Drug Allergy HSJ 19/09/2011

Transcription

1 Drug Allergy HSJ 19/09/2011

2 BSACI Guidelines Definitions Mechanisms Clinical Features Risk factors Diagnosis Investigations Criteria for referral/investigation Mirakian et al. Clin Exp All 2008 ; 39: 43-61

3 Definitions ADR = Adverse drug reaction ADE = Adverse drug event (ie( prscription error) ADR Type A may affect anyone Side Effect Physiological ADR Type B Affects only susceptible individuals Allergy Immunological Non-immune eg genetic

4 Mechanisms - Immunological Type I IgE-mediated, immediate, eg Penicillin anaphylaxis, urticaria, brochospasm etc Type II IG mediated cytotoxic eg Heparin Anaemia, cytopenia Type III IG mediated immune complexes eg ACEI, alllopurinol Vasculitis,, fever, LN, arthropathy,, serum sickness

5 Mechanisms - Immunological Type IV T Cell driven, variety of effector mechanisms Inc monocytes, eosinophils,, CD8 cells, neutrophils Contact Dermatitis eg Neomycin Classical Maculopapular Drug eruption eg Penicillin Pustular Exanthem (AGEP) eg Itraconazole Bullous eruptions eg TEN, Stevens-Johnson syndrome eg sulphonamides

6 Organ-specific Lung Asthma Cough Interstitial pneumonitis Eosinophilia Organising Pneumonia NSAID ACE MTX NSAID Amiodarone Liver Cholestasis,, Hepatitis Renal Interstitial nephritis

7 Systemic Anaphylactoid Serum sickness Lupus-like DRESS drug rash with eosinophilia systemic symptoms eg anticonvulsants TEN SJS

8 Skin Urticaria/Angioedema Maculopapular rash Contact Dermatitis Photodermatitis eg tetracycline AGEP Acute generalised exenthamatous pustulosis FDE fixed drug eruption Erythema Multiforme

9 History Taking Detailed decsription of reaction Symptom sequence and duration Treatment, outcome Witness desription Photos, compare to reference images Timing of symtoms in relation to drug administration How long had the drug been taken for? Had the drug been taken previously? Drugs of similar class taken previously? Indication for drug Other drugs taken (inc OTC and complimentary) Prev drug allergy Other allergic conditions

10 Investigation Use known mechanisms, especially IgE mediation Many reactions need no further investigation, esp organ specific and non- immune Contraindicated in certain severe reactions (eg TEN) Depends on clinical context Eg In penicillin alllergy,, indicated where: Reaction occurred when on multiple drugs eg GA Allergy to multiple antibiotics, esp if chronic disease Absolute indication for penicillin eg splenectomy

11 Investigation Serum tryptase,, acute and baseline RAST (specific IgE) Skin prick testing Intradermal skin testing Patch testing Delayed intradermal test Basophil release assays Oral provocation test Gold standard With index drug to confirm/refute diagnosis With alternative/related drug to define safe alternative

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13 Accuracy of History Caubet et al. J Allergy Clin Immunol children labelled as allergic to Penicillin, on basis of delayed onset urticaria or maculopapular rash All underwent detailed work-up 11 had positive intradermal test 2 had positive RAST 6 had positive oral challenge test (6.8%) 65% of OCT neg children had positive viral study Conclusion B-lactam allergy is clearly overdiagnosed in childhood infective illness, only confirmed in 6.8%

14 Importance of Challenge test Torres et al, Clin Exp Allergy 2002; 32 (2): pt with good hx of penicillin allergy 241 had positive result on SPT, IDT or RAST 89 patients negative on all tests, underwent OCT 49 developed immediate allergic reaction 22 penicillin, 27 amoxicillin Conc skin tests and Specific IgE are insufficent to exclude diagnosis of penicillin allergy

