🩺 FCPS Paediatrics TOACS · Serum Sickness (Type III Hypersensitivity)

✅ Serum sickness (type III hypersensitivity reaction). Justification:
• Exposure to equine ATG (foreign protein).
• Onset 7-14 days post-exposure – typical for immune complex formation.
• Triad: fever, urticarial rash, arthralgia + lymphadenopathy.
• Subsequent proteinuria/hematuria → immune complex glomerulonephritis.
This is NOT a serum sickness-like reaction (which lacks immune complexes and renal involvement).

✅ Pathogenesis: Type III hypersensitivity (immune complex-mediated).
• Antibodies (IgG/IgM) form against the foreign protein (equine ATG).
• Antigen-antibody complexes deposit in vessel walls, glomeruli, synovium, choroid plexus.
• Complement activation (C3a, C5a) → neutrophil chemotaxis → release of lysosomal enzymes → vasculitis and tissue injury.
• C3 and C4 levels are decreased during active disease.

✅ Serum sickness: true immune complex-mediated (type III), hypocomplementemia, vasculitis, renal involvement, occurs 7-14 days after foreign protein/drug.
SSLR: clinically similar (rash, fever, arthralgia) but no immune complexes, no hypocomplementemia, no renal lesions. Commonly caused by drugs (cefaclor, amoxicillin, TMP-SMX). Onset earlier (1-3 weeks) but resolves with drug discontinuation; does not cause glomerulonephritis.

✅ Immediate investigations:
• Complement levels – C3, C4, CH50 (low in serum sickness).
• Urinalysis with microscopy – quantify protein, RBC casts (glomerulonephritis).
• Serum creatinine, BUN – assess renal function.
• Anti-dsDNA, ANCA – to rule out lupus or vasculitis.
• ESR, CRP – inflammatory markers (elevated).
• Skin biopsy of urticarial lesion (if diagnosis uncertain) – leukocytoclastic vasculitis with immune complex deposition.

✅ Low C3, low C4, low CH50 – classical pathway activation (because immune complexes fix C1q). This contrasts with alternative pathway activation (e.g., C3 glomerulopathy) where C4 is normal. Serial complement levels: low at disease peak, normalize with resolution.

✅ • Serum sickness (post-foreign protein/drug)
• Systemic lupus erythematosus (SLE) – ANA, anti-dsDNA positive; chronic course.
• IgA vasculitis (Henoch-Schönlein purpura) – palpable purpura, abdominal pain, IgA deposition.
• Hypersensitivity vasculitis – drug-induced.
• Post-streptococcal glomerulonephritis – history of pharyngitis, low C3 (but C4 normal).
• Acute rheumatic fever – migratory polyarthritis, carditis, chorea, elevated ASO.

✅ • Discontinue offending agent (equine ATG already stopped).
• Supportive care: antihistamines (for pruritus), NSAIDs or acetaminophen for arthralgia (avoid if renal impairment).
• Systemic corticosteroids indicated for significant renal involvement (proteinuria + hematuria) – prednisone 1-2 mg/kg/day (max 60 mg) for 1-2 weeks, then taper.
• Monitor renal function, blood pressure, and urinalysis daily initially.
• If severe glomerulonephritis or rapidly progressive course, consider pulse methylprednisolone or cyclophosphamide (rare in serum sickness).
• Plasmapheresis is NOT typically needed.

✅ • Symptoms usually resolve spontaneously over 1-4 weeks after discontinuation of the offending agent.
• Renal involvement (proteinuria, hematuria) typically resolves within weeks with corticosteroids; permanent renal damage is rare if treated.
• However, prolonged immune complex deposition can lead to membranoproliferative glomerulonephritis in some cases.
• Monitor urinalysis and complement levels until normalization.

✅ Drug-induced lupus is caused by hydralazine, procainamide, isoniazid, minocycline – not ATG. Features: positive ANA, anti-histone antibodies, but usually no hypocomplementemia and no renal involvement (except rare cases). Onset after months of exposure, not 10 days. Differentiate by history and complement levels (low in serum sickness, normal in drug-induced lupus).

✅ Skin biopsy of urticarial lesions shows leukocytoclastic vasculitis (neutrophilic infiltration, fibrinoid necrosis, red cell extravasation). Direct immunofluorescence demonstrates immune complex deposition (IgG, IgM, C3) in vessel walls. Biopsy is not always required if classic history and complement profile.

✅ Prevention of recurrence: avoid re-exposure to equine ATG. Use humanized or recombinant alternatives (e.g., rabbit ATG or human ATG). If equine ATG is the only option, premedication with corticosteroids, antihistamines does NOT reliably prevent serum sickness (desensitization may help for IgE-mediated anaphylaxis but not type III). Informed consent about high risk of recurrence.

✅ Persistent hypocomplementemia >6 weeks after discontinuation of the offending agent suggests an alternative or chronic immune complex-mediated disease (e.g., SLE, C3 glomerulopathy, chronic infection). Requires further evaluation for autoimmune disease.