“Acute Rheumatic Fever” by Emmanuel Rusingiza, MD, for OPENPediatrics

“Acute Rheumatic Fever” by Emmanuel Rusingiza, MD, for OPENPediatrics


Acute Rheumatic Fever, by Dr. Emmanuel Rusingiza. My name is Emmanuel Rusingiza. I am a Pediatric
Cardiologist at Kigali University Teaching Hospital. This morning I’m going to talk about
the diagnosis and management or acute rheumatic fever. As outlined, we will go through the
definition and overview of acute rheumatic fever, the epidemiology, pathophysiology,
diagnosis, investigations, differential diagnosis, and management. Overview. Acute rheumatic fever is defined as a delayed
autoimmune response to an untreated Group A streptococcal infection, mainly affecting
the throat. Acute rheumatic fever may involve the heart, the joints, the central nervous
system, and/or the skin. The signs and symptoms may include any or all of the following: arthritis,
fever, carditis, rash, Sydenham’s chorea, and subcutaneous nodules. Group A streptococcal throat infections occur
in children throughout the world, with peak ages between 5 and 15 years. The number of
children affected in each region varies depending on environmental conditions, level of poverty,
quality and availability of health care. Over the past century, acute rheumatic fever and
rheumatic heart disease have become rare in developed countries as living conditions have
become more hygienic and less crowded with improved nutrition and access to appropriate
medical care. Repeated Group A streptococcal infections
and recurrent acute rheumatic fever can lead to chronic heart valve damage that is called
rheumatic heart disease. Rheumatic heart disease requires expensive heart valve surgery. If
damaged heart valves are not repaired or replaced by major open heart surgery, the condition
is often fatal. Epidemiology. It is estimated that about 15.6
million people are affected world-wide, and among them, 2.4 million are children between
5 and 14 years old in developing countries. Acute rheumatic fever and rheumatic heart
disease are the disease of poverty but they are indicated in industrialized countries
since 20th century, as thought previously. The following factors increase the risk of
developing acute rheumatic fever: overcrowding and poor standards of housing, reduced access
to health care, and living in tropical climates. Acute rheumatic fever is most common in children
between the ages of 5 and 15 years. It is less common after the age of 35 years and
is rare under 4 years and over 40 years of age. Pathophysiology. As pathophysiology, not everyone
is susceptible to acute rheumatic fever, and not all Group A streptococcus strains are
capable of causing acute rheumatic fever in a susceptible host. It is likely that 3-5%
of people in any population have an inherent susceptibility to acute rheumatic fever, although
the basis of susceptibility is unknown. Some strains of Group A streptococcus are called
rheumatogenic, particularly streptococcal M-protein, although the basis of rheumatogenicity
is also unknown. This is a picture of a patient who presents
tonsillopharynx infection by Group A streptococcus. It shows severely inflamed tonsils with presence
of pus. And the culture has revealed Group A streptococcus. So acute rheumatic fever
is sequela of untreated or inadequately treated Group A streptococcus infection of the tonsillopharynx. Studies have concluded that there is a molecular
mimicry between Group A streptococcus antigens and human host tissue that is believed to
be the basis of pathogen host cross-reactivity, best documented with cardiac proteins such
as myosin, laminin, and vimentin. Point of clarification. In acute rheumatic
fever, the patient’s immune system produces antibodies against the M-protein of the Group
A streptococcus bacterium. These antibodies appropriately bind to the antigen on the surface
of the bacteria to eradicate the primary infection. But occasionally, these same antibodies cross-react
with the patient’s own cardiac proteins, given the structural similarities between those
proteins and the end protein of Group A strep. This molecular mimicry is believed to be the
basis for cardiac pathology related to acute rheumatic fever and rheumatic heart disease. The patient’s immune response is initiated
after initial exposure to the bacteria. However, there is a latency period of about three weeks
before the patient develops symptoms of acute rheumatic fever. This is due to the lag between
initial antibody production and the cross-reactivity of these antibodies with the patient’s own
tissue proteins. At the time of development of acute rheumatic fever symptoms, the host
immune system has eradicated the initial Group A strep infection. The progression of the disease is done as
following. It starts initially by a Group A streptococcus throat infection which, due
to a certain number or factors, leads to acute rheumatic fever. And during repetitive episodes
of Group A streptococcus infection in the future, it causes recurrent acute rheumatic
fever. That leads to rheumatic heart disease with all its complications. Diagnosis. The diagnosis of acute rheumatic
fever remains a clinical decision. It’s the original specific laboratory test. It is known
that overdiagnosis of acute rheumatic fever will lead to unnecessary treatment over a
long time, while underdiagnosis leads to further attacks of acute rheumatic fever, cardiac
damage, and premature death. The diagnosis of acute rheumatic fever is
usually guided by Jones criteria developed in 1944 and adopted most recently by the World
Health Organization. The Jones criteria include major criteria and minor manifestations, plus
evidence of preceding group A streptococcus infection. This table summarizes the Jones criteria.
