Strategies to Successfully Manage Complex Drug Allergy Patients

Transcription

1 Strategies to Successfully Manage Complex Drug Allergy Patients David A. Khan, MD Professor of Medicine and Pediatrics Allergy & Immunology Program Director 1

2 Disclosures Research Grants NIH, Vanberg Family Fund Honoraria UpToDate, Genentech Consulting Aimmune (DSMB) Organizations: Joint Task Force on Practice Parameters AAAAI BOD 2

3 Objectives Be able to identify patients appropriate for drug skin testing vs. drug challenges and understand the techniques involved Be able to identify patients in whom placebo testing may be beneficial Be able to identify patients appropriate for drug desensitization and understand which protocols are appropriate 3

4 Reasons To Hate Drug Allergy Patients are crazy Few validated testing materials Safety concerns Dislike of inpatient consults Poor reimbursement Frustrating 4

5 Reasons to Embrace Drug Allergy Patient satisfaction Provider satisfaction Nobody does it better than we do You can still pay the rent All procedures safe to do in the office 5

6 Strategies for Success Be patient with history taking Establish expectations Break it up Establish a relationship with a pharmacist Be adventurous Don t get too hung up on protocols Sniff out VCD 6

7 The Odds Are on Your Side! Frequency of Confirmed Drug Allergy Not Allergic Allergic Drug Challenges confirm not allergic : ok to treat with drug Skin tests and history confirm allergic : avoid drug or desensitize 7

8 What s In Our Drug Allergy Toolbox? History/History/History Immediate Skin Testing Delayed Skin Testing Drug Challenges Placebo Challenges Laryngoscopy In vitro tests??? Drug Desensitizations Not Allergic Allergic 8

9 History Taking in Drug Allergy 9

10 Key Features of Drug Allergy History Question How long ago was reaction? Description of rash or hives (showing pictures helps???) Symptoms objective or subjective? When did reaction occur? What therapy required? Similar symptoms in absence of drug? Relevance Some drug allergies tend to wane over time (e.g. penicillin, cephalosporins Most patients can t differentiate urticaria from other rashes Urticaria more suggestive of IgEmediated reaction Subjective symptoms often anxietyrelated Immediate vs. delayed reaction Gauge of severity Underlying disease not drug allergy (e.g. chronic urticaria) Khan DA, Solensky R. J Allergy Clin Immunol 2010;125:S

11 Features Suggestive of True Drug Allergy Objective findings Rash Wheezing, hypoxia Hypotension Rational temporal relationship to drug allergy-prone drug Resolution with discontinuation 11

12 Features Less Suggestive of Drug Allergy Subjective symptoms only swelling, pruritus isolated throat symptoms High number of listed drug allergies Stereotypical reactions History of a childhood reaction 12

13 Is This Angioedema? 13

14 Immediate Skin Testing 14

15 Drug Antibiotics Immediate Skin Tests in Drug Allergy Chemotherapeutics Perioperative agents Biologics Corticosteroids, PPIs Insulin, Heterologous sera Local anesthetics NSAIDs Radiocontrast media ACE-I Comment Penicillin best characterized with good NPV Cephalosporins may have good NPV Other antibiotics have unknown NPV Platinum based drug ST useful ST helpful in cases of perioperative anaphylaxis Non-irritating concentrations not well established May be useful May be useful Not useful Not useful?? useful Not useful NPV: negative predictive value Solensky R, Khan DA et al. Ann Allergy Asthma Immunol 2010;105:273e1-e78.

16 Immediate Drug Skin Testing Always Penicillin Platinum based chemotherapeutics Perioperative agents Local Anesthetic Drug anaphylaxis Insulin Corticosteroids Maybe Other antibiotics Biologics PPIs Never Anti-hypertensives Lipid lowering agents Anti-seizure agents 16

17 Penicillin Skin Test Reagents Major determinant (BPO) 95% PCN reacts with self-proteins via beta-lactam ring to form benzylpenicilloyl (BPO) PRE-PEN (penicilloyl-polylysine) used as major determinant skin test reagent Minor determinants (referred to as minor determinant mixture [MDM]) penicilloate Penilloate penicillin G

18 MDM Needed 10% detected only by MDM Good NPV with higher prevalence of positive skin tests anaphylaxis histories more recent reactions MDM Not Needed Clinical significance of MDM+ skin tests unknown MDM not a commercial product and not analyzed for potency Amoxicillin challenge after negative PRE-PEN and PCN-G safe in >1500 patients Solensky R, Macy E. J Allergy Clin Immunol Practice 2015;3:

