Penicillin allergy: Delayed hypersensitivity reactions
- Roland Solensky, MD
Roland Solensky, MD
- Oregon State University/Oregon Health and Science University College of Pharmacy
Penicillins are the medications to which allergy is most commonly reported. Penicillin allergy in all of its forms is self-reported by about 5 to 10 percent of patients [1-3]. Many of these patients have delayed forms of hypersensitivity, which typically begin more than six hours after the last administered dose and often after days of treatment. The epidemiology, risk factors, diagnosis, and management of the most common types of delayed reactions to penicillins will be discussed here.
A drug allergy (or hypersensitivity) reaction is defined as a specific immunologic reaction to a drug. The classification and pathogenesis of drug allergies are discussed in detail separately. (See "Drug allergy: Classification and clinical features" and "Drug allergy: Pathogenesis".)
The World Allergy Organization (WAO) has recommended categorizing immunologic drug reactions based upon the timing of the appearance of symptoms . This system defines two general types of reactions: immediate and delayed.
●Immediate reactions – Immediate reactions classically begin within one hour of the initial dose in a course or within one hour of the last administered dose. Symptoms may appear slightly later if the drug was administered orally or taken with food so that absorption is slowed. Nevertheless, the period of one hour identifies many of these reactions. When allergic sensitization first develops, the initial symptoms may appear during the latter days of treatment (ie, not following the first dose of the course) but usually within one hour of the last administered dose and then escalate rapidly. Immediate reactions to penicillins are often immunoglobulin E (IgE)-mediated, and signs and symptoms reflect widespread activation of mast cells (table 1). (See "Penicillin allergy: Immediate reactions".)
●Delayed (nonimmediate) reactions – Delayed (nonimmediate) reactions usually appear after more than one dose of drug and typically after days of treatment. For example, delayed cutaneous maculopapular eruptions to amoxicillin classically start on day 7 to 10 of treatment and may even begin 1 to 3 days after cessation of treatment. The symptoms typically begin several hours after the last administered dose, although the timing relative to the last administered dose is variable. However, symptoms should not begin within one hour of the initial dose of a medication. There are different mechanisms underlying various forms of delayed reactions, but they are not IgE-mediated.
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- TAKING A USEFUL DRUG ALLERGY HISTORY
- Focused questions
- Warning signs of potentially severe reactions
- COMMON CUTANEOUS REACTIONS
- - Maculopapular cutaneous eruptions
- - Delayed urticarial eruptions
- Relationship with viral infections
- Management of symptoms
- Referral for allergy evaluation
- Future use of penicillins in patients with low-risk reactions
- - Studies in children
- Our approach
- - Adults
- Our approach
- RARE REACTIONS
- - Fixed drug eruption
- - Acute generalized exanthematous pustulosis
- - DRESS/DiHS
- - Stevens-Johnson syndrome or toxic epidermal necrolysis
- - Serum sickness-like reactions
- - Drug fever
- - Drug-induced cytopenias
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS