Rheumatic fever is an inflammatory disease that occurs as a delayed reaction to a Group A streptococcal throat infection. It most commonly affects children between 5-18 years old. The main manifestations include arthritis, carditis, chorea, and less commonly subcutaneous nodules and erythema marginatum. It is diagnosed using the revised Jones criteria which requires evidence of a preceding streptococcal infection and either two major manifestations or one major and two minor manifestations. Treatment involves primary prevention through antibiotic treatment of streptococcal infections, anti-inflammatory treatment such as aspirin for arthritis and steroids for carditis, supportive management of complications, and long-term secondary prevention through antibiotic prophylaxis.
2. INTRODUCTION
Rheumatic fever is an immunologically mediated inflammatory disease, that occurs as a delayed
sequel to group A streptococcal throat infection, in genetically susceptible individuals.
Chronic rheumatic heart disease remains an important public health problem in developing
countries.
In developing areas, the prevalence is about 24 per 1000.
Rheumatic fever occurs most frequently among children and adolescents between 5 and 18
years, coinciding with the age distribution of the highest prevalence of streptococcal infections.
Risk Factors: Poverty, overcrowded living conditions.
3. PATHOGENESIS
After GAS infection of the pharynx, neutrophils, macrophages and dendritic cells
phagocytose bacteria and present antigen to T cells.
Both B and T cells respond to the GAS infection, initially by antibody production (IgM and
IgG) and subsequently through T cell activation (mainly CD4+ cells).
In susceptible individuals, the host response against GAS will trigger autoimmune reactions
against host - a process called molecular mimicry.
Molecular mimicry is the sharing of antibody or T cell epitopes between the host and the
microorganism.
In the case of ARF, these host antigens are located in tissues such as the heart and the brain.
6. CLINICAL MANIFESTATIONS
There is a latent period of ~3 weeks (1-5 weeks) between the precipitating
group A streptococcal infection and the appearance of the clinical features
of ARF.
Common Clinical Features:
Arthritis (present in 60-80% of cases)
Carditis (50-60%)
Chorea (<2- 30%)
Erythema marginatum and subcutaneous nodules (<5% of cases)
7. ARTHRITIS
Most common manifestation.
It usually affects the peripheral large joints; knees, ankles, elbows and wrists are
the most frequently affected.
In addition to arthralgia, the joints are red, warm and swollen.
Arthritis is characteristically asymmetrical, migratory, and very painful, although
some patients may present mild joint complaints.
It usually resolves spontaneously at the most in 2 or 3 weeks.
Arthritis in ARF has an excellent response to salicylates
8. CARDITIS
It is a pancarditis, but valvular involvement is the rule.
The commonest involved valve is the mitral, frequently associated with aortic valve involvement.
On pathological examination, the valves are thickened and display rows of small vegetations
(Aschoff body) along their apposing surfaces.
The clinical picture includes high pulse rate, congestive heart failure, arrhytmias and pericardial
friction rubs.
Murmurs:
Valvulitis – low pitched mid diastolic murmur at apex (Carey Coombs)
Mitral regurgitation – mid frequency pansystolic murmur
Aortic regurgitation – high pitched decrescendo diastolic murmur.
Cardiomegaly on CXR and Echocardiogram.
10. SYDENHAM‘S CHOREA
Characterized by involuntary movements, specially of the face and limbs, muscle weakness,
disturbances of speech and gait.
Children usually exhibit concomitant psycologic dysfunction, especially obsessive-compulsive
disorder, increased emotional lability, hyperactivity, irritablility and age-regressed behaviour.
It is usually a delayed manifestation, and is often the sole manifestation of ARF.
However, chorea may occur in association with other major manifestations of RF, particularly
in the first attack.
Most of the patients experience resolution of the symptomatology after a few months.
11. SUBCUTANEOUS NODULES
Subcutaneous nodules are rarely seen
and when present, they are usually
associated with severe carditis.
They are painless, firm, movable,
measuring around 0.5 to 2 cm.
