From the 2016 BSACI Guidelines for adrenaline prescription (Please see website below for full guidelines)
Patients at risk of anaphylaxis that should be considered for long-term provision of an adrenaline auto-injector include those;
Adrenaline auto-injector dosing: Standard adult adrenaline autoinjectors are available in the form of JEXT or Epi-pen. A standard dose is 300mcg per injection. Some patients may require 500mcg based on weight and other risk factors. Currently, the only manufacturer for the high dose pens is Emerade, but supplies have been low for many months. All patients should have training in how to use these pens. Videos on the manufacturer websites can be used and “dummy pens” given through the local allergy unit for practice. Any patient being issued adrenaline autoinjectors should be referred to the Allergy Department for formal review.
Angioedema is a transient localised swelling of the skin and/or mucosa.
If a patient presents with isolated angioedema, the first step is to determine the mechanism, i.e. mast-cell or bradykinin mediated and refer appropriately (likely mast-cell mediated = allergy services; likely bradykinin mediated = immunology services). Much of the specific management will be undertaken by the allergy/immunology clinic, but a thorough history trying to delineate the two pathologies should be undertaken by all encountering cases of angioedema.
Mast-cell Mediated angioedema
Manage acutely with antihistamines, steroids, trigger avoidance advice +/- adrenaline autoinjectors in cases featuring anaphylaxis.
Bradykinin Mediated angioedema
All patients with isolated angioedema should have serum C4, C1i level, C1i function, C1q, C1q autoantibody, plus C1i autoantibody (if available) performed ideally during an attack. Those at risk of acquired angioedema (i.e. malignancy/autoimmune disease) should also be investigated as appropriate. Most of these tests will be performed through immunology clinics but if encountering an acute episode, consider testing for these if possible.
Many options are available for pharmacological treatment with specifics beyond the scope of this module. Clinical immunology should prescribe acute therapy (e.g. Berinert/Cinryze/Ruconest/Icatibant), and if necessary long-term prophylaxis (e.g. Danazol/Berinert/Cinryze). Patients should have emergency and pre-surgical/dental work management plans.
Other angioedema conditions
Hereditary angioedema (autosomal dominant). Most patients present by adolescence. Attacks usually affect the skin peripherally or GI tract, and less commonly the face/upper airway, however multiple sites may be affected at once.
Acquired angioedema. Secondary to lymphoproliferative disease (67%), autoimmune disease (8%), other malignancies (6%). Most patients present in or after the 4th decade Attacks more often affect the face than the limbs, and less commonly the GI tract. Underlying cause should be treated as appropriate.
Chronic idiopathic angioedema without urticaria (in whom other causes have been ruled out). Trial on antihistamines (+/- montelukast), or tranexamic acid. Response to either will suggest the underlying mechanism and should be treated appropriately. Chronic idiopathic angioedema with urticaria is mast-cell mediated (see section on chronic spontaneous urticaria for further information).
Quick tip; IM adrenaline is first-line treatment for anaphylaxis – not corticosteroids (which are now no longer part of anaphylaxis treatment) and anti-histamines (which are a third line treatment)
Anaphylaxis is a potentially life-threatening allergic reaction. Anaphylaxis is highly likely when any ONE of the following three criteria is fulfilled:
1) Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING:
2) TWO or more of the following that occur rapidly after exposure to a LIKELY allergen for that patient (minutes to several hours):
3) Reduced BP after exposure to a KNOWN allergen for that patient (minutes to several hours):
* Low systolic blood pressure for children is defined as: Less than 70 mmHg from 1 month to 1 year. Less than (70 mmHg + [2 x age]) from 1 to 10 years. Less than 90 mmHg from 11 to 17 years.
(Information above taken from; Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol 2006; 117:391.)
Follow the Resuscitation Council UK algorithm for anaphylaxis management:
Refractory anaphylaxis has a separate algorithm
NB – IM adrenaline is first-line treatment for anaphylaxis – not corticosteroids (which are now no longer part of anaphylaxis treatment) and anti-histamines (which are a third line treatment)
The National Institute for Health and Care Excellence (NICE) have guidelines specific for anaphylaxis which include the assessment and referral of patients suspected to have had anaphylaxis. Specifically:
Information to include in an Allergy referral:-
- Exact clinical symptoms
- Allergens involved (ingredient lists/venom/drugs etc)
- Amount of allergen exposed to (e.g. nut trace vs five peanuts)
- Objective signs of allergy (discharge or A&E notes, observations at presentation)
NICE Guideline: https://www.nice.org.uk/guidance/cg134
Quick Tip; Large local reactions to bites/stings do not usually need allergy referrals (if no systemic features)
IgE mediated reactions/Type 1 hypersensitivity reactions are due to antigen exposure (eg. peanut protein in peanut allergy) causing IgE-mediated activation of mast cells and basophils, with release of vasoactive substances, such as histamine, prostaglandins, and leukotrienes. These are immediate reactions and cause clinical features of an IgE mediated reaction eg. anaphylaxis, angioedema, bronchospasm, urticarial (hives) and hypotension, present within an hour of allergen exposure.
