DEFINITION
Acute rheumatic fever is an auto immune disease, triggered by infection with specific strains of Streptococcus pyogenes, i.e. group A Streptococcus (GAS), occurring after a latent period of approximately 3 weeks.
ETIOLOGY
Pharyngitis with Lancefield group A Streptococcus; This causes attack of rheumatic fever 2-3 wk later in >3% of children.
Rheumatogenic strains: M type 1, 3, 5, 6, 14, 18, 19, 27 and 29.
PATHOGENESIS
- Antigenic mimicry explains the pathology.
- Antigens on bacillary cell wall mimics glycoproteins in cardiac tissues. Hence, cross reaction/an autoimmune reaction.
- Auto antibodies also cross react with cardiac myosin and myocardial sarcolemma → myocarditis.
- Antibodies against caudate nucleus → chorea.
Latent period: Period of building up antibody response (3 wk).
Note:
- Only pharyngeal infection, not skin infection initiates rheumatic fever, in majority of cases. All the patients with streptococcal sore throat do not develop Rheumatic fever only 3%. “Individual susceptibility” explains this.
- Virulence of the infection depends on organism's M protein sero type.
- Host factors play a role in risk: a specific B cell alloantigen and certain HLAs: CLass II HLA DR4,DR2 and HLAB5.
- Like any immune reaction recurrences and relapses occur.
HISTOLOGY AND PATHOLOGY
The inflammation causes exudative and proliferative reaction, with-damage to collagen fibers and connective tissue ground substance and 2typical lesion is called fibrinoid degeneration which produces Aschoff's bodies, which are paravascular submiliary granulomas; found mainly in the heart.
Organs Predominantly Affected by Rheumatic Fever
Heart—Pancarditis (Fig. 1.1).
- Extracardiac organs – joints.
- Subcutaneous tissue—nodules.
- Brain – chorea.
- Less frequently – pleura–pleural effusion.
Rheumatic Endocarditis
- Heals with fibrous thickening – adhesion of valve cusps
- Commonest valve involved – mitral valve:
- Next aortic (AI then AS)
- Last tricuspid;
- Pulmonary by 15th year of age.
Joints
Exudative/proliferative lesion; Capsule and synovium affected.
Healing occurs without much scarring so, no residual deformity.
Subcutaneous Nodules
Aggregates of Aschoff's nodules with predominant fibroblasts.
Brain
Non-specific lesions in cerebral cortex, cerebellum and basal ganglion.
DIAGNOSIS
Mainly clinical and is based on revised Jones criteria:
- Evidence of preceding streptococcal infection (GAS) (is required for revised criteria) with
- Two major criteria or
- One major and two minor criteria
- In India skin lesions and rheumatic nodules are rare.
- Cannot be used to define diagnosis with absolute certainty; only a guide to determine high risk group.
JONE'S CRITERIA
Major | Minor | In addition |
|---|---|---|
Carditis | Fever | Supporting evidence of preceding streptococcal infection: (A) Positive throat swab culture. (B) Raised ASO titer (C) rise in other streptococcal antibody titer. |
Polyarthritis | Arthralgia | |
Chorea | Rising ASO titer | |
Erythema marginatum | Raised ESR/CRP | |
Subcutaneous nodules | H/o preceding streptococcal sorethroat | |
Long PR interval | ||
Abdominal pain, Epistaxis due to serositis. | Note: Evidence of recent strepto infection is important if there is only one major criteria. |
CLINICAL FEATURES
Classical rheumatic fever appears as acute migrating polyarthritis with signs and symptoms of febrile illness. This might be variably associated with other major manifestations.4
History of antecedent streptococcal infection is often elicitable.
Revised criteria give importance to diagnosis of ‘initial'attack of streptococcal infection.
Incidence
Usually affects children and young adults
Most common age-between 5-15 years
Rare under age of 5 and initial attacks are rare after 20 years
If not prevented 3 or more attacks recur by 20 years
Incidence is declining in western countries though it is quite prevalent in India and in other developing countries.
Epidemiology
Over crowding, dampness and poor socioeconomic conditions predispose.
Clinically carditis and arthritis are only common.
