• First described in 1600s by Sydenham.

Epidemiology

  • Group A beta hemolytic Streptococcus (GABHS) is also called Streptococcus pyogenes.
  • Globally, around 15 million people develop rheumatic fever (RF) or rheumatic heart disease (RHD) annually.
  • Only pharyngitis leads to RF.
  • RF is uncommon below age 5 years.
  • RF recurrence is uncommon above age 34 years.
  • 0.3 to 3% of untreated GABHS pharyngitis leads to RF.
  • With past history of RF, 50% of untreated GABHS pharyngitis leads to RF.
  • After RF, MS and post-pubertal chorea are more likely to develop in females.
  • GABHS carrier state (no symptoms or antibodies) will not cause RF.
  • Preceding pharyngitis is reported differently in different studies – from in most cases to in 30% cases only.
  • The decline in incidence of RF began even before the development of penicillin and accelerated with penicillin introduction.

Pathophysiology

  • M-protein
    • Surface molecule on GABHS
    • More than 100 subtypes.
    • Some subtypes make the strains mucoid- these can adhere better to the pharynx and are more rheumatogenic.
    • Antiphagocytic- persist in tissues for upto 2 weeks- leads to antibody production.
  • Rheumatogenic strains produce serum opacity factor while glomerulonephritis producing strains do not.
  • Antibodies-
    • Produced against M protein and N-acetyl glucosamine.
    • Cross-react against
      • Heart valves- laminin
      • Myocardium- myosin and tropomyosin
      • Skin- keratin
      • Synovium- vimentin
      • Subthalamic and caudate nuclei- lysogangliosides.
  • The B cell alloantigen D8/17 predisposes to RF.

Pathology

  • First few weeks- exudative phase
    • Valves-
      • Verrucous vegetations
      • Edematous inflammation with lymphocytes and macrohages.
      • Fibrinoid degeneration of collagen

1 to 6 months- proliferative phase

  • Aschoff bodies-
    • Granulomas
    • Pathognomonic for rheumatic carditis
    • May occur earlier- at 2 weeks
    • May persist chronically without ongoing carditis

Evaluation

Timing

  • Within first month-
    • Carditis
    • Arthritis
    • Erythema marginatum
  • After first month-
    • Subcutaneous nodules
    • Chorea

Jones criteria

  • Introduced in 1944
  • In 1992, the guidelines changed to diagnosis of first attack of RF only.
  • A diagnosis of RF can be made if-
    • Essential + 2 major
    • Essential + 1 major + 2 minor
    • Essential + RHD + 2 minor
    • Chorea
    • Low-grade carditis (insidious onset carditis)
  • Jones and WHO criteria have being criticized as being poorly sensitive.
  • If RF occurs for first time in adulthood-
    • Arthritis dominates, carditis is less common and other manifestations are rare.
    • Jones criteria become less specific.

Carditis

  • 40 to 60 % of RF causes carditis.
  • MR-
    • More common than AR
    • Myocarditis or pericarditis will not occur without valvulitis.
    • Soft, blowing PSM conducted to axilla.
    • S3 does not indicate severe MR as it can occur normally in children.
    • Carey Coombs murmur occurs in severe MR due to flow. Turbulence due to valvulitis also contributes.
    • Severe MR can cause heart failure.
    • Those with severe MR are more likely to get RHD subsequently.
    • Echo is more sensitive but less specific.
    • Echo features suggestive of pathological MR are-
      • Posterior direction
      • Holosystolic flow
      • Significant turbulence
      • Visualization in orthogonal planes
      • Echo shows valve nodularity in 25%.
      • Valvulitis extends into submitral apparatus in a significant percentage.
      • Chordal rupture can occur.
  • AR-
    • Seen only along with MR.
    • A2 is still loud as valve mobility is not affected.
  • Myocarditis-
    • Heart failure is more likely to be due to MR than due to myocarditis.
    • PR interval may be prolonged.
    • If LV function is preserved, troponin is not elevated.
    • RWMA of inferobasal segment may occur.
  • Pericarditis-
    • Rub present.
    • Effusion may occur.
    • Does not cause tamponade or constriction.
  • Subclinical carditis-
    • Can lead to chronic sequelae.
  • Silent carditis-
    • Clinically silent, but echo abnormal.
    • Also called echocarditis.
    • Importance is controversial.
  • Recurrent carditis –
    • RF in a known case of RHD.
    • Also called mimetic carditis.
    • DD is infective endocarditis.

