What is anaphylaxis?
NICE defines anaphylaxis as ‘a severe, lifethreatening, generalised or systemic hypersensitivity reaction’. It is characterised by rapidly developing problems involving the airway (pharyngeal or laryngeal oedema) and/or breathing (bronchospasm) and/or circulation (hypotension). Usually there are associated skin and mucosal changes (urticaria, angioedema) (Box 1).
NICE also says that anaphylaxis may be an allergic response that is immunologically mediated, or a nonimmunologically mediated response, or idiopathic. The commonest causes of immunoglobulin E (IgE)- mediated allergic anaphylaxis are foods (e.g., egg, milk, peanuts, tree nuts, fish, shell fish), insect venoms, some drugs and latex. Many drugs can also induce anaphylaxis via non allergic mechanisms. A significant proportion of anaphylaxis is classified as idiopathic, in which there is no readily identifiable cause. The relative likelihood of the reaction being allergic, non allergic or idiopathic varies considerably with age.
Other forms of anaphylaxis include exerciseinduced anaphylaxis (EIA) and food and exercise dependant anaphylaxis (FEIDA). With EIA, anaphylaxis develops with exercise; this can be differentiated from asthma by the presence of cutaneous features of an IgE-mediated allergic reaction. With FEIDA, a patient typically develops anaphylaxis after exercising, having ingested the culprit food. Rarely reactions can occur after exercise when eating the food. Wheat is the typical food, but others can be involved such as shellfish.
These unusual presentations may only become apparent with a detailed history and provocation testing in specialist units. The Anaphylaxis Campaign fact sheet recommends avoiding the implicated foods on days when exercising.
Sometimes idiopathic angioedema and urticaria are confused with anaphylaxis.
How does anaphylaxis present in primary care?
Anaphylaxis most commonly presents in primary care after the event as a follow up consultation advised by the emergency department, or from the patient mentioning the event during a consultation. Rarely, a duty doctor may need to manage an acute presentation of anaphylaxis.
As GP practices give vaccinations they should be prepared for anaphylaxis, but it is always good to look at how the whole team responds within the context of their environment. Aspects to consider include how would the
team recognise the symptoms if a patient presented after a flu jab? Does everyone know the location of adrenaline in the surgery? Does the surgery have an accessible chart of adrenaline doses for different age groups and weights in the practice? Is everyone aware of where other equipment is kept, for example oxygen.
It is therefore worth considering how prepared your practice would be in the event of an acute anaphylaxis incident on site, and some situational awareness training may be useful. There are now educational teams and simulation training centres that offer mobile training that come to GP practices to do in house training re-enacting scenarios, e.g., http://www.montagusimulation.co.uk/simulation/mobile-training.
When should patients be referred to a specialist allergy service?
The first NICE quality statement says that any person who has had emergency treatment for suspected anaphylaxis should be referred to specialist allergy services. You can find details about your local allergy clinic on a link on the BSACI website (http://www.bsaci.org/).
Ideally, the referral would have been addressed in the emergency department if that is where they have presented, but this depends on local referral patterns and the level of experience of the staff reviewing the patient and service time pressures. Patients should have had an assessment, treatment with adrenaline and a tryptase level. They should have advice on the potential trigger if known and what to avoid, have been given patient support group advice, issued with adrenaline pens, shown how and when to use them and advised to carry them at all times. In reality, they often come for review to the GP without having any medications prescribed, asking for referral or advice on what to do next. After taking a history or reviewing the discharge letters, it is a good opportunity to go over the key features of the reaction with the patient. Safety net with the prescription for adrenaline autoinjectors prior to referral, bearing in mind in some areas there can be a long wait for review.
Once you are satisfied that they have had suspected anaphylaxis and treatment refer to secondary care.
What information can GPs provide to help secondary care professionals?
A The following information is helpful to the allergy unit:
- A short summary of the symptoms experienced, the temporal relationship to any potential trigger foods or drugs or stings (within one to two hours is suggestive of an IgE mediated reactions)
- The treatments given
- Tryptase level (if one is taken)
- Whether there is co-existing asthma, as this is a risk factor for anaphylaxis
- Whether there were any co-factors such as alcohol, exercise, NSAID or stress (co-factors are features that can augment the size of the reaction)
- Whether there have been any previous similar reactions
- Whether you have prescribed adrenaline devices
- What avoidance advice has been given, and
- Any support group advice.
