Drug Allergy: Diagnosis and Management

• LTHT adult drug allergy referral form
• Anaesthetic allergy referral form
• Paediatric Allergy Record/Referral Form
• Standard operating procedure (SOP) for updating allergy status on eMeds

• Aims
• Objectives
• Background
• Diagnosis of suspected drug allergy
• Investigations
• Management of suspected drug allergy in a non-specialist setting
• Management of drug allergy following review in a specialist drug allergy clinic
• Specific advice for patients with a suspected drug allergy to:
  • Non-steroidal anti-inflammatory drugs (including selective cyclooxygenase 2 inhibitors)
  • Beta-lactam antibiotics
• Indications for referral to a specialist drug allergy clinic
• How do I refer a patient for review within a specialist drug allergy clinic?
• Patients who have had an allergy excluded
• Future management of patients with an allergy

Summary of Guideline

See flow chart below

Paediatric Drug Allergy:

Suspected antibiotic allergy is the most common reason for referral of children to drug allergy clinic. Common presentations are maculopapular rash (exanthema) and urticaria. Antibiotic allergy is often over-diagnosed and can lead to increase in health care costs and development of antibiotic resistance.  Children with clinical history of severe allergic reaction, or those requiring drug for ongoing clinical care where there is no equally effective, structurally unrelated alternative or those who had a reaction to multiple drugs should be investigated in order to identify culprit agent and confirm allergy or demonstrate tolerance.

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Background

If you suspect your patient is currently experiencing anaphylaxis please follow the Resuscitation Council (UK) guidelines on the management of anaphylaxis (https://www.resus.org.uk/anaphylaxis/emergency-treatment-of-anaphylactic-reactions/)

All medicines have the potential to cause adverse effects but not all of these are allergic in nature.  The British Society for Allergy and Clinical Immunology (BSACI) defines drug allergy as an adverse drug reaction with an established immunological mechanism.  This may not be apparent from the clinical history at presentation and it cannot always be established whether a drug reaction is allergic or non-allergic without investigation.  This guideline outlines the procedures to follow when considering the possibility of drug allergy, in line with the NICE CG 183.

Please note there is an additional NICE guidance (CG134) for the diagnosis and treatment of anaphylaxis http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=5373 and a separate LTHT guideline on anaphylaxis in children http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=60. 

There is also a separate LTHT guideline on penicillin allergy http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=3226

A separate allergy care pathway for drug allergy in children can be accessed through RCPCH website here
https://www.rcpch.ac.uk/sites/default/files/RCPCH_Care_Pathway_for_Children_with_Drug_Allergy.pdf

Note: within this guideline the term ‘non-specialist setting’ is used to describe any clinical area outside of a specialist drug allergy clinic.

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Diagnosis

All patients with a suspected drug allergy should have a detailed history and clinical examination undertaken.

The following should be used as a guide when deciding whether to suspect drug allergy:

Immediate, rapidly evolving reactions - onset usually less than 1 hour after drug exposure (previous exposure not always confirmed) 

• Anaphylaxis - a severe multi-system reaction characterized by erythema, urticaria or angioedema and hypotension and/or bronchospasm 
• Urticaria or angioedema without systemic features 
• Exacerbation of asthma (for example, with non-steroids anti-inflammatory drugs) 

Non-immediate reactions without systemic involvement - onset usually 6-10 days after first drug exposure or within 3 days of second exposure 

• Widespread red macules or papules (exanthema-like)
• Fixed drug eruption (localized inflamed skin)

Non-immediate reactions with systemic involvement - see individual sub-categories for time of onset

• Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome (DHS) characterised by:
  • widespread red macules, papules or erythroderma
  • fever
  • lymphadenopathy
  • liver dysfunction
  • eosinophilia
  • onset usually 2-6 weeks after first drug exposure or within 3 days of second exposure

• Toxic epidermal necrolysis or Steven-Johnson syndrome characterised by:
  • painful rash and fever (often early signs)
  • mucosal or cutaneous erosions
  • vesicles, blistering or epidermal detachment
  • red purpuric macules or erythema multiform
  • onset usually 7-14 days after first drug exposure or within 3 days of second exposure

• Acute generalised exanthematous pustulosis (AGEP) characterised by:
  • widespread pustules
  • fever
  • neutrophilia
  • onset usually 3-5 days after first drug exposure

• Common disorders caused, rarely, by drug allergy:
  • eczema
  • hepatitis
  • nephritis
  • photosensitivity
  • vasculitis
  • time of onset variable

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

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, they had similar symptoms when not taking the drug) or
• the person has gastrointestinal symptoms only

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Investigations

After a suspected drug-related anaphylactic reaction two blood samples for mast cell tryptase should be taken.  This should be a yellow serum gel immunology tube (http://www.pathology.leedsth.nhs.uk/testandtubes/ShowTest.asp?ACT=ShowTest&TestID=303)

Sample 1 – as soon as possible after emergency treatment has started
Sample 2 –ideally within 1-2 hours from the onset of symptoms (but no later than 4 hours)

The time the samples were taken must be recorded in the patient’s medical notes and on the blood sample request form.

Do not use blood testing for serum specific immunoglobulin E (IgE) to diagnose drug allergy in a non-specialist setting

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Treatment / Management

Management of suspected drug allergy in a non-specialist setting:

• Stop the drug suspected to have caused the allergic reaction
• Treat the symptoms of the acute reaction if needed
• For anaphylaxis take tryptase levels as described above
• Consider whether an alternative medication is required for the indication for which the medication was being given for (if you are unsure of cross-reactivity of a medication then please contact pharmacy, immunology, the medicines advisory service or microbiology for antibiotics).
• For cutaneous reactions consider photograph (medical illustration)

Documentation:
It is important to communicate a patients drug allergy status to all their healthcare providers as it will have implications on their future treatment and avoid them being exposed to a medication they are allergic to again.

