Apparently when I was little, I was given penicillin and had terrible hives,
and the pediatricians told my parents that if I was ever given it again, I would die.
So my entire life I was told that if I ever took penicillin, it would kill me.
Over 95% of people labelled as penicillin allergic are not.
Despite the fears expressed by this patient and those like her, for most people,
penicillin antibiotics are safe and effective.
They are also the optimal treatment for many infections.
It's important for individual patients, as well as the healthcare system as a whole,
that these inappropriate diagnoses be removed from patients medical records.
So all patients with a penicillin allergy diagnosis should be evaluated.
The over-diagnosis of penicillin allergy is the subject of a new JAMA clinical review.
This video covers five toolkits from that review that are a resource for clinicians interested
in performing penicillin allergy testing in their practice.
This video will explain risk stratification of patients undergoing penicillin allergy testing,
patient preparation for testing, testing low risk patients and management of reactions
to oral penicillin challenge including anaphylaxis,
testing moderate risk patients, and follow-up management.
Before testing, you must first determine your patient's penicillin allergy risk level
through a thorough history.
Since there are three parts to penicillin allergy testing-- skin prick, intradermal,
and oral challenge-- identifying a patient as low, moderate,
or high-risk for having a true penicillin allergy will determine what types
of testing they'll need.
The history should include details of the past reaction, if the patient knows any, including
timing relative to the penicillin dose,
and what treatment the patient received at the time of the reaction.
Some examples of low risk patients include the patient who says theyÕre allergic
to penicillin but also reports tolerating a course of Augmentin prescribed
to them at urgent care last year.
Patients like this can be reassured they are not allergic to penicillin.
Patients who report reactions to penicillin that are consistent with intolerance rather
than a true allergy-- such as nausea, vomiting, diarrhea, or headache--
can also be reassured, though a direct amoxicillin challenge may be needed
to provide maximal reassurance to the patient.
On the other hand, patients who have experienced severe reactions to penicillin
in the past, including blistering rash, hemolytic anemia, thrombocytopenia, nephritis,
hepatitis, fever, joint pain, or anaphylaxis, are considered high-risk
and should not be tested, but can be considered for specialist referral.
Patients with unstable or compromised hemodynamic or respiratory status
or pregnancy are always considered to be at least moderate risk
for having a true penicillin allergy.
Anyone else with a history of a reaction temporally associated
with penicillin should undergo some form of penicillin allergy testing.
Once you've determined your patientÕs risk level, you can move on to testing.
Review what medications your patient is currently taking before beginning any part
of penicillin allergy testing.
For higher risk patients, beta-blockers should be held for two days before testing
because beta-blockade can inhibit the action of epinephrine during anaphylaxis.
If challenges are routinely performed in patients on beta-blockers,
your anaphylaxis kit should include glucagon to overcome beta-blockade if necessary.
For skin testing, the patient should not have taken an antihistamine
in the last five days.
Tricyclic antidepressants and antipsychotics can have strong antihistamine activity
that can last a week or longer after stopping the medication.
High doses of immunosuppressants, including steroids, are most likely to interfere
with a delayed response, but may also interfere with skin testing
to rule out IgE-mediated reactions.
However, you can do a skin test as long as there is a positive histamine response,
so you can check a histamine prick test before canceling the test.
After medication review, perform a physical exam, including vitals,
inspection of the oropharynx and uvula, and, if available,
establishing a baseline peak flow meter reading.
Confirm that the patient is in their usual state of health.
Contraindications to testing include acute illness, new medications,
increased rescue inhaler use, increased oxygen requirement, or new chest tightness.
Toolkit E provides a sample anaphylaxis kit checklist.
Prior to any testing, you must have an anaphylaxis kit in the clinical area
that has medications needed to rescue someone in the event of an anaphylactic reaction.
It should also include IV fluids and an IV start kit.
Check the kit before each test to make sure nothing is missing or expired.
Any drug used should be immediately replaced.
Although all sites should have access to a similar kit,
keep in mind that anaphylaxis resulting
from oral amoxicillin challenge testing is an extremely rare event.
If your patient is low-risk, then they can proceed
to the direct oral amoxicillin challenge.
Toolkit B covers the oral amoxicillin challenge for low risk patients, which is a single 250 mg
or 500 mg dose of amoxicillin followed by observation for a minimum of an hour,
with vital sign checks every 30 minutes.
Going directly to the oral challenge is appropriate
for patients who report these symptoms.
Toolkit C outlines oral challenges for moderate risk patients in clinics
without the resources for skin testing.
Following an oral challenge, the most common reactions will be subjective symptoms
such as itching without a rash, a scratchy throat, or vague gastrointestinal symptoms.
