These guidelines have been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and are intended for allergists and others with a special interest in allergy. As routine or validated tests are not available for the majority of drugs, considerable experience is required for the investigation of allergic drug reactions and to undertake specific drug challenge. A missed or incorrect diagnosis of drug allergy can have serious consequences. Therefore, investigation and management of drug allergy is best carried out in specialist centres with large patient numbers and adequate competence and resources to manage complex cases. The recommendations are evidence based but where evidence was lacking consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, clinical patterns of drug allergy, diagnosis and treatment procedures. In order to achieve a correct diagnosis we have placed particular emphasis on obtaining an accurate clinical history and on the physical examination, as these are critical to the choice of skin tests and subsequent drug provocation.
After the diagnosis of drug allergy has been established, communication of results and patient education are vital components of overall patient management.
This guideline focuses on a difficult problem faced by clinicians in everyday practice – the diagnosis and management of drug allergy. Routine and validated tests are not available for many allergic drug reactions but a body of knowledge has been developed by centres seeing large numbers of patients with adverse reactions to a number of drug classes particularly b-lactams, neuromuscular blockers, (NMBA) aspirin/non-steroidal anti-inflammatory drugs (NSAIDs), local anaesthetics and opiates. Considerable experience is required to guide management, to interpret results of investigations and undertake drug challenges. For some drugs (e.g. non-b-lactam antibiotics, insulin, patent blue dye, plasma expanders) there is a paucity of published data and/or few patients have been investigated. Every case must be individually evaluated and managed. For these reasons the investigation of drug allergy is best focussed on specialist centres with adequate experience, regular exposure to a complex case mix and competence in skin testing and drug challenges. This document provides a general overview for the investigation of drug allergy and subsequent guidelines will focus on specific drug classes. During the development of these guidelines, all British Society for Allergy and Clinical Immunology (BSACI) members were consulted using a web-based system and their comments and suggestions were carefully considered by the Standards of Care Committee (SOCC). Where evidence was lacking a consensus was reached among the experts on the committee. Conflicts of interests were recorded by the BSACI. None jeopardized unbiased guideline development.
Grades of recommendations are defined as in Powell et al. :
- Adverse drug reactions (ADRs) account for approximately 6.5% of all hospital admissions.
- Up to 15% of in-patients have a hospital stay prolonged as a result of ADR.
- ADRs affect quality of life, may lead to delayed treatment, unnecessary investigations or even death.
- Statistics of ADRs and also subsequent deaths resulting from ADRs are likely to be unreliable with widespread underreporting in both adults and children.
- Topical and particularly cutaneous routes of administration and prolonged or frequent doses are more likely to lead to sensitization.
- Atopy is not a risk factor for the majority of allergic drug reactions but may lead to a more severe reaction.
- Cutaneous reactions are among the most common of all the different patterns of ADRs.
- Some infections such as by Herpes viruses (EBV, CMV and others) as well as HIV, increase the likelihood of drug reactions and repeated use of antibiotics in diseases such as cystic fibrosis is associated with more frequent reactions.
- A detailed history is required for an accurate diagnosis of a drug-induced reaction and should include details of drug formulation, dose, an assessment of the time course and clinical pattern of the reaction. This will inform the likely immunological mechanism and direct investigation and management (grade of recommendation =A).
- When investigating reactions during general anaesthesia it is particularly important to review the anaesthetic chart, medical notes, drug and nursing charts (grade of recommendation = C).
- Skin prick test (SPT) and intradermal test provide evidence of IgE-mediated sensitization and patch tests or delayed reading of an intradermal test provide evidence for a delayed or T cell-mediated process to a specific drug. However, all skin test results must always be interpreted within the appropriate clinical context (grade of recommendation = B).
- If the reaction is not IgE-mediated, a negative skin test result does not exclude the drug as the cause of the reaction and further investigation should be considered (grade of recommendation = C).
- Skin tests may be falsely negative even if the reaction is IgE-mediated because of limitations in the availability of the relevant skin test reagents.
- Skin tests are particularly difficult to interpret for drugs known to be direct histamine releasers, e.g. opiates and some neuromuscular blocking agents (NMBA) or if the drug has been tested at a concentration causing local skin irritation.
- Skin tests should not be used to screen for drug allergy in the absence of a clinical history compatible with IgEmediated drug allergy (grade of recommendation = C).
- Skin testing for immediate hypersensitivity is not indicated for type III serum sickness reactions or for T cell-mediated reactions including severe cutaneous reactions such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction/rash with eosinophilia and systemic symptoms (DRESS) (grade of recommendation = B).
- Skin testing for delayed-type hypersensitivity with patch tests can be helpful in T cell-mediated hypersensitivities such as DRESS syndrome and SJS/TEN. (grade of recommendation = C).
- Serial blood samples for serum tryptase should be taken at the time of suspected anaphylaxis, at 2 and 24 h or later (baseline sample) after onset of anaphylaxis (grade of recommendation = C).
- Drug challenge should only be considered after other investigations have been exhausted and the diagnosis remains in doubt. The primary aim of provocation testing should be to exclude drug sensitivity/intolerance but it can also be used to confirm diagnosis or to demonstrate tolerance to an alternative drug (grade of recommendation = B).
- It is not usually advisable to carry out provocation testing if the reaction has resulted in a life-threatening reaction. Drug provocation should be carried out by personnel experienced in drug challenges with adequate resuscitation facilities readily available (grade of recommendation = C).
- If there are no suitable alternatives, drug desensitisation may be possible for one course of treatment particularly for antibiotics, aspirin, taxenes and platinum-based cancer chemotherapeutic agents (grade of recommendation = B).
- Prevention of future reactions is an essential part of patient management. The patient should be provided with written information about which drugs to avoid, the drugs highlighted in hospital notes and the GP informed (grade of recommendation = B).
- Engraved allergy-bracelets are useful when there is a risk of intravenous drug administration in an emergency, e.g. muscle relaxants, opiates or penicillin or when drugs, e.g. NSAIDs are readily available without prescription (grade of recommendation = B).
- Health Care Professionals should report ADRs via the Yellow Card Scheme run by the Medicines and Healthcare products Regulatory Agency (MHRA) and the Commission on Human Medicines.
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