Antibiotic and Latex Allery

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Slide 1 : Antibiotic and latex allergy Dr Alexandra Croom Consultant Allergist Glenfield Hospital, Leicester
Slide 2 : Epidemiology Adverse Drug Reactions 20% type B idiosyncratic Approx half of these immune mediated Most reactions cutaneous Urticaria Maculopapular rash EN, TEN, SJS 10% Europeans think they have drug allergy – most commonly penicillin SPT suggests actual figure may be 5% (although up to 25% in some selected populations)
Slide 3 : Immune reactions to antibiotics – based on Gell and Coombes classification Based on Gruchalla N Engl J Med 2006 on-line
Slide 4 : Immune reactions to antibiotics – based on Gell and Coombes classification
Slide 5 : History Skin prick testing Intradermal testing Challenge/provocation
Slide 6 : History taking in antibiotic allergy History of event often lost in sands of time Important to consider Nature of symptoms and their timing Risk factors Drug-related – route of administration, how many previous courses and rate of repetition Host-determined – gender, co-morbidity, family history, atopy
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Slide 8 : Antibiotic allergy in cystic fibrosis Incidence of ADRs to antibiotics increased – 4.5-25% in adults with CF Immediate reaction in 1.9% of antibiotic courses Dependent on which antibiotic being used piperacillin highest risk azithromycin no greater than placebo Parmar Thorax 2005 Koch Rev Infect Dis 1991
Slide 9 : Why is incidence higher in cystic fibrosis? Antibiotics given intravenously Number of course of antibiotics received Danish study 121 patients received 2800 courses Haptenisation (formation of allergenic determinant) enhanced by presence of infection/inflammation Atopic children with CF more likely to be colonised by pseudomonas
Slide 10 : Looking for drug specific IgE: skin prick testing
Slide 11 : Skin prick testing Lancet through allergen test solution Preformed allergen specific IgE Release of histamine Weal formation Itch
Slide 12 : Skin prick testing For aeroallergens quick, cheap and safe Not so straightforward for antibiotics only well validated for penicillin risk of anaphylaxis during prick testing for penicillins 5/147 patients with penicillin allergy had systemic reaction following skin prick testing more likely if initial reaction was anaphylaxis stop ß blockers prior to testing and optimise asthma management perform in supervised clinical environment Minh J Allergy Clin Immunol Feb 2006
Slide 13 : Intradermal testing Allergen solution introduced intradermally – Dilute solutions required Increased sensitivity – use when SPT negative Increased risk of systemic reactions Painful
Slide 14 : Allergens in antibiotic allergy Allergens arise 2 ways: Drugs low molecular weight <1000 Da - to become immunogenic need to covalently bind to HMW proteins (allergens present in parent drug) Novel allergens may be generated through metabolism prior to haptenisation (allergens not present in parent drug)
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Slide 18 : Gruchalla J Allergy Clin Immunol 2001
Slide 19 : Skin testing for penicillin allergy Replaced Allergopen after withdrawal in 2006 Contains BPO (major determinant) PPL (minor determinant mix) Used in conjunction with SPTs using solutions of amoxycillin and ampicillin
Slide 20 : Testing for penicillin allergy <20% of those who report penicillin allergy have positive skin prick tests Negative testing indicates previous reaction not IgE mediated or drug specific antibodies ‘lost’ Readminstration is safe if SPTS using major and minor determinants are negative– rate of reaction is = 4% (same as general population rate)
Slide 21 : Evolution of skin test sensitivity with time 5 year prospective study BPO/MDM positive 25/31 positive 12/12 18 positive at 36/12 (2 lost to follow up) 12 positive at 60/12 (1 lost to follow up) Amoxycillin positive 12/24 positive at 12/12 6 positive at 36/12 (1 lost to follow up) 0 positive at 60/12 (1 lost to follow up)
Slide 22 : Specific IgE assays for penicillin allergy Poor predictive value Do not contain minor determinants Negative result does not exclude allergy Positive result confirms allergy and prevents unnecessary skin prick testing
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Slide 24 : Prescribing imipenem in patients with ß lactam allergy First reports of cross reactivity (9/19) between imipenem and penicillins published 1988 (Saxon J Allergy Clin Immunol) Romano et al (NEJM 2006): 112 patients with history of immediate reactions to ß lactams and positive skin prick tests 1/112 skin prick test positive with imipenem 110/111 with negative skin prick tests underwent graded IM challenge with imipenem – no reactions
Slide 25 : Tolerability of meropenem in patients with penicillin allergy – prospective study 104 participants, 14-83 y, history of immediate response to penicillins 104/104 positive skin test to at least one penicillin reagent 1/104 reacted to meropenem Initial reaction anaphylaxis after amoxycillin and clavulinic acid combination Reacted to all penicillin reagents on skin testing including imipenem Romano et al Annals Internal Med 07
Slide 26 : Giving cephalosporins to patients with history of penicillin allergy Increased risk of reactions to cephalosporins if penicillin allergic 6/135 patients with penicillin allergy 2/351 with no history of penicillin allergy Increase risk of fatal anaphylaxis if cephalosporins given where history of penicillin allergy 6/12 deaths due to antibiotics related to 1st dose cephalosporins – 3/6 history of penicillin allergy Kelkar N Engl J Med 2001, Pumphrey Lancet 1999
