Advances in Bioscience and Biotechnology, 2013, 4, 143-146 ABB Published Online January 2013 (
Complications of physician misdiagnosis/treatment of
rheumatic fever in the United States
Diana C. Peterson
Department of Biomedical Sciences, Iowa State University, Ames, USA
Received 1 November 2012; revised 10 December 2012; accepted 8 January 2013
Rheumatic fever is an auto-immune disease caused by
exposure to Streptococcus pyogenes. Over the last 50
years, reports of rheumatic fever within the United
States have diminished. The decrease was attributed
to the advent of penicillin in the treatment of strepto-
coccus infections. We propose that current diagnostic
and treatment methodologies may adversely increase
the morbidity rate of rheumatic fever within the Uni-
ted States. Publication rates and interest in rheumatic
fever has diminished over the last 30 years. Because of
this decline, many physicians are only vaguely aware
of the disorder. Additionally, the fear of antibiotic
resistance has influenced the Center of Disease Con-
trol to suggest a significant decrease in the use of an-
tibiotics by physicians. Although extremely valid for
the future health and well-being of the population,
such policies must be examined for each individual
case carefully. The American Heart Association pre-
scribes long-term antibiotic prophylaxis as the only
current treatment; however literature reviews indi-
cate that such therapy is rarely used. Therefore indi-
viduals diagnosed with rheumatic fever are not being
treated. Additionally, because many physicians are
not routinely testing for streptococcus or early signs
of endocarditis, it is likely that cases of rheumatic
fever will increase in the future, and many individuals
may not be diagnosed until sever damage or morbid-
ity occurs. Physician education and clear revised
guide-lines are necessary to ensure adequate treat-
ment of individuals with rheumatic fever. Misun-
derstandings of the disease and how it should be trea-
ted by first responders (i.e. primary care providers
and pediatricians) are discussed.
Keywords: Physician Guidelines; Prophylaxis;
Antibiotic Resistance; Penicillin; Rh eumatic Heart
Disease; Endocarditis
Rheumatic fever (RF) is an auto-immune disease me-
diated by humoral and cellular auto-immune responses to
Streptococcus pyogenes infections [1,2]. Initial RF epi-
sodes can produce either mild or severe symptoms and
damage, however milder outcomes are more common
with an initial presentation (e.g., endocarditis, heart valve
damage, Sydenham’s chorea, rheumatoid arthritis, and
potentially depression and obsessive compulsive disor-
der) [3]. When diagnosed and treated early, most RF
individuals have little to no life-altering symptomology.
However, misdiagnosis and/or lack of prophylactic treat-
ment lead to progressive damage, invasive interventions,
decreased quality of life, and increased morbidity.
The following article is designed to increase the awa re-
ness of RF among physicians, explain reasonable guide-
lines for the detection of RF, and highlight treatment
guidelines fo r health care providers.
All data and subsequent treatment recommendations are
derived from Pubmed, Medline, Center for Disease Con-
trol, and American Heart Association searches for arti-
cles containing rheumatic fever, rheumatic heart disease,
endocarditis, and Streptococcus pyogenes from 2009-
2012. Based on the relevancy of the article, 115 articles
were selected for in-depth analysis. In addition, all semi-
nal articles referenced in these papers were also exam-
ined and used for the current analysis.
3.1. Mechanism of Disease
Rheumatic Fever (RF) is an auto-immune disease medi-
ated by humoral and cellular autoimmune responses to
Streptococcus pyogenes infections [1]. 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 pro-
tein 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
D. C. Peterson / Advances in Bioscience and Biotechnology 4 (2013) 143-146
phase, the initial antibody response to the streptococcal
infection can directly damage cellular tissue, mediate
signal transduction, and trigger dopamine release in neu-
ral cells. Additional damage is mediated by antibody up-
regulation of adhesion molecule VCAM-1 which leads to
inflammation of one or more body regions and valve
scaring [4-6] .
Similarities of disease patterns between siblings and
identical twins as well as HLA correlation studies [7,8]
provide strong evidence for a genetic influence over RF
susceptibility and potentially RF manifestation. Because
the specific molecu lar components of the proteins targeted
by the auto-immune response are genetically determined,
and the different components of the immunological cas-
cade are also genetically deter mined, a genetic predisposi-
tion for RF is not only plausible, but probable.
