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Practice Guidelines

Diagnosis and management of drug allergy in adults, children and young people: summary of NICE guidance

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4852 (Published 03 September 2014) Cite this as: BMJ 2014;349:g4852
  1. Katharina Dworzynski, senior research fellow1,
  2. Michael Ardern-Jones, guideline development group member2,
  3. Shuaib Nasser, guideline chair3
  4. on behalf of the Guideline Development Group (GDG)
  1. 1National Clinical Guideline Centre, Royal College of Physicians of London, London NW1 4LE, UK
  2. 2Department of Dermatopharmacology, Southampton General Hospital, University of Southampton, Southampton, UK
  3. 3Department of Allergy, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
  1. Correspondence to: K Dworzynski Katharina.Dworzynski{at}rcplondon.ac.uk

All drugs have the potential to cause side effects or “adverse drug reactions,” but not all of these are allergic in nature. The diagnosis of drug allergy can be challenging, and there is considerable variation both in how drug allergy is managed and in geographical access to specialist drug allergy services.1 On the basis of a National Institute for Health and Care Excellence (NICE) analysis of hospital episode statistics, about half a million people admitted to NHS hospitals each year in England and Wales have a diagnostic label of “drug allergy,” with the most common being penicillin allergy.2 Fewer than 10% of people who think they are allergic to penicillin are truly allergic.3 Inadequate clinical documentation of allergic drug reactions and a lack of patient information (provided to and by patients) may lead to an inappropriate label of allergy to penicillin or other drugs remaining on a medical record. This can prevent future prescription even when clinically indicated. This article summarises the most recent recommendations from NICE on drug allergy.4

Recommendations

NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets.

Assessment

When a course of treatment with a drug is started a patient may experience adverse symptoms for a variety of reasons. Not all reactions are caused by the drug itself and careful assessment is needed to establish the correct cause.

Figure1

Signs and allergic patterns of suspected drug allergy

  • When assessing a person who presents with possible drug allergy, take a history and undertake a clinical examination. The figure details the signs and allergic patterns of suspected drug allergy along with the timing of onset and should be used as a guide when deciding whether to suspect drug allergy. Although the figure describes common and important presenting features of drug allergy, other presentations are also recognised. [Based on moderate quality evidence from observational studies and the experience and opinion of the Guideline Development Group (GDG)]

  • Be aware that the reaction is more likely to be caused by drug allergy if it occurred during or after use of the drug and:

    • -The drug is known to cause that type of reaction or

    • -The person has previously had a similar reaction to that drug or drug class

  • Be aware that the reaction is less likely to be caused by drug allergy if:

    • -There is a possible non-drug cause for the person’s symptoms (for example, he or she has had similar symptoms when not taking the drug) or

    • -The person has gastrointestinal symptoms only.

  • [Based on the experience and opinion of the GDG]

Non-specialist management

General

If drug allergy is suspected:

  • Consider stopping the drug suspected to have caused the allergic reaction and advise the person to avoid that drug in future

  • Treat the symptoms arising from the acute reaction if necessary; send people with severe reactions to hospital.

Non-steroidal anti-inflammatory drugs (NSAIDs)

  • Do not offer a selective cyclo-oxygenase 2 (COX-2) inhibitor to people in a non-specialist setting if they have had a severe reaction, such as anaphylaxis, severe angio-oedema, or an asthmatic reaction, to a non-selective NSAID.

  • For people who have had a mild allergic reaction to a non-selective NSAID but need an anti-inflammatory drug:

    • -Discuss the benefits and risks of selective COX-2 inhibitors (including the low risk of drug allergy)

    • -Consider introducing a selective COX-2 inhibitor at the lowest starting dose with only a single dose on the first day.

  • [Based on very low quality evidence from observational studies and the experience and opinion of the GDG]

Measuring serum tryptase after suspected anaphylaxis

  • After a suspected drug related anaphylactic reaction, take two blood samples for mast cell tryptase in line with recommendations on anaphylaxis.5

  • Record the exact timing of both blood samples taken for mast cell tryptase:

    • -In the person’s medical records and

    • -In the pathology request form.

  • [Based on very low quality evidence from observational studies]

Measuring serum specific IgE

  • Do not use blood testing for serum specific IgE to diagnose drug allergy in a non-specialist setting.