Slide 27 : Giving cephalosporins to patients with history of penicillin allergy Controversial ‘indiscriminate administration cannot be recommended especially for patients with life threatening reactions’ ‘ may be attractive if allergy to penicillin is mild, indication for use of that drug is strong, skin testing is impracticable, treatment for reactions is readily available’ Gruchalla N Engl J Med 2006, Kelkar N Engl J Med 2001
Slide 28 : Allergy to non-beta lactam antibiotics Presumed IgE mediated reactions documented – 1-3% of prescribed courses No large scale validation of skin testing Allergenic determinants may be metabolites and thus absent from solutions of parent drug If low non-irritative concentrations used and positive response provoked may indicate IgE responsible Negative skin tests do not exclude the presence of drug specific IgE; should drug be absolute requirement next step would be incremental administration to induce tolerance
Slide 29 : Non-Ige mediated reactions with antibiotics
Slide 30 : Maculopapular rash after penicillins 195 patients with cutaneous reactions after penicillins Evaluated with SPT + intradermal testing patch testing oral challenge (if appropriate) 60/195 maculopapular rash 33/60 positive patch tests 18/30 agreed to rechallenge with culprit drug – all reacted with rash developing 6-24 hrs after drug given Romano Ann Allergy Asthma Immunol 1998
Slide 31 : Maculopapular rash after penicillins 30/33 reacted to ampicillin or amoxycillin; 3/33 reacted to Pen G No patients reacted to MDM or PPL Conclusion that reactions triggered by side chain binding and not beta lactam structure ? MHC restricted – HLA A2 and DRW52 over-represented Romano Ann Allergy Asthma Immunol 1998
Slide 32 : Ampicillin Amoxicillin Penicillin G
Slide 33 : Red man syndrome and vancomycin Pruritus, erythema, flushing and hypotension 50-90% of patients treated experience some histamine release – most mild Histamine release is non-specific and related to rate of infusion Antihistamines will alleviate symptoms Some cases of IgE mediated reactions (including anaphylaxis) to vancomycin are reported with positive SPTs (but false positives common with vancomycin concentrations > 10µg/ml)
Slide 34 : Desensitisation in antibiotic allergy Possible with all antibiotics Risk only justified when drug in question is sole treatment option Mechanism not fully understood Tolerance achieved in hours
Slide 35 : Who to test? ALL? NONE? SOME?
Slide 36 : Who to test? ALL? Tests not good enough for that NONE? As is often the case SOME? Those with a current need for specific antibiotics Those with a predictable need for specific antibiotics in the future Confirmation of a recent serious reaction
Slide 37 : Antibiotic allergy: summary Misconceptions about antibiotic allergy affect clinical practice Testing can inform rational prescribing Testing is safe (in specialist hands – www.bsaci.org.uk for drug allergy clinics) When antibiotic allergy is present desensitisation is effective at producing tolerance and allowing treatment
Slide 38 : Latex allergy Obtained from tree - hevea brasiliensis Original reports of latex allergy from Germany in 1930s First modern day reports of latex allergy early 1980s
Slide 39 : Epidemiology of latex allergy Few studies of incidence – none of incidence over time Prevalence studies predominantly in at risk groups Serological studies on blood donors 3.3-7.6% of population studied; sensitisation rates higher in men
Slide 40 : Epidemiology of latex allergy – risk factors Spina bifida (OR 6.73) Multiple surgery (OR 1.14 per op) Atopic predisposition (OR 3.37) Occupational exposure HCWs Rubber industry Electronic industry ‘Hidden’ - textiles Hochleitner J Urol 2001
Slide 41 : Latex allergy and HCWs 7 March 1994
Slide 42 : Latex allergy and HCWs Increased prevalence of HCWs sensitisation to latex attributed to glove use Sensitisation rates 8-17% Sensitisation enhanced by Glove protein content Whether powdered or not Exposure duration
Slide 43 : Reducing allergy in HCWs In 1997 Germany passed legislation to make use of low-allergen, powder free NRL gloves mandatory Prior to that about 80% gloves were powdered Incidence of latex-related contact urticaria was monitored by statutory system of health insurance and reporting of suspected occupational disease
Slide 44 : Allmers et al J Allergy Clin Immunol 2004
Slide 45 : Latex allergens Levels of allergens may be affected by growing and manufacturing methods Majority of allergens are defence proteins – production enhanced when tree under ‘stress’ Risk group reflected in allergen profile
Slide 46 : Kurup et al Clinical Molecular Allergy 2005
Slide 47 : Kurup et al Clinical Molecular Allergy 2005
Slide 48 : Diagnosing latex allergy Standardised skin prick test solutions available Results correlate with spIgE assays Anaphylaxis reported with latex skin prick testing False negatives occur – if a good history of acute type symptoms provocation test essential
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Slide 51 : Desensitisation in latex allergy Subcutaneous immunotherapy (SCIT) Leynadier J Allergy Clin Immunol 2000 Sastre J Allergy Clin Immunol 2003 Tabar Int Arch Allergy Immunol 2006 Sublingual immunotherapy (SLIT) Cistero Bahima J Invest Allergol Clin Immunol 2004 Bernadini Curr Med Res Opin 2006 Nettis Br J Dermatol 2007
Slide 52 : Conclusions Latex allergy is a phenomenon of last 3 decades Much of it was/is preventable Improved understanding of latex allergens has enhanced diagnostics Effective treatment is currently available for those most at risk of re- exposure
Slide 53 : Conclusions Latex allergy is a phenomenon of last 3 decades Much of it was/is preventable Improved understanding of latex allergens has enhanced diagnostics Effective treatment is currently available for those most at risk of re- exposure - but not in the UK
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