Serum Sickness

Aka: Serum Sickness, Serum Sickness Like Reaction

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II. Pathophysiology

  1. Type 3 Hypersensitivity Reaction (Immune Complex-Mediated Reaction)
    1. Small immune-complex tissue deposition
    2. Results in Nephritis, Arthritis, Vasculitis

III. History

  1. Diphtheria Antitoxin reaction in the early 1900s was the original defining condition
    1. Antitoxin had historically been harvested from horses who had been injected with Diphtheria toxin
    2. Similar reactions were seen with Scarlet Fever antitoxin
    3. Modern day Diphtheria antitoxin is no longer produced in horses and does not cause Serum Sickness
  2. Snake Antivenom
    1. Older Snake Antivenoms were also harvested from horses and resulted in frequent reactions
    2. Newer Snake Antivenoms (e.g. CroFab) are now produced in sheep and associated with less common reactions

IV. Symptoms

  1. Onset of symptoms 4-21 days after exposure (mean 8-10 days)
  2. High Fever spikes
  3. Pruritic rash (including Urticaria)
    1. No mucous membrane involvement
    2. Rash starts in region of original injection
  4. Lymphadenopathy
  5. Polyarthralgias

V. Causes

  1. Equine-based microbial antitoxins (anti-Rabies, anti-botulinum, and anti-diphtheria Immunoglobulin)
  2. Antivenoms (Snake Antivenom, Anti-Lactrodectus Spider venom)
  3. Rabies Vaccine
  4. Stretokinase
  5. Insect Bite Proteins
  6. Monoclonal Antibodies (e.g. Rituximab, Infliximab)

VI. Differential Diagnosis

  1. Rheumatologic Conditions
    1. Hypersensitivity Vasculitis
    2. Reactive Arthritis
    3. Juvenile Rheumatoid Arthritis
    4. Sweet Syndrome
  2. Drug Reactions
    1. Medication Hypersensitivity
    2. Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis
    3. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  3. Bacterial Syndromes
    1. Acute Rheumatic Fever
    2. Disseminated Gonorrhea
    3. Meningococcemia
    4. Scarlet Fever
    5. Lyme Disease
  4. Viral syndromes
    1. See Viral Exanthem
    2. Chikungunya
    3. Dengue Fever
    4. Kawasaki Disease
  5. Serum Sickness Like Reaction Causes
    1. Cefaclor (Ceclor)
    2. Penicillin (high dose IV)
    3. Amoxicillin
    4. Trimethoprim-Sulfamethoxazole (Bactrim, Septra)
    5. Hepatitis B Infection

VII. Labs

  1. Complete Blood Count (CBC)
    1. Neutropenia
    2. Reactive Lymphocytes
    3. Mild Thrombocytopenia
  2. Comprehensive Metabolic Panel
    1. Transient Serum Creatinine increase may occur
  3. Acute Phase Reactant elevations
    1. Erythrocyte Sedimentation Rate
    2. C-Reactive Protein
  4. Urinalysis
    1. Mild Proteinuria

VIII. Management

  1. Withdraw causative agent
  2. Symptomatic management
    1. NSAIDs
    2. Corticosteroids in severe cases

IX. Prevention

  1. No study (including Skin Test for Horse Serum Sensitivity) predicts Serum Sickness reaction
    1. Tantawichien (1995) Clin Infect Dis 21(3): 660 +PMID: 8527562 [PubMed]

X. References

  1. Rixe (2020) Serum Sickness, Stat Pearls, accessed 9/27/2020
    1. https://www.ncbi.nlm.nih.gov/books/NBK538312/
  2. Wener in Adkinson (2020) Serum Sickness and Serum Sickness-like Reactions, UpToDate, accessed 9/27/2020

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