Rheumatic fever

Rheumatic fever
Classification and external resources
File:Streptococcus pyogenes 01.jpg Streptococcus pyogenes bacteria Pappenheim's stain
ICD-10	I00.-I02.
ICD-9	390–392
DiseasesDB	11487
MedlinePlus	003940
eMedicine	med/3435 med/2922 emerg/509 ped/2006
MeSH	D012213

Rheumatic fever is an inflammatory disease that occurs following a Group A streptococcal infection, (such as strep throat or scarlet fever). Believed to be caused by antibody cross-reactivity that can involve the heart, joints, skin, and brain, the illness typically develops two to three weeks after a streptococcal infection. Acute rheumatic fever commonly appears in children between the ages of 5 and 15, with only 20% of first-time attacks occurring in adults. The illness is so named because of its similarity in presentation to rheumatism.

Diagnosis

File:Rheumatic heart disease, gross pathology 20G0013 lores.jpg

Rheumatic heart disease at autopsy with characteristic findings (thickened mitral valve, thickened chordae tendineae, hypertrophied left ventricular myocardium).

Modified Jones criteria were first published in 1944 by T. Duckett Jones, MD. They have been periodically revised by the American Heart Association in collaboration with other groups. According to revised Jones criteria, the diagnosis of rheumatic fever can be made when two of the major criteria, or one major criterion plus two minor criteria, are present along with evidence of streptococcal infection. Exceptions are chorea and indolent carditis, each of which by itself can indicate rheumatic fever.

Major criteria

• Migratory polyarthritis: a temporary migrating inflammation of the large joints, usually starting in the legs and migrating upwards.
• Carditis: inflammation of the heart muscle which can manifest as congestive heart failure with shortness of breath, pericarditis with a rub, or a new heart murmur.
• Subcutaneous nodules: painless, firm collections of collagen fibers over bones or tendons. They commonly appear on the back of the wrist, the outside elbow, and the front of the knees.
• Erythema marginatum: a long lasting rash that begins on the trunk or arms as macules and spreads outward to form a snake like ring while clearing in the middle. This rash never starts on the face and it is made worse with heat.
• Sydenham's chorea (St. Vitus' dance): a characteristic series of rapid movements without purpose of the face and arms. This can occur very late in the disease.

Minor criteria

• Fever
• Arthralgia: Joint pain without swelling
• Raised Erythrocyte sedimentation rate or C reactive protein
• Leukocytosis
• ECG showing features of heart block, such as a prolonged PR interval
• Supporting evidence of Streptococcal infection: elevated or rising Antistreptolysin O titre or DNAase..
• Previous episode of rheumatic fever or inactive heart disease

Other signs and symptoms

• Abdominal pain
• Nose bleeds

Pathophysiology

Rheumatic fever is a systemic disease affecting the peri-arteriolar connective tissue and can occur after an untreated Group A Beta hemolytic streptococcal pharyngeal infection. It is believed to be caused by antibody cross-reactivity. This cross-reactivity is a Type II hypersensitivity reaction and is termed molecular mimicry. Usually, self reactive B cells remain anergic in the periphery without T cell co-stimulation. During a Strep. infection, mature antigen presenting cells such as B cells present the bacterial antigen to CD4-T cells which differentiate into helper T₂ cells. Helper T₂ cells subsequently activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints, producing the symptoms of rheumatic fever.

Group A streptococcus pyogenes has a cell wall composed of branched polymers which sometimes contain M protein that are highly antigenic. The antibodies which the immune system generates against the M protein may cross react with cardiac myofiber protein myosin,heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. However, the only proven cross reaction is with perivascular connective tissue. This inflammation occurs through direct attachment of complement and Fc receptor-mediated recruitment of neutrophils and macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Aschoff giant cells. Acute rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these lesions predominantly contain T-helper cells and macrophages.

In acute RF, these lesions can be found in any layer of the heart and is hence called pancarditis. The inflammation may cause a serofibrinous pericardial exudates described as “bread-and-butter” pericarditis, which usually resolves without sequelae. Involvement of the endocardium typically results in fibrinoid necrosis and verrucae formation along the lines of closure of the left-sided heart valves. Warty projections arise from the deposition, while subendothelial lesions may induce irregular thickenings called MacCallum plaques.

