Pathophysiology of Rheumatic Fever
Introduction
Rheumatic Fever (RF) is the type of inflammatory disease that can develop due to untreated or inadequately treated throat infection (scarlet fever or strep throat) caused by a type of bacteria known as streptococcus (Carapetis, McDonald & Wilson, 2005). This paper is going to cover pathophysiology of the Rheumatic Fever. It will begin with the symptoms associated with RF. A description of mechanisms or processes that take place in a person infected with RF will be described. This will be followed by a discussion of the causes of RF. There is a section dedicated to the pathophysiology of RF where more discussion of the pathology and physiology of the disease is provided. This is followed by methods of treatment of RF, complications that can arise out of RF, its prevalence, outlook, and finally the conclusion.
Symptoms of Rheumatic Fever.
The symptoms of RF include inflammation of the heart, pain and swelling in the joint (arthritis), chest pain, and shortness of breath. Although symptoms usually last for approximately four weeks, the condition can persist for several months. The earliest symptoms and which also happens to be the most common characteristic of RF is migratory arthritis that is painful (Meador, 2016). Up to 80% of the people affected by RF has been found to exhibit this symptom. RF affects large joints that include ankles, knees, shoulders, and elbows (Lawrence et al., 2013). Although Sydenham chorea used to be a common clinical manifestation whose onset occur late, it is now rare feature. One of the most lethal manifestations which is attributed to past episodes of RF is carditis and may be one of the features that are a sign of episodes that were not recognized in the past. Of the various symptoms associated with RF, only damage to the heart’s valve tissue can become a chronic condition that leads to endocarditis, strokes, congestive heart failure, and even death (Seckeler & Hoke, 2011; Kumar & Tandon, 2013).
Causes of Rheumatic Fever
Group A Streptococcus, a type of bacteria, is responsible for a throat infection. Although throat infection is associated with RF, studies have shown that the streptococcus bacteria does not directly cause RF. Rather, the symptoms of RF are caused by the response of the immune system to the bacteria itself. Acute rheumatic fever (ARF) is an autoimmune condition that causes inflammations that occur as a sequela of an infection associated with a type of bacteria that is known as Streptococcus (Wallace, 2016). When the streptococcus infects the throat, the body senses it and responds by sending antibodies to fight the bacteria. The antibodies attack the bacteria. However, sometimes the antibodies attack certain tissues in some parts of the body such as tissues in the heart and joints instead of attacking bacteria. When antibodies attack the human heart, it causes heart valves to swell. Swollen valves can result in scarring of the leaflets of the valves.
Pathophysiology
Despite being known that acute RF is an autoimmune clinical condition, the precise nature of its pathogenesis has remained elusive (Best Practice, 2016; Kaplan, 2005; Kumar & Tandon, 2013; Stollerman, 2001). Acute rheumatic fever is characterized by non-suppurative inflammatory lesions that affect the central nervous system, heart, joints, and subcutaneous tissues (Wallace, 2016). It is believed that both cross-reactive T cells and cross-reactive antibodies play a key role in RF. The genesis of the cross-reactivity is thought to be emanating from a molecular mimicry that takes place between antigens of group A Streptococcus pyogenes host tissue of a human being (Best Practice, 2016). Although the causative bacterial agent is well known, factors that make one susceptible to RF have remained unclear (Meador, 2016). However, the part where streptococcal infection occurs appears to play a significant role. Despite the fact that a clinical syndrome often precedes a streptococcal pharyngitis, there has been no association between the clinical syndrome and streptococcal cellulitis. Extensive studies have revealed that RF occurs after a pharyngeal infection with streptococci of the type known as rheumatogenic group A and the symptoms can be detected 2-3 weeks after infection (Meador, 2016). The risk of developing RF following an episode of streptococcal pharyngitis has been found to be 0.3-3%. Recent investigations of RF affecting the aboriginal populations of Australia revealed that streptococcal skin infections are also likely to be associated with the development of RF. Studies carried out in Hawaii and Oceania revealed that certain strains of streptococcus which are not usually associated with RF had been linked with the disease. Tissue injury that is often a characteristic of RF is linked with molecular mimicry. Cellular hosts, as well as humoral host defences of a host who is genetically vulnerable, are involved. The immune responses (B- and T- cell mediated) of the patient in this process are not in a position to differentiate between certain host tissues and invading microbes. The major mediators associated with rheumatic heart disease are cytokine Th17 and T helper 1. The resulting inflammation may continue to stay beyond the period of acute infection and cause protean manifestations of RF (Wallace, 2016).
The increase in incidences of RF in certain families suggests that genetics is likely to be a contributing factor (Meador, 2016; Bryant, 2014; Stollerman, 2001). Although there has been no relationship with class-I human leukocyte antigens (HLAs), investigations have revealed that class-II HLA antigens DR4 and DR2 increases in white and black patients respectively. Research carried out by Yoshinoya and Pope (1980) revealed that increased immune-complex levels of blood samples drawn from people affected by ARF exhibited a strong association with HLA-B5.
