Adult-onset acute rheumatic fever with chorea and carditis.

Rheumatic fever is a major cause of cardiovascular morbidity and mortality in low-income and middle-income countries, and it usually occurs at a young age. Adult-onset acute rheumatic fever is a rare condition and usually represents a recurrence of childhood-onset disease. We report a case of an elderly man presenting with rheumatic carditis and rheumatic chorea subsequently diagnosed with adult-onset rheumatic fever.

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.

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.

Outcome following acute and recurrent rheumatic fever.

BACKGROUND: Rheumatic carditis is the leading cause of permanent disability caused by damage of the cardiac valve. This study aimed to determine the outcome and predictors of valve surgery in patients with acute rheumatic fever (ARF) and recurrent rheumatic fever (RRF). METHODS: This was a retrospective study of patients diagnosed with ARF and RRF between 2006 and 2021. The predictors of valve surgery were analysed using multivariable Cox proportional regression. RESULTS: The median age of patients with ARF and RRF (n=92) was 11 years (range 5-18). Seventeen patients (18%) were diagnosed with RRF. The most common presenting symptoms included clinical carditis (87%), heart failure (HF) (63%), fever (49%) and polyarthralgia (24%). Patients with moderate-to-severe rheumatic carditis (88%) were given prednisolone. After treatment, the severity of valvular regurgitation was reduced in 52 patients (59%). Twenty-three patients (25%) underwent valve surgery. The incidence of HF, RRF, severe mitral regurgitation on presentation, left ventricular enlargement and pulmonary hypertension was greater in the surgical group than in the non-surgical group. Recurrent rheumatic fever (hazard ratio 7.9, 95% CI 1.9-33.1), tricuspid regurgitation (TR) gradient ≥ 42 mmHg (HR 6.3, 95%CI 1.1-38.7) and left ventricular end-diastolic dimension (LVEDD) ≥6 cm (HR 8.7, 95% CI 2.1-35.9) were predictors of valve surgery (multivariable Cox proportional regression analysis). CONCLUSION: Clinical carditis was the most common presenting symptom in patients with ARF and RRF. The majority of patients responded positively to prednisolone. These findings highlight the predictors of valve surgery following ARF, including RRF, TR gradient ≥ 42 mmHg and LVEDD ≥ 6 cm.Abbreviations: ARF: acute rheumatic fever; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GAS: group A beta-haemolytic Streptococcus; HF: heart failure; HR: hazard ratio; LVEDD: left ventricular end-diastolic dimension; MR: mitral regurgitation; RHD: rheumatic heart disease; RRF: recurrent rheumatic fever; TR: tricuspid regurgitation.

The gut microbiome in systemic lupus erythematosus: lessons from rheumatic fever.

For more than a century, certain bacterial infections that can breach the skin and mucosal barriers have been implicated as common triggers of autoimmune syndromes, especially post-infection autoimmune diseases that include rheumatic fever and post-streptococcal glomerulonephritis. However, only in the past few years has the importance of imbalances within our own commensal microbiota communities, and within the gut, in the absence of infection, in promoting autoimmune pathogenesis become fully appreciated. A diversity of species and mechanisms have been implicated, including disruption of the gut barrier. Emerging data suggest that expansions (or blooms) of pathobiont species are involved in autoimmune pathogenesis and stimulate clonal expansion of T cells and B cells that recognize microbial antigens. This Review discusses the relationship between the gut microbiome and the immune system, and the potential consequence of disrupting the community balance in terms of autoimmune development, focusing on systemic lupus erythematosus. Notably, inter-relationships between expansions of certain members within gut microbiota communities and concurrent autoimmune responses bear features reminiscent of classical post-infection autoimmune disease. From such insights, new therapeutic opportunities are being considered to restore the balance within microbiota communities or re-establishing the gut-barrier integrity to reinforce immune homeostasis in the host.

