Beta-Lactam Hypersensitivity Reaction: CROSS-REACTIVITY
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1 Beta-Lactam Hypersensitivity Reaction: CROSS-REACTIVITY Daniel Yerly, PhD Drug Allergy Research Laboratory University-hospital, Bern Switzerland WAO Cancun December 7th 2011 Beta-Lactam Hypersensitivity Reactions Immediate-type IgE mediated Symptoms Urticaria Anaphylaxis First encounter: silent sensitization Re-exposition: rapid occurrence of the symptoms Beta-Lactam Hypersensitivity Reactions Delayed-type T cell mediated Symptoms: Maculo-papular Erythema Skin-Rash Severe reaction: Bullae, SJS / TEN, DRESS, AGEP Lesions in intern organs Occurance after 8-12 days after starting the therapy 1
2 Immediate Hypersensitivity Delayed-type Hypersensitivity First Encounter: silent sensitization Rexposition: rapid occurrence of symptoms Occurrence after 8-12 days therapy Expansion of drug reacting T cells β-lactam Antibiotika Core Structure Defines The Class Penicillin G Penicillin V Amoxicillin Cephalosporins Aztreonam Azactam Ertapenem INVANZ Imipenem Tienam Meropenem Meronem Ertapenem Inva Sanfetrinem Core-structure and Side-chain Side Chain Core-structure (Cephem) 2
3 Antigenic determinant in β-lactams Antigenic determinant for T cells Core structure (Cephem) Total structure Antigenic determinant for IgE Side chain Total structure Possible cross-reactivity between different classes Antibodies (IgE) are able to recognize very tiny determinants on a molecule. Amoxicillin Cefadroxil Cave: Possible cross-reactivity between penicillin and cephalosporin due to identical side chain Possible cross-reactivity between different clases High affinity, but low cross-reactivity 3
4 Crossreactivity Concepts Type of the involved immune mechanism T cell mediated? IgE mediated Analysis of the chemical structure of the culprit β-lactam Identical core structure? Delayed type DHR Switch to another β-lactam class Identical side chain? Immediate reaction Choose a molecule with another side chain Clinic Skin test By negative skin test Provocation test Cave anaphylaxis! Cephalosporin Challenges in Penicillin ST-Positive (IgE) Patients Reference (Year) # of Patients # (%) Comment of Reactions Girard (1968) 23 2 (8.7) Both reactions to cephaloridine* Assem (1974) 3 3 (100) All reactions to cephaloridine* Warrington (1978) 3 0 Solley (1982) 27 0 Saxon (1987) 62 1 (1.6) Specific cephalosporin not noted Blanca (1989) 16 2 (12.5) Both reactions to cefamandole* Shepherd (1993) 9 0 Audicana (1994) 12 0 Novalbos (2001) 23 0 Macy (2002) 42 1 (2.4) Reaction to cefixime TOTAL (4.1) * These cephalosporins have R-group side chains similar to benzylpenicillin. Cross-reactivity Penicillin - Cephalosporin Cross-reactivity between Penicillin and Cephalosporin is probably over-evaluated Cross-reactivity is rare (only 4.1% of skin tests with positive IgE) z.t. bedingt durch Kontaminationen des Cphalosporins mit Penizillinen z.t. bedingt durch gleiche Seitenkette 4
5 Case # 1 Patient mit Urtikaria 2 hr nach Amoxicillin: Kann er Cephalosporine 3. Generation haben? Hautteste prick/i.d. mit PPL +++ mit Amoxicillin ++ Cephadroxil - Case # 2 Patient with a severe exanthem after 7 days of Amoxicillin treatment May he recieve a Cephalosporine of 3rd generation? Skintest i.d. Epicutan PPL - nd Amoxicillin - ++ Cephadroxil nd - Kefrol (Cefazolin) nd - Aknowledgements Division of Allergologie, Inselspital Prof. Dr. Werner PICHLER Jacqueline ADAM Klara K. ERIKSSON Heidi JAMIN Karin SCHNYDER Steve WATKINS Natascha WUILLEMIN James YUN ADR-AC: Adverse Drug Reactions -Analysis & Consulting Monika KELLER Barbara Monika Gertrud Gudrun DAUBNER Thomas GENTINETTA Tatjana PETKOVIC Yuttana SRINOULPRASERT Swiss Centre for Applied Human Toxicology Schweizerisches Zentrum für Angewandte Humantoxikologie Centre Suisse de Toxicologie Humaine Appliquée Centro Svizzero di Tossicologie Umana Applicata 5
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