Serum Sickness


  • Most commonly associated with a drug hypersensitivity reaction



  • Type III Hypersensitivity Reaction
    • Does not involve a preformed antibody -> requires development of antibody via adaptive immune system
    • Drug (as a hapten) binds to a plasma protein
    • Time Required for Primary Sensitization to an Offending Agent: 1-3 wks (however, symptoms may develop within 12-36 hrs, if there has been a prior immunizing exposure)
    • Role of Circulating Immune Complexes: clinical disease correlates with high levels of circulating immune complexes and decreased C3/C4/CH50 complement components


  • 125I-Labeled C1q Binding Assay: detects high levels of circulating immune complexes
  • C3/C4/CH50: markedly decreased
  • Direct Immunofluorescence of Skin Bx: imunoglobulin + C3 deposits in walls of small cutaneous blood vessels

Clinical Manifestations

Dermatologic Manifestations

  • Serpiginous Erthematous Band Along Sides of Hands/Feet/Fingers/Toes (at junction of palmar and plantar skin surfaces): early clinical sign
  • Rash (see Urticaria-Angioedema, [[Urticaria-Angioedema]]): mobilliform (maculo-papular, measles-like) and/or urticarial

Systemic Manifestations

Rheumatologic Manifestations

  • Arthralgia: common
  • Arthritis (see Arthritis, [[Arthritis]]): uncommon
    • Large joint involvement has been reported ATG-associated serum sickness
  • Vasculitis (see Vasculitis, [[Vasculitis]]): uncommon

Renal Manifestations

Neurologic Manifestations

Gastrointestinal Manifestations

  • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]]): has been reported with ATG-associated serum sickness
  • Melena (see Gastrointestinal Bleed, [[Gastrointestinal Bleed]]): has been reported with ATG-associated serum sickness


  • Drug-Related Serum Sickness: symptoms usually subside within days after drug withdrawal (may take longer in cases associated with long-acting agents)


  • Transfusion-induced serum sickness. Transfusion 2009 Feb;49(2):372-45 [MEDLINE]