Understanding rheumatic fever

Area of Science:

• Rheumatic fever and rheumatic heart disease research
• Post-infectious autoimmune disease mechanisms
• Immunogenetics and disease susceptibility

Background:

• Rheumatic fever (RF) continues to be a major cause of mortality, particularly in developing nations, with nearly 500,000 deaths yearly.
• Despite its impact, scientific interest in RF has declined significantly since the mid-20th century.
• Understanding the physiopathology of RF is crucial for addressing this persistent global health challenge.

Purpose of the Study:

• To propose a novel physiopathologic model for rheumatic fever based on recent scientific findings.
• To review and synthesize current knowledge regarding the genetic and immunologic underpinnings of RF susceptibility.
• To explore how genetic background influences the varied clinical manifestations of RF.

Main Methods:

• Comprehensive literature review of articles on rheumatic fever and rheumatic heart disease.
• Medline database search from 1970 to 2011 using specific keywords.
• Application of the best evidence qualitative technique for article selection.

Main Results:

• Evidence suggests a significant genetic influence on RF susceptibility, supported by family, twin, and HLA studies.
• Genes implicated in immunologic mediation are key suspects in RF pathogenesis.
• Molecular mimicry is identified as a trigger, but sustained inflammation, potentially influenced by Th1/Th2 immune responses, is necessary for sequelae.

Conclusions:

• Recent findings offer critical insights into the physiopathology of rheumatic fever, highlighting its nature as a prototype post-infectious autoimmune disease.
• Genetic predisposition plays a crucial role in determining individual susceptibility and the clinical spectrum of RF.
• This understanding may provide valuable insights applicable to other autoimmune conditions.