Every patient with a suspected drug allergy should have the following documented in their medical notes as soon as possible following the reaction:

• The generic and brand name of the drug(s) suspected to have caused the reaction, including the strength and formulation
• A description of the reaction as per the categories described above
• The indication for the drug being taken
• The date and time of the reaction
• The number of doses taken or numbers of days on the drug before onset of the reaction
• Time interval between the last does and the onset of symptoms
• The route of administration
• The drug and/or drug classes that should be avoided in the future

Ensure drug allergy status is updated on the patient’s allergy band, patient medical records, eMeds/drug chart and discharge letters.

Information for patients (and their family members or carers as appropriate):

• Discuss the person’s suspected drug allergy with them
• Ensure the person is aware of the drugs or drug classes that they need to avoid
• Advise them to check with a pharmacist before taking any over-the-counter preparations
• Advise people to carry information about their drug allergy with them and to share this information whenever they visit a healthcare professional or are prescribed, dispensed or about to be administered a drug
• Provide structured written information – this can be done as part of the discharge summary
• Allergy UK and The Anaphylaxis Campaign have good general information on drug allergy and patients can be signposted to these for more information
• Record within the medical notes who provided the information and when

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Following review in a specialist drug allergy clinic:

Documentation:
Following review within a specialist drug allergy clinic the following should be documented:

• The diagnosis, drug name and whether the person had an allergic or non-allergic reaction
• The investigations used to confirm or exclude the diagnosis
• Drugs or drug classes to avoid in the future
• If allergy is excluded, then all the patient’s medical records should be updated to state that this has been investigated and excluded

Information for patients (and their family members or carers as appropriate):
The following written information should be provided to patients:

• The diagnosis - whether they had an allergic or non-allergic reaction
• The drug name and a description of their reaction
• 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
• Patients who have had a drug allergy excluded by specialist investigation should be informed that they can now take this drug safely

Specific advice for patients with a suspected drug allergy to:

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Non-steroidal anti-inflammatory drugs (including selective cyclooxygenase 2 inhibitors)

• Advise patients they need to avoid all non-selective NSAIDs including over-the-counter preparations
• For people who have had a mild allergic reaction to a non-selective NSAID but need an anti-inflammatory:
  • Discuss the benefits and risks of selective cyclooxygenase 2 (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
• Do not offer a selective COX-2 inhibitor to people in a non-specialist setting if they have had a severe reaction, such as anaphylaxis, severe angioedema or an asthmatic reaction, to a non-selective NSAID
• 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 angioedema or an asthmatic reaction
• Be aware that people with asthma who also have nasal polyps are likely to have NSAID-sensitive asthma unless they are known to have tolerated NSAIDs in the last 12 months

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Beta-lactam antibiotics:

See separate guideline http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=3226

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Indications for referral to a specialist drug allergy clinic:

• Suspected anaphylaxis, if causative agent is unclear
• NSAID reactions, involving severe angioedema or an asthmatic reaction, where there are limited other options for pain relief
• Beta-lactam allergy when beta-lactams are considered essential for management or when there is likely to be frequent need for beta-lactam antibiotics in the future or there is suspected allergy to at least one other class of antibiotics in addition to beta-lactams
• People who need a procedure involving a local anaesthetic that they are unable to have because of a suspected allergy to any local anaesthetic
• Anaphylaxis or another suspected allergic reaction during or immediately after general anaesthesia
• Severe non-immediate cutaneous reaction - these patients should be referred to dermatology.

Some other departments (e.g. dermatology) already look after patients with drug induced rashes (and have expertise).  Not all patients with drug induced rashes need to be referred to immunology/allergy if the patient has been assessed and advised appropriately by other clinicians.

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How do I refer a patient for review within a specialist drug allergy clinic?

Paediatric drug allergy:

Children with suspected drug allergy or perioperative anaphylaxis are seen in designated paediatric drug allergy clinic. 
The paediatric drug allergy clinic referral form can be found here
Paediatric Allergy Record/Referral Form 
For anaesthetic allergy please use 'Form A' below and send t othe paediatric allergy department.

Adult drug allergy:

The following form should be used to refer a patient to the adult drug allergy clinic:
LTHT adult drug allergy referral form

Please note a separate form must be completed for each suspected drug.

Anaesthetic drug allergy:
Patients with a suspected allergy to general anaesthetics are reviewed within a dedicated general anaesthetic allergy clinic involving both clinical immunology and anaesthetics.

The following document should be used to refer to a patient for review within this clinic:
Anaesthetic allergy referral form

Note: paediatric anaesthetic drug allergy referrals should be sent to the paediatric allergy department (Form A to be used).

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Patients who have had an allergy excluded

It is equally important to remove a drug allergy label from a patient (‘delabel’) if they are found (intentionally or unintentionally) not to be allergic as this can have a significant impact on their future management.  For antibiotics this is important to promote good anti-microbial stewardship.  Ensure drug allergy status is updated on the patient’s allergy band, patient medical records, eMeds/drug chart and discharge letters.

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Future management of patients with an allergy

In some rare instances there may be a clinical need for the medication the patient is allergic to and no other suitable alternative.  Desensitisation to the medication may be appropriate in some cases.  This is not possible with all medications and individual cases should be discussed with immunology; with the exception of antibiotic allergy in patients with cystic fibrosis/bronchiecstasis and aspirin desensitisation in cardiology patients who already have a guideline for this http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=5259.

Note desensitisation is a procedure that alters the immune response to a drug and results in TEMPORARY tolerance, allowing the patient with a drug hypersensitivity reaction to receive an uninterrupted course of the medication safely.  This is different to a drug challenge which is used to exclude a drug allergy.