National Clinical Guideline Centre NICE clinical guideline 183 Drug allergy Diagnosis and management of drug allergy in adults, children and young people Clinical guideline 183 Methods, evidence and recommendations September 2014 Final Commissioned by the National Institute for Health and Care Excellence DDrruugg aalllleerrggyy Contents Disclaimer Healthcare professionals are expected to take NICE clinical guidelines fully into account when exercising their clinical judgement. However, the guidance does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of each patient, in consultation with the patient and/or their guardian or carer. Copyright National Clinical Guideline Centre, 2014 Funding National Institute for Health and Care Excellence National Clinical Guideline Centre, 2014 Drug allergy Contents Contents Contents ............................................................................................................................................ 4 Guideline Development Group members .................................................................................... 8 NCGC technical team members .................................................................................................. 8 Co-optees ................................................................................................................................... 8 Acknowledgements ........................................................................................................................... 9 1 Introduction ............................................................................................................................. 10 2 Development of the guideline ................................................................................................. 12 2.1 What is a NICE clinical guideline? .................................................................................... 12 2.2 Remit .............................................................................................................................. 12 2.3 Who developed this guideline? ....................................................................................... 13 3 Methods .................................................................................................................................. 14 3.1 Developing the review questions and outcomes ............................................................. 14 3.2 Searching for evidence.................................................................................................... 16 3.2.1 Clinical literature search ..................................................................................... 16 3.2.2 Health economic literature search ...................................................................... 16 3.3 Evidence of effectiveness ................................................................................................ 17 3.3.1 Inclusion and exclusion criteria ........................................................................... 18 3.3.2 Methods of combining clinical studies ................................................................ 19 3.3.3 Type of studies ................................................................................................... 21 3.3.4 Appraising the quality of evidence by outcomes ................................................. 22 3.3.5 Grading the quality of clinical evidence............................................................... 23 3.3.6 Risk of bias ......................................................................................................... 23 3.3.7 Inconsistency...................................................................................................... 27 3.3.8 Indirectness ........................................................................................................ 27 3.3.9 Imprecision ........................................................................................................ 27 3.3.10 Evidence statements .......................................................................................... 28 3.4 Evidence of cost effectiveness ........................................................................................ 29 3.4.1 Literature review ................................................................................................ 29 3.4.2 Undertaking new health economic analysis ........................................................ 30 3.4.3 Cost-effectiveness criteria .................................................................................. 30 3.4.4 In the absence of economic evidence ................................................................. 31 3.5 Developing recommendations ........................................................................................ 31 3.5.1 Research recommendations ............................................................................... 32 3.5.2 Validation process .............................................................................................. 32 3.5.3 Updating the guideline ....................................................................................... 32 3.5.4 Disclaimer .......................................................................................................... 32 National Clinical Guideline Centre, 2014 4 Drug allergy Contents 3.5.5 Funding .............................................................................................................. 32 4 Algorithm ................................................................................................................................. 33 5 Guideline summary .................................................................................................................. 34 5.1 Key priorities for implementation ................................................................................... 34 Assessment .............................................................................................................................. 34 Documenting and sharing information with other healthcare professionals.............................. 