Rheumatic Polyarthritis
- Acute painful inflammation of multiple large joints
- Exudative then proliferative
- Characteristically migrating or flitting and fleeting
- Clinically shows pain, tenderness, redness and sometimes effusion
- Joints affected are—of limbs (Rarely of spine, temperomandibular joint, costoclavicular joint)
- Order of frequency—knee, ankle, elbow, wrist (hip and small joints rare)
- No X-ray changes appear even in prolonged arthritis
- Does not assume chronic form
- Uncommon variant can occur
- Differential: Migrating arthralgia of Systemic Lupus Erythematosis.
Acute Rheumatic Carditis
It is the most important manifestation of rheumatic fever.
Earliest evidence: Tachycardia disproportionate to degree of fever; CHF in severe cases.
Valvular involvement: Occurs in 50% of cases with rheumatic fever
- First evidence is a soft apical systolic murmur due to edema of the valves and or a soft pericardial rub.
- If disease regresses (murmur) disappears completely
- Mild pericardial effusion —may occur; no constriction/tamponade
- In fulminant forms — severe aortic and mitral incompetence -severe CHF.
Frequency of Valvular Involvement
Mitral valve is most frequently involved 80%– either alone or with aortic and tricuspid.
Aortic valve next 30% – usually with mitral or alone.
Mitral involvement, perhaps due to greater pressure on left side.
Next – tricuspid but never alone.
Initially edema of cusps occur (Soft murmur). In later course fusion of cusps, destruction, rupture of chordae take place.
Majority of patients with acute carditis do not have symptoms referable to the heart. Rheumatic carditis, unless very severe is often missed. So patients in later years are diagnosed to have rheumatic carditis without a definite H/o rheumatic fever.
Involvement of myocardium: Clinicaly manifests with tachycardia, cardiac enlargement, and in ECG as T wave inversion and prolonged PR interval.
Involvement of pericardium: Pericarditis—serofibrinous pericarditis – clinically pericardial rub – pericardial effusion has grave prognosis, myocarditis or pericarditis without valvular involvement is unlikely to be rheumatic fever.
Conduction tissue involvement – arrhythmias and syncope.
Subcutaneous nodules:
- Significance: It is presence indicates acute activity of rheumatic fever
- Description: Small, painless, >pea size, transient swellings – skin over them moves freely; appear in crops and disappear; occur in conjunction with carditis, last for 1-2 weeks
- Location: Extensor tendons of hands and feet, elbow, wrist, ankle, margins of patellae, over ulnar border of forearm, scalp posterior occipital line, over scapulae, spines of vertebrae
- Number: Vary from 1 to 200, rare; <5%of cases
- Age common in children than in adults.
Rheumatic chorea or Sydenham's chorea (Chorea minor, St. Vitus dance)
- This is a delayed manifestation of rheumatic fever
- Other manifestations may or may not be present with it; may be the 1st
- Commoner in females
- Clinically manifests as – quasi purposive, non-repetitive, sudden jerky involuntary movements involving the extremities –uni/bilateral
- Often accompanied by muscle weakness, emotional instability
- Exaggerated by excitement, effort, fatigue
- Subsides during sleep
- Can also be associated with movements of lips, and facial grimacing
- Insidious in onset and manifests in early stage with fidgetiness and clumsiness
- Tongue movements are specially characteristic— “ jack in the box tongue” or “lizard tongue”—suddenly protruded and suddenly shot back into the mouth with lightening speed
- Associated muscle weakness and hypotonia bring about certain signs. Pronator sign — on putting arms up – forearm is pronated with flexion at the wrist hyperextension at MP joints.Milk maid's grip – grip is waxing and waning – due to inability to maintain tonic contraction.
Types of Chorea
- Chorea mollis chorea associated with severe hypotonia simulating paralysis
- Pure chorea – when no previous rheumatic manifestations are noted.
- Chorea gravidorum: Rheumatic chorea precipitated during pregnancy- common in primi; does not require termination of pregnancy.
Skin Rashes in Rheumatic Fever
Erythema Marginatum
- Incidence: Occurs in 10 to 20% of children with rheumatic fever Morphology of lesion: have pale center, red serpiginious margins, painless, evanescent Blanches on pressure
- Location: Prominent parts of limbs and trunk never on face
- Spread: Concentrically
Brought on by application of heat or warm bath
Significance–does not indicate rheumatic activity but characteristic of rheumatic fever.
