An ENT Guide to Penicillin Allergy Testing

An ENT Guide to Penicillin
Allergy Testing
Bryan D. Leatherman, M.D., FAAOA
Coastal Ear Nose and Throat Associates
Coastal Sinus and Allergy Center
Penicillin Allergy
Frequency of all adverse reactions to penicillin in
the general population ranges from 0.7% to 10%
The prevalence of true penicillin allergy in the
general population is unknown.
The incidence of self-reported penicillin allergy
ranges from 1% to 10%
90% of these not truly allergic
Frequency of life-threatening anaphylaxis
estimated at 0.004% to 0.015% of penicillin
courses.
Mayo Clin Proc. • March 2005;80(3):405-410
JAMA, May 16, 2001—Vol 285, No. 19
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Frequency of Allergic Skin Reactions to Drugs Among 22,227 Inpatients
All Other Drugs
B Lactam Antibiotics
(50%)
Quinidine
Dypyrone
Blood Products
Arndt and Jick, J.A.M.A. 235:918,1976
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Why Test
Most people who think they are penicillin
allergic are not.
– Rash part of viral syndrome
– Penicillin sensitivity diminishes over time
50% of lose their sensitivity after 5 years
80% by 10 years
Ann Allergy 2010; 105:273e1 - 273e78
Allows advantages of penicillin use
– Efficacy, low cost, decrease resistance, etc.
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History Alone Not Sufficient
The positive predictive value for the
clinical history of penicillin allergy is 14%
(95% CI, 12%-18%)
– JAMA, May 16, 2001—Vol 285, No. 19
Approximately one third of patients with
positive penicillin skin test results report
vague reaction histories.
– Clin Allergy. 1981;11:579–587.
Safety
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Contraindications to Testing
Patients with clear histories of severe skin
reactions such as Stevens-Johnson
syndrome or toxic epidermal necrolysis
PRE-PEN is contraindicated in those
patients who have exhibited either a
systemic or marked local reaction to its
previous administration
Clear history of life-threatening
anaphylaxis to penicillin
Use the Right Testing Products
Depending on the population studied, as many
as 75% of penicillin skin test–positive patients
showed positive responses to only
penicilloylpolylysine
10% to 20% of penicillin-allergic patients show
skin test reactivity only to penicilloate or
penilloate.
Need test with:
– Major determinant - penicilloyl
– Minor determinants
penicilloate and penilloate most important – not available
Ann Allergy 2010; 105:273e1 - 273e78.
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Use the Right Testing Products
Penicillin challenge of individuals skin test
negative to penicilloylpolylysine and pen G
have similar reaction rates compared with
individuals skin test negative to the full set
of major and minor penicillin determinants.
Until full MDM commercially available,
penicilloylpolylysine and pen G are
adequate for testing for penicillin allergy
Ann Allergy 2010; 105:273e1 - 273e78.
Testing for Penicillin Allergy
In-vitro IgE Testing
Allergen specific IgE testing (in vitro)
– Four penicillin forms available
Penicilloyl G
Ampicilloyl
Penicilloyl V
Amoxicilloyl
High specificity, but about 70% sensitivity
– High IgE values have can help confirm Type I allergy
– Negative test does not rule out Type I allergy
Does not test minor determinants
I sometimes use these in patients with history
of severe reaction (not clearly from drug
reaction) prior to skin testing.
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Basic Testing Procedure
Initial skin prick tests
– Histamine, saline, PRE-PEN, and Pen G
– If “negative”, proceed to intradermal tests
Intradermal tests
– PRE-PEN and Pen G in duplicates
– Saline control
– If “negative” proceed with oral challenge
Oral Challenge
– Oral agent, such as amoxicillin, in clinic
– Graded challenge if high risk by history
Systemic Reaction During Penicillin
Skin Testing
1710 patients with penicillin allergy history
were skin-tested for penicillin
Tested with benzylpenicilloyl polylysine (PrePen), penicillin G (10,000 units/ml), and
penicilloate (0.01M).
86 patients had positive penicillin skin tests
– 2 had systemic reactions.
Overall systemic reaction rate = 0.12%
– 2.3% for the penicillin skin test-positive group
– no fatalities.
Valyasevi MA, VanDellen RG. Frequency of systematic reactions to
penicillin skin tests. Ann Allergy Asthma Immunol. 2000;85:363–365.
