#371 It’s time to challenge penicillin allergy labels!
CLINICAL QUESTION
Can low-risk patients with beta-lactam allergy receive an oral beta-lactam challenge safely?
BOTTOM LINE
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
- 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.
- First RCT (382 adults), amoxicillin 250-500mg:2
- 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
- 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
- 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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How exactly do we do these challenges? Should they be done in the office and have the patient stay in the waiting room for an hour and keep an antihistamine and epi nearby? Or just send them home and tell them to call/go to the emergency if they have a problem?
can try oral challenge
Wow, new life for penicillin in a previously allergic person,
WIll have to dispell “fear” in patients about their “allergy”
This makes sense and can allow most patients previously labelled as allergic to penicillin to use it.
I must confess that I have never thought to challenge old documented Penicillin allergies. I might just do this!
Most patients with a “penicillin allergy” have been carrying that albatross since childhood. “I was told” and there is no clear history of a rash or severe allergic reaction. Penicillin is still a very useful antibiotic!
I have been sending most pts without a clear history of anaphylaxis to allergy clinic to get the designation removed. If I was in a remote area I would likely do allergy challenge in office.