Management of drug allergy PART II
Outline 1 2 3 General management Beta lactam allergy NSAIDs allergy
General management Refer to allergist for confirm or find safe alternative drug Especially 1. Beta-lactam antibiotics 2. Local and general anaesthesia Stop, avoid culprit and cross reactive drug 3. Radiocontrast media Supportive & symptomatic treatment Drug allergy card
General management Non Immediate immediate reaction reaction Anaphylaxis : Epinephrine Urticaria, Angioedema : Antihistamine Symptomatic (body & mind) and multidisciplinary care
Please consider risk and benefit ratio before start procedure Pre-medication Desensitization Graded challenge Non IgE, immediate (Anaphylactoid) High probability IgE mediated Low probability Condition stable High molecular weight drugs eg. contrast media, monoclonal antibody Produce temporary tolerance Confirm or exclude Steroid, Antihistamine, Aspirin, Paracetamol Start 1/100,000-1/10,000, > 10 steps Start 1/100-1/10, 3-5 steps Discontinue drug and treatment Hold drug, treatment and go on with modified protocol Discontinue test, treatment and diagnosis Cernadas et al, Desensitization for drug hypersensitivity, Allergy 2010 Santos & Galva õ,monoclonal Antibodies Hypersensitivity, Immunol Allergy Clin N Am 37 (2017) 695 711
cap caps Graded challenge Drug provocation test Desensitization
In some situations What should I do? Pregnancy with VDRL positive and history of penicillin allergy Coronary syndrome with history of aspirin allergy
Outline 1 2 3 General management Beta lactam allergy NSAIDs allergy
Beta lactam allergy Increase hospital stay Increase cost Increase rate of serious drug resistance Su et al, Clin transl allergy (2017) 7:18 https://penallergytest.com/penicillin-allergy-facts/ A. Sangasapasviliya et al, J Med Assoc Thai Vol. 93 Suppl. 6 2010
Beta lactam allergy Penicillin metabolized to -benzylpenicilloyl (major determinant) Penicilloyl polylysine (PPL, pre-pen ) -benzylpenicilloate & benzylpenilloate (minor determinants) Skin test panel Major determinant Minor determinant Penicillin G sodium Amoxicillin Ampicillin Skin test panel Penicillin G sodium Amoxicillin Ampicillin and DPT all cases In immediate reaction : skin test had NPV > 95, sensitivity 70% In delayed reaction : limited data, sensitivity 30% In immediate reaction : skin test without PPL had lower NPV Bob Geng,Utility of minor determinants in penicillin allergy skin testing. World allergy organization journal 2015 8(Suppl 1):A228 Har & Solensky,Penicillin and Beta-Lactam Hypersensitivity, Immunol Allergy Clin N Am 2017
Beta lactam allergy Allergy center SiPH
Beta lactam allergy Cross reactivity between group via R side chain < 2% < 1% Trubiano et al,j ALLERGY CLIN IMMUNOL PRACT MONTH 2017
10-27% cross reactivity rate between aminopenicillin and R1 identical cephalosporin ( first/second generation ) Har & Solensky Penicillin and Beta-Lactam Hypersensitivity, Immunol Allergy Clin N Am(2017)
Penicillin allergy in pregnancy Recommendation in 2010 STD treatment No proven alternatives to penicillin are available for treating neurosyphilis, congenital syphilis, or syphilis in pregnant women Full battery penicillin skin test available : Major determinant, MDM Positive Desensitization Negative Give penicillin Full battery penicillin skin test unavailable Major determonant, PGS Positive Negative Desensitization Graded challenge Unavailable major determinant IgE mediated : Desensitization non IgE mediated : Graded challenge
Penicillin desensitization Amount (unit/ml) ml Unit Cumulative dose 1 1,000 0.1 100 100 2 1,000 0.2 200 300 3 1,000 0.4 400 700 4 1,000 0.8 800 1,500 5 1,000 1.6 1,600 3,100 6 1,000 3.2 3,200 6,300 7 1,000 6.4 6,400 12,700 8 10,000 1.2 12,000 24,700 9 10,000 2.4 24,000 48,700 10 10,000 4.8 48,000 96,700 11 80,000 1.0 80,000 176,700 12 80,000 2.0 160,000 336,700 13 80,000 4.0 320,000 656,700 Wendel GO, Jr, Stark BJ, Jamison RB, Melina RD, Sullivan TJ. Penicillin allergy and desensitization in serious infections during pregnancy. N Engl J Med 1985;312:1229 32.