They are usually located over extensor
surfaces of the joints, particularly
knees, wrists and elbows.
12. ERYTHEMA MARGINATUM
This is an evanescent,
erythematous, non-pruritic rash
with pale centers and rounded or
serpiginous margins.
Lesions occur mainly on the trunk
and proximal extremities and may
be induced by application of heat
13. DIAGNOSIS
With the exception of Sydenham's chorea, which has a latency period of
several months, the clinical manifestations of acute RF present after about
3 weeks following the streptococcal throat infection.
It usually begins with nonspecific symptoms, such as fever, malaise and
persistent pallor.
Diagnosis is based on the revised Jones Criteria.
Arthritis, carditis, chorea, and less frequently, subcutaneous nodules and
erythema marginatum are major manifestations of RF.
14. REVISED JONES CRITERIA
If supported by evidence of preceding streptococcal infection, the presence of two major
manifestations or one major and two minor manifestations indicates a high probability of
acute RF
16. LABORATORY STUDIES
Acute phase reactants are useful in helping to recognize acute RF and also to exclude
other diseases.
C-reactive protein and erythrocyte sedimentation rates are helpful in monitoring
inflammatory activity.
Laboratory evidence of a preceding GAS infection should be sought, either by
demonstration of GAS in the throat by culture or rapid streptoccocal antigen test, or using
streptococcal antibody tests.
Elevated or rising titers of antistreptolysin O (ASO) occur in more than 80% of patients
with acute GAS pharyngitis.
Prolonged P-R interval relative to heart rate is a nonspecific finding.
Cardiac scanning scintigraphy has been shown to be a reliable method distinguishing
acute from chronic, inactive RHD and also in the follow-up of active carditis
20. STEP II: Anti Inflammatory Treatment
Arthritis
NSAIDS - Aspirin
75- 100mg/kg/day, QID for 6 weeks
Attain blood level 20-30mg/dL
Carditis
Corticosteroids – Prednisolone
2- 2.5mg/kg/day, BID for 2 weeks
Taper over 2 weeks, add aspirin 75mg/kg/day for 2 weeks
Continue aspirin alone 100mg/kg/day for another 4 weeks.
21. STEP III: Supportive Management
Bed rest
Treatment of congestive cardiac failure - digitalis, diuretics and vasodilators.
Treatment of chorea
Carbamazepine has also been suggested as a first-line treatment for Sydenham's
chorea.
haloperidol (initial dose of 0.5 to 1mg/kg/day, maximum, 5mg/day)
valproic acid (15-20 mg/kg/day)
Rest to joints & supportive splinting
23. PROPHYLAXIS
WHO GUIDELINES
At least 5 years of prophylaxis or if child until age 18 if not cardiac
involvement.
10 years prophylaxis or if child until age 25 if has mild mitral regurgitation.
Lifelong prophylaxis if has severe valve disease.
24. PROGNOSIS
Rheumatic fever can recur whenever the individual experience new GAS
infection, if not on prophylactic medicines.
Good prognosis for older age group & if no carditis during the initial
attack.
Bad prognosis for younger children & those with carditis with valvar
lesions.
25. REFERENCE
Stollerman GH. Rheumatic fever. Lancet. 1997;349:935–942. [PubMed]
Pomerance A. Cardiac involvement in rheumatic and ‘collagen’ diseases. In: Pomerance A, Davies MJ,
editors. The pathology of the heart. Oxford: Blackwell Scientific Publications; 1975. pp. 279–306.
Denny FW, Wannamaker LW, Brink WR, Rammelkamp CH, Jr, Custer E. A Prevention of rheumatic fever;
treatment of the preceding streptococcic infection. J Am Med Assoc. 1950;143:151–153. [PubMed]
Carapetis JR. The stark reality of rheumatic heart disease. Eur Heart J. 2015;36:1070–1073. [PubMed]
Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds.Harrison's Principles of Internal Medicine,
18e. New York, NY: McGraw-Hill; 2012.