood in a significant proportion of children. We report two cases of choreoathetosis in children as the first manifestation of ARF. CASE PRESENTATION: A previously healthy 8-year-old boy presented with right hemichorea with a predominance in the brachial region, orofacial dyskinesias and speech difficulties for the past 2 weeks. The only medical history of interest was a common catarrhal illness 3 weeks before and nonspecific bilateral tenosynovitis in both feet since a year prior. A brain computerized tomography was normal and the echocardiogram showed mild mitral and aortic regurgitation, meeting ARF criteria. He demonstrated clinical improvement with treatment based on prednisone and carbamazepine. The second patient was a 10-year-old girl with choreic movements of the right half of the body and repetitive right eye closure of 1 week duration. She had symptoms of fever and rash the previous week and pharyngitis that resolved without antibiotic 2 months before. Blood tests revealed elevated C reactive protein (12 mg/dl) and erythrocyte sedimentation rate (96 mm/h). Brain magnetic resonance was normal and echocardiogram showed left ventricle dilation and mild mitral regurgitation, leading to the diagnosis of ARF. Due to neurological involvement, she received corticosteroids and intravenous immunoglobulin treatment, with worsening of neurological symptoms that required valproic acid with remission of the hemichorea. In addition skin lessions compatible with erythema marginatum appeared on the upper limbs. CONCLUSIONS: SC should be the main diagnostic consideration in cases of hemichorea with normal neuroimaging in children. The cases reported highlight the need to maintain a high index of suspicion even in settings where incidende of ARF is low and the need to perform cardiological investigations in all patients with suspected SC, due to the possibility of subclinical valve lesions. Good adherence to secondary prophylaxis is crucial to avoid chorea relapses and worsening valve disease.

Vaginal microbiota in pregnant women with inflammatory rheumatic and inflammatory bowel disease: A matched case-control study.

BACKGROUND: Rheumatic diseases and vaginal infections both increase the risk of preterm birth. It is unclear whether pregnant women with rheumatic disease are more likely to experience vaginal infections, which might potentially accumulate modifiable risk factors. OBJECTIVE: In this study, we sought to evaluate the vaginal microbiota of pregnant women with inflammatory rheumatic and inflammatory bowel disease. METHODS: A total of 539 asymptomatic women with singleton pregnancy were routinely screened for an abnormal vaginal microbiota between 10 + 0 and 16 + 0 gestational weeks. Vaginal smears were Gram-stained and microscopically analysed. Those with inflammatory diseases (with or without immunomodulatory therapy) were assigned to the case group and matched in a 1:3 ratio to healthy pregnant controls. RESULTS: Overall, an abnormal vaginal microbiota occurred more frequently among women of the case group, compared with those of the control group (33.8% vs 15.6%; 95% CI: 1.78-4.27, p < .001). In particular, Candida colonisation (22.3% vs 9.2%; 95% CI: 1.69-4.75, p < .001), but also bacterial vaginosis (14.9% vs 7.2%; 95% CI: 1.25-4.1, p = .006), occurred more often in the case than in the control group. No significant difference was found with regard to the occurrence of an abnormal vaginal microbiota between subgroups with and without immunomodulatory treatment (37.0% vs 27.1%; 95% CI: 0.29-1.35, p = .232). CONCLUSION: Pregnant women with inflammatory rheumatic and inflammatory bowel disease are at risk for bacterial vaginosis and Candida colonisation, which might pose a risk for preterm birth. Prospective studies are needed to further evaluate the influence of autoimmune conditions and immunosuppressive therapy on the vaginal microbiota.

Morbidity and mortality of rheumatic heart disease and acute rheumatic fever in the inpatient setting in Timor-Leste.