19 Single Dose vs Extended Penicillin Challenges Overall ~4-6% patients will report benign rashes after extended (5-7 day) challenges All of these rashes are self-reported Are they really drug allergic reactions? I personally do not perform extended challenges educate patient that low risk of having a delayed mild rash, if rash occurs to contact us Avoids an unnecessary course of antibiotics Hjortlund et al. Acta Derm Venereol 2012;92:307. Mori F et al. J Allergy Clin Immunol Pract 2015;3: Ratzon R et al. Ann Allergy Asthma Immunol Apr;116(4):

20 Are Penicillin Skin Tests Needed in Children? Mill C, et al. JAMA Pediatr. 2016;170(6):e

21 Challenge Protocol: 10% dose then 20 min later 90% dose amoxicillin All immediate and delayed reactions were mild (few cases of SSL reactions) 21

22 No features predicted immediate reactions to challenge. Children with histories of rashes persisting > 7 days (OR=4.8) and those with a parental history (OR=3.0) were more likely to have a delayed reaction 22

23 PCN Allergy Label Associated with Higher Serious Infections Patients labeled with PCN allergy more likely to receive quinolones, clindamycin and vancomycin These patients had longer hospitalizations and higher prevalence of C.difficile, MRSA and VRE infections J Allergy Clin Immunol 2014;133:

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25 Penicillin Allergy Testing Service (PATS) Established November 2014 Collaboration between the UT Southwestern Division of Allergy & Immunology and Pharmacy Services at Parkland Utilizes a dedicated allergy pharmacist trained by A&I physicians Patients seen by referral from the primary team or through a selection process to be discussed in this presentation

26 Selection of Inpatients to Undergo Penicillin Testing Chen J et al. J Allergy Clin Immunol Pract 2016 (in press). 26

27 Outcomes of Proactive In Patient Penicillin Testing Chen J et al. J Allergy Clin Immunol Pract 2016 (in press). 27

28 PCN Allergy Testing We need to do more!! Developing a partnership with local hospitals may be a consideration 28

29 Cross-Reactivity Amongst Cephalosporins 102 subjects from Italy with immediate (mostly anaphylactic) reactions to cephalosporins underwent skin testing to alternative cephalosporins Subjects divided into 4 groups based on skin test reactions A: common R1 methoxyamino group (71%) B: common R1 amino group (13%) C: other structurally unrelated cephalosporins (7%) D: 2 or more of above groups A, B, C (9%) In this study, 91% of cephalosporin allergy is based on sidechain structure All 102 subjects tolerated 326 challenges to other cephalosporin groups that were skin test negative Romano A et al. J Allergy Clin Immunol 2015;136:

30 Cephalosporin Cross-Reactivity Group A (common methoxyamino group) Ceftriaxone,cefotaxime, cefuroxime, cefepime, ceftazidime* Group B (common amino R1 group) Cefaclor, cephalexin, ceadroxil Group C (unique R1 side chains) Cefazolin Cefamandole Cefoperazone Ceftibuten Romano A et al. J Allergy Clin Immunol 2015;136:

31 Antimicrobial drug Nonirritating concentration Full-strength concentration Dilution from full strength azithromycin 10 g/ml 100 mg/ml 1:10,000 cefotaxime 10 mg/ml 100 mg/ml 1:10 cefuroxime 10 mg/ml 100 mg/ml 1:10 cefazolin 33 mg/ml 330 mg/ml 1:10 ceftazidime 10 mg/ml 100 mg/ml 1:10 ceftriaxone 10 mg/ml 100 mg/ml 1:10 clindamycin 15 mg/ml 150 mg/ml 1:10 cotrimoxazole 800 g/ml 80 mg/ml 1:100 erythromycin 50 g/ml 50 mg/ml 1:1000 gentamicin 4 mg/ml 40 mg/ml 1:10 levofloxacin 25 g/ml 25 mg/ml 1:1000 imipenem/cilastin 0.5 mg/ml 500 mg/100 ml 1:10 meropenem 1 mg/ml 50 mg/ml 1: 50 nafcillin 25 g/ml 250 mg/ml 1:10,000 ticarcillin 20 mg/ml 200 mg/ml 1:10 tobramycin 4 mg/ml 80 mg/2 ml 1:10 vancomycin 5 g/ml 50 mg/ml 1:10,000 Khan DA. Drug Allergy. In Manual of Allergy & Immunology 5 th Ed. (2012) 31

