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Delayed Hypersensitivity Reactions

Delayed Hypersensitivity Reactions

Morbilliform Drug Eruption (Benign Exanthem)

Typically occurs within 1-2 weeks of exposure. May occur more quickly (several days) in previously sensitized patients

Morbilliform rashes sometimes resolve despite continued treatment. Coadministration of an antihistamine may limit symptoms and allow for continued treatment (i.e., a “treat-through” approach)

Morbilliform rashes generally DO NOT progress to more severe cutaenous manifestations

Cytotoxic Reactions

Clinical Phenotype:

  • Hemolytic anemia
  • Thrombocytopenia
  • Petechia

Typically occurs > 72 hours after exposure (often weeks into therapy)

Immune-Complex Reactions

Clinical Phenotype:

  • Small-vessel vasculitis
  • Serum sickness
  • Arthus reaction

Typically occurs within 1-3 weeks of exposure

T-Cell-Mediated Reactions

Clinical Phenotype:

  • Drug Rash with Eosinophilia and Systemic Symptoms (DRESS): epidermal edema, fever, lymphadenopathy, eosinophilia, atypical lymphocytosis, and infiltration of skin and internal organs. Mucosal involvement often occurs
  • Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN): exfoliative dermatitis, epidermal necrosis, subepidermal bullae, and involvement of multiple mucous membranes
    • May evolve from initial erythroderma, purpuric target lesions, or blisters
    • NOT predicted by a history of morbilliform rash OR by skin tests
  • Acute Generalized Exanthematous Pustulosis (AGEP): fever, neutrophilic leukocytosis, sterile pustules in stratum corneum and epidermis, dermal edema, and infiltration of neutrophils, CD4+ T-cells, CD8+ T-cells, and some eosinophils

Typical Timing:

  • DRESS: 2-3 weeks after exposure
  • SJS/TEN: 4 days-8 weeks after exposure
  • AGEP: 24-48 hours after exposure