Any substance may cause anaphylaxis, however some foods are much more common causes than others. The most common causes of food allergy include:-
Most allergens involved in food allergy are heat stable and acid stable (stomach acid). Please refer the patient to the Allergy clinic for further investigation.
Systemic reactions to bee and wasp stings should be referred to the Allergy clinic for further investigations and management. A baseline tryptase should be checked in these patients and adrenaline prescription considered.
Large local reactions are common and due to the nature of venom injected, rather than an allergy. Large local reactions do not usually require further investigations and should be treated with antihistamines and steroids.
Allergens causing perennial symptoms:
Allergens causing seasonal symptoms
Refer patients to the allergy clinic with suspected symptoms on inhalant allergen exposure, not controlled by maximum medical therapy
Additional therapies that can be helpful include nasal/sinus rinse, combination nasal spray with antihistamines (e.g. Azelastine/fluticasone ‘Dymista’) and ipratropium nasal sprays for rhinorrhoea. Desensitisation therapy may be offered by the Allergy Clinic for some inhalant allergens in the form of sublingual or subcutaneous immunotherapy, usually taken over three years.
Oral Allergy Syndrome
Oral allergy syndrome (OAS) is caused by IgE to the heat-labile allergens in fruits and vegetables, which are highly cross-reactive. OAS occurs in people who have pollen allergy (although not all patients have obvious hay fever or seasonal allergy symptoms). Patients are often sensitised to the Bet v1 birch pollen allergen. Patients typically report itching and/or mild swelling of the mouth and throat immediately following ingestion of certain uncooked fruits (including nuts) or raw vegetables. Systemic reactions are rare.
Investigation of OAS:
Patients with any of the following characteristics should be referred to an allergy expert for further evaluation:
Urticaria aka hives, are pruritic wheals (i.e. transient, raised lesions caused by dermal oedema) with or without surrounding erythema (aka “flare”). They are the result of mast cell degranulation.
Urticaria can be classified by frequency, i.e. acute (<6 weeks) vs chronic (regular occurrence >6 weeks), and by aetiology, i.e. inducible vs spontaneous.
Urticaria often occurs alongside angioedema and investigations/management are the same (the exception being in life-threatening angioedema – see “anaphylaxis management”). Isolated angioedema requires additional investigations and is explored separately.
Acute Inducible Urticaria (+/- angioedema)
Acute inducible urticaria should be managed with removal of the trigger if possible (e.g. extract wasp sting), antihistamines +/- topical/oral steroids. It is more likely than other forms to be associated with life-threatening angioedema, i.e. anaphylaxis. Severe refractory, or anaphylactic episodes should result in referral to allergy. Triggers include:
Chronic Inducible Urticaria (+/- angioedema)
Chronic inducible urticaria only occurs on exposure to specific triggers. It can usually be managed with avoidance strategies, antihistamines +/- short courses of topical/oral steroids. Triggers include:
Acute Spontaneous Urticaria (+/- angioedema)
Acute spontaneous urticaria has no identifiable cause and resolves in <6 weeks. It should be treated with antihistamines +/- short courses of topical/oral steroids. 1 in 5 individuals will have such an episode at least once in their life.
Chronic Spontaneous Urticaria (+/- angioedema)
Chronic spontaneous urticaria has no obvious trigger. It may be associated with anti-thyroid peroxidase antibodies (anti-TPO) in which case it is termed, “autoimmune urticaria”, though the treatment protocol is unchanged. 80% resolve after 10 years, but this is less likely with concomitant angioedema or anti-TPO. This can usually be managed in primary care with antihistamines but refractory cases should be referred to allergy.
Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis. S. Guillén-Aguinaga et al. British Journal or dermatology. Volume 175, Issue 6. December 2016. Pages 1153-1165
The Green Book is a useful resource for information about vaccinations, dosage, contra-indications and allergy to vaccines.
There is helpful information about use of seasonal influenza vaccination in patients with egg allergy. There is also information about coronavirus vaccinations in patients with prior allergies, and management of patients who react to these vaccinations.