Type IV

Overview

• Type IV hypersensitivity reactions are delayed and cell-mediated.

• See “Hypersensitivity classification” for the specific causes of type IV hypersensitivity.

• Clinical features, diagnostics, and treatment depend on the underlying etiology.

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., IFNγ, TNF α) → macrophages activation → phagocytosis of target cells

   • CD8+ T cells recognize antigens on somatic cells → cell-mediated cytotoxicity → direct cell destruction

• Severe cutaneous adverse reactions (SCAR)

  • DRESS

  • Stevens-Johnson syndrome (SJS)

  • Toxic epidermal necrolysis (TEN)

  • Acute generalized exanthematous pustulosis (AGEP)

• 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

  • Most commonly caused by antibiotics, e.g., “ampicillin rash” following ampicillin administration for infectious mononucleosis

  • Resolves after discontinuation of the offending drug

• Allergic contact dermatitis: local drug reaction following topical application of drug

• Skin tests

  • Candida skin test (to test the immune function of T cells)

  • Mantoux tuberculin skin test for latent tuberculosis

• Systemic disorders

  • Hashimoto thyroiditis

  • Multiple sclerosis

  • Type 1 diabetes mellitus