  • [Based on very low quality evidence from observational studies]

Documenting and sharing information with other healthcare professionals

Computerised primary care record systems currently do not distinguish between drug allergy and non-allergic adverse drug reactions. This can lead to a false label of drug allergy, particularly if the person’s reaction took place many years earlier and details about the drug and the reaction were never recorded or were misplaced.

  • When people present with suspected drug allergy, document their reaction using a structured approach that includes:

    • -The generic and proprietary name of the drug or drugs suspected to have caused the reaction, including the strength and formulation

    • -A description of the reaction (see figure)

    • -The indication for the drug being taken (if there is no clinical diagnosis, describe the illness)

    • -The date and time of the reaction

    • -The number of doses taken or number of days that the person had been taking the drug before onset of the reaction

    • -The route of administration

    • -Which drugs or drug classes should be avoided in future.

  • Ensure that information about drug allergy status is updated and included in all:

    • -GP referral letters

    • -Hospital discharge letters.

  • Prescriptions (paper or electronic) issued in any healthcare setting should be standardised and re-designed to record information on which drugs or drug classes to avoid to reduce the risk of drug allergy.

  • [Recommendations in this section were based on very low quality evidence from observational studies and the experience and opinion of the GDG]

Providing information and support to patients

Patients are often left bewildered after a suspected allergic reaction to a drug. Their fear of experiencing a further reaction can be heightened by a lack of information, especially if the original reaction was severe.

  • Discuss the suspected drug allergy with the person (and family members or carers as appropriate) and provide structured written information (see documenting and sharing above). Record who provided the information and when.

  • [Based on moderate quality evidence from qualitative studies and the experience and opinion of the GDG]

  • Ensure that the person (and family members or carers as appropriate) is aware of the drugs or drug classes that need to be avoided, and advise the person to check with a pharmacist before taking any over-the-counter preparations.

  • [Based on moderate quality evidence from qualitative studies and the experience and opinion of the GDG]

After specialist drug allergy investigations

  • Allergy specialists should give the following written information to people who have undergone specialist drug allergy investigation:

    • -The diagnosis—whether the reaction was allergic or non-allergic

    • -The drug name and a description of the reaction (see figure)

    • -The investigations used to confirm or exclude the diagnosis

    • -Drugs or drug classes to avoid in the future

    • -Any safe alternative drugs that may be used.

  • [Based on moderate quality evidence from qualitative studies and the experience and opinion of the GDG]

Referral to specialist services

This should enable either confirmation or exclusion of the drug allergy. Exclusion will allow the patient to have the same and related drugs in the future. It is not appropriate to refer all patients with a label of drug allergy because this would be costly and would overwhelm specialist drug allergy services. Therefore the GDG made the following recommendations relating to the causes of suspected allergy to drugs that most commonly lead to a referral to specialist drug allergy services.

General

  • Refer people to a specialist drug allergy service if they have had:

    • -A suspected anaphylactic reaction (also see NICE guideline on anaphylaxis5) or

    • -A severe non-immediate cutaneous reaction (such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, or toxic epidermal necrolysis).

  • [Based on previous NICE guidance and the experience and opinion of the GDG]

β lactam antibiotics

  • Refer people with a suspected allergy to β lactam antibiotics to a specialist drug allergy service if they:

    • -Need treatment for a disease or condition that can be treated only by a β lactam antibiotic or

    • -Are likely to need β lactam antibiotics often in the future (for example, people with recurrent bacterial infections or immune deficiency).

  • [Based on cost effectiveness scenarios calculating the potential costs of referral to specialist services or non-specialist management, and the experience and opinion of the GDG]

Non-steroidal anti-inflammatory drugs

  • Refer people who need treatment with an NSAID to a specialist drug allergy service if they have had a suspected allergic reaction to an NSAID with symptoms such as anaphylaxis, severe angio-oedema, or an asthmatic reaction.

  • [Based on cost effectiveness scenarios calculating the potential costs of either referral to specialist services or non-specialist management, and the experience and opinion of the GDG]

Local anaesthesia

  • Refer people to a specialist drug allergy service if they need a procedure involving a local anaesthetic that they are unable to have because of suspected allergy to local anaesthetics.

  • [Based on the experience and opinion of the GDG]

General anaesthesia

  • Refer people who have had anaphylaxis or another suspected allergic reaction during or immediately after general anaesthesia to a specialist drug allergy service.