Arthritis

  • Most frequent manifestation- 75%.
  • Earliest manifestation- within 2 to 3 weeks.
  • Only manifestation in one-third to half.
  • Very painful.
  • Each joint is affected for 1 to 2 weeks.
  • Total duration of polyarthritis is 1 month.
  • Usually no chronic sequel. Rarely Jaccoud arthropathy, a non-specific pericarticular fibrosis.
  • Arthritis and carditis are inversely related in severity.
  • Salicylates may cause arthritis to be mono instead of poly.
  • Failure to respond to salicylates goes against RF as the cause of arthritis.
  • Large limb joints are affected.
  • Post streptococcal reactive arthritis
    • Early after pharyngitis
    • ASO is positive.
    • Small joints of upper limbs
    • Less responsive to salicylates
    • Lasts for longer period than RF
    • Other manifestations of RF are absent
    • Patients can develop RHD
    • Secondary prophylaxis is recommended.

Chorea

  • Also called Sydenham chorea
  • Neurological features
    • Spooning with external rotation of hands
    • Fibrillatory tongue movements
    • Absence of chorea with sleep
  • ASO and ESR/CRP will be normal.
  • Incidence is 5 to 35%
  • Presents at 1 to 7 months
  • May last for months or years
  • Recurrence is common.
  • Chance of chronic cardiac squeals is more than 50%.
  • Can cause psychiatric disturbances after decades.
  • Other neurological problems in RF are-
    • Emotional lability
    • Obsessive compulsive behavior
    • Seizures
    • Migraine
  • DD of RF associated neurological disease is PANDAS
    • Pediatric autoimmune neuropsychiatric disorders associated with Streptococcal infections
    • Occurs after Streptococcal infection
    • Not related to RF.

Cutaneous manifestations

  • Erythema marginatum and subcutaneous nodules
  • Both occur in single digit percentages only
  • Subcutaneous nodules appear after many weeks, but resolves within 2 months. Erythema marginatum is an early manifestation, but may last for months or years.
  • Subcutaneous nodules are firm and occur over major joints and bony prominences.
  • Erythema marginatum occurs over trunk and proximal extremities.

Laboratory findings

  • ESR and CRP
    • Parallel disease activity
    • ESR is affected by anemia and heart failure while CRP is not.
  • ECG-
    • Tachycardia due to fever, pericarditis or myocarditis
    • Conduction disturbances
      • In 30%
      • Usually first degree heart block, rarely second or third degree
      • Does not predict chronic sequels
      • Prognostically  unimportant
      • QT prolongation is frequent, TDP is rare
      • Sudden death rarely
  • Demonstration of antecedent Strep infection
    • Methods
      • Throat culture
      • Streptococcal antigen testing
      • Elevated or rising Streptococcal antibodies
    • Throat culture
      • False positive in carriers
      • False negative if antibiotic treatment
    • Streptococcal antigen tests
      • Specific, but low sensitivity
    • Streptococcal antibody tests
      • Rising level is more specific than elevated level
      • Elevated in non-GABHS infections also
      • Anti streptolysin O, anti deoxyribonuclease B, anti hyaluronidase and streptozyme
      • Rises in first month, plateaus for 3 to 6 months and returns to normal within one year.

Treatment

  • General
    • Bed rest is not needed.
    • Anti-inflammatory agents (salicylates and steoids) do not influence the natural history.
  • Eradication of GABHS from the throat
    • Effective antibiotic therapy within 10 days of pharyngitis eliminates the risk of RF.
    • GABHS is always penicillin sensitive.
    • Benzathine Pn is the best as compliance is not an issue.
    • Benzathine Pn 1.2 MU IM once, Penicillin V 500 mg bid for 10 days, amoxicillin 500 mg tds for 10 days, cephalosporins for 10 days or erythromycin for 10 days.
    • For penicillin allergy, erythromycin is recommended.
  • Carditis
    • There is no role for salicylates, except for pericarditis.
    • Treated with steroids, though the utility is contested.
    • If valvular regurgitation leads to heart failure that cannot be medically controlled, valve sugery is needed. There is a higher than normal incidence of failed repair, morbidity and mortality.
  • Arthritis
    • Salicylates are used. NSAIDs are alternatives.
    • Steroids are not given as the DD is infectious arthritis.
    • Aspirin 100 mg/kg/day in four or more divided doses.
    • Therapeutic blood level is 15 to 30 mg/dl.
    • Failure of pain to resolve within 24 hours suggests alternative diagnosis.
    • Monitor for GI side effects and tinnitus.
  • Follow-up
    • Even if RF manifestations are mild, patient needs to be monitored long term for chronic sequels.
    • Benzathine Pn 1.2 MU IM every 4 weeks is the best regimen for secondary prevention of GABHS infection. If the chance of getting reinfected is thought to be high it is better given every 3 weeks.
    • Benzathine Pn is best as compliance is better.
    • Alternatives (oral)-
      • Penicillin V 250 mg bid
      • Erythromycin 250 mg bid
      • Sulfonamides 1 gm daily
    • Duration of prophylaxis-
      • No carditis- 5 years or age 18 (take whichever is longer)
      • Mild or healed carditis- 10 years or age 25 (take whichever is longer)
      • Moderate or severe carditis- Life long