Beta lactam allergy What is the reaction? Urticaria Presence of danger signs? No Duration? 1 hr and It s gone without any scar 24 years-old Penicillin allergic history since childhood Plan to elective surgery (GYN) OB doctor need cefazolin for prevention wound infection A. Skin test penicillin B. Skin test cefazolin C. Graded challenge cefazolin D. Desensitization cefazolin E. Give cefazolin routinely F. Suggest avoid cefazolin
Cases Allergic to penicillin Need penicillin Need cephalosporin In situation that penicillin skin test, skilled Skin pharmacist test to penicillin or allergist not Skin available test to penicillin Before you start graded IF 4 challenge YES / desensitization please answer 4 questions Negative : Give penicillin Positive YOU YOU HAVE : Avoid HAVE or 3 OPTIONS 3 OPTIONS Negative : Give cephalosporin Is the patient really need this antibiotics? you can do graded challenge or Desensitization desensitization Graded challenge Positive : Alternative drug, Graded challenge cephalosporin, Desensitisation to cephalosporin Is current status stable? Did the Skin previous test to penicillin reaction was not anaphylaxis, SCARs or Negative organ specific IF Desensitization : Give penicillin eg. any cytopenia NO, serum sickness? Allergic to cephalosporin Positive : Alternative drug, Positive : Alternative drug, Is the patient/dr. understand and accept risk of procedure? Skin test to new cephalosporin Negative : Graded challenge Suggest Desensitization Alternative : use to penicillin alternative antibiotics antibiotics Alternative antibiotics Desensitisation to cephalosporin Har & Solensky Penicillin and Beta-Lactam Hypersensitivity, Immunol Allergy Clin N Am(2017)
Outline 1 2 3 General management Beta lactam allergy NSAIDs allergy
Classification of NSAIDs allergy
Mechanism of NSAIDs allergy Decrease PGE2 level Tanya M. Laidlaw and Joshua A. Boyce, n engl j med 374;5 nejm.org February 4, 2016
3 Questions for evaluation of NSAIDs allergy When & What is the reaction? Any previous history of urticaria / rhinitis / asthma? Any previous history reaction to others NSAIDs, acetaminophen and COX-2 inhibitor? Immediate Vs Delay Skin, Airway, Anaphylaxis Induced or Exacerbated Evaluation cross reactivity pattern
Classification of NSAIDs allergy Aspirin triad Asthma triad Samter s syndrome Suggestion Widal syndrome Avoid conventional NSAIDs Usually tolerated selective COX-2 inhibition and acetaminophen Suggestion Avoid culprit drug and structural related drugs
Classification of NSAIDs allergy Immediate Reaction Delayed Reaction SNIUAA NIUA NERD NECD Single NSAIDs Induced Urticaria Angioedema or Anaphylaxis NSAIDs Induced Urticaria Angioedema NSAIDs Exacerbated Respiratory Disease NSAIDs Exacerbated Cutaneous Disease SNIDR Single NSAIDs Induced Delayed Reaction Mostly limited at skin FDE, MPE Ibuprofen, Naproxen Isolated periorbital angioedema : associated with rhinitis/asthma, dust mite sensitive Kowalski et al. Hypersensitivity to NSAIDs,Allergy 68 (2013) 1219 1232 J Quiralte, et al,j Investig Allergol Clin Immunol 2007; Vol. 17(3): 182-188 pic : Laurence Valeyrie-Allanore, Grace Obeid and Jean Revuz Dermatology, 21, 348-375
WAO Journal & Volume 1, Number 2, February 2008
Role of aspirin desensitization NERD Coronary artery disease Rossini et al Antiplatelet Desensitization Registry, Circ Cardiovasc Interv. 2017;1 White & Stevenson, Immunol Allergy Clin N Am 33 (2013) 211 222
Take home message We are 0.3% of Thai doctors but we appreciate to help all of you. Patient safety is very important Only stop culprit drug that decrease mortality Encourage to drug allergy work up esp. penicillin
Thank You for your kind attention