These symptoms are often side effects, or result from patient anxiety.
If a patient complains of any of these, check their vital signs and examine them,
looking for objective signs of allergic reaction,
and observe for an additional 30 minutes.
If at that point there are no objective symptoms, the patient can be reassured
that the symptoms were likely not an allergic reaction.
If there are doubts about symptoms resulting from an oral challenge,
then consider specialty referral.
The next most common reactions are mild cutaneous ones that can be treated
with antihistamines like cetirizine or fexofenadine.
Diphenhydramine can be used but will cause drowsiness.
Epinephrine may be used for more diffuse urticarial reactions
and will work more rapidly than antihistamines.
Again, increase the observation period by 30 minutes to make sure there are no signs
of a systemic reaction and that the cutaneous reaction subsides.
These symptoms represent a potential penicillin-allergic response,
so the patient should remain labeled as penicillin allergic
and specialty referral may be considered.
Anaphylaxis typically involves more than two organ systems.
Look for these cutaneous, respiratory, cardiovascular, and gastrointestinal symptoms.
Low blood pressure alone in the setting
of a known allergen exposure is also considered anaphylaxis.
Again, epinephrine can be considered for diffuse urticaria to abort a reaction quickly
and avoid progression to anaphylaxis.
If a patient is having an anaphylactic reaction, get out the anaphylactic kit and open it up.
Lay the patient supine and elevate their legs.
Check the airway, breathing, circulation, and vitals.
Bring the AED if one is available.
Give epinephrine, adjunctive medications, and IV fluids.
And call 911.
For patients determined to be of moderate risk,
skin testing is performed before an oral amoxicillin challenge.
For penicillin allergy skin testing,Êthis is what youÕll need.
These are usually provided in commercially available kits.
In the US, there is one such kit on the market.
The optimal site for both prick and intradermal skin testing is the volar surface
of the forearm or extensor surface of the upper arm.
Note any rash, irritation, or tattoos.
You want to avoid these during skin testing.
Use an alcohol swab to clean the skin.
Once that's dried, use a permanent marker to mark where each reagent will be placed.
Because most negative skin tests are going to be completely invisible,
the markings help you remember where you put the skin test.
We use a plus to indicate the histamine control and a minus to mark the saline negative control.
We use "PP" to indicate PrePen, or the major antigenic determinant.
The placement doesn't matter, though itÕs best to place the histamine furthest
from the major determinant because the flare can bleed into the next test
if a patient has a very strong reaction to the histamine.
Take the applicator from the reagent, then place the applicator on clean, dry, intact skin.
You need to apply a little bit of pressure to break the epidermis.
A small drop of the reagent is going to sit on top of the skin and be absorbed
through the small punctum you've created.
Repeat with the other reagents.
Set a timer for 15 to 20 minutes before interpreting the results.
The test is interpreted by comparing the reaction to the major determinant
with the reactions to the histamine and saline controls.
Begin by blotting off extra reagents from the skin.
Using a reaction measurement guide, measure the size of the wheal,
and the flare across the widest diameter at each site.
There are different acceptable criteria for determining a positive test.
One is a wheal larger than 5 millimeters, as long as the flare is larger than the wheal.
Another is a wheal larger than 3 millimeters,
with a change in the baseline erythema of the flare larger than 5 millimeters.
This histamine site is about 4 millimeters
across the widest diameter of the wheal, and about 42 millimeters across the widest diameter
of the flare, so this is positive as expected.
This saline control is negative as expected.
And at the major determinant site, you see a 5 millimeter wheal and a 31 millimeter flare,
so this skin prick test is positive, which is rarely seen.
Application of topical diphenhydramine or hydrocortisone to the positive histamine control
and other positive tests is rarely needed but can be used to relieve short-lived symptoms.
The histamine test should be clearly positive.
Common reasons for a negative histamine test include inappropriate placement of the test
or inhibition by medications, often antihistamines.
And chronically ill patients may not respond appropriately.
The saline control should be clearly negative.
Common reasons for a positive saline include dermatographia and chronic urticaria.
The next step after negative skin testing is intradermal testing,
before proceeding to the final step, the oral amoxicillin challenge.
Each step increases the negative predictive value of penicillin allergy testing.
The skin preparation and placement of the markings are the same, except you don't have
to place an intradermal histamine control.
For intradermal testing, only sterile reagents in vials are used,
drawn up into tuberculin syringes.
The technique is similar to that used for placing a PPD.
Inject a tiny amount of reagent, approximately 0.02 milliliters,
just below the epidermis, to raise a tiny bleb.