AIM: To describe the clinical features, treatment and outcomes of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children admitted to the national referral hospital in Dili, Timor-Leste. METHODS: This prospective study documented cases of ARF and RHD in children aged 14 years and under who were admitted between June 2017 and May 2019. ARF was diagnosed using an adapted version of the 2015 Jones criteria and presumed (rather than proven) exposure to group A Streptococcus. Clinical and echocardiographic findings, comorbidities and discharge outcomes are reported. RESULTS: A total of 63 patients were admitted with ARF or RHD; 54 were diagnosed with RHD for the first time. Median age was 11 years (range 3-14); 48% were female. Of those with echocardiograms, 56/58 had RHD, 55/56 (98%) had mitral regurgitation (37/55 (67%) severe), 11/56 (20%) had mitral stenosis and 43/56 (77%) had aortic regurgitation. Left ventricular dysfunction (55%), pulmonary hypertension (64%) and cardiac failure (78%) were common. Four (6%) patients died in hospital, and 30/59 (51%) of surviving patients were lost to follow up. CONCLUSIONS: Community echocardiography screening has reported a high prevalence of undetected mild to moderate cases of RHD in Timor-Leste, whereas this hospital study documents mostly severe disease among hospitalised patients with a high case fatality rate and loss to follow up. RHD is a significant health problem in Timor-Leste and improved recognition and diagnosis, as well as effective delivery of treatment and follow-up are imperative.

Sydenham's Chorea with Silent Cardiac Lesions, Mimicking.

Sydenham's chorea is an uncommon neurological manifestation of rheumatic fever and has many and varied differential diagnosis. It may mimic encephalitis when presents as an isolated feature even when silent cardiac lesions are present. Early diagnosis, treatment and penicillin prophylaxis prevents recurrence and progression of cardiac lesions. Prompt symptomatic relief and alleviation of distress is obtained with therapeutic intervention. A case of rheumatic chorea with silent cardiac valve lesions which mimicked herpes simplex encephalitis with choreoathetosis, in a 13 year old girl is presented along with review of literature.

Characteristics of Children with Acute Rheumatic Carditis from a High-Incidence Region: Importance of Unexplained Worsening of Functional Class.

BACKGROUND: Acute rheumatic fever (ARF) and acute rheumatic carditis (ARC) continue to be a major public health problem in developing countries. OBJECTIVE: To study the characteristics of children with ARC being treated at a tertiary centre. METHODS AND RESULTS: We studied 126 children (mean age 10.4 ± 2.3 years, range 5-15 years, 60% males) diagnosed with ARC by treating cardiologists. Most had lower socio-economic status. Fifty of 126 (40%) presented with a first episode of ARC. Joint symptoms were present in 29% and fever in 25%. Only 2.4% had subcutaneous nodules and none had erythema marginatum or chorea. Fifty-one percent presented in NYHA class II and 29% in NYHA class III or IV. Tachycardia and heart failure were present in 53% and 21%, respectively. Recent worsening of NYHA class (dyspnoea) was the commonest feature (48%). Laboratory investigations showed raised antistreptolysin O titres (>333 units) in only 36.7% of patients. Raised C-reactive protein (CRP) was present in 70%, while raised erythrocyte sedimentation rate was found in only 37% of patients. On the basis of above findings, the modified Jones criteria (2015) for the diagnosis of ARF were satisfied only in 46% of children. Echocardiography showed mitral valve thickening in 77% and small nodules on the tip of the leaflets in 43% (27 and 8%, respectively for aortic valve). Left ventricular ejection fraction was <50% in only 3 patients. The dominant valve lesion was mitral regurgitation (MR) (present in 95% of patients; severe in 78%, moderate in 15%), while aortic regurgitation was present in 44% (severe in 14%). CONCLUSIONS: The criteria are often not satisfied by patients being treated for ARC. Recent unexplained worsening of dyspnoea, young age, significant MR, echocardiographic nodules, and elevated CRP are important indicators.

Ending rheumatic heart disease in Australia: the evidence for a new approach.