35 Documenting new suspected drug allergic reactions................................................................. 35 Maintaining and sharing drug allergy information..................................................................... 35 Providing information and support to patients ......................................................................... 36 Providing information and support to people who have had specialist drug allergy investigations ................................................................................................................. 36 Non-specialist management and referral to specialist services.................................................. 36 General .................................................................................................................................... 36 Non-steroidal anti-inflammatory drugs (including selective cyclooxygenase 2 inhibitors) .......... 36 Beta-lactam antibiotics ............................................................................................................. 37 General anaesthesia ................................................................................................................. 37 5.2 Full list of recommendations ........................................................................................... 38 5.3 Key research recommendations ...................................................................................... 43 5.3.1 Designing systems for documenting drug allergy ................................................ 43 5.3.2 Communicating information about drug allergy.................................................. 43 5.3.3 Using selective cyclooxygenase 2 inhibitors in people with previous severe allergic reactions to non-selective non-steroidal anti-inflammatory drugs .......... 43 5.3.4 Oral antibiotic challenge for diagnosing antibiotic allergy in children .................. 43 6 Assessment .............................................................................................................................. 44 6.1 Review question: What is the clinical and cost effectiveness of clinical probability scores or algorithms in identifying or excluding drug allergies? ....................................... 44 6.2 Clinical evidence ............................................................................................................. 44 6.2.1 Algorithms.......................................................................................................... 44 6.2.2 Probability scores ............................................................................................... 52 6.2.3 Comparative studies ........................................................................................... 53 6.2.4 Most commonly used algorithm criteria ............................................................. 55 6.3 Economic evidence ......................................................................................................... 55 6.4 Evidence statements....................................................................................................... 56 6.5 Recommendations and link to evidence .......................................................................... 56 7 Measuring serum tryptase after suspected anaphylaxis .......................................................... 61 7.1 Review question: What is the clinical and cost effectiveness of serum tryptase testing compared with reference standard tests for the diagnosis of an anaphylactic reaction due to suspected drug allergy? ....................................................................................... 61 7.2 Clinical evidence ............................................................................................................. 62 7.3 Economic evidence ......................................................................................................... 66 National Clinical Guideline Centre, 2014 5 Drug allergy Contents 7.4 Evidence statements....................................................................................................... 66 7.5 Recommendations and link to evidence .......................................................................... 66 8 Measuring serum specific immunoglobulin E (IgE) ................................................................... 69 8.1 Review question: What is the clinical and cost effectiveness of serum specific IgE testing compared with reference standard tests in the diagnosis of drug allergy for the following drugs? ....................................................................................................... 69 8.2 Clinical evidence ............................................................................................................. 70 8.3 Economic evidence ......................................................................................................... 78 8.4 Evidence statements....................................................................................................... 78 8.5 Recommendations and link to evidence .......................................................................... 79 9 Documenting and sharing information with other healthcare professionals ........................... 81 9.1 Review question: What are the most clinically and cost effective documentation strategies for communicating drug allergy information across all NHS services to prevent patients from receiving drugs to which they are allergic? ................................... 81 9.2 Clinical evidence ............................................................................................................. 82 9.2.1 Summary of included studies .............................................................................. 83 9.2.2 Computerised prescribing systems ..................................................................... 94 9.2.3 Pro formas or structured charts .......................................................................... 95 9.2.4 Other documentation strategies ......................................................................... 