Serum sickness is a classic example of a type III hypersensitivity reaction, which usually develops as a complication of antitoxin or antivenom administration. t
Epidemiology
Etiology
- Antivenom or antitoxin containing animal proteins or serum (→ “serum” sickness), such as:
- Equine anti-snake venom
- Equine anti-spider venom
- Equine or bovine anti-rabies antitoxin
- Equine botulinum antitoxin
- Medications: most frequently antibiotics (e.g., penicillin, amoxicillin, cefaclor, trimethoprim-sulfamethoxazole) t
- Infections: Hepatitis B virus
Pathophysiology
Exposure to an antigen (e.g., antivenom, drug) → formation of antibodies → deposition of antibody-antigen complexes in tissue → activation of the complement cascade → tissue damage and systemic inflammation t
Clinical features
- Classic Triad:
- Fever (low to moderate grade).
- Rash: Pruritic, urticarial or polycyclic erythematous maculopapular eruptions; characteristically begins on the trunk/groin or lateral margins of fingers/toes and spreads.
- Arthralgias / Polyarthritis: Symmetric or migratory; most commonly affects metacarpophalangeal joints, knees, wrists, and ankles without destructive joint changes.
- Other PE Findings:
- Lymphadenopathy (diffuse, tender; prominently cervical and axillary).
- Facial edema / Angioedema.
- Palpable purpura or cutaneous vasculitis (severe cases).
- Malaise, myalgias, and headache.
Tip
Symptoms appear 1–3 weeks following initial exposure (because antibodies take several days to form) and typically resolve within a few weeks after discontinuation of the offending agent.
Diagnostics
- Initial / Primary: Clinical diagnosis based on timeline of drug/protein exposure + classic triad (fever, rash, arthralgia).
- Key Labs:
- Complement levels: ↓ C3, ↓ C4, ↓ CH50 (due to consumption in classical serum sickness; may be normal in SSLR).
- Inflammatory markers: ↑ ESR and ↑ CRP.
- CBC: Mild leukocytosis (or transient neutropenia) ± mild eosinophilia.
- Urinalysis (UA): Proteinuria, microscopic hematuria, or RBC casts (indicates immune-complex glomerulonephritis).
- Confirmatory / Skin Biopsy (rarely required, reserved for atypical presentations):
- Leukocytoclastic vasculitis on light microscopy.
- Direct Immunofluorescence (DIF): Deposition of IgG/IgM and C3 in dermal vessel walls.
Differential Diagnostics
- Drug-Induced Urticaria (Type I Hypersensitivity):
- Diff by: Onset within minutes to hours of ingestion; IgE-mediated; responds rapidly to antihistamines/epinephrine; normal complement levels; lacks fever, polyarthritis, and LAD.
- Henoch-Schönlein Purpura (IgA Vasculitis):
- Diff by: Predominantly in pediatrics; palpable purpura concentrated on lower extremities/buttocks; colicky abdominal pain/intussusception; IgA deposition on biopsy; normal complement levels.
- Acute Rheumatic Fever (ARF):
- Diff by: Follows Group A Strep pharyngitis by 2–4 weeks; migratory polyarthritis of large joints; presence of carditis, Sydenham chorea, subcutaneous nodules, erythema marginatum; ↑ ASO / anti-DNase B titers.
- Disseminated Gonococcal Infection (DGI):
- Diff by: Triad of tenosynovitis, migratory polyarthralgia, and pustular/vesicular skin lesions on distal extremities; (+) NAAT/blood/synovial cultures.
- Systemic Lupus Erythematosus (SLE):
- Diff by: Chronic relapsing course; malar/discoid rash, serositis, (+) ANA and (+) anti-dsDNA/anti-Smith antibodies.
Serum sickness-like reaction
- Epidemiology: much more common than actual serum sickness
- Etiology: similar to that of serum sickness
- Infections (e.g., hepatitis B, rabies)
- Medications that can act as haptens (e.g., allopurinol, cephalosporins, penicillin)
- Pathogenesis: unclear (likely not the result of a type III hypersensitivity reaction)
- Clinical features
- Similar to classic serum sickness