Complications of Untreated Strep Throat: Rheumatic Fever and Post-Streptococcal Glomerulonephritis

Untreated or inadequately treated Group A Streptococcal (GAS) pharyngitis can trigger two major immune-mediated sequelae—acute rheumatic fever (ARF) and post-streptococcal glomerulonephritis (PSGN)—via molecular mimicry and immune complex deposition, respectively.

Acute Rheumatic Fever (ARF)

Pathogenesis

• Molecular mimicry: Antibodies against GAS M protein cross-react with cardiac (myosin, valvular), joint, CNS (basal ganglia), skin, and subcutaneous tissues.
• Type II/III hypersensitivity; CD4+ T-cell infiltration.

Jones Criteria (2015 Revision) — Diagnosis Requires:

• 2 Major OR 1 Major + 2 Minor + evidence of antecedent GAS infection.
• Major: Carditis (most serious, 50–70%), Polyarthritis (migratory, large joints), Chorea (Sydenham’s), Erythema marginatum, Subcutaneous nodules.
• Minor: Arthralgia, Fever, Elevated acute phase reactants (ESR/CRP), Prolonged PR interval.
• GAS evidence: Positive RADT/culture, elevated ASO/anti-DNase B.

Outcomes

• Rheumatic heart disease (RHD): Chronic valvular damage (mitral > aortic) → stenosis/regurgitation → heart failure, atrial fibrillation, stroke, need for valve surgery.
• Global burden: ~40 million RHD; 300,000 deaths/year (mostly <50 in low-resource settings).

Post-Streptococcal Glomerulonephritis (PSGN)

Pathogenesis

• Immune complexes (GAS antigens + antibodies) deposit in glomerular capillary walls → complement activation (low C3) → inflammation → nephritic syndrome.
• Nephritogenic strains: M types 1, 2, 4, 12, 25, 49, 55, 57, 60.

Clinical Presentation (1–3 weeks post-infection)

• Hematuria (cola-colored urine), proteinuria, edema (periorbital → generalized), hypertension.
• Oliguria, azotemia in severe cases.
• Self-limited in 95% of children; adults higher risk of progressive CKD.

Diagnosis

• Urinalysis: RBC casts, dysmorphic RBCs, proteinuria.
• Low C3 (1–8 weeks), normal C4; elevated ASO/anti-DNase B.
• Biopsy rarely needed; shows diffuse proliferative GN with “humps” (subepithelial deposits).

Prevention

• ARF: Antibiotics within 9 days of pharyngitis onset (penicillin 10 days).
• PSGN: Not reliably prevented by antibiotics (immune complexes may form before treatment); skin infection control (impetigo) also important.
• Secondary prophylaxis: Benzathine penicillin G IM every 3–4 weeks for ARF/RHD (duration: years to lifelong).

Key Distinction

ARF damages heart valves (chronic); PSGN damages kidney filters (usually acute, self-limited). Both are preventable with timely penicillin—one of medicine’s most cost-effective interventions.