32 Anesthetic Drugs Perioperative Period Preoperative Intraoperative Postoperative Medications Used Antibiotics, opiods, latex, chlorhexidine, blood/colloids, benzodiazepines Neuromuscular blocking agents (NMBA), hypnotics, opioids, neuroleptics, benzodiazepines, local anesthetics, dyes, contrast, latex, aprotinin, chlorhexidine, blood/colloid Opioids, NSAIDs, neostigmine, atropine/glycopyrrolate Thong BYH et al. Ann Allergy Asthma Immunol. 2004;92:

33 Kuhlen JL et al. J Allergy Clin Immunol Pract Jul-Aug;4(4):

34 43/45 tolerated subsequent anesthesia Guyer AC et al. J Allergy Clin Immunol Pract 2015;3:

35 Subsequent Anesthesia after Perioperative Anaphylaxis Data from Sydney reported largest experience of follow up of perioperative anaphylaxis patients 52 patients with negative skin and in vitro tests 1/52 had a reaction likely due to latex which was not tested at the time 301 patients with positive skin tests 295 had no reaction 6/301 (2%) had 2 nd anaphylactic reaction 2 NMBA not tested 4 NMBA with false-negative reaction Fisher MM, Doig GS. Drug Safety 2004;26:

36 Perioperative Testing Skin testing and history is most useful tool to identify causal agent < 2/3 cases a causal agent can be identified by skin testing 1/3 cases the causal agent is unclear Referred to as non-ige-mediated reactions in literature After diagnostic evaluation (even if an agent is not identified), majority of patients undergo anesthesia safely

37 Key Principles in Drug Skin Testing Ensure you are using non-irritating concentrations Always start with prick tests Dilute with saline (not sterile water) Even patients who have coded from anaphylaxis can be skin tested Start with 1/100 th of final concentration Repeat skin tests if results questionable A negative skin test does not mean they are not allergic 37

38 Skin Testing for Delayed Drug Reactions Role of Drug Patch Tests 38

39 Drug Allergy Skin Testing in Delayed Cutaneous Reactions Eruption Patch Test Prick/ Intracutaneous Test Maculopapular rash Useful (10-40% cases +) may be useful Eczema may be useful may be useful SDRIFE Useful (50-80% of cases)? AGEP may be useful? Fixed Drug may be useful? (on residual area) DRESS Useful (30-60% of cases) Not recommended Perform 6 months SJS/TEN Rarely helpful (9-23% positive) Not recommended Barbaud A. Curr Allergy Asthma Rep (2014) 14:

40 In Situ Patch Testing for Fixed Drug Eruptions Maximum Strength Menstrual Relief Acetaminophe n Acetaminophen MSMR Ibuprofen Naproxen Aspirin Petrolatum control

41 Patch Tests in Severe Cutaneous Adverse Reactions (SCAR) Patch tests with 30-10% drug in petrolatum Started at 1% for SJS/TEN Read on day 2 and 4 Average time from reaction to patch test was 3.7 months Barbaud et al. Br J Dermatol 2013;168:

42 Patch Tests in SCAR DRESS 64% + (46/72) 18% + to multiple classes of drugs 5 due to PPIs AGEP 58% + (26/45) 1 pt had flare of AGEP after patch tests SJS/TEN 24% + (4/17) Barbaud et al. Br J Dermatol 2013;168:

43 Drug Patch Testing Conclusions Appears to have an evolving role for some delayed drug reactions Safe Lack of standardized materials makes it cumbersome to do Predictive values not well established May be better than nothing for more severe drug reactions where our only option is avoidance 43

44 Drug Challenges Gold standard for determining tolerance to a drug 44

45 Drug Challenges Given lack of predictive value for most drug skin testing, drug challenges are best method to determine if a patient is not allergic to a drug A patient who passes a drug challenge can be considered not allergic to the drug, and the drug allergy label removed from the chart 45

46 Drug Challenges Intended for patients who are unlikely to be allergic to the given drug May be done in a graded manner or 1 step (full dose) Graded challenges often start at 1/100 th or 1/10 th of final dose The intention of a drug challenge is to verify that a patient will not experience an adverse reaction to a given drug Solensky R, Khan DA et al. Ann Allergy Asthma Immunol 2010;105:273e1-e78. 46