  • [Based on the experience and opinion of the GDG]

Overcoming barriers

Major problems identified by this guideline include: poor clinical documentation of drug allergy; the lack of provision of patient information; lack of a specific section to record drug allergy on prescriptions issued in general practice; and inability of current clinical information systems to differentiate between adverse drug reaction and drug allergy. Measures that would help overcome these barriers to implementation include improved clinical systems that provide the relevant codes or options to differentiate and record specific drug allergies separately from adverse drug reactions, with outputs that are sensitive but do not lead to unnecessary alerts (which can induce clinicians to habitually over-ride the system). A re-design of standard prescription forms and hospital drug charts to enable the inclusion of structured drug allergy information would also improve patient safety. Implementation of this guideline would be further enhanced if the BNF included a section on the recognition of symptoms and signs of drug allergy. In addition, clinician training, including e-learning modules and auditing, would facilitate the documentation of drug allergies.

Further information on the guidance

The guideline made further recommendations on information held by the person with a drug allergy after specialist investigation.

After specialist drug allergy investigation
  • Advise people (and their family members or carers as appropriate) to carry information that they have been given about their drug allergy at all times and to share this whenever they visit a healthcare professional or are prescribed, dispensed, or about to be given a drug.

Methods

The guideline was developed according to National Institute for Health and Care Excellence (NICE) guideline methodology (www.nice.org.uk/guidelinesmanual). The Guideline Development Group (GDG) consisted of two consultant allergists, a consultant dermatologist, two general practitioners, a specialist nurse, a consultant paediatrician, two patient or carer members, two pharmacists, and a specialist respiratory consultant. The scope and full guideline were posted on the NICE website as part of a stakeholder consultation. A new cost effectiveness analysis was not undertaken owing to a lack of suitable data, but the cost implications of referral in some circumstances were calculated. NICE has produced four different versions of the guideline: a full version; a pathway; a version known as the “NICE guideline” that summarises the recommendations; and a version for patients and the public. All these versions are available from the NICE website (www.nice.org.uk/Guidance/CG183). Future updates of the guideline will be published according to the NICE guideline development programme.

Future research and remaining uncertainties

The GDG highlighted some important research questions:

  • What is the most effective documentation strategy to prevent people from being re-exposed to drugs to which they have a suspected or confirmed allergy (particularly electronic health records and different formats for patient held documentation)?

  • Which information strategies could be used to make people more likely to disclose their drug allergy in clinical practice?

  • Should all patients who have experienced a severe allergic reaction to a non-selective non-steroidal anti-inflammatory drug (NSAID) be assessed by specialist drug allergy services or should they be advised to take a selective cyclo-oxygenase 2 (COX-2) inhibitor without further investigations?

  • In children who have a suspected allergy to an antibiotic, is it clinically and cost effective to proceed directly (without skin or intradermal tests) to challenge with a diagnostic oral antibiotic rather than to refer them to specialist drug allergy services?

Notes

Cite this as: BMJ 2014;349:g4852

Footnotes

  • This is one of a series of BMJ summaries of new guidelines based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists.

  • The members of the Guideline Development Group were: Michael Ardern-Jones, Lee Yee Chong, Margaret Constanti, David Cousins, Kathleen deMott, Tamara Diaz, Matthew Doyle, George Du Toit, Katharina Dworzynski, Mandy East, Pam Ewan, Martin Harker, Kate Kelley, James Larcombe, Grace Marsden, Nicola Mundy, Shuaib Nasser (chair), Alice Osborne, Su Park, Vicki Pollit, Gill Ritchie (guideline lead), Carlos Sharpin, Paul Whittaker, and Andrew Williams.

  • Contributors: KD, MA-J, and SN drafted the article. All authors revised it critically for important intellectual content, approved the final version to be published, and are guarantors.

  • Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: KD and SN; none. MA-J has received consulting fees, consulting income (University of Southampton), research grants (University of Southampton), and travel support from Novartis, Lilly, Genus, Abbvie, AllergyTherapeutics, Celgene, Emblation, and Unilever as well as income from royalties for books. All of these interests were considered to be outside the scope of this guideline. The authors’ full statements can be viewed at www.bmj.com/content/bmj/349/bmj.g4356/related#datasupp.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

References

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