What should GPs consider when prescribing adrenaline?
People who are prescribed adrenaline should be given training on how and when to us it, and this is covered by the second quality standard.
The management of suspected anaphylaxis depends on a risk assessment, which relies on the ability and time to take a good allergy focused clinical history and the training to prescribe adrenaline to those at risk of future anaphylaxis. It is helpful to be aware of features that may increase risk, such as poorly controlled asthma, previous reaction to small amount of allergen and previous requirement of several doses of adrenaline. This may be hard to cover in the time allocated, and GPs may not always have a good summary of the previous reaction from the hospital.
GPs may not feel confident in this risk assessment and this can then result in either underprescribing or overprescribing of adrenaline pens.
Further work is ongoing to create a document to provide user friendly guidance for GPs on history assessment, risk assessment, adrenaline prescribing and management anaphylaxis. The specialist unit can review the number of adrenaline pens on their subsequent assessment and advise accordingly on what ongoing level of cover is required.
There is an ongoing discussion in the specialist allergy community about the numbers of adrenaline pens required and the risk assessments. This is despite the current MHRA and EMA guidance being that two devices should be prescribed. The reasons for this are that adrenaline pens may misfire or be injected incorrectly. Additionally, a fifth of patients are thought to experience a biphasic reaction where symptoms return up to 24 hours later.
Should any special allowances be made for teenagers and young adults?
Teenagers and young adults are a particularly at risk group and need sensitive consultations, with the awareness that they may find it hard to remember to carry their adrenaline or find it awkward to bring this up in peer groups.
The Anaphylaxis Campaign (https://www.anaphylaxis.org.uk/) have a video called “Take the kit”, which is a reminder to carry the devices at all times. Other videos on their website deal with frequently asked questions, advice on travelling by air, how to get translation cards and what to do as a patient with a newly diagnosed food allergy [https://www.anaphylaxis.org.uk/corporate/corporate-what-is-anaphylaxis/corporate-resources/corporate-our-films/].
There have also been reports of bullying of food allergy children at schools. The family or patient may be anxious about possible further reactions; patients with food allergy may have as impaired quality of life as those with type one diabetes.
How should patients be trained to use their adrenaline autoinjector?
To provide training in the use of an adrenaline autoinjector, a trainer device for each of the three types of pens needs to be available. Demonstrate how to use it whilst talking about the symptoms that might trigger the need to use the injector. Ask the patient to show you how they would use it on the trainer pen, while also explaining the best position to adopt and to call an ambulance using the phrase “ANI PHY Laxis” after administering it. Explain that a second dose may be needed 5-10 minutes after the first dose and about the possibility of biphasic reactions. The type of adrenaline device might be guided by local formularies, but this should also be a shared decision between the prescriber and patient as to their preference. There are different dosages available and the different brands of adrenaline devices have needles with different lengths. There is ongoing discussion in the allergy community about the ideal length of needle needed to deliver the dose of adrenaline intramuscularly, especially in obese patients. Currently, emerade has the longest needle and a higher adrenaline dose of 500mcg. Further pharmacodynamics studies are needed to inform this debate. When renewing adrenaline devices it is important to consider that the patient is trained to the device you are prescribing and that it is named on the prescription.
What should a patient do if they accidentally inject themselves?
There have been reports of accidental injection into thumbs and fingers, so patients need clear advice on identifying the needle end. They should be told to grasp the pen firmly in the dominant hand and not put thumbs either end. If the injection is given into the digit by mistake this can cause pain, discoloration and numbness of the digit as adrenaline is a vasoconstrictor.
In this situation, patients should seek medical advice at an emergency department where they can be observed and treatment administered to the digit if necessary. They should be calling for an ambulance as part of their anaphylaxis plan. They may need to administer another dose intramuscularly into the thigh as there may be poor absorption from a peripheral site.
