Question
10-year-old girl presented with migrating joint pain, painless small nodules on the feet, and fever for the past 4 days. O/E murmur was observed on auscultation. ECG showed prolonged PR interval. ESR and CRP were raised. Parents gave a history of repeated sore throat infections earlier. (
- (a) What is your diagnosis ( 1 mark(s)
- (b) Name the causative agent ( 1 mark(s)
- (c) Describe the virulence factors and pathogenesis in detail ( 5 mark(s)
- (d) Describe the lab diagnosis (e) Describe the criteria used for final diagnosis 5 mark(s)
Answer
a) Diagnosis: Acute rheumatic fever — migratory polyarthritis, subcutaneous nodules, fever, carditis (murmur, prolonged PR interval on ECG), raised ESR/CRP, and a history of preceding streptococcal pharyngitis (repeated sore throat) fits the Jones criteria.
b) Causative agent: Streptococcus pyogenes (Group A beta-haemolytic Streptococcus) — the preceding pharyngitis, not rheumatic fever itself, is directly caused by the organism.
c) Virulence factors and pathogenesis Virulence factors: M protein (major virulence factor, antiphagocytic, anchors to the cell wall, highly variable — basis of serotyping and of the antigenic mimicry below); lipoteichoic acid (adherence); streptolysin O and S (haemolysins, cytotoxic); streptokinase (fibrinolysin, promotes spread); hyaluronidase (“spreading factor”); pyrogenic exotoxins (superantigens, cause scarlet fever rash and can drive toxic shock).
Pathogenesis of rheumatic fever: this is an immune-mediated, non-suppurative delayed sequela — NOT direct bacterial invasion of the heart/joints. Antibodies raised against the streptococcal M protein during pharyngitis cross-react (molecular mimicry) with structurally similar host antigens — cardiac myosin and valve glycoproteins (causing carditis/valvulitis), synovial tissue (causing migratory arthritis), and basal ganglia neurons (causing Sydenham’s chorea) — because the host’s own tissue antigens share epitopes recognized by the anti-streptococcal antibody. This autoimmune cross-reaction, occurring typically 2–4 weeks after the initial pharyngitis, drives the inflammatory damage characteristic of acute rheumatic fever, and repeated streptococcal infections cause cumulative valvular damage (rheumatic heart disease).
d) Laboratory diagnosis
- Throat swab culture — beta-haemolytic colonies, bacitracin-sensitive, Lancefield Group A antigen — confirms current/recent streptococcal infection if positive (often negative by the time rheumatic fever manifests).
- Rapid antigen detection test — for Group A streptococcal antigen from throat swab.
- ASO (antistreptolysin O) titre, and anti-DNase B titre — rise 1–3 weeks after infection, the key serological evidence of recent streptococcal infection supporting the diagnosis of rheumatic fever.
- Echocardiography — assesses valvular involvement (carditis).
- ECG — prolonged PR interval (as in this case), other conduction abnormalities.
- Inflammatory markers — raised ESR, CRP.
e) Criteria for final diagnosis — revised Jones criteria Diagnosis requires evidence of a preceding Group A streptococcal infection (positive throat culture/rapid antigen test, or elevated/rising streptococcal antibody titre) PLUS either 2 major criteria, or 1 major plus 2 minor criteria.
- Major criteria: carditis, polyarthritis (migratory), Sydenham’s chorea, subcutaneous nodules, erythema marginatum.
- Minor criteria: fever, arthralgia, raised ESR/CRP, prolonged PR interval on ECG. In this patient: major criteria present — carditis (murmur), migratory polyarthralgia, subcutaneous nodules; minor criteria — fever, raised ESR/CRP, prolonged PR interval — together with the history of preceding streptococcal pharyngitis, fulfilling the revised Jones criteria for acute rheumatic fever.