Epidemiology

• Most commonly associated with a drug hypersensitivity reaction

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Etiology

• Blood Products
  • Packed Red Blood Cells (PRBC) (see Packed Red Blood Cells)
• Drugs
  • Aspirin (see Acetylsalicylic Acid)
  • Barbiturates (see Barbiturates)
  • Cephalosporins (see Cephalosporins)
  • Fluoxetine (Prozac) (see Fluoxetine)
  • Minocycline (see Minocycline)
  • P-Aminosalicylic Acid
  • Penicillin (see Penicillins)
  • Phenylbutazone
  • Phenytoin (see Phenytoin)
  • Sulfonamides (see Sulfonamides)
  • Thiazides
    • Hydrochlorothiazide (see Hydrochlorothiazide)
  • Thiouracils
• Foreign Antisera
  • Anti-Thymocyte Globulin (ATG) (see Anti-Thymocyte Globulin): horse or rabbit-derived antibodies against human T cells
    • Onset of symptoms: 8-13 days after ATG
  • Crofab (see Crofab): incidence from meta-analyses has been reported to be 13% [MEDLINE]
  • Widow Spider Antivenom (see Widow Spider Antivenom)
• Toxic
  • Bee Sting (see Bee Sting)
  • Wasp Sting (see Wasp Sting)

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Physiology

• 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

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Diagnosis

• 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

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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): mobilliform (maculo-papular, measles-like) and/or urticarial

Systemic Manifestations

• Fever (see Fever)
• Lymphadenopathy (see Lymphadenopathy)

Rheumatologic Manifestations

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

Renal Manifestations

• Albuminuria (see Proteinuria)
• Nephritis (see Acute Kidney Injury): uncommon

Neurologic Manifestations

• Peripheral Neuropathy (see Peripheral Neuropathy): uncommon

Gastrointestinal Manifestations

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

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Treatment

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

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References

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