Erythema Nodosum
Dusky red raised papules, over shin of tibia; less specific and less commoner than erythema marginatum.7
Minor Manifestations of Rheumatic Fever
- Fever, tachycardia
- Abdominal pain
- Pleurisy
- Rheumatic pneumonitis (rare)
- Arthralgia
- Epistaxis
- Pleural effusion
- Long PR interval
The Natural Course of the Disease
(1) Highly variable (2) in majority acute lesions subside within 6 weeks (3) in 5% persists beyond 6 weeks (4) valve lesion may heal completely (5) or may remain stationary (6) or may undergo progressive thickening with calcification especially in later life (7) if untreated the disease may recur (8) with each recurrence more and more damage to the heart takes place (9) severe carditis is associated with cardiac failure.
Differential Diagnosis
- Acute juvenile rheumatoid arthritis –Still's disease.
- Joint deformities can occur in rheumatoid.
- Infective endocarditis.
- Serum sickness.
- Drug hypersensitivity.
- Viral illness causing pericarditis.
Infective endocarditis: Sudden onset, high fever, rigors H/o pre-existing heart disease and Clubbing.
Rheumatoid arthritis: Peripheral joints involved, persistant synovitis, thick synovium, Joint deformities can occur.
Serum sickness: 1-3 weeks after injection of serum, fever, arthralgia, lymphadenopathy, rash.
Viral myocarditis: 2 weeks after viral fever, fatigue, palpitation, CHF.
SLE: Women of child bearing age, multiple organs involved, butterfly rash, ANA factors.
INVESTIGATIONS
- Evidence of systemic illness.
- Evidence of preceding streptococcal infection.
- Evidence of carditis.
Evidence of Systemic Illness
Evidence of Preceding Streptococcal Infection
- Positive culture from throat swab for GrA Streptococcus. But by the time rheumatic fever becomes manifest it is only occasionally positive-11%.
- Positive test does not differentiate recent infection and chronic carrier.
- Rapid antigen test-useful for screening but culture is more definite.
- Antibody test; done when culture and antigen tests are negative. Raised ASO titer - especially raising titer is of value- levels >200 or 300 Tods unit in children is diagnostic.ASO titer can be normal in adults and rheumatic chorea.Note: Isolated +ve ASO titer can be found in children without acute rheumatic fever and in rheumatoid arthritis and Takayasu arteritis.
- Other antibodies –anti-deoxyribo nucleus antibody >120 todd units, antihyaluronidase >1:256. (false +ves occur)In 95% raised titer of at least one of these antibodies indicates strepto infection.
- Acute phase reactants-creative protein +ve, ESR raised.
Evidence of Carditis
- X-ray chest-cardiac enlargement, pulmonary congestion
- ECG: I and II degree AV block, T↓ reduction in QRS voltage, features of pericarditis
- Echo: Valve abnormality and cardiac dilatation;very early change –stretching of anterior mitral chordae.
MANAGEMENT
- Bed rest
- Drug therapy.
It is important to establish diagnosis; may mean waiting until arthritis/carditis is definite.
Bed Rest
(1) During acute phase of rheumatic fever. (2) Until ESR and temperature comes to normal. (3) In patients with carditis further 2-6 weeks rest.
Drug Therapy
Note: Drugs do not shorten the duration of attack but suppress the inflammation and minimize the damage.
Drug therapy consists of: (a) Aspirin, (b) steroids, (c) antibiotics
- Salicylates - Aspirin (acetyl salicylic acid).Start with 60-100 mg/kg/day in divided doses (4 or 5 divided doses in children).In adults upto120 mg/kg/day- maximum 8 gm/day.
- Toxic effects: Nausea, tinnitus, deafness, vomiting, hyperventilation, acidosis.
- Duration: Approximately for a month/ (upto 3 mths in some) or until ESR is normal. But after 2 weeks dose is reduced to 60 mg/kg/day for remaining 4 weeks.Rarely a “rebound” of inflammatory activity can occur after stopping aspirin and may require aspirin again.NSAIDs have not been adequately assessed, may help only those allergic or intolerant to aspirin.Intravenous immunoglobulins – have been shown to be ineffective.
