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Drug allergy
Drug allergy
Specialty	Immunology, pharmacology

A drug allergy is an allergy to a drug, most commonly a medication, and is a form of adverse drug reaction. Medical attention should be sought immediately if an allergic reaction is suspected.

An allergic reaction will not occur on the first exposure to a substance. The first exposure allows the body to create antibodies and memory lymphocyte cells for the antigen. However, drugs often contain many different substances, including dyes, which could cause allergic reactions. This can cause an allergic reaction on the first administration of a drug. For example, a person who developed an allergy to a red dye will be allergic to any new drug which contains that red dye.

A drug allergy is different from an intolerance. A drug intolerance, which is often a milder, non-immune-mediated reaction, does not depend on prior exposure.

Signs and symptoms

Symptoms of drug hypersensitivity reactions can be similar to non-allergic adverse effects. Common symptoms include:^[1]

Hives
Itching
Rash
Fever
Facial swelling
Shortness of breath due to the short-term constriction of lung airways or longer-term damage to lung tissue
Anaphylaxis, a life-threatening drug reaction (produces most of these symptoms as well as low blood pressure)
Cardiac symptoms such as chest pain, shortness of breath, fatigue, chest palpitations, light headedness, and syncope due to a rare drug-induced reaction, eosinophilic myocarditis

Causes

Some classes of medications have a higher rate of drug reactions than others. These include antiepileptics, antibiotics, antiretrovirals, NSAIDs, and general and local anesthetics.^[2]

Risk factors

Risk factors for drug allergies can be attributed to the drug itself or the characteristics of the patient. Drug-specific risk factors include the dose, route of administration, duration of treatment, repetitive exposure to the drug, and concurrent illnesses. Host risk factors include age, sex, atopy, specific genetic polymorphisms, and inherent predisposition to react to multiple unrelated drugs (multiple drug allergy syndrome).^[3] A drug allergy is more likely to develop with large doses and extended exposure.^{[citation needed]}

People with immunological diseases, such as HIV and cystic fibrosis,^[2] or infection with EBV, CMV, or HHV6,^[4] are more susceptible to drug hypersensitivity reactions.^[2] These conditions lower the threshold for T-cell stimulation.^[4]

Mechanisms

There are two broad mechanisms for a drug allergy to occur: IgE or non-IgE mediated. In IgE-mediated reactions, also known as immunoglobulin E mediated reactions, drug allergens bind to IgE antibodies, which are attached to mast cells and basophils, resulting in IgE cross-linking, cell activation and release of preformed and newly formed mediators.^[5]

Most drugs do not cause reactions in themselves, but by the formation of haptens.^[2]

Types

Drug allergies or hypersensitivities can be broadly divided into two types: immediate reactions and delayed reactions. Immediate reactions take place within an hour of administration and are IgE mediated, while delayed reactions take place hours to weeks after administration and are T-cell mediated. The first category is mostly mediated through specific IgE, whereas the latter is specifically T-cell mediated.^[2]

Management

Management of drug allergy consists principally of avoidance or discontinuation of the causative drug.^[6] Treatment is largely supportive and symptomatic.^[6] It may consist of topical corticosteroids and oral antihistamines for cutaneous symptoms such as hives and itching.^[6] Mild cutaneous reactions can be managed with antihistamines only.^[6] However, antihistamines cannot antagonize activated histamine that has already been released from mast cells.^[7] In severe cases of drug allergy, systemic corticosteroids may be used.^[6] Corticosteroids are limited by a delayed onset of action of greater than 45 minutes as they act via gene modulation.^[7] If anaphylaxis occurs, injectable epinephrine is to be used.^[6]^[8] If a person is allergic to a drug and no suitable alternative exists, a desensitization procedure with the drug, in which the drug is introduced slowly at very low doses such that tolerance to the drug allergy develops, can be employed.^[6]

References

^ "Drug Allergy". Mayo Clinic.
^ ^a ^b ^c ^d ^e Holgate, Steven (2011). Allergy (4th ed.). Elsevier Saunders. pp. 321–330. ISBN 9780723436584.
^ "Drug Allergy: An Updated Practice Parameter" (PDF). Retrieved 2013-12-02.
^ ^a ^b Adkinson, Franklin (18 October 2013). Middleton's allergy : principles and practice (8 ed.). Saunders Elsevier. pp. 1274–1295. ISBN 978-0-323-08593-9.
^ "World Allergy Organization". Retrieved 2013-11-25.
^ ^a ^b ^c ^d ^e ^f ^g Warrington R, Silviu-Dan F, Wong T (2018). "Drug allergy". Allergy Asthma Clin Immunol. 14 (Suppl 2): 60. doi:10.1186/s13223-018-0289-y. PMC 6157123. PMID 30275849.
^ ^a ^b Schnyder B (August 2009). "Approach to the patient with drug allergy". Immunol Allergy Clin North Am. 29 (3): 405–18. doi:10.1016/j.iac.2009.04.005. PMID 19563988.
^ Kemp SF, Lockey RF, Simons FE (July 2008). "Epinephrine: the drug of choice for anaphylaxis-a statement of the world allergy organization". World Allergy Organ J. 1 (7 Suppl): S18–26. doi:10.1097/WOX.0b013e31817c9338. PMC 3666145. PMID 23282530.