Chronic rheumatic heart disease is characterized by repeated inflammation with fibrinous resolution. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion and shortening and thickening of the tendinous cords.

Prevention

Prevention of recurrence is achieved by eradicating the acute infection and prophylaxis with antibiotics. The American Heart Association recommends daily or monthly prophylaxis continue long-term, perhaps for life.

Treatment

The management of acute rheumatic fever is geared toward the reduction of inflammation with anti-inflammatory medications such as aspirin or corticosteroids. Individuals with positive cultures for strep throat should also be treated with antibiotics. Aspirin is the drug of choice and should be given at high doses of 100 mg/kg/day. One should watch for side effects like gastritis and salicylate poisoning. In children and teenagers, the use of aspirin and aspirin-containing products can be associated with Reye's syndrome, a serious and potentially deadly condition. The risks, benefits and alternative treatments must always be considered when administering aspirin and aspirin-containing products in children and teenagers. Ibuprofen for pain and discomfort and corticosteroids for moderate to severe inflammatory reactions manifested by rheumatic fever should be considered in children and teenagers. Steroids are reserved for cases where there is evidence of involvement of heart. The use of steroids may prevent further scarring of tissue and may prevent development of sequelae such as mitral stenosis. Monthly injections of longacting penicillin must be given for a period of five years in patients having one attack of rheumatic fever. If there is evidence of carditis, the length of Penidure therapy may be up to 40 years. Another important cornerstone in treating rheumatic fever includes the continual use of low-dose antibiotics (such as penicillin, sulfadiazine, or erythromycin) to prevent recurrence.

Infection

Patients with positive cultures for Streptococcus pyogenes should be treated with penicillin as long as allergy is not present. This treatment will not alter the course of the acute disease.

The most appropriate treatment stated in the Oxford Handbook of Clinical Medicine for rheumatic fever is benzylpenicillin.

Inflammation

Patients with significant symptoms may require corticosteroids. Salicylates are useful for pain.

Heart failure

Some patients develop significant carditis which manifests as congestive heart failure. This requires the usual treatment for heart failure: diuretics and digoxin. Unlike normal heart failure, rheumatic heart failure responds well to corticosteroids.

Epidemiology

File:Rheumatic heart disease world map - DALY - WHO2004.svg

Disability-adjusted life year for rheumatic heart disease per 100,000 inhabitants in 2004.

     no data      less than 20      20-40      40-60      60-80      80-100      100-120      120-140      140-160      160-180      180-200      200-330      more than 330

Rheumatic fever is common worldwide and responsible for many cases of damaged heart valves. In Western countries, it became fairly rare since the 1960s, probably due to widespread use of antibiotics to treat streptococcus infections. While it is far less common in the United States since the beginning of the 20th century, there have been a few outbreaks since the 1980s. Although the disease seldom occurs, it is serious and has a mortality of 2–5%.

Rheumatic fever primarily affects children between ages 5 and 15 years and occurs approximately 20 days after strep throat. In up to a third of cases, the underlying strep infection may not have caused any symptoms.

The rate of development of rheumatic fever in individuals with untreated strep infection is estimated to be 3%. The incidence of recurrence with a subsequent untreated infection is substantially greater (about 50%). The rate of development is far lower in individuals who have received antibiotic treatment. Persons who have suffered a case of rheumatic fever have a tendency to develop flare-ups with repeated strep infections.

The recurrence of rheumatic fever is relatively common in the absence of maintenance of low dose antibiotics, especially during the first three to five years after the first episode. Heart complications may be long-term and severe, particularly if valves are involved.

Survivors of Rheumatic fever often have to take penicillin to prevent streptococcal infection which could possibly lead to another case of Rheumatic fever that could prove fatal.

External links

• Rheumatic fever information from Seattle Children's Hospital Heart Center
• Jones major criteria, Mnemonic

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