'When renewing adrenaline devices it is important to consider that the patient is trained to the device you are prescribing and that it is named on the prescription.'
What is the GPs role in developing an anaphylaxis plan?
The anaphylaxis plans on the BSACI website are specific to each device and inform patients of the symptoms that they should recognise and use the device with. These can also be issued by GPs whilst waiting for allergy clinic appointments. The plans might be updated once the patient has been reviewed. In between appointments it is vital to get good control of asthma. This can be done within the annual asthma reviews; training in the used of adrenaline devices could be part of this.
There is also a wider potential role here in the future for practice nurses and pharmacists. The dose of adrenaline might need to change as children get older. Many allergy units run courses for local primary care workers and the BSACI has primary care days where there is demonstration training and some specialist nurses are teaching GP practices or joining CCG training days. The Allergy Academy also runs primary care days alongside the RCGP and RCP (http://allergyacademy.org).
For an example of an Allergy Action Plan, see Figure 1.
How should GPs respond to cases of wasp or bee stings?
The third quality statement refers to a systemic reaction to wasp or bee stings, and says patients should be referred to a centre experienced in venom immunotherapy. It is important to refer to confirm the diagnosis and consider immunotherapy.
It is often difficult for patients to be sure visually whether it’s a wasp or bee that has stung them. Sometimes, pointers from the history with bees is that the sting is left in the skin and wasps can sting repeatedly whereas bees sting once. After systemic venom reactions patients can often present with rapid cardiovascular symptoms only such as hypotension, they may collapse, or they may have poor recollection of the event.
Allergy units usually test for both bee and wasp routinely with venom allergy cases and may go onto do further testing if required to identify the trigger for desensitisation. Immunotherapy has shown to be effective in reducing both the severity and rate of systemic reactions and improving the quality of life compared to just the provision of adrenaline devices. Patients continue to carry their adrenaline devices during treatment and are advised to carry a charged mobile phone with them and also some units advise to carry a flat plastic card that can scrape out the bee sting apparatus from under the skin if they are stung again. Immunotherapy in the UK is normally a three-year course involving up dosing and maintenance treatment.
In venom cases it’s helpful to do a baseline tryptase level prior to referral as a raised baseline tryptase is a risk factor for further reactions.6 The allergy unit can also advise on the treatment of co-morbidities, such as hypertension with beta-blockers and ACE inhibitors which is common in elderly patients.
Once back under the auspices of general practice, what can GPs and health professionals do to ensure these patients at risk of anaphylaxis are successfully managed?
Ongoing training remains key, and the GP and the wider primary care team are well-placed to help patients self-manage. Also, better communication and training can help identify potential problems.
Themes from studies of fatalities are that the patients were not carrying adrenaline, they didn’t know how to use the devices, the adrenaline devices were out of date, there was delayed administration of adrenaline and there was poorly controlled asthma; all these circumstances could be improved with better communication and training at both the primary care and secondary care level.
Allergy units should be clear in their letters about the ongoing need for adrenaline devices. Some children may outgrow allergies such as milk and egg allergy; these should be reviewed and assessed by the specialist unit and advice given. Allergies to food such as peanuts and tree nuts tend to persist so will require lifelong adrenaline cover. As the child gets older their adrenaline dose prescription on renewal should be reviewed according to age.
There are some research studies looking at whether oral immunotherapy can be used to manage food allergies. These are still in the research phase and are only to be conducted within hospital based trials.
1. NICE. Anaphylaxis. NICE Quality Standard119. NICE, 2016. Available at: nice.org.uk/qs119
3. Muraro A, Roberts G, Worm M et al.Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy 2014; 69 (8): 1026–1045
4. MHRA. Adrenaline auto-injectors: a review of clinical and quality considerationsMHRA, 2014. Available at:www.mhra.gov.uk/home/groups/comms-ic/documents/websiteresources/con423091.pdf
5. BSACI. Allergy action plans for children under 19. http://www.bsaci.org/about/pag-allergy-action-plans-for-children
6. NICE. Venom guidance https://www.nice.org.uk/guidance/TA246/chapter/1-guidance