Original Article
Oral Challenge without Skin Testing Safely Excludes Clinically Significant Delayed-Onset Penicillin Hypersensitivity

https://doi.org/10.1016/j.jaip.2017.02.023Get rights and content

Background

Penicillins are the drug family most commonly associated with hypersensitivity reactions. Current guidelines recommend negative skin tests (ST) before re-administering penicillins to patients with previous nonimmediate reactions (NIR).

Objective

The objective of this study was to examine whether ST are necessary before re-administering penicillin to patients with NIR.

Methods

Patients with NIR to penicillins starting longer than 1 hour after last dose administration or starting any time after the first treatment day or patients with vague recollection of their reaction underwent penicillin ST. Disregarding ST results, patients were challenged with the relevant penicillins. One-tenth of the therapeutic dose followed by the full dose was administered at 1-hour interval and patients continued taking the full dose for 5 days.

Results

A total of 710 patients with alleged BL allergy were evaluated. Patients with a history of immediate reaction (52, 7.3%) or cephalosporin allergy (16, 2.2%) were excluded. Of the remaining 642 patients, 62.3% had negative ST, 5.3% positive ST, and 32.4% equivocal ST. A total of 617 (96.1%) patients were challenged. Immediate reaction was observed in 9 patients (1.5%): 1—positive ST, 7—negative ST, and 1—equivocal ST (P = .7). Late reaction to the first-day challenge occurred in 24 patients (4%). An at-home challenge was continued by 491 patients. Complete 5-day and partial challenges were well tolerated by 417 (85%) and 44 patients (8.9%), respectively, disregarding ST results. Thirty patients (6.1%) developed mild reactions to the home challenge regardless of their ST results.

Conclusion

A 5-day oral challenge without preceding ST is safe and sufficient to exclude penicillin allergy after NIR developing during penicillin treatment.

Section snippets

Patients and skin tests

From June 2011 to April 2015 all subjects referred for allergic evaluation of BL hypersensitivity underwent ID ST with PPL (0.04 mg/mL, 1:10 and 1:1), minor determinants mixture (0.5 mg/mL, 1:10 and 1:1) and amoxicillin (20 mg/mL, 1:10 and 1:1) (all produced by Diater, Madrid, Spain), and penicillin G 10,000 U/mL (Teva, Petach-Tikva, Israel). If the culprit BL was different, patients were also tested ID with the relevant drug: amoxicillin-clavulanic acid 20 mg/mL (Augmentin by GSK, Brentford,

Patients

Seven hundred and ten patients with alleged beta-lactam hypersensitivity were screened (Figure 1). Fifty-two patients (7.3%) had histories of an immediate reaction to BL. Therefore, they were excluded from the oral challenge portion of the study. Sixteen patients with cephalosporin hypersensitivity were prospectively identified. Because this group was too small to analyze, and because they are potentially different than the penicillin patients, they were excluded from the rest of the results.

Discussion

Beta-lactams are the most prescribed group of antibiotics, with somewhere between 3.6 g and 23 g per 1000 people per day prescribed in Europe.5 Delayed skin rashes, mostly described as maculopapular or urticarial, are frequently reported in patients administered BL, especially in children. Such rashes are assumed to be a drug-related or viral infection-induced.6 Most physicians, for fear of a future anaphylactic reaction, state to the patients that they are allergic to penicillin and ought to

References (26)

  • E. Macy et al.

    The falling rate of positive penicillin skin tests from 1995 to 2007

    Perm J

    (2009)
  • O. Idsoe et al.

    Nature and extent of penicillin side-reactions, with particular reference to fatalities from anaphylactic shock

    Bull World Health Organ

    (1968)
  • R. Solansky et al.

    Drug allergy: an updated practice parameter

    Ann Allergy Asthma Immunol

    (2010)
  • Cited by (0)

    No funding was received for this work.

    Conflicts of interest: The authors declare that they have no relevant conflicts of interest.

    This study is dedicated to Prof. Arnon Goldberg our beloved mentor, friend, and colleague who passed away in the course of this research.

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