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Other Studies of Systemic Reactions
with Penicillin Skin Testing
Green, et al. J Allergy Clin Immunol
1977;60:339 –343.
– 3 systemic reactions among 412 with positive
skin tests
– No fatalities
Gadde, et al JAMA 1993;270:2456–2463
– 5063 patients penicillin skin tested
– Systemic reaction rate of 0.26%
– No fatalities
Do Not Be Complacent
3 fatalities reported in the literature after both
scratch and intradermal skin tests to penicillin
– Van Dellen RG, Gleich GJ. Penicillin skin test as
predictive and diagnostic aids in penicillin allergy.
Med Clin North Am 1970;54:997–1007.
– Van Dellen RG. Skin testing for penicillin allergy.
J Allergy Clin Immunol 1981;68:169.
2 deaths during penicillin testing
– Valyasevi. Ann Allergy Asthma Immunol.
2000;85:363–365
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Oral Challenge Safety
In high-risk patients, if testing is performed
with only PRE-PEN and penicillin G, initial
administration of penicillin may need to be
done via graded challenge (ie, 1/100 of the
dose
– followed by the full dose if no problems
Resensitization to Penicillin
Several studies have addressed the issue
of resensitization (ie, redevelopment of
penicillin allergy) in patients with negative
penicillin skin test results.
– Resensitization after oral treatment with
penicillin is rare
– Resensitization after high-dose parenteral
treatment with penicillin appears to be more
likely; therefore, repeat penicillin skin testing
in this situation may be warranted.
Ann Allergy 2010; 105:273e1 - 273e78
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Systemic Reactions After Negative
Penicillin Skin Test
Macy reported an adverse reaction rate to
therapeutic courses of penicillin class
antibiotics during the year after a negative
penicillin skin test of 3.2% (3 of 93).
– J Allergy Clin Immunol 1998;102:281–285.
Systemic Reactions After Negative
Penicillin Skin Test
6739 patients with positive histories of
penicillin allergy and negative skin test
results were given penicillin
– 101 (1.49%) developed an IgE-mediated
reaction
– 43 (0.63%) developed a delayed reaction
– No anaphylaxis
JAMA, May 16, 2001—Vol 285, No. 19
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Systemic Reactions After Negative
Penicillin Skin Test
American Academy of Allergy sponsored study
346 patients with a skin test that was negative to
the major determinant and penicillin G were
challenged with penicillin.
– Twelve patients (3%) had an ADR
– Only 3 of the 12 (1% of total patients) were believed
to be IgE-mediated.
– 97% to 99% of patients with negative penicillin skin
tests will tolerate penicillin with no risk of an
immediate reaction
Systemic Reaction Rates After
Penicillin Testing
Gadde, et al JAMA 1993;270:2456–2463
– 73% high-dose parenteral challenge
– 649 positive by history and skin-test negative were
challenged
2.9% (N=17) IgE mediated adverse reactions
– 9 immediate (<1 hour)
– 8 accelerated (1-72 hours)
2 of these were anaphylactic
8 additional delayed reactions (>72 hours)
– 0.5% of subjects negative by history had IgE reaction
3 immediate
16 accelerated
No anaphylaxis
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Implementing Penicillin Allergy
Testing Into Your Practice
Where To Start
Get Information
– ALK
Website: PRE-PEN.com
Representatives
– Published literature
Assess your clinic space and staff
– Minimal space needed
– Fits well into existing allergy practices
Skills needed likely already in place
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Where To Start
Obtain supplies
Appropriate support paperwork
Physician education
Education of office staff
Start testing
– Self generated patients first
Referring physician and community
marketing
Office Space and Staff
Requirements
Testing room
Observation area for oral challenge
– Can be testing rooms if available
– Reception/waiting room area – educate front
staff
Allergy testing staff
– Same staff and skill sets as inhalant allergy
skin testing
– Does your existing staff have time?
