Understanding rheumatic fever

Abstract

Through a comprehensive review of the recent findings on rheumatic fever, we intend to propose a new physiopathologic model for this disease. A Medline search was performed for all articles containing the terms rheumatic fever or rheumatic heart disease in title or abstract from 1970 to 2011. Best evidence qualitative technique was used to select the most relevant. The scientific interest on rheumatic fever has notably diminished throughout the twentieth century as evidenced by the comparison of the proportion of articles in which RF was a subject in 1950 (0.26%) and today (0.03%) [Pubmed]. However, RF remains a major medical and social problem in the developing world and in the so-called hotspots, where it still causes around 500.000 deaths each year, not too different from the pre-antibiotic era. The role of genetic factors in RF susceptibility is discussed. Familiar aggregation, similarity of disease patterns between siblings, identical twin, and HLA correlation studies are evidence for a genetic influence on RF susceptibility. The suspect-involved genes fall mainly into those capable of immunologic mediation. Molecular mimicry explains the triggering of RF, but an intense and sustained inflammation is needed to cause sequels. Also, RF patients vary greatly in terms of symptoms. It is likely that a genetic background directing immune response towards a predominantly Th1 or Th2 pattern contributes to these features. The recent findings on rheumatic fever provide important insight on its physiopathology that helps understanding this prototype post-infectious autoimmune disease giving insights on other autoimmune conditions.

Complications of physician misdiagnosis/treatment of rheumatic fever in the United States

“…Deaths associated with RF in the developing world are not dramatically different than reports of RF pre-antibiotic discovery (20-51/100,000 people), while deaths in the developed world are much more rare (0.2-1.9/ 100,000 people) [4]. This disparity has caused several investigators to assume a socio-economic proclivity for RF among disparate populations.…”

“…In RF patients, antibody production to the streptococcal infection is cross-reactive with other cells or proteins within the host. Examples of cross-reactive proteins are: laminin, a protein in the extracellular matrix of the heart and heart valves; several cardiac myosin epitopes; vimentin; or lysoganglioside GM1 from neural cells [4,5]. In the acute phase, the initial antibody response to the streptococcal infection can directly damage cellular tissue, mediate signal transduction, and trigger dopamine release in neural cells.…”

“…In the acute phase, the initial antibody response to the streptococcal infection can directly damage cellular tissue, mediate signal transduction, and trigger dopamine release in neural cells. Additional damage is mediated by antibody upregulation of adhesion molecule VCAM-1 which leads to inflammation of one or more body regions and valve scaring [4][5][6].…”

Revisiting the old link between infection and autoimmune disease with commensals and T helper 17 cells

“…The dominant theory is “molecular mimicry”, or more specifically “epitope mimicry”, where self-reactive B or T cells are activated inappropriately upon recognition of peptides derived from pathogens that share sequence or structural homology with peptides derived from self-antigens (reviewed in [30]). However, molecular mimicry, especially in the case of T cell epitope mimicry, has been controversial due to varying views regarding the experimental evidence in animal models, and the lack of strong evidence in human disease [5, 31–34]. The case may be stronger for B cell epitope mimicry with recent evidence in human SLE (more on this below) [35].…”

Gene Specific Impedimetric Bacterial DNA Sensor for Rheumatic Heart Disease

“…The bacteria colonize in the throat and are responsible for initial infection pharyngitis and if it is not treated may leads to rheumatic fever [1][2][3][4][5]. Rheumatic heart disease (RHD), causing damage of heart valves, is the most serious autoimmune sequelae of streptococcal infection which leads to disability and death among children worldwide.…”