• Clinical science

Rheumatic fever

Abstract

Rheumatic fever is an inflammatory sequela involving the heart, joints, skin, and central nervous system (CNS) that occurs two to four weeks after an untreated infection with group A streptococcus (GAS). The pathogenic mechanisms that cause rheumatic fever are not completely understood, but molecular mimicry between streptococcal M protein and human cardiac myosin proteins is thought to play a role. Because of the structural similarities between the two proteins, antibodies and T cells activated to respond to streptococcal proteins also react with the human proteins, causing tissue injury and inflammation. In addition to nonspecific symptoms (e.g., fever, malaise, and fatigue), patients present with symptoms involving the heart (pancarditis), joints (migratory polyarthritis), skin (subcutaneous nodules, erythema marginatum), and/or CNS (Sydenham's chorea). The diagnosis of acute rheumatic fever is primarily a clinical one, and is based on the Jones criteria. Diagnostic evaluation in acute rheumatic fever typically shows elevated inflammatory markers, positive antistreptococcal antibodies, and valvular damage on echocardiogram. The first-line treatment is penicillin, and is combined with symptomatic anti-inflammatory treatment, typically with salicylates or glucocorticoids (if salicylates are not effective). Acute rheumatic fever may be complicated by progressive, permanent damage to the heart valves (especially the mitral valve), resulting in chronic rheumatic heart disease. Preventing the cardiac complications of rheumatic fever is the goal of both primary prophylaxis (i.e., antibiotic therapy for GAS pharyngitis) and secondary prophylaxis (antibiotic administration following an episode of acute rheumatic fever.

Definition

  • Delayed inflammatory complication of group A β-hemolytic streptococcal (GAS) pharyngitis that usually occurs within 2–4 weeks of acute infection
  • Rheumatic heart disease refers to two clinical entities:
    • Acute pancarditis as a sequela of GAS infection
    • Chronic cardiac valvular changes as a complication of acute rheumatic fever

References:[1]

Epidemiology

  • Peak incidence: 5–15 years
  • Prevalence
    • Developing countries: the most common cause of cardiovascular disease in children and adolescents
    • Developed countries: rare

References:[2][3][4]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[3][5][6][7][8]

Clinical features

The symptoms of acute rheumatic fever can be remembered with the JONES criteria, written with a heart-shaped O (see also “Diagnostics” above): J = Joints, ♥ = Pancarditis, N = Nodules, E = Erythema marginatum, S = Sydenham chorea

  • Constitutional symptoms: fever, malaise, fatigue
  • Joints: (∼ 75% of cases): migratory polyarthritis
  • Heart (30–60% of cases)
  • CNS (up to 25% of cases)
    • Sydenham chorea
      • Occurs 1–8 months after the inciting infection
      • Involuntary, irregular, nonrepetitive movements of the limbs, neck, head, and/or face, sometimes asymmetrical or confined to one side (hemichorea)
      • Additional motor symptoms (e.g., ballismus, muscle weakness) and speech disorders (slurred or “jerky” speech)
      • Neuropsychiatric symptoms (e.g., inappropriate laughing/crying, agitation, anxiety, apathy, obsessive-compulsive behavior)
      • Epidemiology
      • Pathophysiology: Streptococcal antigens lead to antibody production → antibodies cross-react with structures of the basal ganglia; (particularly the striatum) and cortical structures → reversible dysfunction of cortical and striatal circuits
      • Diagnosis: usually based on the clinical picture (specific evidence of GAS infection is not always present)
      • Treatment
      • Prognosis:
        • Usually self-limiting
        • If treated, full remission usually occurs within 3–4 months.
        • Recurrences in up to 30% of patients
  • Skin (∼ 10% of cases)
    • Subcutaneous nodules
    • Erythema marginatum
      • Centrifugally expanding pink or light red rash; with a well-defined outer border (erythema marginatum → marginated rash) and central clearing.
      • Location: The trunk and limbs are affected; the face is spared. May rapidly appear and disappear at different locations.
      • Painless and nonpruritic

Rheumatic heart disease tends to involve the high-pressure valves, i.e., the mitral and aortic valves!

References:[9][10][1][4][11][12][13]

Diagnostics

Diagnosis of acute rheumatic fever is based on the Jones criteria; , which primarily describe the clinical findings of the condition. Evidence of a preceding GAS infection is also preferred (unless carditis or chorea are present). Laboratory tests and imaging may be necessary to assess any outstanding Jones criteria.

Jones criteria

  • Interpretation: two major OR one major plus two minor criteria are required for diagnosis.
    • Repeat episodes, episodes with complications → Other criteria may be sufficient for diagnosis.
  • Major criteria
    • Arthritis (migratory polyarthritis involving primarily the large joints)
    • Carditis (pancarditis, including valvulitis)
    • Sydenham chorea (CNS involvement)
    • Subcutaneous nodules
    • Erythema marginatum
  • Minor criteria

Additional findings

References:[1][4][14]

Pathology

References:[10][15]

Treatment

References:[4][16][17]

Prognosis

  • Cardiac involvement is the most important prognostic factor.
    • Early death in rheumatic fever is usually due to myocarditis rather than valvular defects.
    • Patients with a history of carditis during an initial rheumatic fever episode are at high risk of developing valvular heart defects with recurrent episodes → rheumatic heart disease

References:[18]

Prevention

References:[19]