RARE DISEASE
Rheumatic fever
Rheumatic fever
Rheumatic fever
Synonyms: Acute rheumatic fever
Synonyms: Acute rheumatic fever
Synonyms: Acute rheumatic fever
Drug discovery
0
drugs
With orphan designations
Overview
Rheumatic fever (RF) is an autoimmune sequela of group A streptococcal pharyngitis, predominantly affecting children aged 5-15 years. It manifests with migratory polyarthritis, carditis, chorea, erythema marginatum, or subcutaneous nodules, diagnosed via modified Jones criteria [1][6]. Management includes antibiotic eradication of streptococcal infection, anti-inflammatory agents (NSAIDs/corticosteroids), and long-term penicillin prophylaxis to prevent recurrent attacks and rheumatic heart disease (RHD), a major cause of acquired valvular disease in resource-limited settings [1][3][17].
Therapies
Acute management: Penicillin G for streptococcal eradication; NSAIDs (naproxen) or aspirin for arthritis; corticosteroids for moderate-severe carditis [1][3][6].
Secondary prophylaxis: Monthly intramuscular benzathine penicillin G for ≥5-10 years post-episode, extending to age 21+ if cardiac involvement exists [1][3][13].
Surgical intervention: Valve repair/replacement for advanced RHD-related complications [1][13].
Categories: rare systemic and rheumatological diseases
Research Papers
1,006 drug discovery papers about Rheumatic fever, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,006 drug discovery papers about Rheumatic fever, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-12 | Myocardial Infarction With Non-obstructive Coronary Arteries (MINOCA) Revealing Coronary Embolism From Left Atrial Appendage Thrombus in Rheumatic Valvular Atrial Fibrillation.
Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a diagnostic challenge with multiple underlying mechanisms, including coronary embolism. We report the case of a 50-year-old woman with a history of rheumatic fever who was admitted for acute chest pain. Electrocardiography showed atrial fibrillation with inferolateral ischemic changes, and elevated troponin levels confirmed myocardial infarction. Transthoracic echocardiography revealed moderate mitral stenosis, severe aortic stenosis, and left atrial enlargement. Coronary angiography demonstrated thrombotic occlusion of the second obtuse marginal branch without significant atherosclerotic disease. Transesophageal echocardiography identified a left atrial appendage thrombus, supporting a cardioembolic mechanism. This case emphasizes the importance of considering coronary embolism in MINOCA, particularly in patients with valvular atrial fibrillation, and highlights the role of a structured diagnostic approach in guiding diagnosis and management.
2026-07-08 | Inflammatory and hormonal crosstalk linking rheumatic fever to chronic valvular heart disease.
Rheumatic heart disease (RHD) is a chronic, immune-mediated valvular disorder triggered by Group A β-hemolytic streptococcal infection. Persistent inflammation and immune-mediated tissue injury are central features of disease progression, whereas the roles of hormonal and metabolic regulatory pathways remain less well defined. Emerging evidence suggests that inflammatory signaling may intersect with hormonal and metabolic pathways during the transition from rheumatic fever to chronic valvular disease. Pro-inflammatory mediators have been associated with immune activation and extracellular matrix remodeling, with potential involvement of pathways such as nuclear factor-κB, Janus kinase/signal transducer and activator of transcription, and the NOD-like receptor protein 3 inflammasome. Chronic inflammation may also be accompanied by altered neuroendocrine anti-inflammatory feedback, including changes in glucocorticoid receptor signaling and hypothalamic-pituitary-adrenal axis regulation. In addition, sex hormones, thyroid hormones, and metabolic hormones may be linked to immune-cell differentiation, endothelial function, and valvular cell phenotypes, suggesting a possible inflammatory-endocrine regulatory loop that remains insufficiently validated in RHD-specific studies. These relationships may provide a context for understanding valvular interstitial cell activation, endothelial dysfunction, endothelial-mesenchymal transition, metabolic reprogramming, energy imbalance, fibrosis, and calcification, but direct causal evidence remains limited. Future dual-target strategies addressing both inflammatory and hormonal signaling may provide a theoretical framework for individualized intervention; however, their efficacy and safety require rigorous RHD-specific validation. This review summarizes current evidence and discusses the inflammatory-hormonal network as a hypothesis-generating framework for understanding chronic rheumatic valvular remodeling.