[Rheumatic cardiopathies and its risk factors: about 50 cases]. / Les complications cardiaques du rhumatisme articulaire aigu et ses facteurs de risque : étude de 50 observations.

INTRODUCTION: Acute rheumatic fever (ARF) is a multi-systemic disease, in which cardiac involvement is the most serious major manifestation of disease. The aim of this study was to analyse cardiac involvement in children with ARF and his risk factors. MATERIALS AND METHODS: It were a retrospective study including all children under the age of 14 years who were hospitalized for ARF in the pediatric department of the CHU Hédi Chaker of Sfax, during a period of twelve years (2010-2022). RESULTS: We collected 50 cases (31 boys and 19 girls). Twenty-two patients (44%) developed cardiac lesions. The mean age at diagnosis was 9.6 years [5-14 years]. A pathological heart murmur was detected in 14 cases (n = 14/22) was classified as mild carditis in 15 cases, moderate carditis in 5 cases and severe in 2 cases. The median follow-up time was 3,3 years. Nineteen patients developed valvular sequelae Risk factors of cardiac lesions was: age more than 8 years, heart murmur, allonged PR, CRP > 100 mg/l and VS > 100 mm. CONCLUSION: CR is still a public health problem in Tunisia. It is a serious pathology that can cause serious increases in morbidity rates. Thus, we must strengthen preventive strategies.

Research priorities for the secondary prevention and management of acute rheumatic fever and rheumatic heart disease: a National Heart, Lung, and Blood Institute workshop report.

Secondary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) involves continuous antimicrobial prophylaxis among affected individuals and is recognised as a cornerstone of public health programmes that address these conditions. However, several important scientific issues around the secondary prevention paradigm remain unresolved. This report details research priorities for secondary prevention that were developed as part of a workshop convened by the US National Heart, Lung, and Blood Institute in November 2021. These span basic, translational, clinical and population science research disciplines and are built on four pillars. First, we need a better understanding of RHD epidemiology to guide programmes, policies, and clinical and public health practice. Second, we need better strategies to find and diagnose people affected by ARF and RHD. Third, we urgently need better tools to manage acute RF and slow the progression of RHD. Fourth, new and existing technologies for these conditions need to be better integrated into healthcare systems. We intend for this document to be a reference point for research organisations and research sponsors interested in contributing to the growing scientific community focused on RHD prevention and control.

Research priorities for the primordial prevention of acute rheumatic fever and rheumatic heart disease by modifying the social determinants of health.

The social determinants of health (SDH), such as access to income, education, housing and healthcare, strongly shape the occurrence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) at the household, community and national levels. The SDH are systemic factors that privilege some more than others and result in poverty and inequitable access to resources to support health and well-being. Primordial prevention is the modification of SDH to improve health and reduce the risk of disease acquisition and the subsequent progression to RHD. Modifying these determinants using primordial prevention strategies can reduce the risk of exposure to Group A Streptococcus, a causative agent of throat and skin infections, thereby lowering the risk of initiating ARF and its subsequent progression to RHD.This report summarises the findings of the Primordial Prevention Working Group-SDH, which was convened in November 2021 by the National Heart, Lung, and Blood Institute to assess how SDH influence the risk of developing RHD. Working group members identified a series of knowledge gaps and proposed research priorities, while recognising that community engagement and partnerships with those with lived experience will be integral to the success of these activities. Specifically, members emphasised the need for: (1) global analysis of disease incidence, prevalence and SDH characteristics concurrently to inform policy and interventions, (2) global assessment of legacy primordial prevention programmes to help inform the co-design of interventions alongside affected communities, (3) research to develop, implement and evaluate scalable primordial prevention interventions in diverse settings and (4) research to improve access to and equity of services across the RHD continuum. Addressing SDH, through the implementation of primordial prevention strategies, could have broader implications, not only improving RHD-related health outcomes but also impacting other neglected diseases in low-resource settings.

Secondary Prophylaxis Among First Nations People With Acute Rheumatic Fever in Australia: An Integrative Review.

