Anaphylaxis: Pathophysiology, Clinical Features, and Management

Flashcards covering the epidemiology, Gell and Coombs classification, pathophysiology, clinical presentation, differential diagnosis, acute emergency management, and post-reaction care of anaphylaxis.

How is anaphylaxis defined?

Anaphylaxis is a severe, life-threatening, generalised or systemic hypersensitivity reaction involving the airway, breathing, and circulation.

What is the estimated lifetime prevalence of anaphylaxis in England, and approximately how many deaths occur annually in the UK?

It is estimated that $1\text{ in }1333$ of the population in England has experienced anaphylaxis during their lifetime, with approximately $20$ deaths per year due to anaphylaxis in the UK.

Which type of hypersensitivity reaction is anaphylaxis according to the Gell and Coombs classification?

Anaphylaxis is a Type $1$ hypersensitivity reaction.

What immunological process occurs during the first exposure to an allergen in Type 1 hypersensitivity?

Th2 cells are primed, and the release of IL-4 causes B cells to switch their production of IgM to IgE antibodies. These IgE antibodies bind to mast cells and basophils, sensitising the cells to the allergen.

What occurs upon the second exposure to an allergen in Type 1 hypersensitivity?

Cross linkage of the antigen-specific IgE antibody bound to sensitised cells causes mast cell degranulation and the release of mediators (leukotrienes, histamine, and prostaglandins), resulting in widespread vasodilation, bronchoconstriction, and increased vascular endothelial permeability.

According to the Gell and Coombs classification, what are the definition, reaction timing, immune reactant, and an example for Type 2 hypersensitivity?

Type $2$ is defined as cytotoxic, has variable timing, uses IgG as the immune reactant, and an example is an acute transfusion reaction.

According to the Gell and Coombs classification, what are the characteristics of Type 3 and Type 4 hypersensitivity reactions?

Type $3$ is immune complex-mediated, develops over weeks, involves IgG, and examples include rheumatoid arthritis, vasculitis, and glomerulonephritis. Type $4$ is cellular/delayed, develops over days, involves T effector cells, and an example is contact dermatitis.

What are common aetiological triggers of anaphylaxis across drug, injection, venom, and food categories?

Drugs (antibiotics, NSAIDs, neuromuscular blocking agents), injections (radiocontrast dyes), venom from stings and bites (bees, wasps), and food (shellfish, nuts, peanuts, eggs, strawberries, wheat). Food triggers are particularly common in children.

What patient comorbidities and cofactors increase the risk or severity of an anaphylactic reaction?

Risk factors include existing comorbidities (e.g. asthma, mast cell disorders, cardiovascular disease) and likelihood of re-exposure. Cofactors include exercise, fever, acute infection, premenstrual status, and emotional stress.

What is a key diagnostic feature of anaphylaxis elicited during history taking?

A history of an acute onset of symptoms.

What clinical signs and symptoms affecting the airway can occur in anaphylaxis?

Lip, tongue, pharynx, and epiglottis swelling, possibly causing cough, swallowing difficulty, hoarse voice, and stridor.

What breathing signs and symptoms can manifest during anaphylaxis?

Tachypnoea, wheezing, cough, chest tightness, dyspnoea, hypoxia, hypercapnia, acute airway obstruction with laryngeal oedema, and bronchospasm.

What cardiovascular signs develop in anaphylaxis, and what is the underlying circulatory mechanism?

Dizziness, pallor, tachycardia, clammy skin, drowsiness, collapse, hypotension, prolonged CRT, shock, arrhythmias, and ECG changes. These occur due to peripheral vasodilation and increased permeability causing plasma leakage from the circulation and decreased intravascular volume.

What signs may be identified under Disability/Other and Exposure during examination of an anaphylactic patient?

Disability/Other includes neuro symptoms (confusion, anxiety, collapse, loss of consciousness), GI symptoms (abdominal cramping, D&V), and the feeling of impending death. Exposure includes skin changes such as urticaria, angioedema, pruritus, and erythema.

How is life-threatening asthma clinically differentiated from anaphylaxis?

Life-threatening asthma presents with respiratory features and is unlikely to involve the skin, cardiovascular system (CVS), and gastrointestinal tract (GIT).

How does temperature differentiate septic shock from anaphylaxis?

Septic shock typically presents with a core temperature of $< 36$ or $> 38$, whereas body temperature is usually normal in anaphylaxis.

What differentiating feature distinguishes hereditary angioedema from anaphylaxis?

Hereditary angioedema is not usually accompanied by urticaria.

What clinical features differentiate a vasovagal episode from anaphylaxis?

A vasovagal episode is characterized by the absence of urticarial rash, angioedema, hoarseness, and wheezing; bradycardia (as opposed to tachycardia in anaphylaxis); abrupt onset of pallor (as opposed to erythema); and improvement upon lying down.

What positioning should be used initially for a patient presenting with anaphylaxis?

Lie the patient flat and raise their legs, though a sitting position may be more comfortable in cases of breathing difficulty or pregnancy.

What is the initial medication dose concentration, route, and anatomical site for treating anaphylaxis?

IM adrenaline $1:1000$, administered without delay into the anterolateral thigh.

How frequently can IM adrenaline be repeated if there is no clinical improvement?

IM adrenaline can be repeated every $5\text{ minutes}$ if there is no improvement.

What physiological actions are mediated by the alpha and beta adrenergic actions of adrenaline?

The $\alpha$-adrenergic action increases blood pressure, while the $\beta$-agonist adrenergic effect increases cardiac contractility, increases heart rate, and causes dilation of bronchioles.

According to the refractory anaphylaxis algorithm, how should persistent upper airway obstruction and bronchospasm be managed?

Upper airway obstruction/stridor requires nebulised adrenaline and senior airway support. Bronchospasm requires respiratory support via bag/mask or ventilation, nebulised salbutamol/ipratropium, and IV salbutamol/aminophylline if required.

What is mast cell tryptase, and what is its limitation when testing children?

Mast cell tryptase is an enzyme produced almost exclusively by mast cells in IgE-mediated anaphylaxis (and some haematological disorders). It is not consistently elevated in children when food is the allergen or when the main severe feature is respiratory.

What are the recommended timings for obtaining blood samples for mast cell tryptase testing?

Take the first blood sample immediately after starting treatment, and a second sample within $1\text{ to }2\text{ hours}$ (no later than $4\text{ hours}$) from the onset of symptoms.

Why should children under 16 who receive emergency treatment for suspected anaphylaxis be admitted under paediatrics?

They should be admitted because biphasic responses may occur.

What is biphasic anaphylaxis, and how is it managed?

Biphasic anaphylaxis is a recurrence of symptoms within $72\text{ hours}$ after complete recovery from anaphylaxis with no further exposure to the allergen. It is managed in the same way as initial anaphylaxis.

What four elements must be recorded in clinical documentation following suspected anaphylaxis?

Document all acute clinical features of the suspected reaction, the time of onset of the reaction, the circumstances immediately before the onset of symptoms, and the trigger, if known.

What guidance and management steps should be provided to a patient and family before discharge?

Discuss signs and symptoms of anaphylaxis, biphasic reaction risks, trigger avoidance, auto-injector use (with demonstration), referral to a specialist allergy service and patient support groups, provide an adrenaline autoinjector (EpiPen) to carry at all times until seen, and consider an individualised allergy action plan (e.g. BSACI).

What factors significantly increase the risk of death from anaphylaxis?

The risk of death increases in patients with pre-existing asthma (particularly if poorly controlled) or in asthmatics who fail to use or delay administering adrenaline.