47 6 year retrospective review of safety of drug challenges Excluded patients at known low risk Amoxicillin challenge after negative penicillin skin tests Cephalosporin to penicillin allergic patients Local anesthetic challenges Excluded patients at known high risk AERD patients undergoing aspirin challenge/desensitization Contraindicated patients (e.g. SJS/TEN, DRESS) 47

48 48

49 Safety of Drug Challenges: Adults 1/123 challenges positive Subjective symptoms in 20 patients and were higher with Historically subjective symptoms Female gender >10 listed drug allergies associated Kao L et al. Ann Allergy Asthma Immunol 2013;110:

50 Subjective Symptoms During Drug Challenge Correlate with # Reported Drug Allergies Kao L et al. Ann Allergy Asthma Immunol 2013;110:

51 Retrospective study from Mass General between Low risk history, remote (>10 yrs), and mild reactions Compared 3-4 step (n=74) vs. 1-2 step (n=497) 1 step (n=117) or 2 step (n=380) Antimicrobials (76%), NSAIDs (12%), others Iammatteo M et al. J Allergy Clin Immunol Pract 2014;2:

52 Similar Reaction Rate: Test Dose vs. Multistep challenge 1 or 2 step test dose Multistep challenge Number of Patients Reaction Rate 11% 12% Severe Reactions with Challenge 0% 0% -lactams, quinolones, NSAIDs, opiods most common tested drugs Iammatteo M et al. J Allergy Clin Immunol Pract 2014;2:

53 Common Drug Challenge Methods History of Immediate Drug Reaction Dose Observation 1/10 th dose* 30 minutes Full dose 60 minutes History of Delayed Drug Reaction Dose Day of Challenge 1/10 th dose* 1 Full dose 3-7** *Starting dose may be lower (e.g. 1/100th) if concerning history or comorbid factors **Interval between dose dependent on history and delay in appearance of rash. Depending on patients reaction and physician judgment, observation can be varied but patients should be clearly instructed to return for any symptoms for re-evaluation. 53

54 Local Anesthetic Testing Protocol Prick test with undiluted local anesthetics Subcutaneous challenge with 1.0 ml saline If placebo challenge negative after 20 min., 1.0 ml undiluted local anesthetic subcutaneous injection(s) sequentially Modified from: Macy E et al. Permanente J 2002;6:

55 Subjective Drug Reactions 55

56 Case 39 yo F has a recent history of aspirin ingestion and within 20 minutes developed tongue numbness, tingling in her arms, chest pressure, and lightheadedness. She went to ED and was given another dose of aspirin and had worsening of her symptoms which resolved in hrs Past history notable for latex allergy with contact urticaria, and rhinitis symptoms when exposed to powdered gloves Family history of CAD, HTN 56

57 Case Continued In light of subjective symptoms with aspirin (tongue numbness and lightheadedness) and low likelihood of true allergy a placebo controlled challenge was performed 57

58 Placebo Challenge Results 1 capsule (placebo) administered 30 minutes later complained of tongue numbness Physical exam normal 2 capsules (placebo administered) 15 minutes later Tongue numbness increased and complained of lightheadedness (BP unchanged) All symptoms spontaneously resolved after another 90 minutes 58

59 Aspirin Challenge Discussed results of placebo challenge and reassured her that her symptoms were not medication-induced and no sign of an allergic reaction Proceeded to open challenge with 325 mg aspirin Observed for an hour with no symptoms 59

60 Placebo Controlled Drug Challenges The choice of performing an open vs. a placebo controlled challenge is based on reaction type and patient characteristics Clinical features suggestive of needing a placebo challenge Subjective symptoms of drug allergy (e.g. pruritus) Anxiety level of patient regarding challenge to particular drug Multiple drug allergy patients

61 Placebo Controlled Drug Challenges Techniques Opaque capsules Inert filler Multiple placebos in highly anxious patients For history of delayed reactions, consider full day of placebo followed by active drug on separate day

62 Fagron Placebo Tools

63 Symptoms with Placebo UT Southwestern study of drug challenges 19 patients underwent 21 placebo controlled challenges as an outpatient 57% of placebo challenges resulted in symptoms Signs/symptoms Flushing Pruritus Tongue numbness Throat tightness Kao L et al. Ann Allergy Asthma Immunol 110 (2013) 86e91