INTRODUCTION: The prevalence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Australia's First Nations populations are some of the highest in the world, accounting for 95% of the 2,244 ARF notifications between 2015 and 2019 in Australia. A key issue in treating ARF is long-term secondary prophylaxis, yet only one in five patients received treatment in 2019. This review identifies barriers to secondary prophylaxis of ARF in Australia's First Nations people. METHODS: An integrative review was undertaken utilizing PubMed, CINAHL, ProQuest, and Wiley Online. Joanna Briggs Institute critical appraisal tools were used, followed by thematic analysis. RESULTS: The key themes uncovered included: issues with database and recall systems, patient/family characteristics, service delivery location and site, pain of injection, education (including language barriers), and patient-clinician relationship. CONCLUSIONS: A national RHD register, change in operation model, improved pain management, improved education, and need for consistent personnel is suggested.

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.

Assessment of Myocardial Mechanics in Acute Rheumatic Fever Using Speckle-Tracking Echocardiography.

BACKGROUND: This study aims to evaluate the role of speckle-tracking echocardiography to identify myocardial deformation in acute rheumatic fever. METHODS: Twenty-seven patients and 27 healthy children were prospectively evaluated. The patient group was divided into 2 subgroups based on echocardiographic findings, with or without carditis. The left ventricular global longitudinal strain and strain rate, left ventricular global circumferential strain and strain rate, and right ventricular global lon-gitudinal strain and strain rate were assessed by speckle-tracking echocardiography. RESULTS: In the acute phase of the disease, all values except the right ventricular global longitudinal strain were found to be significantly below the control group in the patient cohort. No significant difference was found between the patients grouped as carditis and non-carditis in the acute period. Comparison of the acute period with the post-treatment period revealed a significant increase in all strain values of the patients with carditis and significant increases observed in all values except left ventricular global longitudinal strain rate, left ventricular global circumferential strain rate, and right ventricular global longitudinal strain rate values in patients without carditis. Apart from the right ventricular global longitudinal strain rate, which was significantly lower in the non-carditis group compared to the control group, there was no significant difference in strain values between the patient and control groups following treatment. CONCLUSION: In the present study, we found that all patients, including patients in whom no valvular involvement was detected by echocardiography in the acute phase of acute rheumatic fever, had a lower right and left ventricular strain and strain rate measurements and that these findings improved after treatment, suggesting that strain echocardiography may be a helpful diagnostic method, especially in patients without valvular involvement.

Coexistence of Graves' disease with acute rheumatic fever treated as thyroid storm in young Thai patient.

OBJECTIVES: This report presents a case of acute onset of chorea, concurrent Graves' disease, and acute rheumatic fever in an 8-year-old female patient. CASE PRESENTATION: The child had intermittent involuntary movement of all extremities and both eyes for 4 days, with a previous history of increased appetite, weight lost, and heat intolerance over a period of two months. Physical examination revealed fever, tachycardia, exophthalmos, eyelid retraction, as well as diffused thyroid enlargement. Initial clinical features and thyroid function testing suggested a thyroid storm due to Graves' disease. Methimazole, propranolol, potassium iodide (SSKI), and dexamethasone were prescribed. Congestive heart failure developed after propranolol and cardiovascular re-evaluation and Revised Jones criteria suggested acute rheumatic fever. Chorea was successfully treated with pulse methylprednisolone. CONCLUSIONS: We reported Graves' disease patients with acute rheumatic fever simulating a thyroid storm. The underlying cardiac disease must be considered, especially where chorea and congestive heart failure are present.

[Inflammatory rheumatic diseases in migrants]. / Entzündlich-rheumatische Erkrankungen bei Migranten.