Corticosteroids: Cortisone/ACTH/prednisone
Indications for Steroids
Severe carditis
Severe arthritis
As additive to aspirin, if aspirin alone is not effective.
STEROIDS
Dose: Oral prednisolone 1-2 mg/kg/day in divided doses until ESR is normal.
Patients with severe carditis appear to respond more promptly to steroids.
In severe cases 2-3 months of steroid therapy may be needed.
Some authors advise IV methyl prednisolone in extreme cases.
For chorea
- Diazepam/haloperidol; neither salicylates nor steroids help.
- And penicillin prophylaxis even if it is isolated chorea.
- Haloperidol dose 0.5-2 mg bid/tds-PO.
Anti-streptococcal therapy
- Clearance of streptococcal infection and prevention is a must. For this penicillin is used
Even if throat swab culture result is negative.
- There after secondary prophylaxis should commence.
- Supportive therapy–treatment of CCF; tmt for valve damage; tmt of heart block with drugs –pacemaker not required.
- Most cases settle within 4-6 weeks; occasional case; longer course.
Effectiveness of drug therapy: No evidence that anti-inflammatory therapy reduces incidence of subsequent valvular disease.10
PREVENTION OF RHEUMATIC HEART DISEASE
Primary prevention: Prompt treatment of the initial attack.
Secondary prevention: Prevention of recurrent attacks.
Primary Prevention (During the Course of Acute Rheumatic Fever)
- Depends on prompt recognition of GAS pharyngitis and its effective treatment.
- To be treated earliest–longest within 9 days.
- Drug of choice penicillin–oral penicillin V for 10 days.
- If compliance is likely to be poor –IM benzathine penicillin G administered (but risk of allergy and pain)-dose 1.2 million unit IM-single dose.
- Dose: In children penicillin V-250 mg bid or tds 10 days.In adults penicillin V-500 mg bid or tds 10 days.
- In patients allergic to penicillin–erythromycin estolate dose 20-40 mg/kg/day –for 10 days in 2-4 divided doses.
- Erythromycin estolate is shown superior to erythromycin ethylsuccinate, or
- Azithromycin 500 mg-orally on day 1 and 250 mg oral once a day for 4 days there after.Appropriate antibiotic therapy results in clinical response within 2 days.
- If symptoms are persistent or recurrent, then only repeat throat swab culture is advised.
- If culture is positive 2nd course antibiotic preferably with another agent indicated.– namely–amoxycillin clavulanate, cephalosporin, clindamycin or penicillin and rifampicin.
- Failure of irradication occurs more commonly with oral penicillin than benzathin G.
- Treatment for asymptamatic carriers is indicated if there is previous H/o rheumatic fever.
Secondary Prevention
- Why? To prevent recurrent attacks which increase cardiac damage.
- Consists of continuous antibiotic therapy.
- Even optimal treatment of GAS does not preclude recurrence.
- GAS which triggers a recurrence of rheumatic fever need not be symptomatic.
- In whom? Following primary prevention, in patients who have suffered proven rheumatic fever, Sydeham's chorea, or carditis -long term prophylaxis is recommended.
- The duration of prophylaxis is individualized taking into account the socioeconomic condition and the risk of exposure to GAS.
- In those who have suffered carditis with or without valvular disease,-prophylaxis is for life.
- In those who have not suffered carditis prophylaxis until 21 years of age or 5 years after the last attack.
- The choice of prophylactic agent –benzathine penicillin G –IM –pain can be overcome by using lidocain as a diluent. This assures compliance over many years/not oral penicillin.
- Dose: 1.2 million units every 3 weeks given intra muscular.
- 3 weekly dosage has been found superior to 4 weekly dose in clinical trials.
- Even when compliance is optimal oral prophylaxis has been shown to be inferior.
- Patients on warfarin for atrial fibrillation/on prosthetic valve will be running a risk of hematoma if intramuscular penicillin is given. This situation may necessitate oral prophylactic regimen (penicillinV 250 mg × 2/day) for adults and children.