Give an 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.
Describe the 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:
T cell sensitization: skin penetration by the antigen → uptake of the antigen by Langerhans cell → migration to lymph nodes → formation of sensitized T lymphocytes
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)
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
Candida skin test (to test the immune function of T cells)
Mantoux tuberculin skin test for latent tuberculosis
Type 1 diabetes mellitus