15 Cephalosporins X-reactivity (with Pen) does exist, but is exaggerated 4-10% Greater with early generation cephs Usually predicted by side chain homology Eg amoxicillin with cefaclor, cephalexin, cefadroxil Not cefixime, cefuroxime, ceftraxone Usual testing protocols can be used OCT is reasonable for a patient with Pen allergy

16 Drug Allergy Female, 42,? Penicillin Allergy After 1 tab amoxyl,, tongue/throat swelling, lips, ears Collapse, given adrenaline Had amoxycillin several times before 2 months later stroked cat (on antibiotics) lip/eye swelling, itch face? Will react to traces in hospital RAST Penicillin neg SPT Neg Major and Minor determinants Strong Positive Amoxycillin proximal tracking, systemic itch Diagnosis Severe Allergy Amoxycillin,, reaction to trace quantities

17 Conclusions A history of penicillin allergy is common and can limit treatment options If in doubt, don t t give Accurate history is crucial Diagnosis is confirmed on objective testing in 10-20% of cases, increasing where history is more recent and more convincing Testing indicated in defined clinical scenarios Testing protocol should involve RAST, SPT, IDT, OCT

18 Drug Allergy Female, 46,? Anaphylaxis during GA, further surgery needed 2008 Obstruction (slipped gastric band) Severe anaphylaxis after induction larngeal oedema, hypoension, bradycardia,, raised airway pressures. Tryptase 36 Thiopentone, Fentanyl, Suxamethonium,, Colloid Hay fever, cat allergy SPTs Negative (neat, 1/10) all except vecuronium, Sux neat Intradermal testing Sux strong positive, Pancuronium/Rocuronium also positive. Atrocurium negative Diagnosis Suxamethonium allergy, cross sensitivity

19 Drug Allergy Male, 56, dramatic anaphylaxis during anaesthesia for hernia at private hospital. Transferred ITU. Max tryptase 92 Fentanyl, propofol, dex, ondansetron, vecuronium Augmentin,, Morphine hypotension, urticaria, bronchospasm No h/o atopy or penicillin allergy SPT/IDT negative for NMBA, Fent, propofol, Augmentin,, Pen Maj and minor determinants, Latex, Chlorhexidine,, Colloid RAST penicillin negative Baseline tryptase 20.6 Diagnosis -? Isolated systemic mastocytosis.. Anaphylaxis? Morphine? augmentin

20 Drug Allergy Female, 42,? Penicillin Allergy After 1 tab amoxyl,, tongue/throat swelling, lips, ears Collapse, given adrenaline Had amoxycillin several times before 2 months later stroked cat (on antibiotics) lip/eye swelling, itch face? Will react to traces in hospital RAST Penicillin neg SPT Neg Major and Minor determinants Strong Positive Amoxycillin proximal tracking, systemic itch Diagnosis Severe Allergy Amoxycillin,, reaction to trace quantities

21 Angioedema/Anaphylaxis Male 63, Surgical referral? Cholecystitis RUQ pain, vomiting, fever PMH nil Penicillin Allergy recorded on GP letter summary Mild angioedema many years previously Rx IV Augmentin Pt denied recollection of allergy when asked by Dr and Nurse Fatal anaphylactic reaction

22 Drug Allergy Female, 38? Allergy to steroids Kenalogue intra articular 2 hours, itch/swelling upper lip, throat tightness. OK previously with depomedrone Severe hip pain keen on further steroid injection Mild HF, penicillin allergy SPT negative (neat, 1/10) depomedrone, kenalogue IDT negative to both I/M challenge kenalogue positive I/M challenge depomedrone negative Diagnosis Allergy Kenalogue? Steroid component? excipient

23 Drug Allergy 42 year old female Very bad painful teeth, infected Not been to dentist many years Prev told by dentist could not have LA When in teens, several episodes of collapse, LOC after LA SPT negative Lignocaine, bupivicaine IDT, serial dilutions, negative Subcut challenge test, ¼ full dose negative No evidence of LA allergy