Drug Allergy: Introduction and Epidemiology

Author: V. Dimov, M.D., Allergist/Immunologist, Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D.; Faculty Adviser: A. Bewtra, M.B.B.S., Professor, Creighton University Division of Allergy & Immunology

Introduction

Adverse drug reactions (ADRs) are organized into 2 subtypes:

- type A reactions - predictable from known pharmacologic properties
- type B reactions - unpredictable and restricted to a vulnerable subpopulation - hypersensitivity reactions

Idiosyncratic drug reactions are different from the known pharmacologic toxicity profiles. Such reactions may result from a defined genetic defect, e.g. primaquine-induced hemolytic anemia, which depends on deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD).

The mechanism of most idiosyncratic drug reactions remains obscure and often reflects a complex interaction of metabolic and constitutional factors (e.g., radiocontrast media reactions).

Drug reactions resulting from a drug-specific immune response constitute immunologic drug reactions, often referred to as drug allergy.

Drug hypersensitivity (allergy) is an immune-mediated reaction to a drug.

The distinction between idiosyncratic drug reactions and drug allergy can be difficult to make clinically.

The effector mechanisms in drug allergy are different from idiosyncratic reactions that mimic drug allergy (‘non-allergic or pseudoallergic drug hypersensitivity’).



Classification of adverse reactions to drugs: "SOAP III" mnemonic (click to enlarge the image).

Epidemiology

Adverse drug reactions (ADRs) affect 10–20% of hospitalized patients and 25% of outpatients.

Rule of 10s in ADR

10% of patients develop ADR
10% of these are due to allergy
10% of these lead to anaphylaxis
10% of these lead to death

It is estimated that allergic reactions occur in about 5% of all treatments. Fatal drug reactions occur in 0.01-0.1% of inpatients mainly due to antibiotics and NSAIDs. Adverse reactions to drugs are twice as common in women. Antibiotics are the commonest cause of allergic reactions.

ADR are more common in women, this predilection to female gender is similar to urticaria and angioedema. Women have a 35% higher incidence of skin ADRs than men.

The majority of ADRs are type A reactions. Type B reactions are much less common, with an estimated frequency of 10–15% of all ADRs. Immune-mediated drug reactions constitute 6–10% of all ADRs.

The most common drug groups causing hypersensitivity reactions are:

- β-lactam antibiotics
- non-steroidal antiinflammatory drugs (NSAIDs)
- radiocontrast media
- neuromuscular blocking agents
- antiepileptic drugs

Immediate hypersensitivity to local anesthetics is exceptionally rare, despite common complaints.

Skin reactions, such as maculopapular eruptions and urticaria are the most common clinical presentations for ADRs.

Rarely, drugs induce more severe and potentially life-threatening reactions such as toxic epidermal necrolysis, Stevens–Johnson syndrome, and immune hepatitis. Serum granulysin (level greater than 10 ng/mL) predicts Stevens-Johnson syndrome and toxic epidermal necrolysis and the test takes just 5 minutes. J Am Acad Dermatol. 2011;65:65-68.

In the USA, about 1 in 300 hospitalized patients dies from ADRs, amounting to 106,000 estimated deaths in 1994, of which 6–10% may be allergic in origin.

References

Drug Allergy. Middleton's Allergy: Principles and Practice, Mosby; 7 edition (November 19, 2008).
Clinical review: ABC of allergies. Adverse reactions to drugs. BMJ 1998;316:1511-1514.
Severe Cutaneous Adverse Reactions to Drugs. Current Opinion in Allergy and Clinical Immunology. Faith L. Chia; Khai Pang Leong. Published on Medscape, 08/2007.

Multiple choice questions

Chapter 57: Drug Allergy. Allergy and Immunology Review Corner: Chapter 57 of Pediatric Allergy: Principles & Practices, edited by Donald Y.M. Leung, et al.

Published: 07/11/2007
Updated: 02/01/2012