2026-07-03 | Acute rheumatic fever — a late complication of streptococcal infection: results of a 25-year study
Despite a decline in incidence, acute rheumatic fever (ARF) and recurrent ARF is a late autoimmune complication of S. pyogenes infection — remain a significant public health problem, being a cause of chronic rheumatic heart disease. Objective : to provide a clinical and epidemiological characterization and describe the outcomes of ARF based on observations of patients hospitalized between 2001 and 2025 at the Morozovskaya children’s city clinical hospital of the Moscow Department of Health. Materials and methods . We observed 113 children (60 girls, 53 boys), aged 4—17 years (median age 10 [8; 13] years), with a diagnosis of ARF (101 children) or recurrent ARF (12 children). We assessed clinical and anamnestic data, laboratory test results (antistreptolysin-O (ASO), C-reactive protein), electrocardiography (ECG), and echocardiography. Children with Sydenham's chorea underwent additional examinations. Results. A high rate of underdiagnosis of ARF was identified (63.7%). The onset of ARF most commonly occurred during the winter-spring period (61.9 %). To confirm markers of previous streptococcal infection, measuring ASO levels is more informative; an elevated ASO level (median 795 [385; 1440] IU/mL) was detected in 86.7% of children. In theclinical presentation of ARF, carditis was the predominant manifestation (81.4 %), and its frequency increased with age (p = 0,003). The mitral valve (MV) was most commonly affected (54%); combined involvement of the MV and aortic valve (AV) was observed in 34.5% of children, while isolated AV involvement occurred in 11.5 %. Arthritis was detected in 44.2% of children, with a high frequency (36/50, 72%) of atypical joint syndrome. Our study recorded a high incidence of Sydenham's chorea (56 children, 49.6%), including isolated Sydenham's chorea in 30.4%. The incidence of Sydenham's chorea decreased with age (p = 0,004). Rare manifestations of ARF — erythema marginatum and subcutaneous nodules — were observed in 14.2% and 3.4% of patients, respectively. A high incidence of chronic rheumatic heart disease (42%) was noted, with the development of rheumatic heart valve defects in 38% of cases. Conclusion . The study highlights the need for vigilance regarding ARF in patients following streptococcal infection to prevent severe outcomes such as the development of acquired heart valve defects.
2026-07-12 | Myocardial Infarction With Non-obstructive Coronary Arteries (MINOCA) Revealing Coronary Embolism From Left Atrial Appendage Thrombus in Rheumatic Valvular Atrial Fibrillation.
Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a diagnostic challenge with multiple underlying mechanisms, including coronary embolism. We report the case of a 50-year-old woman with a history of rheumatic fever who was admitted for acute chest pain. Electrocardiography showed atrial fibrillation with inferolateral ischemic changes, and elevated troponin levels confirmed myocardial infarction. Transthoracic echocardiography revealed moderate mitral stenosis, severe aortic stenosis, and left atrial enlargement. Coronary angiography demonstrated thrombotic occlusion of the second obtuse marginal branch without significant atherosclerotic disease. Transesophageal echocardiography identified a left atrial appendage thrombus, supporting a cardioembolic mechanism. This case emphasizes the importance of considering coronary embolism in MINOCA, particularly in patients with valvular atrial fibrillation, and highlights the role of a structured diagnostic approach in guiding diagnosis and management.
2026-07-08 | Inflammatory and hormonal crosstalk linking rheumatic fever to chronic valvular heart disease.