64 Tips for the Placebo Talk Validate their reactions are legitimate Reassure them that anxiety is normal with drug challenges Inform them that anxiety reactions can mimic drug allergy and make it hard for you to discern Discuss that placebo challenges help you determine if reaction is anxiety or allergy Indicate that this is a routine practice 64

65 Tips for Management of Placebo/Subjective Reactions Examine the patient Take photos of swelling Reassure that reaction does not appear to be severe Delay next dose of challenge until symptoms resolved or nearly resolved Avoid medications Oxygen may be used if needed as a soothing measure 65

66 Laryngoscopy in the Evaluation of Drug Reactions 66

67 Case 71 yo woman with E. coli UTI and bacteremia developed throat itching, swelling and dysphonia after 4 th dose of ciprofloxacin Changed to meropenem and had similar reaction to 3 rd dose History of multiple drug-induced anaphylaxis with throat closure and dysphonia including penicillin, cephalexin, sulfonamides, tetracycline and clarithromycin Khan DA. Ann Allergy Asthma Immunol 110 (2013) 2e6. 67

68 Case Further questioning No other symptoms with reactions All symptoms localized to throat No witnessed orofacial swelling 68

69 Case After baseline laryngoscopy, open ciprofloxacin IV challenge performed 15 minutes later developed throat itching, tightness and dysphonia Symptoms identical to prior reactions Laryngoscopy showed paradoxical adduction of vocal cords with inspiration Patient informed about findings, taught throat relaxation methods and anaphylactic symptoms aborted in 5 minutes 69

70 Vocal Cord Dysfunction (VCD) Normal glottis Adduction of vocal cords during VCD attack 70

71 Drug-Induced Vocal Cord Dysfunction Histories usually described as anaphylaxis Symptoms localized to throat May have subjective swelling of lips/tongue but lack objective evidence of orofacial swelling May have multiple drugs involved Fiberoptic laryngoscopy is another useful tool in evaluating drug allergy patients Khan DA. Ann Allergy Asthma Immunol 110 (2013) 2e6. 71

72 Few in vitro tests have decent levels of evidence Best evidence based on case control studies for specific IgE, BAT for beta lactams and NMBA and HLA typing for certain drugs (e.g. abacavir) Evidence designations used an old somewhat outdated methodology Allergy 2016;71:

73 Management of Drug Allergic Patients Avoidance and Selection of Alternative Therapies Rapid Drug Desensitization 73

74 Rapid Drug Desensitizations Indicated for patients with: High likelihood or confirmed drug allergy In need of culprit drug where no similarly effective alternative therapy exists Many Rapid Drug Desensitizations Antibiotics Chemotherapeutics Monoclonals Others 74

75 Beta-lactam Drug Desensitization Typical starting dose is 1/10,000 th of target therapeutic dose Can also use calculated dose from skin test as starting point Further dosage increases are typically twice the previous dose Administered at minute intervals until therapeutic dosage achieved 75

76 Oral Penicillin Desensitization Wendel GD et al. New Engl J Med 1985;312:

77 Outcomes and Safety of Penicillin Desensitizations Most all patients can be desensitized ~1/3 patients have mild cutaneous reactions during desensitization Severe reactions extremely rare Delayed reactions (cutaneous, serum sickness, nephritis) <10% Long-acting benzathine penicillin may be administered after desensitization safely at intervals of 1-3 weeks* *Wendel GD et al. New Engl J Med 1985;312:

78 Intravenous Drug Desensitization Protocol: Target Dose 1,000 mg Preparation of Solutions Volume of diluent Total amount drug in each solution Drug Concentration Solution ml 10 mg 0.04 mg/ml Solution ml 100 mg 0.4 mg/ml Solution ml 1000 mg 4 mg/ml Drug Desensitization Protocol Step Solution Rate (ml/hr) Time (min) Administered Dose (mg) Cumulative dose (mg) Total time= 219 min 78

79 Reactions with Rapid Drug Desensitizations Chemotherapy and Biologics 74% had no reaction Severe reactions in 4% Epinephrine administered only twice (0.09%) Most reactions in last few steps of RDD Retrospective Review of 370 patients who underwent 2177 rapid drug desensitizations Sloane D et al. J Allergy Clin Immunol Pract May-Jun;4(3):

80 Location of Rapid Drug Desensitizations Chemotherapy and Biologics 98% Rapid Drug Desensitizations now done in outpatient area 80

