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#371 It’s time to challenge penicillin allergy labels!


CLINICAL QUESTION
QUESTION CLINIQUE
 Can low-risk patients with beta-lactam allergy receive an oral beta-lactam challenge safely?

BOTTOM LINE
RÉSULTAT FINAL
 In adults with a history of non-severe cutaneous reaction to a beta-lactam over 5-10 years ago, the penicillin allergy label can be removed 87-98% of the time. Direct oral challenge with a beta-lactam is likely as safe and effective as doing a skin test first. Risk of severe adverse reactions <1%.


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EVIDENCE
DONNÉES PROBANTES
  • Oral challenge alone versus skin testing followed (if negative) by oral challenge:
    • Two randomized controlled trials (RCTs) in patients recruited from allergy outpatient clinics, with non-severe cutaneous reaction to beta-lactam >1 year ago (children)1 or >10 years ago (adults).1,2
      • First RCT (382 adults), amoxicillin 250-500mg:2
        • No serious adverse effects, hospitalizations or emergency room visits.
        • Penicillin allergy label removed: >98% (both groups).
        • Immune mediated reaction <1 hour after test: One in each group (cutaneous, mild).
        • Delayed rash/urticaria: 3.2% versus 1.6% (skin test first), no statistical difference.
      • Second RCT (159 adults/children), amoxicillin 20-40mg then 200-400mg 30 minutes later based on age/weight:1
        • Reaction <30 minutes after test: 4% (cutaneous, mild) versus 0% (skin test first), no statistical difference (PEER calculation).
        • Penicillin allergy label removed: 96% versus 87% (skin test), no statistical difference.
  • Oral challenges with no prior skin testing: Six systematic reviews of cohort studies, children/adults, mostly outpatients (2-31 cohorts, 595-6,980 oral challenges):3-8
    • Immediate/delayed hypersensitivity reactions: 2.7-8.8%.3-7
    • Severe reactions (examples: anaphylaxis needing epinephrine, serum-like illness, interstitial nephritis): 0-0.04%.6-8 Additional systematic review: Inconsistent reporting.3
  • Limitations: Various definitions of “low-risk patients” or harms (example: anaphylaxis), limited data in primary care.
CONTEXT
CONTEXTE
  • Penicillin “allergy”: Reported in ~10% of the general population.9
  • Amoxicillin associated with non-IgE (delayed onset) rash in ≤7% children; associated with concurrent viral infection.10
  • Guidelines recommend:10
    • Direct amoxicillin challenge (with no preceding skin test): Adults with remote (>5 years ago) and benign cutaneous history.
    • Skin test: Patients with history of anaphylaxis/recent IgE-mediated reaction (example: immediate onset urticaria).
    • Avoid testing: Patients with severe cutaneous reactions to beta-lactams (examples: DRESS, Stevens-Johnson syndrome).
    • Single-step or 2-step challenge (10% of therapeutic dose then remaining dose after 30-60 minutes), with 60-minute observation.

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Author(s)
Auteur(s)
  • Émélie Braschi MD PhD CCFP
  • Samantha S. Moe PharmD

1. Mustafa SS, Conn K, Ramsey A, et al. J Allergy Clin Immunol Pract. 2019; 7(7):2163-2170.

2. Copaescu AM, Vogrin S, James F, et al. JAMA Intern Med. 2023 Sep 1; 183(9):944-952.

3. Loprete J, Richardson R, Bramah V, et al. J Allergy Clin Immunol Glob. 2023 Aug 9; 2(4):100160.

4. Powell N, Stephens J, Kohl D, et al. Int J Infect Dis. 2023 Apr; 129:152-161.

5. DesBiens M, Scalia P, Ravikumar S, et al. Am J Med. 2020 Apr; 133(4):452-462.e4.

6. Cooper L, Harbour J, Sneddon J, et al. JAC Antimicrob Resist. 2021 Jan 27; 3(1):dlaa123.

7. Srisuwatchari W, Phinyo P, Chiriac AC, et al. J Allergy Clin Immunol Pract. 2023 Feb; 11(2):506-518.

8. Cardoso-Fernandes A, Blumenthal KG, Chiriac AM, et al. Clin Transl Allergy. 2021 Jun; 11(4):e12008.

9. Jeimy S, Ben-Shoshan M, Abrams EM, et al. Allergy Asthma Clin Immunol. 2020 Nov 10; 16(1):95.

10. Khan DA, Banerji A, Blumenthal KG, et al. J Allergy Clin Immunol 2022; 150(6):1333-93.

Authors do not have any conflicts of interest to declare.