96 9.3 Economic evidence ......................................................................................................... 97 9.4 Evidence statements....................................................................................................... 97 9.5 Recommendations and link to evidence .......................................................................... 97 10 Providing information and support to patients...................................................................... 102 10.1 Review question 1: What information and support should individuals with suspected drug allergy or their parents and carers receive? .......................................................... 102 10.2 Review question 2: What information and support should individuals who have had specialist investigations or their parents and carers receive? ........................................ 102 10.3 Clinical evidence ........................................................................................................... 103 10.3.1 Study summary and quality .............................................................................. 103 10.3.2 Summary of themes ......................................................................................... 106 10.4 Economic evidence ....................................................................................................... 108 10.5 Evidence statements..................................................................................................... 108 10.6 Recommendations and link to evidence ........................................................................ 109 11 Non-specialist management .................................................................................................. 112 Selective COX-2 inhibitors ............................................................................................. 112 11.1 Review question: In patients who have had allergic reactions to NSAIDs what are the factors that indicate whether they can or cannot tolerate selective COX-2 inhibitors? .. 112 11.2 Clinical evidence ........................................................................................................... 113 11.2.1 Summary of events induced by COX-2 inhibitors in NSAID-sensitive patients according to the specific drug administered ..................................................... 118 National Clinical Guideline Centre, 2014 6 Drug allergy Contents 11.2.2 Prognostic factors............................................................................................. 119 11.3 Economic evidence ....................................................................................................... 121 11.4 Evidence statements..................................................................................................... 121 11.5 Recommendations and link to evidence ........................................................................ 122 12 Referral to specialist drug allergy services ............................................................................. 126 12.1 Review question 1: What is the clinical and cost effectiveness of referral to specialist drug allergy services for people with suspected allergy to beta-lactam antibiotics? ...... 126 12.2 Review question 2: What is the clinical and cost effectiveness of referral to specialist drug allergy services for people with suspected allergy to NSAIDs? ............................... 126 12.3 Review question 3: What is the clinical and cost effectiveness of referral to specialist drug allergy services for people with suspected allergy to local anaesthetics? .............. 126 12.4 Review question 4: What is the clinical and cost effectiveness of referral to specialist drug allergy services for people with suspected anaphylaxis due to drug allergy during general anaesthesia? .................................................................................................... 126 12.5 Clinical evidence ........................................................................................................... 127 12.5.1 Benefit of referral ............................................................................................. 127 12.6 Economic evidence ....................................................................................................... 129 12.6.1 People with suspected allergy to beta-lactam antibiotics.................................. 129 12.6.2 People with suspected allergy to NSAIDs .......................................................... 133 12.6.3 People with suspected allergy to local anaesthetics .......................................... 135 12.6.4 People with suspected anaphylaxis due to drug allergy during general anaesthesia ...................................................................................................... 135 12.7 Evidence statements..................................................................................................... 135 12.8 Recommendations and link to evidence: beta-lactam antibiotics .................................. 135 12.9 Recommendations and link to evidence: NSAIDs........................................................... 138 12.10 Recommendations and link to evidence: local anaesthetics .......................................... 140 12.11 Recommendations and link to evidence: general anaesthesia ....................................... 141 13 Acronyms and glossaries of terms used in the guideline........................................................ 143 13.1 Acronyms and abbreviations ......................................................................................... 143 13.2 Glossary of medical terms ............................................................................................. 144 13.3 Glossary of methodological terms ................................................................................. 145 14 References ............................................................................................................................. 