■The RHD Endgame Strategy: the blueprint to eliminate rheumatic heart disease in Australia by 2031 (the Endgame Strategy) is the blueprint to eliminate rheumatic heart disease (RHD) in Australia by 2031. Aboriginal and Torres Strait Islander people live with one of the highest per capita burdens of RHD in the world. ■The Endgame Strategy synthesises information compiled across the 5-year lifespan of the End Rheumatic Heart Disease Centre of Research Excellence (END RHD CRE). Data and results from priority research projects across several disciplines of research complemented literature reviews, systematic reviews and narrative reviews. Further, the experiences of those working in acute rheumatic fever (ARF) and RHD control and those living with RHD to provide the technical evidence for eliminating RHD in Australia were included. ■The lived experience of RHD is a critical factor in health outcomes. All future strategies to address ARF and RHD must prioritise Aboriginal and Torres Strait Islander people's knowledge, perspectives and experiences and develop co-designed approaches to RHD elimination. The environmental, economic, social and political context of RHD in Australia is inexorably linked to ending the disease. ■Statistical modelling undertaken in 2019 looked at the economic and health impacts of implementing an indicative strategy to eliminate RHD by 2031. Beginning in 2019, the strategy would include: reducing household crowding, improving hygiene infrastructure, strengthening primary health care and improving secondary prophylaxis. It was estimated that the strategy would prevent 663 deaths and save the health care system $188 million. ■The Endgame Strategy provides the evidence for a new approach to RHD elimination. It proposes an implementation framework of five priority action areas. These focus on strategies to prevent new cases of ARF and RHD early in the causal pathway from Streptococcus pyogenes exposure to ARF, and strategies that address the critical systems and structural changes needed to support a comprehensive RHD elimination strategy.

Acute rheumatic fever in south-east of Turkey: clinical features and epidemiological evaluation of the patients over the last 25 years.

This study evaluates clinical and epidemiological features of acute rheumatic fever using the data of last 25 years in our hospital in south-east of Turkey. The medical records of 377 patients with acute rheumatic fever admitted to Pediatric Cardiology Department of Çukurova University during 1993-2017 were retrospectively analysed. Two hundred and six patients were admitted between 1993 and 2000, 91 between 2001 and 2008, and 80 between 2009 and 2017. The largest age group (52%) were between 9 to 12 years of age and approximately two-thirds of the patients presented in the spring and winter seasons (62.8%). Among the major findings, the most common included carditis 83.6% (n = 315), arthritis at 74% (n = 279), Sydenham's chorea at 13.5% (n = 51), and only two patients (0.5%) had erythema marginatum and two patients (0.5%) had subcutaneous nodule. Carditis was the most common manifestation observed in 315 patients (83.6%). The most commonly affected valve was the mitral valve alone (54.9%), followed by a combined mitral and aortic valves (34%) and aortic valve alone (5.7%). Of the patients with carditis, 48.6% (n = 153) had mild carditis, of which 45 had a subclinical. Sixty-two patients (19.7%) had moderate and 100 patients (31.7%) had severe carditis. At the follow-up, 2 patients died and 16 patients underwent valve surgery. Twenty-eight (7.4%) patients' valve lesions were completely resolved. Conclusion: Although the incidence of acute rheumatic fever decreased, it still is an important disease that can cause serious increases in morbidity and mortality rates in our country.

A population pharmacokinetic study of benzathine benzylpenicillin G administration in children and adolescents with rheumatic heart disease: new insights for improved secondary prophylaxis strategies.

BACKGROUND: Benzathine benzylpenicillin G (BPG) is recommended as secondary prophylaxis to prevent recurrence of acute rheumatic fever and subsequent rheumatic heart disease (RHD). Following intramuscular injection, BPG is hydrolysed to benzylpenicillin. Little is known of the pharmacokinetics of benzylpenicillin following BPG in populations at risk of RHD. METHODS: We conducted a longitudinal pharmacokinetic study of children and adolescents receiving secondary prophylaxis throughout six monthly cycles of BPG. Dried blood spot samples were assayed with LC-MS/MS. Benzylpenicillin concentrations were analysed using non-linear mixed-effects modelling with subsequent simulations based on published BMI-for-age and weight-for-age data. RESULTS: Eighteen participants contributed 256 concentrations for analysis. None had benzylpenicillin concentrations >0.02 mg/L for the full time between doses. The median duration above this target was 9.8 days for those with a lower BMI (<25 kg/m2), who also had lower weights, and 0 days for those with a higher BMI (≥25 kg/m2). Although fat-free mass was a key determinant of benzylpenicillin exposure after a standard dose of BPG, having a higher BMI influenced absorption and almost doubled (increase of 86%) the observed t½. CONCLUSIONS: Few children and adolescents receiving BPG as secondary prophylaxis will achieve concentrations >0.02 mg/L for the majority of the time between injections. The discordance of this observation with reported efficacy of BPG to prevent rheumatic fever implies a major knowledge gap relating to pharmacokinetic/pharmacodynamic relationships between benzylpenicillin exposure and clinical outcomes.

