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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.


Perminder Sahota August 11, 2024

can try oral challenge

Michael Hancock September 30, 2024

Wow, new life for penicillin in a previously allergic person,

Martin Potter October 6, 2024

WIll have to dispell “fear” in patients about their “allergy”

Donald HIckman November 20, 2024

This makes sense and can allow most patients previously labelled as allergic to penicillin to use it.

Dennis Neufeld December 4, 2024

I must confess that I have never thought to challenge old documented Penicillin allergies. I might just do this!


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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.