Treatment of Rheumatic Fever
Treatment of ARF, like any other clinical condition, should be done after diagnosis. However, according to Wallace (2016), ARF occur in various manifestations, and it is a clinical syndrome with no known specific diagnostic tests. According to Meador (2016), diagnosis of RF depends on an amalgamation of clinical manifestations that are linked to streptococcal pharyngitis of group A. these clinical manifestations include migratory polyarthritis, subcutaneous nodules, carditis, erythema marginatum, and chorea. Presently, there is no known cure for rheumatic fever. The only available treatment involves relieving symptoms with some medication and attempting to prevent any likely permanent damage to the heart. Although penicillin has been effectively used to eradicate persistent group A streptococcus infection that usually affects the upper respiratory tract, there is no evidence that the treatment has any impact on changing the cardiac outcome one year following controlled studies (Carapetis, McDonald & Wilson, 2005). Once a person has been attacked by rheumatic fever, there is a high chance that the person will be attached again in the future. The remedy for a likely future infection of the rheumatic fever is by taking a long-term course of drugs, especially antibiotics. According to Ralph et al. (2013), recurrent ARF can be prevented by using long-term secondary prophylaxis in combination with intramuscular benzathine penicillin.
Complications associated with Rheumatic Fever
Rheumatic Fever can cause short term and also long term complications in the body. For example, RF can cause a condition known as rheumatic heart disease. Rheumatic heart disease (RHD) occurs when RF causes permanent damage to the valves of the heart. Rheumatic heart disease is associated with serious complications such as stroke and heart failure.
Prevalence of Rheumatic Fever
Rheumatic fever is highly prevalent in areas where there is limited access to healthcare, poor sanitation, and crowding (NHS, 2015). These are conditions which are found in poorest parts of the world such as parts of South America, Africa, and the Middle East. Estimates show that there are just less than 1 million reported new cases of RF every year. Previous investigations show that most cases of RF initially develop in children aged between five and fifteen years. Although both sexes have an equal chance of being affected, RF is unlikely to affect younger adults, and it is rare to affect adults aged over 35 years.
Rheumatic Fever Outlook
The general appearance of people with RF largely depends on whether they have sustained an advanced case of heart damage. If one’s heart has been damaged, there is a low chance that person is going to recover fully. In such circumstances, the symptoms of rheumatic heart disease such as constant tiredness and shortness of breath will persist. However, if the heart is undamaged, long-term use of an antibiotic can prevent reoccurrence of RF, and this helps to prevent future damage to the heart (NHS, 2015).
Conclusion
Rheumatic fever is a bacterial disease that causes inflammation of the throat. The disease can cause cardiac complications. The pathogenesis of RF is still unknown, and there is no known diagnosis for the disease. As a result, there is also no known cure for RF and RHD. The only cure is to eradicate the bacterial infection. Once a person is infected with the disease, there is a high chance that it will recur in future. The disease is most common in areas with poor sanitation. Research into various aspects of the disease is still ongoing.
References
Best Practice. (2016). Rheumatic Fever. British Medical Journal, August 08, 2016. Retrieved from: http://bestpractice.bmj.com/best-practice/monograph/404/basics/pathophysiology.html
Bryant, P. A., Smyth, G. K., Gooding, T., Oshlack, A., Harrington, Z., Currie, B., & Curtis, N. (2014). Susceptibility to Acute rheumatic fever based on differential expression of genes involved in cytotoxicity, chemotaxis, and apoptosis. Infection and Immunity, 82(2), 753-761.
Carapetis, J.R., McDonald, M. & Wilson, N.J. (2005). Acute rheumatic fever. Lancet, 366, 155-168.
Kaplan, E.L. (2005). Pathogenesis of acute rheumatic fever and rheumatic heart disease: evasive after half a century of clinical, epidemiological, and laboratory investigation. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1768618/
Kumar, R. K., & Tandon, R. (2013). Rheumatic fever & rheumatic heart disease: The last 50 years. Indian Journal of Medical Research, 137(4), 643.
Lawrence, J. G., Carapetis, J. R., Griffiths, K., Edwards, K., & Condon, J. R. (2013). Acute rheumatic fever and rheumatic heart disease: incidence and progression in the Northern Territory of Australia 1997-2010. Circulation, CIRCULATIONAHA-113. Retrieved from: http://circ.ahajournals.org/content/128/5/492
Meador, R.J. (2016). Acute Rheumatic Fever. Medscape, July 31, 2016. Retrieved from: http://emedicine.medscape.com/article/333103-overview#a5
National Health Service (NHS). (2015). Rheumatic fever. Retrieved from: http://www.nhs.uk/Conditions/Rheumatic-fever/Pages/Introduction.aspx
Ralph, A. P., Fittock, M., Schultz, R., Thompson, D., Dowden, M., Clemens, T. & Carapetis, J. R. (2013). Improvement in rheumatic fever and rheumatic heart disease management and prevention using a health centre-based continuous quality improvement approach. BMC health services research, 13(1), 525.
Seckeler, M. D., & Hoke, T. R. (2011). The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease. Clin Epidemiol, 3(1), 67-84.
Stollerman, G.H. (2001). Rheumatic Fever in the 21st Century. Clinical Infectious Diseases, 33(6), 806-814.
Wallace, M.R. (2016). Rheumatic Fever. Medscape, 21 October 2016. Retrieved from: http://emedicine.medscape.com/article/236582-overview
Yoshinoyo, S. & Pope, R.M. (1980). Detection of immune complexes in acute rheumatic fever and their relationship to HLA-B5. Journal of Clinical Investigations, 65(1), 136-145.