And the first column shows the major manifestations that include, arthritis, carditis, subcutaneous
nodules, erythema marginatum, and Sydenham’s chorea. The column in the middle shows minor
manifestations, which are fever, arthralgia, prolonged PR interval on ECG, and raised ECR
or CRP. The evidence of recent group A streptococcus
infection include the positive culture of the throat swab, the raised anti-streptolysin
O titer, and the raised anti-DNase B. Arthritis is the common symptom, and it is characterized
by pain, redness, and swelling in the joints. And it affects commonly the big joints, like
the ankles, the knees, the wrists, the elbow, and less commonly the small joints. It is
often the first complaint, and arthritis is usually migratory, disappearing in one joint
as it begins in another. The carditis, which is defined as an inflammation
of the heart, is commonly present as a heart murmur. Chest pain and/or difficulty breathing
may be present in severe cases. Less commonly, people with acute rheumatic fever present
with subcutaneous nodules and erythema marginatum with specific characteristics. Subcutaneous nodules are painless lumps seen
on the outside surfaces of major joints. They are often present for about one to two weeks
duration, and are more commonly present when the patient also has evidence of carditits.
Erythema marginatum starts out as painless, flat, pink patches on the skin that spread
outward in a circular pattern. This is often an early symptom of acute rheumatic fever
and often spares the face. This rash may be present for months after the onset of acute
rheumatic fever. Sydenham’s chorea is a twitching, jerking
movements and muscle weakness most obvious in the face, hands, and feet. It is more common
in teenagers and females. It may begin up to three to four months after the streptococcal
infection. It may appear on both sides or only one side of the body, and often appears
without other symptoms. Point of clarification. The mean duration
of chorea is documented in the literature as 12-15 weeks, but please note that some
episodes may persist for as long as 6-12 months. The fever is defined as a core temperature
greater than 38 degrees, and it can go up to high values. The evidence of group A streptococcus
infection is required to confirm a case of acute rheumatic fever with the above signs
and symptoms. Group A streptococcus may not be found on a throat swab, since the infection
may be resolved at the time of onset of acute rheumatic fever symptoms. Serum anti-streptolysin O titer reaches the
peak level around three to six weeks after infection and starts to fall at six to eight
weeks. Serum anti-DNase B reaches a peak level up to six to eight weeks after infection,
and starts to fall at around three months after the infection. The first episode of acute rheumatic fever
can be confirmed if there are two major criteria, or one major criteria and two minor manifestations
plus an evidence of preceding group A streptococcus infection. Recurrent acute rheumatic fever
without rheumatic heart disease can be confirmed as the previous first episode. The recurrent
acute rheumatic fever with existing rheumatic heart disease can be confirmed if there are
two minor manifestations, plus evidence of preceding group A streptococcus infection. However, different regions have slightly modified
guidelines to assist clinicians with local variations in acute rheumatic fever presentation.
In this regard, the involvement of only one joint, also called monoarthritis, polyarthralgia
in children who are at high risk of acute rheumatic fever, and subclinical carditis
proved by echocardiogram have been proposed to be among the major criteria. The differential diagnosis is made with septic
arthritis, connective tissue, valvular arthropathy, sickle cell anemia, mitral valve prolapse,
infective endocarditis, and many other diseases which present the similar clinical manifestations
like acute rheumatic fever. Investigations. The investigations should
be FBC, ESR, CRP, blood cultures if febrile– especially for the differential diagnosis
with infective endocarditis– the immunologic markers of group A streptococcus infection,
which are ASO and anti-DNase B, throat swab, EKG, chest x-ray– if there is an evidence
of colitis– and echocardiogram. This echocardiography image shows a severely
damaged mitral valve which is thickened. Look at the posterior leaflet which is also retracted.
And during systole, there is a very bad coaptation of the mitral leaflets that results in massive
mitral regurgitaiton and dilation of the left atrium. This patient was admitted for severe
heart failure due to rheumatic heart disease. Management. The treatment of the acute illness
includes benzathine penicillin G, single injection, or oral penicillin for 10 days. And in case
of allergy, erythromycin is indicated. Relief of symptoms and signs with non-steroid anti-inflammatory
drugs, especially aspirin or corticosteroids. Carbamazepine and valproic acid can be given
for severe cases of Sydenham’s chorea. The management of acute rheumatic fever should
be based on the following principles: admission for acute diagnosis, receive clinical care,
and education about preventing further episodes of acute rheumatic fever. Initial echocardiogram
is very important to identify and measure the heart valve damage. Long-term preventive
management should be organized before this discharge. The long term management includes regular
secondary prophylaxis, regular medical review, regular dental review, echocardiogram following
each episode of acute rheumatic fever, and routine echocardiogram. Secondary prophylaxis
should be done by benzathine penicillin G IM every three to four weeks. And the standard
dose is 1.2 million units for patients who weigh 30 kgs or greater. And the half dose
of 600,000 units for patients who are under 30 kgs. Penicillin V can be used if benzathine penicillin injections
are not tolerated or injections are contraindicated. The standard dose is one tab of 250 milligrams
oral, twice daily. Here, I would like to insist on the necessity to give the injectable form
of penicillin because it has shown better results compared to the oral form of penicillin.
Erythromycin is given if there is proven allergy to penicillin. The standard dose is 250 milligrams
oral twice daily. The duration of secondary prophylaxis should be done as following. When acute rheumatic fever is identified without
proven carditis, the minimum duration should be five years after the last episode of acute
rheumatic fever, or until 18 years. For the mild to moderate forms of rheumatic heart
disease, the minimum duration should be 10 years after the last acute rheumatic fever
or until the age of 25 years. For severe rheumatic heart disease and following cardiac surgery
for rheumatic heart disease, patients should continue medication for life. Thank you for watching. Please help us improve the content by providing
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