You can dance if you want to: A case of Sydenham's chorea.

Isolated motor disturbances in the paediatric population are uncommon presentations to the emergency department. Choreiform movements have a broad differential diagnosis and may present insidiously with progressive worsening of asymmetric clumsiness, hypotonia and dysarthria. The incidence of Sydenham's chorea (SC) caused by acute rheumatic fever (ARF) is very rare in developed countries. We report a previously healthy, vaccinated 9-year old male who presented to our ED with intermittent and progressive right sided clumsiness for four weeks. Physical examination findings showed dysdiadokinesis and dysmetric movements of the right side, which varied in intensity and were less pronounced on serial re-examination during the same ED visit. Basic bloodwork, MRI and MRA/V showed no abnormalities, and the patient was discharged home with urgent neurology follow-up. He re-presented to our ED four days later with worsening gait and inability to hold a pencil at school. He was subsequently diagnosed with chorea by the neurology team. The cause of chorea was later determined to be SC, and the patient's throat swab came back positive for group A-beta hemolytic strep (GAS) infection. We explore current literature regarding the various presentations of ARF, differential considerations in acute chorea, and diagnostic studies needed to determine the etiology of acute chorea. With the low incidence of chorea in developed nations, this diagnosis can be easily overlooked. We highlight the importance of this diagnosis, as well as primary and secondary treatment in ARF.

Acute rheumatic fever presenting with severe endocarditis involving four valves, and ventricular tachycardia.

Acute rheumatic fever is the most commonly acquired heart disease in developing countries. The most common cardiac presentation is valvular disease. Although some rhythm disturbances may occur during the acute stages of the disease, ventricular tachycardia is extremely rare. Here, a case of acute rheumatic fever with severe endocarditis involving four valves and ventricular tachycardia is presented.

Beyond first-degree heart block in the diagnosis of acute rheumatic fever.

OBJECTIVES: First-degree heart block is a minor manifestation of acute rheumatic fever. Second and third degree heart block and junctional rhythms occur less commonly. We report patients presenting with these latter three electrocardiographic abnormalities and investigate their diagnostic utility. DESIGN: Patients admitted to our centre meeting the 2014 New Zealand Rheumatic Fever Guideline Diagnostic Criteria for rheumatic fever over a 5-year period from January 2010 to December 2014 were identified. Clinical, haematologic, electrocardiographic, and echocardiographic records were reviewed. Electrocardiograms (ECG) were considered abnormal if there was second- or third-degree atrioventricular block or junctional rhythms. Comparative data from patients with advanced conduction abnormalities without a diagnosis of rheumatic fever during the same time period were reviewed. RESULTS: A total of 201 patients met inclusion criteria for rheumatic fever. Of these, 17 (8.5%) had transient abnormalities of atrioventricular conduction, 5 (2.5%) with second or third-degree atrioventricular block, and 12 (6%) junctional rhythms. The remaining 173 (86%) patients had evidence of rheumatic valvulitis at presentation. Only one patient without rheumatic fever was found to have advanced conduction abnormalities over the study period, from a total of 3702 ECG. CONCLUSIONS: This large contemporary cohort of acute rheumatic fever shows that 8.5% of cases had either advanced atrioventricular block or junctional rhythms both highly suggestive of the diagnosis in our population.