1.1. Short title

Drug allergy

3.1. Epidemiology

1. The World Health Organisation (WHO) uses the following definition of a “drug”: “A term of varied usage. In medicine, it refers to any substance with the potential to prevent or cure disease or enhance physical or mental welfare, and in pharmacology to any chemical agent that alters the biochemical physiological processes of tissues or organisms”. The European Commission further define a medicinal product as, “any substance or combination of substances presented as having properties for treating or preventing disease in human beings; or any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.”
2. An adverse drug reaction is defined by the European commission as “a response to a medicinal product which is noxious and unintended”. ADRs can be classified into reactions, which may affect anyone (type A) and reactions which, affect only susceptible individuals (type B). Within the definition of drug allergy we have also included any reaction presenting with symptoms commonly associated with immune-mediated reactions such as urticarial, angioedema or asthma because the mechanism at presentation may not be evident from clinical history. True hypersensitivity reactions are immune-mediated and classified into Gell and Coombs categories. Drug allergy requires prior exposure to the same or a cross-reacting compound (sensitization) at a dose tolerated by the majority of individuals. Therefore there may not be a history of prior exposure to the specific drug. A variety of mechanisms underpin the allergic symptoms, experienced with subsequent courses of drug.
3. Diagnosing a drug allergy is challenging, with considerable variation in service provision, practice and referral pattern. This can lead to under-diagnosis, misdiagnosis and self-diagnosis.
4. There is no robust information on the prevalence or incidence of drug allergy alone in the UK population. Information is available for adverse drug reactions of which drug allergy is a subgroup, and anaphylaxis for which drug allergy is a potential cause.
5. The estimated incidence of drug allergy in primary care shows that the incidence in women is twice as high as that in men. The reason for this is unclear.

3.2. Current practice

1. There is variation in referral patterns and in the management of drug allergies. There is also variation in geographical access to specialist allergy centres, as most of the centres are located in cities. The variation may relate to a lack of knowledge of available services or a lack of local provision of a drug allergy centre. Therefore, only a proportion of people are likely to be treated in specialist allergy centres whereas others are never referred and remain in primary care. Some people have their drug allergy managed within other disciplines. For example, cancer centres may manage drug allergies related to their own treatment regimes.
2. The drugs commonly investigated/referred include: penicillins, other beta-lactam antibiotics, non-beta-lactam antibiotics, drugs given during general anaesthesia (for example neuromuscular blocking agents), local anaesthetics, aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors, radio-contrast media and plasma expanders.
3. The investigation of a drug allergy includes:
   • assessing previous history of drug reactions and allergies
   • taking a blood tryptase test at the time of the allergic reaction and when the patient has recovered
   • performing a shin prick test, an intradermal test, a patch test and specific IgE testing (only available for a limited number of drugs)
   • conducting a drug provocation test (controlled administration of a drug to diagnose drug hypersensitivity reactions).
4. Tests undertaken during an acute reaction to confirm or exclude diagnosis may include:
   • Serum tryptase, urea and electrolytes, liver function test, full blood count, differentiated blood count, Coombs' test, antinuclear antibody, antineutrophil cytoplasmic, antibody erythrocyte sedimentation rate, blood coagulation tests and C-reactive protein.
   • skin biopsy
   • urine microscopy
   • electrocardiogram
   • chest X-ray.
5. Managing an adverse drug reaction with a possible immunological cause (including drug allergy) involves identifying alternative drugs, drug avoidance, advice and drug desensitisation.
6. People are often labelled as having drug allergy which can lead to lifelong avoidance of certain drugs, particularly antibiotics. However, studies that performed shin prick test, intradermal test or oral challenge on people who have had a plausible history of drug allergy showed that most were able to tolerate the drug.
7. People who have experienced an adverse event during anaesthesia are often anxious about the possibility of needing surgery in the future and, unless the cause is investigated and diagnosed, they may actively avoid referral for future surgical treatment, with a consequent risk to their health.

This NICE guideline is needed to address the known and unknown variations in the diagnosis and management of drug allergies.

4.1. Population

4.2. Healthcare setting

1. All settings where care is commissioned or provided by the NHS.

4.3. Clinical management

4.4. Main outcomes

1. Mortality.
2. Medication errors
3. Length of hospital stay.
4. Acute admission and/or readmission into secondary care.
5. Number of contacts with healthcare professionals (for example with GP).
6. Inappropriate avoidance of drugs.
7. Health-related quality of life.

4.5. Economic aspects

Developers will take into account both clinical and cost effectiveness when making recommendations involving a choice between alternative interventions or strategies. A review of the economic evidence will be conducted and analyses will be carried out as appropriate. The preferred unit of effectiveness is the quality-adjusted life year (QALY), and the costs considered will usually be only from an NHS and personal social services (PSS) perspective. Further detail on the methods can be found in ‘The guidelines manual’ (see ‘Further information’).

4.6. Status