The immigration of people from other countries or even from other continents represents new challenges even for rheumatologists. Although all inflammatory rheumatic diseases that occur in this country also exist in the countries of origin of immigrants, the frequencies are different. Diseases such as familial Mediterranean fever (FMF) or Behçet syndrome (BS) are rare in western Europe but are often more frequent than rheumatoid arthritis (RA) and spondylarthritis (SPA) in North Africa and Mediterranean countries. Furthermore, FMF is associated with the occurrence of spondyloarthritis, which is then frequently negative for the human leucocyte antigen B27 (HLA-B27). There is also an association with BS. Rheumatic fever also still occurs relatively frequently especially in African countries, whereas it is almost eradicated in Europe. Possible differential diagnoses such as rheumatic symptoms in genetically determined anemia or infections such as human immunodeficiency virus (HIV) infections, hepatitis, tuberculosis and parasitosis need to be considered as they are all much more frequent in the countries of origin of immigrants than in northwestern Europe. Last but not least, the treatment situation with modern diagnostic and treatment modalities is different in the countries of origin of the migrants, either because these possibilities are unavailable due to limited resources or because the situation has dramatically deteriorated due to acute events, such as the recent war in Ukraine.

[Association of the different forms of uveitis with inflammatory rheumatic diseases and their treatment]. / Assoziation der verschiedenen Uveitisformen mit entzündlich rheumatischen Erkrankungen und ihre Therapie.

The etiology of uveitis greatly varies worldwide, whereby in industrial nations noninfectious causes occur relatively more frequently. In Germany, 44% of all cases of uveitis are due to systemic diseases. In rheumatology, uveitis or other kinds of ocular inflammation, such as scleritis or retinal vasculitis, most commonly occur in spondylarthritis, vasculitis and sarcoidosis. Vice versa, ophthalmologists often ask rheumatologists about an underlying rheumatic disease in patients with uveitis. It is of utmost importance to differentiate between the different forms of uveitis. This review article presents the associations with inflammatory rheumatic diseases as well as treatment options from the point of view of both ophthalmologists and rheumatologists.

Recommendations for the Use of Echocardiography in the Evaluation of Rheumatic Heart Disease: A Report from the American Society of Echocardiography.

Acute rheumatic fever and its chronic sequela, rheumatic heart disease (RHD), pose major health problems globally, and remain the most common cardiovascular disease in children and young people worldwide. Echocardiography is the most important diagnostic tool in recognizing this preventable and treatable disease and plays an invaluable role in detecting the presence of subclinical disease needing prompt therapy or follow-up assessment. This document provides recommendations for the comprehensive use of echocardiography in the diagnosis and therapeutic intervention of RHD. Echocardiographic diagnosis of RHD is made when typical findings of valvular and subvalvular abnormalities are seen, including commissural fusion, leaflet thickening, and restricted leaflet mobility, with varying degrees of calcification. The mitral valve is predominantly affected, most often leading to mitral stenosis. Mixed valve disease and associated cardiopulmonary pathology are common. The severity of valvular lesions and hemodynamic effects on the cardiac chambers and pulmonary artery pressures should be rigorously examined. It is essential to take advantage of all available modalities of echocardiography to obtain accurate anatomic and hemodynamic details of the affected valve lesion(s) for diagnostic and strategic pre-treatment planning. Intraprocedural echocardiographic guidance is critical during catheter-based or surgical treatment of RHD, as is echocardiographic surveillance for post-intervention complications or disease progression. The role of echocardiography is indispensable in the entire spectrum of RHD management.

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.

Over-the-counter and direct-to-consumer testing for Group A streptococcus.

Over-the-counter (OTC) and direct-to-consumer (DTC) tests have been gaining popularity due to their potential to provide accurate and quick diagnostic results without any test order from healthcare professionals, while providing patients the opportunity to actively engage in their own health management. Group A streptococcus is a common transmissible pathogen that leads to acute pharyngitis. Accurate and timely diagnosis of Group A streptococcus pharyngitis is critical to urge patients to seek professional healthcare, to support antibiotic stewardship, to reduce disease transmission, and to prevent rare but potentially life-threatening complications such as acute rheumatic fever, rheumatic heart disease, and poststreptococcal glomerulonephritis. This review provides an overview for OTC and DTC testing in general, discusses the clinical utilization of Group A streptococcus testing, analyzes the limitations and challenges of current Group A streptococcus testing methodologies if developed into OTC or DTC tests. Finally, this review provides an outlook for future developments that would further improve healthcare outcomes.

