Diagnosis and Management of Drug Hypersensitivity Reactions

Definition and Classification

Drug hypersensitivity reactions are defined as objectively reproducible symptoms or signs initiated by exposure to a defined drug stimulus at a dose normally tolerated by most people, and are classified into two main types based on onset time after drug exposure, according to the American College of Allergy, Asthma, and Immunology 1, 2, 3, 4
The European Academy of Allergy and Clinical Immunology classifies drug hypersensitivity reactions into four types: Type I (IgE antibody-mediated), Type II (antibody-mediated cytotoxic), Type III (immune complex-mediated), and Type IV (delayed T cell-mediated) 1, 5

The American Academy of Allergy, Asthma, and Immunology states that immediate reactions can present with cutaneous manifestations, such as urticaria, pruritus, flushing, and angioedema, as well as respiratory, cardiovascular, and gastrointestinal symptoms 1, 6
The British Society for Allergy and Clinical Immunology notes that delayed reactions can present with maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) 4, 7, 8

The American College of Allergy, Asthma, and Immunology recommends serum tryptase, plasma histamine, and urinary histamine metabolites for the diagnosis of immediate reactions 1, 3
The European Academy of Allergy and Clinical Immunology suggests complete blood count with differential, liver and kidney function tests, and HLA genotyping for specific drug-gene associations, such as HLA-B*5701 for abacavir hypersensitivity 4, 7

The American Heart Association recommends epinephrine as the first-line treatment for anaphylaxis, administered intramuscularly at 0.01 mg/kg, with repeat doses every 5-10 minutes as necessary, and supportive measures such as antihistamines, corticosteroids, and bronchodilators 1, 5
The British Society for Allergy and Clinical Immunology advises immediate discontinuation of the suspected culprit drug, topical corticosteroids, and oral antihistamines for mild to moderate delayed reactions, and systemic corticosteroids and specialized care for severe reactions like SJS/TEN and DRESS 4

The American Academy of Allergy, Asthma, and Immunology recommends documentation of the reaction in an "allergy passport", allergen identification and avoidance, prescription of epinephrine auto-injectors, patient education, and referral to an allergist for comprehensive evaluation 1, 2

Type 4 HSR is a delayed, T-cell mediated immune response that occurs hours to days after antigen exposure, characterized by lymphocyte activation rather than antibody production, according to the American College of Allergy, Asthma, and Immunology 9

Type 4 HSR presents with diverse cutaneous and systemic manifestations, including maculopapular exanthema, allergic contact dermatitis, severe cutaneous adverse reactions (SCARs), psoriasis, and erythema multiforme, as noted by the American Academy of Dermatology 9
Severe cutaneous adverse reactions (SCARs) include Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), as reported by the Journal of Allergy and Clinical Immunology 10
Acute generalized exanthematous pustulosis (AGEP) is a type of SCAR that can occur in response to certain medications, according to the American College of Allergy, Asthma, and Immunology 9, 10

Type 4 reactions are typically NOT amenable to desensitization, and severe T-cell mediated delayed reactions (SJS/TEN, DRESS) are associated with long-lasting memory T-cell responses, indicating the drug must be completely avoided, as recommended by the American College of Allergy, Asthma, and Immunology 10
Delayed intradermal testing (dIDT) may be useful for certain cutaneous adverse reactions, but should be avoided in SJS/TEN where sensitivity is low, according to the Journal of Allergy and Clinical Immunology 10