Rheumatic heart disease (RHD) is a chronic, immune-mediated valvular disorder triggered by Group A β-hemolytic streptococcal infection. Persistent inflammation and immune-mediated tissue injury are central features of disease progression, whereas the roles of hormonal and metabolic regulatory pathways remain less well defined. Emerging evidence suggests that inflammatory signaling may intersect with hormonal and metabolic pathways during the transition from rheumatic fever to chronic valvular disease. Pro-inflammatory mediators have been associated with immune activation and extracellular matrix remodeling, with potential involvement of pathways such as nuclear factor-κB, Janus kinase/signal transducer and activator of transcription, and the NOD-like receptor protein 3 inflammasome. Chronic inflammation may also be accompanied by altered neuroendocrine anti-inflammatory feedback, including changes in glucocorticoid receptor signaling and hypothalamic-pituitary-adrenal axis regulation. In addition, sex hormones, thyroid hormones, and metabolic hormones may be linked to immune-cell differentiation, endothelial function, and valvular cell phenotypes, suggesting a possible inflammatory-endocrine regulatory loop that remains insufficiently validated in RHD-specific studies. These relationships may provide a context for understanding valvular interstitial cell activation, endothelial dysfunction, endothelial-mesenchymal transition, metabolic reprogramming, energy imbalance, fibrosis, and calcification, but direct causal evidence remains limited. Future dual-target strategies addressing both inflammatory and hormonal signaling may provide a theoretical framework for individualized intervention; however, their efficacy and safety require rigorous RHD-specific validation. This review summarizes current evidence and discusses the inflammatory-hormonal network as a hypothesis-generating framework for understanding chronic rheumatic valvular remodeling.
2026-07-03 | Acute rheumatic fever — a late complication of streptococcal infection: results of a 25-year study
Despite a decline in incidence, acute rheumatic fever (ARF) and recurrent ARF is a late autoimmune complication of S. pyogenes infection — remain a significant public health problem, being a cause of chronic rheumatic heart disease. Objective : to provide a clinical and epidemiological characterization and describe the outcomes of ARF based on observations of patients hospitalized between 2001 and 2025 at the Morozovskaya children’s city clinical hospital of the Moscow Department of Health. Materials and methods . We observed 113 children (60 girls, 53 boys), aged 4—17 years (median age 10 [8; 13] years), with a diagnosis of ARF (101 children) or recurrent ARF (12 children). We assessed clinical and anamnestic data, laboratory test results (antistreptolysin-O (ASO), C-reactive protein), electrocardiography (ECG), and echocardiography. Children with Sydenham's chorea underwent additional examinations. Results. A high rate of underdiagnosis of ARF was identified (63.7%). The onset of ARF most commonly occurred during the winter-spring period (61.9 %). To confirm markers of previous streptococcal infection, measuring ASO levels is more informative; an elevated ASO level (median 795 [385; 1440] IU/mL) was detected in 86.7% of children. In theclinical presentation of ARF, carditis was the predominant manifestation (81.4 %), and its frequency increased with age (p = 0,003). The mitral valve (MV) was most commonly affected (54%); combined involvement of the MV and aortic valve (AV) was observed in 34.5% of children, while isolated AV involvement occurred in 11.5 %. Arthritis was detected in 44.2% of children, with a high frequency (36/50, 72%) of atypical joint syndrome. Our study recorded a high incidence of Sydenham's chorea (56 children, 49.6%), including isolated Sydenham's chorea in 30.4%. The incidence of Sydenham's chorea decreased with age (p = 0,004). Rare manifestations of ARF — erythema marginatum and subcutaneous nodules — were observed in 14.2% and 3.4% of patients, respectively. A high incidence of chronic rheumatic heart disease (42%) was noted, with the development of rheumatic heart valve defects in 38% of cases. Conclusion . The study highlights the need for vigilance regarding ARF in patients following streptococcal infection to prevent severe outcomes such as the development of acquired heart valve defects.
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0 orphan drug designations.
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