An ENT Guide to Penicillin Allergy Testing. Bryan D. Leatherman, M.D., FAAOA Coastal Ear Nose and Throat Associates Coastal Sinus and Allergy Center

Transcription

1 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): JAMA, May 16, 2001 Vol 285, No. 19 1

2 Frequency of Allergic Skin Reactions to Drugs Among 22,227 Inpatients All Other Drugs B Lactam Antibiotics (50%) Quinidine Dypyrone Blood Products 3 3 Arndt and Jick, J.A.M.A. 235:918,1976 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. 2

3 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: Safety 3

4 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. 4

5 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 Penicilloyl V Ampicilloyl 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. 5

6 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 (Pre- Pen), 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:

7 Other Studies of Systemic Reactions with Penicillin Skin Testing Green, et al. J Allergy Clin Immunol 1977;60: systemic reactions among 412 with positive skin tests No fatalities Gadde, et al JAMA 1993;270: 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: Van Dellen RG. Skin testing for penicillin allergy. J Allergy Clin Immunol 1981;68: deaths during penicillin testing Valyasevi. Ann Allergy Asthma Immunol. 2000;85:

8 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 8

9 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: 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 9

10 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: % 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 10

11 Implementing Penicillin Allergy Testing Into Your Practice Get Information Where To Start 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 11

12 Obtain supplies Where To Start 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? 12

13 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 #: Local pharmacy Keep single unit testing vials available in freezer Controls Supplies Plain normal saline (not phenolated) Histamine Skin prick device Duotip, Greer Pick, Brown Morrow, etc Skin marker to label test sites 13

14 Skin testing needles Supplies 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 14

15 Billing* Skin prick testing: Charge x 4 units PrePenx 1 Pen G X 1 Histamine x 1 Saline x 1 Intradermal skin testing: Charge x 5 units PrePenx 2 Pen G x 2 Saline x 1 Ingestion challenge test: charge 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 : Other drug allergy 995.0: Other anaphylactic shock V14.0: Personal history of allergy to penicillin 15

16 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 16

17 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 Oral challenge Practical Office Flow Testing Date 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 17

18 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. 18

19 Positive tests Practical Office Flow Testing Date 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 19

20 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. 20