Epidemiology

Etiology

Pathophysiology

Compared to type I-III hypersensitivity reactions, which are antibody-mediated, type IV reactions are mediated by T cells. Type IV hypersensitivity reactions involve two major steps:

1. T cell sensitization: skin penetration by the antigen → uptake of the antigen by Langerhans cell → migration to lymph nodes → formation of sensitized T lymphocytes
2. Presensitized T cell response (after repeated contact with the antigen)
   • CD4+ T cells recognize antigens on antigen-presenting cells → release of inflammatory lymphokines cytokines (e.g., IFN-γ, TNF-α) → macrophages activation → phagocytosis of target cells
   • CD8+ T cells recognize antigens on somatic cells → cell-mediated cytotoxicity → direct cell destruction

Examples

• Skin tests
  • Candida skin test (to test the immune function of T cells)
    • A diagnostic test in which Candida albicans antigen is injected intradermally to the arm. The injection site is examined 48 hours later. Induration ≥5 mm in diameter is considered a positive reaction and indicates prior exposure to antigen and an intact immune response mediated by T cells.
    • This test requires patients to have encountered Candida before. Luckily, nearly everyone encounters Candida at some point in their lives.
  • Mantoux tuberculin skin test for latent tuberculosis
• Exanthematous drug eruption: morbilliform rash on the trunk and proximal extremities
  • Associated symptoms include pruritus and low-grade fever
  • Typical onset 5-14 days after drug exposure
  • Caused by anticonvulsants, antibiotics, antiretroviral therapy
    • Most commonly caused by antibiotics, e.g., “ampicillin rash” following ampicillin administration for infectious mononucleosis
  • Resolves after discontinuation of the offending drug

Diagnostics

Treatment