After placing the blebs, wait 15 to 20 minutes
and interpret the results using the same criteria as the skin prick test.
After skin testing is completed, wipe the area down with an alcohol swab.
You can apply topical diphenhydramine or hydrocortisone
to relieve itching from a positive test.
Here we have an example of a negative skin prick test on the left arm,
followed by a negative intradermal test on the patient's right arm;
this is a far more common sight than the positive test demonstrated earlier.
If intradermal testing is negative, you can proceed to the oral amoxicillin challenge,
which is the same as the direct oral amoxicillin challenge
for low-risk patient outlined earlier in this video.
But if a patient reacts during either skin test,
do not proceed to an oral challenge and consider specialty referral.
Most patients don't complain of pain from the skin prick test applicators
or the small needles used for intradermal testing--
though almost everyone will have itching at the site of the histamine test.
Occasionally bruising is seen in patients on antiplatelet drugs or anticoagulants,
but this is easy to distinguish from a positive test.
Fewer than 5 in 100 people undergoing penicillin allergy testing will have a reaction.
These are usually the mild skin reactions that can be managed with antihistamine medications
as outlined earlier in this video.
Again, anaphylaxis during penicillin allergy testing is extremely rare.
Once testing is complete, the patient's chart needs
to be clearly and thoroughly updated.
If testing is negative, removing a label of penicillin allergy can be difficult.
First, edit the penicillin allergy entry in the allergy record,
adding details of the thorough allergy history you took prior to testing.
Use the free text box most EMRs will have to document the test date and the result.
Then delete the allergy from the record.
Some EMRs will require a reason to delete an allergy.
Something like "resolution of allergy" is appropriate.
Second, provide documentation for the patient to share with other clinicians and pharmacists.
Ideally, your clinic will take the time
to communicate directly with the patientÕs pharmacy.
If you're not the patient's primary care clinician, the results also need
to be communicated directly to the primary care clinician.
Finally, communicate to the patient that they should call you if they develop new symptoms
like itch or rash in the next 24 hours or if the site of a skin test turns hard and itchy.
A negative test consisting of negative skin testing and a minimum of one hour of observation
after an oral challenge means that the patient does not have a risk
of an immediate reaction, but the risk of a delayed reaction
at the population level is between 2-5%.
If a delayed reaction develops, either at the site of skin testing, or as a rash,
this should be clearly documented, ideally including a photograph,
and specialty referral considered.
If testing is positive, again,
you'll need to first edit the penicillin allergy record in the EMR, adding the details
about the patient's allergy history that you've elicited, and adding the test date
and results that demonstrate allergy, whether it's a positive skin test
or a reaction to an oral challenge.
Specify the subjective and objective findings of the reaction.
Second, provide the patient with documentation for their outside clinicians and pharmacy.
Again, ideally youÕll communicate directly
with the patient's pharmacy and primary care clinician.
Third, let the patient know that positive tests can wane over time
so that re-testing in 5 years should be considered.
Finally, instruct the patient to avoid all penicillins, cephalosporins,
and carbapenems until they undergo further evaluation by specialists if deemed appropriate.
The need for specialty care can be based on the patient's specific health needs.
Some additional considerations: tolerance of a cephalosporin or other beta-lactam
in a patient labelled penicillin allergic does not rule out penicillin allergy.
Tolerance of a penicillin in a patient with a history
of a cephalosporin allergy does not rule out a cephalosporin allergy.
This is because cross-reactivity
between different beta-lactams can occur based on shared side chains.
In the setting of positive penicillin skin testing, consider specialty consultation
for further testing to assess for cross-reactivity
between penicillin and other beta-lactams.
Or, if a patient has a history of a cephalosporin allergy
and negative penicillin skin testing and amoxicillin challenge,
consider specialty referral for further testing to address the cephalosporin allergy.
Patients with a history of reaction to Augmentin may have reacted
to the clavulanate component rather than amoxicillin, so negative penicillin skin testing
and oral amoxicillin challenge does not exclude Augmentin allergy in these patients.
A specialist can test for sensitivity to clavulanate.
Finally, the information provided in this video isÊapplicable toÊadult populations
in the US.
There are extra considerations when testing kids, hospitalized patients, and pregnant women,
so these patients should be evaluated by specialists.
Given the large burden of inaccurate penicillin allergy diagnoses,
a clinician who starts allergy testing
in their practice will be helping their own patients,
should those patients need penicillin therapy in the future, and also be contributing
at the population level, reducing costs and minimizing a major contributing factor
in the antimicrobial resistance crisis.
For more information, read the full clinical review at JAMA.com.