156 National Clinical Guideline Centre, 2014 7 Drug allergy Contents Guideline Development Group members Name Role Mike Ardern Jones Consultant Dermatologist David Cousins Senior Head of Patient Safety for Safe Medication Practice and Medical Devices, NHS England Matthew Doyle General Practitioner George Du Toit Consultant Paediatric Allergist Mandy East Patient member Pamela Ewan Consultant Allergist James Larcombe General Practitioner Nicola Mundy Patient member Shuaib Nasser Chair, Consultant Allergist Alice Oborne Pharmacist Paul Whitaker Respiratory consultant Andrew Williams Specialist Nurse NCGC technical team members Name Role Lee Yee Chong Senior Research Fellow (until May 2013) Margaret Constanti Health Economist (until March 2013) Kathleen DeMott Research Fellow (until August 2013) Tamara Diaz Project Manager Katharina Dworzynski Senior Research Fellow (from June 2013) Martin Harker Health Economist (from April 2013) Kate Kelley Guideline Lead, Associate Director (until January 2013) Grace Marsden Senior Health Economist (from April 2013) Su Park Research Fellow (from August 2013) Vicki Pollit Senior Health Economist (until March 2013) Gill Ritchie Guideline Lead, Associate Director (from February 2013) Carlos Sharpin Information Scientist Co-optees Name Role Mamidipudi Thirumala Co-optee, Laboratory Pathologist and Consultant Allergist Krishna Nigel J N Harper Co-optee, Consultant Anaesthetist Nick Brown Co-optee, Dentist National Clinical Guideline Centre, 2014 8 Drug allergy Acknowledgements Acknowledgements The development of this guideline was greatly assisted by the following people: Name Role Elisabetta Fenu NCGC, Health Economic Lead Jill Cobb NCGC, Information Scientist Tom Kenny NIHR Evaluation Trials and Studies Coordinating Centre (NETS CC), Director, External Relations, Maggie Westby NCGC, Clinical Effectiveness Lead Pamela Young NIHR Evaluation Trials and Studies Coordinating Centre (NETS CC), Scientific Adviser (Identification) - External Relations National Clinical Guideline Centre, 2014 9 Drug allergy Introduction 1 Introduction All drugs have the potential to cause side effects, also known as ‘adverse drug reactions’, but not all of these are allergic in nature. Other reactions are idiosyncratic, pseudo-allergic or caused by drug intolerance. The British Society for Allergy and Clinical Immunology (BSACI) defines drug allergy as an adverse drug reaction with an established immunological mechanism. The mechanism at presentation may not be apparent from the clinical history and it cannot always be established whether a drug reaction is allergic or non-allergic without investigation. Therefore, this guideline has defined drug allergy as any reaction caused by a drug with clinical features compatible with an immunological mechanism. Hospital Episode Statistics from 1996 to 2000 reported that drug allergies and adverse drug reactions accounted for approximately 62,000 hospital admissions in England each year. There is also evidence that these reactions are increasing: between 1998 and 2005 serious adverse drug reactions rose 2.6- fold.116 Up to 15% of inpatients have their hospital stay prolonged as a result of an adverse drug reaction. About half a million people admitted to NHS hospitals each year have a diagnostic ‘label’ of drug allergy, with the most common being penicillin allergy. About 10% of the general population claim to have a penicillin allergy;79 this has often been because of a skin rash that occurred during a course of penicillin in childhood. Fewer than 10% of people who think they are allergic to penicillin are truly allergic.79 Therefore, penicillin allergy can potentially be excluded in 9% of the population.36,61 Studies have shown that those with a label of penicillin allergy are more likely to be treated with broad-spectrum antibiotics, such as quinolones, vancomycin, and third-generation cephalosporins (Lee, 2000)96. Use of broad-spectrum antibiotics is associated with an increased rate of clinical complications, such as antibiotic resistance and Clostridium difficile leading to increased hospital stay (Macy,2014)102. Patients in intensive care who developed vancomycin-resistant enterococcus (VRE) were 5 times more likely to have been treated with vancomycin and third generation cephalosporins during the previous month (Martinez, 2003)108. Therefore, an unsubstantiated label of penicillin allergy may lead to the inappropriate use of broad spectrum, non-penicillin antibiotics leading to antibiotic resistance and in some cases sub-optimal therapy. Allergic reactions to non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac, naproxen and aspirin are common.61,78 In particular, 5–10% of people with asthma are affected. About one-third of people with chronic urticaria have severe reactions to NSAIDs, involving angioedema and anaphylaxis after administration of NSAIDs.34,117 Anaphylaxis-type reactions occur in approximately 1 in 1000 of the general population. Anaphylaxis during general anaesthesia occurs in between 1 in 10,000–20,000 anaesthetics.46,47 These patients may be denied general anaesthesia in the future unless a safe combination of drugs can be identified.115 Major issues identified by this guideline include poor clinical documentation of drug allergy and a lack of patient information. Computerised primary care record systems are often unable to distinguish between intolerance and drug allergy and this can lead to a false label of drug allergy, particularly if the person’s reaction took place many years previously and details about their reaction have been lost. Furthermore, there is no routine system in place for people to keep a record of their own drug allergies. This can lead to confusion over which drugs can be taken safely and can result in people inadvertently taking a drug they are allergic to, particularly when buying over-the-counter preparations from a pharmacy. Analysis of patient safety incidents reported to the National Reporting and Learning System between 2005 and 2013 identified 18,079 incidents involving drug allergy. These included 6 deaths, 19 ‘severe National Clinical Guideline Centre, 2014 10