Drug Hypersensitivity Reactions Classification According to Onset of Reactions
Drug hypersensitivity reactions are primarily classified into two main types based on the timing of onset: immediate reactions occurring within 1 hour of drug administration and delayed reactions occurring more than 1 hour after administration. 1, 2
Immediate Hypersensitivity Reactions
- Immediate reactions typically occur within 1 hour of drug administration and are often IgE-mediated (Type I), though non-IgE mediated mechanisms can also cause immediate reactions 1
- These reactions involve the binding of allergens to IgE antibodies on mast cells and basophils, triggering their degranulation and release of mediators 3
- Histamine is released within 5 minutes of mast cell activation and remains elevated for 15-60 minutes, causing vasodilation, increased vascular permeability, and smooth muscle contraction 3
- Clinical manifestations include urticaria, pruritus, flushing, angioedema, rhinorrhea, bronchospasm, hypotension, tachycardia, and in severe cases, anaphylaxis 3
- Immediate reactions to low-osmolar contrast media and iso-osmolar contrast media occur in 0.3% to 1.4% of injections, with severe reactions being uncommon (0.005% to 0.06%) 1
Delayed Hypersensitivity Reactions
- Delayed reactions occur more than 1 hour after drug administration and can develop at any time, commonly after many days 1, 2
- These reactions are often associated with T-cell-dependent mechanisms (Type IV) 1, 4
- Common clinical presentations include maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) 2, 4
- Delayed reactions can affect various organ systems including skin, liver, and other internal organs 4
- Common culprits include anti-epileptics, antibiotics, anti-gout agents, and anti-viral drugs 4
Gell and Coombs Classification
- Type I (Immediate): IgE-mediated reactions occurring within minutes to hours after exposure 2, 5
- Type II: Antibody-mediated cytotoxic reactions 2
- Type III: Immune complex-mediated reactions 2
- Type IV (Delayed): T-cell-mediated reactions occurring after hours to days 2, 5
Diagnostic Considerations
- For immediate reactions, serum tryptase (optimal collection 15 minutes to 3 hours after onset), plasma histamine, and urinary histamine metabolites can aid diagnosis 2, 3
- For delayed reactions, complete blood count with differential, liver and kidney function tests, and HLA genotyping for specific drug-gene associations may be useful 2, 4
- Skin testing (prick, intradermal) is more likely to be positive in severe immediate reactions, particularly life-threatening ones with cardiovascular symptoms 1
- Lymphocyte transformation test is the most standardized in vitro method for delayed hypersensitivity reactions 6
Management Approach
- For immediate reactions, especially anaphylaxis, epinephrine is the first-line treatment (0.01 mg/kg intramuscularly in the mid-outer thigh) 3
- For delayed reactions, immediate discontinuation of the suspected culprit drug is essential, along with topical corticosteroids and oral antihistamines for mild to moderate reactions 2
- Systemic corticosteroids and specialized care are recommended for severe delayed reactions like SJS/TEN and DRESS 2
- Accurate documentation of the reaction timing, symptoms, and treatment is crucial for future management 1, 5
Common Pitfalls and Caveats
- Misclassifying side effects as true allergies can lead to unnecessary avoidance of effective medications 5
- Delayed administration of epinephrine in anaphylaxis increases morbidity and mortality 3
- Beta-adrenergic blockers and angiotensin-converting enzyme inhibitors can increase the risk of severe anaphylactic reactions and reduce epinephrine effectiveness 3
- Observation periods should be considered after treating anaphylactic reactions due to the risk of biphasic reactions, especially in patients with initially severe symptoms 1