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Supplies
Allergy emergency supplies
– Epinephrine at minimum
– Same as for other skin testing and
immunotherapy
PRE-PEN
Penicillin G (10,000 units/ml)
– Must be intraveneous preparations (Na+ or K+)
– Henry Schein – get single vial, not multi-pack
Product #: 7459156
– Local pharmacy
– Keep single unit testing vials available in freezer
Supplies
Controls
– Plain normal saline (not phenolated)
– Histamine
Skin prick device
– Duotip, Greer Pick, Brown Morrow, etc
Skin marker to label test sites
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Supplies
Skin testing needles
– Standard testing needles with intradermal
bevel
Measuring device
Alcohol swabs
Penicillin product for oral challenge
– Amoxicillin most commonly used
– Amoxicillin 250 mg stock bottle kept in office
– Prescription for amoxicillin liquid
Paperwork
Allergy test instructions
– Stop antihistamines, clothing type, etc.
Penicillin allergy skin testing consent form
– Available from ALK Abello
• Test record - Available from ALK Abello
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Billing*
Skin prick testing: Charge 95010 x 4 units
–
–
–
–
PrePen x 1
Pen G X 1
Histamine x 1
Saline x 1
Intradermal skin testing: Charge 95015 x 5 units
– PrePen x 2
– Pen G x 2
– Saline x 1
Ingestion challenge test: charge 95075 x 1 unit
* Dr. Leatherman’s personal billing strategy. Each physician is responsible to
ensure they are billing according to the policies of individual payers.
Billing
ICD-9 Codes available
– 995.27: Other drug allergy
– 995.0: Other anaphylactic shock
– V14.0: Personal history of allergy to penicillin
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Practical Office Flow
Patient Identification
Patient identified as potentially penicillin
allergic
– In office: I discuss testing with any patient who
indicates penicillin allergy on their history form.
– Referrals: I choose to see the patient first to
evaluate their history and determine if allergy
testing is appropriate.
– Those appropriate for testing are offered testing
and scheduled for another date if they accept.
– Testing date scheduled and information sheet
given
Amoxicillin for Oral Challenge
Amoxicillin 250 mg pills
– Keep a stock bottle in office
– Write your practice a prescription
Liquid amoxicillin for pediatric testing
– I write prescription for amoxicillin 250 mg/5 mL
Dispense 50 mL
Instructions: take to physicians office for allergy
testing, do not use at home.
Give appropriate dose for weight in office
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Practical Office Flow
Testing Date
Standard pre-skin testing safety questions
Initial histamine positive control applied
– Prior to opening PRE-PEN product
– If appropriate reaction, proceed with testing
Skin testing performed in allergy testing
room
– Skin prick
– Intradermal
Practical Office Flow
Testing Date
Oral challenge
– Appropriate amoxicillin dose given
– Patient stays in office for one hour observation
Patient remains in testing area if space available
Patient can go to standard reception/waiting area
– Instructed to inform staff of any new symptoms
– Front office staff educated
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Practical Office Flow
Testing Date
Physician reviews results with patient
Negative results
– Inform patient still very small risk of having an
immediate reaction
– Inform patient to notify other physicians they
have been tested and are no longer
considered penicillin allergic
– Inform patient it is safe for them to use
penicillin antibiotic products
Practical Office Flow
Testing Date
Negative results
– Inform patients of small possibility of developing
penicillin allergy again in the future. Notify you if
any questionable reactions.
– Inform patients that high-dose intravenous
penicillin may present a higher risk of recurrence
of penicillin allergy, so consider coming for
retesting after any such treatment.
– Encourage patients to use this information!
– Patient released unless followed for other
reasons.
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Practical Office Flow
Testing Date
Positive tests
– Inform patients testing has confirmed
penicillin allergy
– It is best to avoid any penicillin related
products
– Patient released from clinic unless followed
for other reasons
Personal Experience
A large number of my existing patients claim
penicillin allergy that has not been confirmed.
– Most have vague history with low likelihood of
true allergy
– Most patients are eager to be tested
Most penicillin allergy testing comes from
patients in my office for other reasons
– I have a brochure about penicillin allergy
displayed in my waiting area
– I have started getting some referrals specifically
for penicillin allergy testing
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Personal Experience
Penicillin allergy testing was an easy addition
to my existing allergy testing
There is no product label restriction on
patient age
– I have tested children down to age 2
Especially if have multiple potential antibiotic allergies
which are limiting treatment options for infections
Penicillin allergy testing has been reasonably
profitable
Penicillin allergy testing is yet another service
your practice can offer to patients and
referring physicians. This boosts your overall
value and reputation.
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