Drug allergy classification

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Charmaine Patel, M.D. [2]

Drug Allergy
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Overview

Drug allergies are classified using two main sets of criteria. One is set forth by the World Allergy Association, and classifies the reaction as to whether it occurs within one hour of treatment, or after one hour. The other set of criteria are based on the type of immunologic reaction that occurred and the mediators involved.

Classification

Classification of Adverse Drug Reactions

Type A: Predictable	Type B: Unpredictable
Drug overdose	Drug allergy: an immunologically mediated adverse drug reaction
Secondary drug effects	Pseudoallergic (non-allergic):has the same clinical manifestations as a drug allergy, but lacks immunological specificity.
Side effects	Drug intolerance: an undesirable pharmacologic effect that can occur at low doses, and is not caused by underlying abnormalities in metabolism or drug excretion.
Drug interactions	Drug idiosyncrasy: an abnormal, unexpected effect, usually caused by underlying abnormalities in drug metabolism or excretion

Classification Based on Timing of Symptoms

There are recommendations on the classification of drug allergy reactions based on the World Allergy Association (WAO) guidelines. The two categories of classification are based on whether the reaction occurs less than one hour of medication administration, or more than one hour afterwards.

• Immediate- these reactions occur within one hour, and are most likely due to IgE mediated type I reactions. At times, type I reactions can occur after one hour if the absorption of the drug is delayed, for example due to an oral medication or ingesting a medication with food. These types of reactions have the risk of anaphylaxis if the patient is re-exposed.
• Delayed- these reactions occur after one hour, although most occur 6 hours after the administration of the drug, and some occur up to 7 to 10 days after treatment. Some reactions can even occur days after the treatment has been stopped.

Classification Based on Reaction Type

One type of classification of drug allergies, is based on the type of autoimmune process. This is the same type of classification that is used for other types of immunological reactions, and is based on the Gell and Coombs system. Drugs usually cause type III and type IV reactions, however certain medications such as penecillin, can cause all four .

Immune Reaction	Mechanism of Action	Manifestations	Timing of Reaction
Type I IgE mediated	Immediate onset caused by IgE binding to mast cells causing degranulation and release of histamine.	Urticaria, anaphylaxis, angioedema, bronchospasm.	Minutes or hours after drug ingestion.
Type II antibody mediated cell destruction/ cytotoxic	Delayed onset reaction caused by IgG or IgM antibodies, directed at drug-hapten coated cells.	Thrombocytopenia, anemia, cytopenia.	Variable
Type III immune complex deposition	Delayed in onset and caused by IgG immune complex formation and deposition, and complement activation.	Vasculitis, serum sickness, arthralgia, fever, rash.	One to three weeks after exposure to drug.
Type IV cell mediated/ delayed-type hypersensitivity reaction	The presentation of drug molecules by major histocompatability complexes to T cells, causing the release of cytokines and other inflammatory mediators. Also associated with the activation of eosinophils, monocytes, and neutrophils.	Skin rashes, organ tissue damage, contact sensitivity.	Two to seven days after exposure to a drug.