Most RF patients have distinct but limited cells and
organs with proteins that are cross-reactive to antibodies
that attack streptococcal bacterium (mimic cells), and are
thus affected by RF. Such genetic variability is likely to
contribute to the vast differences in RF damage and
symptomology. In all cases, the mimic cells are perma-
nently susceptible to RF damage. Therefore with each
repeated streptococcal infection, the previous damage is
perpetuated and expanded.
3.2. Environmental Factors
The proclivity for streptococcal infection increases in
several populations of individuals regardless of societal
local. Group settings such as day-cares, schools, hos-
pitals, and military facilities are specifically prone to the
spread of streptococcus throughout a population. Day-
care facilities and schools are predominantly prone to
such infections due to the lack of sanitary precautions by
young children (e.g., hand-washing and covering their
mouths when sneezing). Although numerous studies
have determined a higher incidence of RF in school-aged
children, in-dep th analysis of these individuals over time
has not been performed.
3.3. Environment-Location
Deaths associated with RF in the developing world are
not dramatically different than reports of RF pre-antibi-
otic 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. Populations with lower
socio-economic status have less access to health care,
antibiotics, and less knowledge about simple ways to
fight disease perpetuation such as hand washing. There-
fore populations within the developing world have a high
risk of being infected multiple times. Because each inci-
dence of infection increases damage, these individuals
have a high risk of mortality from RF.
Closer examination of cases within the United States
over the last several years show an increase in RF infec-
tion rate (Utah 1986: 11 .8/100,000 people) [9 ]. Although
socioeconomic factors may play a role in RF formation
within the United States, in the study above 56% of the
patient families had attended or completed college and
were above the poverty line [9]. Deaths associated with
these cases are less common within the United States,
and are likely to be mitigated by access to health care
and adherence to treatment regimens.
3.4. Current Clinical Guidelines
Global guidelines by the Center for Disease Control
recommend no antibiotic treatment unless a diagnosis of
streptococcal infection is confirmed by a laboratory test
[10-12]. These guides are meant to decrease unnecessary
antibiotic use throughout the United States. RF directed
guidelines were published by the American Heart Asso-
ciation in 2009. They indicate a treatment of continuous
antibiotic prophylaxis for 10 years or age 40 for RF pa-
tients with persistent valvular disease, 10 years or age 21
for RF patients with RF and no valvular disease, and 5
years or age 21 for RF patients without carditis. Indi-
viduals with evidence of valvular damage or those at
high risk of recurrence (e.g., children, military recruits,
students, teachers, physicians, and health care workers)
are recommended to continue prophylactic treatment
permanently, or until the risk of infection is reduced [13].
This guideline proposes an tibiotic prophylactic treatment
during any stage of life in which the likelihood of strep-
tococcal infection is high to prevent recurrence of infec-
tion and subsequent physical damage.
4.1. Decrease of RF in States
Reports of RF within the United States have dramatically
decreased. These findings are based on population-based
surveys and state surveillance systems. State surv eillance
for most states ceased during the mid 1980s [9]. There-
fore accurate counts of RF within the States have been
lacking for numerous years. It is possible that the RF
infection rate has decreased due to differences in strep-
tococcal strains in the last 50 years, however it is also
probable that many RF cases are not diagnosed due to
lack of physician knowledge and testing for the disease.
Analysis of accurate trends within the United States will
require physician training in RF diagnosis as well as ad-
ditional surveys or re-instated state surveillance systems.
4.2. Misconceptions
4.2.1. Age Misconcepti o ns
Numerous reports indicate that RF is a childhood-ado-
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D. C. Peterson / Advances in Bioscience and Biotechnology 4 (2013) 143-146 145
lescent disease. These statements are based on larger per-
centages of younger patients than older patients world-
wide. This is a widely held misconception. RF has been
shown to be induced by proteins on mimic cells that are
targeted by the body’s immune response to streptococcus.
Over a life-time, the genetics of an RF individual do not
change. Therefore a 65-year-old individual would be just
as susceptible to recurrent RF episodes as a 13-year-old.