Assessment of serum galectin-3 levels in acute rheumatic fever.

BACKGROUND: Galectin-3 is a biomarker which takes a role in both acute and chronic inflammation as well as fibrosis and oxidative stress. Increased levels of it are associated with cardiovascular diseases. This study was performed to investigate the levels of galectin-3 in acute rheumatic fever (ARF). METHODS: 30 patients with ARF and 26 healthy children were included. Galectin-3 levels of the patients were compared with the controls, as well as within the patients before and after the treatment. RESULTS: The patients had significantly lower galectin-3 levels on admission than the control (p=0.02), but its levels were not significantly different between these groups at the end of treatment (p=0.714). The mean galectin-3 levels of the patients were increased after the treatment (p < 0.001). Severity of carditis and galectin-3 levels were negatively correlated (r=-539, p=0.02). CONCLUSIONS: Children with ARF have significantly reduced levels of galectin-3 and there is a negative correlation between the severity of the carditis and galectin-3 levels. Studies with larger sample sizes may give more accurate data about the role of galectin-3 in ARF.

Cytokine imbalance in acute rheumatic fever and rheumatic heart disease: Mechanisms and therapeutic implications.

Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD) are autoimmune sequelae of Group A Streptococcus infection with significant global disease burden. The pathogenesis of these diseases is poorly understood, and no immune modulating therapies are available to stop progression from ARF to RHD. Cytokines and chemokines are immune signaling molecules critical to the development of autoimmune diseases. An increasing number of studies point to a central role for pro-inflammatory cytokines and chemokines in ARF and RHD pathogenesis, in particular IL-6, IL-8/CXCL8, and TNFα, which are elevated in circulation in both ARF and RHD patients. Histological studies of RHD valve tissue implicates Th1 and Th17 associated pro-inflammatory cytokines, chemokine CXCL9, and the fibrosis-associated cytokine TGF-ß in progressive cycles of inflammatory damage and fibrotic repair. Taken together, this suggests immune molecules contribute to both the acute inflammatory disease stage of ARF, as well as cardiac remodeling and valve dysfunction in RHD. Monoclonal antibody blockade of pro-inflammatory cytokines IL-6 and TNFα are approved therapies for many autoimmune diseases and the most successful immunomodulating therapies for rheumatoid arthritis. Current evidence suggests possible benefit for ARF patients from IL-6 and TNFα blockade, in particular to interrupt progression to RHD, and warrants immediate investigation.

Tailoring gut microbiota with a combination of Vitamin K and probiotics as a possible adjuvant in the treatment of rheumatic arthritis: a systematic review.

Rheumatoid arthritis (RA) is an autoimmune disease of multifactorial etiology, characterized by a chronic inflammatory reaction of the joints, but can also affect other tissues. Some environmental factors can trigger an immune system response in genetically susceptible individuals, activating the disease. Lower diversity of gut microbiota, and dysbiosis, have been observed in RA patients. In this regard, approaches to decrease inflammation, and to restore the microbiota, have been suggested. These include oral administration of single probiotics, or probiotic mixtures, on their own, or in combination with drugs. Vitamin K (VitK) is one of the many products of the intestinal microbiota. Lower levels of some forms of VitK have been measured in the serum and stools of RA patients and some studies have found an inverse correlation between VitK levels and the clinical severity of the disease. Additionally, some forms of this vitamin, when given orally, have been shown to exert positive effects in decreasing RA activity, and delaying its onset and progress. This review aims at describing the link between the gut microbiota and RA, focusing on the role of VitK and probiotics as possible adjuvant therapies in this disease.