81 Aspirin Desensitization Cases Aspirin Reactions Desensitization vs. Desensitization

82 Aspirin Allergy Cases Case 1 Urticaria/AE with aspirin How to desensitize? Case 2 Aspirin exacerbated respiratory disease (AERD) How to desensitize? Is the approach the same? 82

83 Aspirin/NSAID Hypersensitivity Phenotypes Hypersensitivity Reaction Cross- Reactivity Onset Clinical Features Underlying Disease Mechanism Aspirin Exacerbated Respiratory Disease (AERD) Yes Immediat e Naso-ocular Respiratory (GI, skin less often) Asthma, nasal polyps COX-1 Inhibition Aspirin Exacerbated Cutaneous Disease Yes Immediat e Urticaria/Angioede ma Chronic urticaria COX-1 Inhibition Multiple NSAID- Induced Urticaria Yes Immediat e Urticaria/Angioede ma None COX-1 Inhibition? Single NSAID Induced Urticaria/Anaphyla xis No Immediat e Urticaria/Angioede ma Anaphylaxis None IgE mediated? Variable No Delayed Fixed drug eruption, SJS/TEN, MP exanthem, HP, None T cell mediated? 83

84 Urgent Need for Aspirin Many studies have performed aspirin desensitizations in patients with histories of both cutaneous and respiratory reactions to aspirin, all with similar high rate of success (>80%) Patients with chronic urticaria have higher failure rate Surprisingly good results in AERD patients Likely due to lower doses used Wong JT et al. J Allergy Clin Immunol 2000;105: Silberman S et al. Am J Cardiol 2005;95: Rossini R et al. Am J Cardiol 2008;101:

85 Are These Really Desensitizations? Patients in these studies never had confirmatory challenges to determine if truly allergic to aspirin Whether these protocols truly induce drug tolerance or are simply a multistepped graded challenge is unclear 85

86 Rapid Aspirin Desensitization Protocol Solensky R, Khan DA et al. Ann Allergy Asthma Immunol 2010;105:273e1-e78. Adapted from: Wong JT et al. J Allergy Clin Immunol 2000;105:

87 Aspirin Challenge for Acute Cardiac Needs yes Premedicate with montelukast, ICS/LABA, prednisone Does patient have asthma that is worsened by ASA/NSAIDs (AERD) No Administer 40.5 mg aspirin 90 min Modified from White AA et al. Allergy Asthma Proc 2013;34: Administer 40.5 mg aspirin Observe 90 min & no reaction: ok to take 81 mg aspirin 87

88 UT Southwestern Protocol for Urgent ASA Needs Historical Reaction to ASA/NSAID Dosing strategy Pretreatment AERD Split dosing, give 40.5 mg and wait 90 minutes then give another 40.5 mg ASA-induced urticarial or angioedema 1 hr before: 40 mg prednisone, montelukast 10 mg, ICS/LABA 81 mg ASA None Vague 81 mg ASA None SJS or TEN to NSAID (not ASA) 81 mg ASA None 88

89 ASA Desensitization for AERD Therapy Lee RU et al. Ann Allergy Asthma Immunol. 2010;105:

90 Chen J, et al. J Allergy Clin Immunol Pract 2015;3:

91 UT Southwestern AERD Desensitization Protocol Patients pre-medicated with montelukast, ICS/LABA Some patients pre-medicated with prednisone Chen J, et al. J Allergy Clin Immunol Pract 2015;3:

92 UT Southwestern Protocol Indicated for patients with a history of reactions to ASA or NSAIDs within 1 hour 57 hourly dose-escalation aspirin desensitizations performed in AERD subjects All but 1 patient successfully desensitized 40% completed in 1 day 60% in 2 days Chen J, et al. J Allergy Clin Immunol Pract 2015;3:

93 ASA Desensitizations for AERD Risk of these procedures has been overblown These can be performed in the office If you can give nebulized albuterol and follow a protocol, you can do an aspirin desensitization Immunotherapy reactions scare me far more than ASA desensitization reactions 93

94 Conclusions The history is our best tool to guide management Penicillin skin testing can be safely performed with currently available tools Drug challenges are safe and preferred to empiric desensitization Placebo challenges are very helpful for subjective drug reactions Drug desensitizations can be used for immediate reactions to many medications Approach to aspirin allergy varies by urgency and nature of reaction but both ASA challenges and desensitizations can be done in the office 94