The decrease in RF in older populations is resultant from
a decrease in the risk of streptococcal contact for the
older population. Older populations in environments
prone to streptococcal exposure should be considered at
high risk for repeated streptococcal infection, repeated
RF damage, and at a high risk for severe damage and
4.2.2. Treatment Misconceptions
Common guidelines for both RF and non-RF patients
have been guided primarily by the fear of the develop-
ment of antibiotic resistance. Such arguments are valid
for maintaining the overall health and safety of the gen-
eral population. However caution should be taken when
applying this principle to all patients. Treatment of ex-
isting streptococcal infections may decrease the overall
damage from that episode, but it will not eliminate dam-
age from the initial infection. In the Utah study, 53% of
patients who received antibiotic treatment for a strepto-
coccal infection were subsequently diagnosed with heart
damage associated with RF [9]. Therefore treatment of
each streptococcal infection will not stop the progression
of the RF damage associated with those infections. Sec-
ond, at least one third of episodes of acute RF result from
non-symptomatic streptococcal infections [13]. If physi-
cians only treat symptomatic infections, a large percent-
age of infections would go un-noticed and un-treated.
Therefore, broad application of the CDC guidelines would
deny treatment and health to RF patients.
4.3. Initial Diagnosis
The symptoms of streptococcal infections are similar to
those of the common cold as well as viral infections such
as the flu (e.g., sore throat, pain when swallowing, fever
101 or above, swollen tonsils, petechiae on soft or hard
palate, headache, and nausea) [10]. Current CDC guide-
lines indicate that antibiotic treatment should not be im-
plemented until after streptococcal laboratory diagnosis.
Because physicians routinely test for streptococcus only
when an infected individual does not recover after 10
days (the time necessary for viral infections to cease), the
first acute RF episode in children is likely to be more
severe. To alleviate this possibility, two vital diagnostic
tools should be utilized by physicians. First, for each sore
throat, a throat swab should be performed to determine
whether the infection is caused by streptococcus. The test
is inexpensive, fast, and easy to perform. This fast diag-
nosis will lead to faster treatment, shorter infectio n times,
and less sever RF immunological reactivity. Second,
physicians should become more aware of the cardiac
health of their patients. Although heart auscultations are
standard, endocarditis is commonly not audible in RF
patients. Therefore echocardiograms should be added to
the standard physician repertoire in patients with a fa-
milial history of RF. This added vigilance would assist
with early detection of RF damage. Because RF damage
is cumulative, early diagnosis and treatment would im-
prove the future health and wellness of the patient.
4.4. Patient Physician Interaction in Treatment
Once diagnosed, physicians should initiate open and in-
formed discussions of the costs, benefits, and life events
for each patient to identify the prophylactic treatment
that is best suited for an RF patient. As indicated by the
AHA, individuals at high risk for streptococcal infection
should seriously consider antibiotic prophylactic treat-
ment until they are no longer in a streptococcal prone
environment. Individuals not in high-risk environments
should continue to be monitored for potential relapses at
intervals agreed upon by the physician and patient through-
out life. These informed discussions will contribute to
patient physician confidence and places some of the pa-
tient’s health decisions back into the patient’s hands.
This may potentially alleviate legal complications from
advancing RF damage if it occurs in the future.
Insufficient physician/patient interaction, physician
inattention, or ph ysician misunderstanding of the disease
may lead to denial of monitoring and necessary prophy-
lactic treatment for RF patients. Once RF is diagnosed,
denial of treatment will leave the physician liable for
subsequent RF damage from streptococcal infections in
those patients. Although litigation should not be a factor
in treatment, it is a common occurrence within the Uni-
ted States, and physicians should be aware of their re-
sponsibilities and potential liability in these cases.
RF is a misunderstood disease that affects numerous
people around the wo rld. Catastrophic damage associated
with RF damage is easily prevented through adequate
physician monitoring and prophylactic treatment. Be-
cause the morbidity rate for RF has decreased within the
United States, knowledge of RF within the physician
population has waned. As a result, it is likely that fewer
patients are being tested, diagnosed, and treated for RF.
Therefore we predict that the incidence of RF with se-
vere symptomology will increase within the United
States. To prevent this possibility, physicians should be
aware of the disease and the progressive nature of RF
Copyright © 2013 SciRes. OPEN ACCESS
D. C. Peterson / Advances in Bioscience and Biotechnology 4 (2013) 143-146
Copyright © 2013 SciRes.
damage to be able to adequately communicate treatment
options and treat RF patients.
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