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Angio-oedema and anaphylaxis

SNOMED: 238694002967 words•Updated 03/03/2026
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Exam Tips

  • If airway/breathing/circulation are compromised, treat first as anaphylaxis with IM adrenaline; do not wait for tryptase.
  • Urticaria plus rapid trigger-linked swelling suggests histamine-mediated disease; isolated recurrent non-itchy swelling (especially abdominal) suggests bradykinin-mediated angio-oedema.
  • ACE-inhibitor angio-oedema can begin months after starting treatment and may persist after stopping; never restart the ACE inhibitor.
  • In OSCEs, explicitly state dose and route of adrenaline and that doses can be repeated every 5 minutes.
  • Raised tryptase supports anaphylaxis but a normal value does not exclude it.
  • For pathophysiology viva answers, contrast mast-cell histamine pathways with kallikrein-bradykinin pathways (see Figure: mediator pathways in allergy/immunology teaching texts).

Definition

Angio-oedema is localized swelling of deeper dermal, subcutaneous, or submucosal tissues, commonly affecting lips, tongue, eyelids, hands, feet, and sometimes the bowel or upper airway. Anaphylaxis is a rapidly evolving, life-threatening systemic hypersensitivity reaction with airway, breathing, and/or circulatory compromise, usually with skin or mucosal features; both conditions may share mediator pathways (histamine and/or bradykinin) but anaphylaxis causes more severe capillary leak and shock.

Pathophysiology

Two main mediator pathways are clinically important. Histamine-mediated disease (often IgE/mast-cell driven) causes rapid-onset urticaria/angio-oedema and can progress to anaphylaxis through widespread vasodilation, increased vascular permeability, bronchospasm, and distributive shock. Bradykinin-mediated angio-oedema (for example ACE-inhibitor related, hereditary C1-inhibitor deficiency, acquired C1-inhibitor deficiency) typically has no urticaria, develops over hours, responds poorly to antihistamines/steroids/adrenaline, and may involve severe abdominal or laryngeal oedema. In hereditary angio-oedema, loss or dysfunction of C1-inhibitor permits excessive kallikrein-bradykinin activity. See Figure: mast-cell degranulation and bradykinin pathways in standard immunology/allergy texts.

Risk Factors

  • Atopy and prior immediate hypersensitivity reactions
  • Exposure to common triggers: nuts, shellfish, milk, egg, penicillins/cephalosporins, NSAIDs/aspirin, anaesthetic agents, venom, latex, radiocontrast
  • Current ACE-inhibitor therapy (higher risk in people of Black ethnicity)
  • Family history of hereditary angio-oedema (autosomal dominant; can occur de novo)
  • Co-existing asthma, especially poorly controlled (higher anaphylaxis fatality risk)
  • Mastocytosis (associated with more severe anaphylaxis)
  • Autoimmune disease or lymphoproliferative disease (risk of acquired C1-inhibitor deficiency)

Clinical Features

Symptoms

  • Sudden swelling of lips, tongue, eyelids, face, hands, feet, or genitalia
  • Throat tightness, hoarse voice, dysphagia, or sense of airway closing
  • Wheeze, breathlessness, chest tightness
  • Dizziness, collapse, palpitations, syncope
  • Abdominal pain, nausea, vomiting, diarrhoea (particularly in bradykinin-mediated/HAE attacks)
  • Itch and weals in histamine-mediated reactions; pain/pressure more than itch in deeper swelling

Signs

  • Non-pitting deep tissue oedema; may be ill-defined compared with urticaria
  • Urticaria/flushing in many histamine-mediated cases
  • Stridor, tachypnoea, hypoxia, wheeze, increased work of breathing
  • Hypotension, tachycardia, prolonged capillary refill, reduced conscious level
  • Absence of urticaria with recurrent angio-oedema suggests bradykinin-mediated disease
  • Laryngeal oedema signs: muffled voice, drooling, agitation

Investigations

Clinical diagnosis of anaphylaxis (ABCDE assessment):Rapid onset airway/breathing/circulation compromise, often with skin or mucosal changes; do not delay treatment for tests
Serum mast cell tryptase:May be raised in anaphylaxis; take as soon as possible after emergency treatment and ideally within 1-2 hours (up to 4 hours), with later baseline sample for interpretation
Complement C4 level:Typically low between and during attacks in hereditary/acquired C1-inhibitor deficiency
C1-inhibitor antigenic level and functional assay:Low level in type 1 HAE; normal/high but dysfunctional in type 2 HAE
C1q level:Often low in acquired C1-inhibitor deficiency, usually normal in hereditary disease
Screen for secondary causes (if recurrent/chronic or atypical):CRP/ESR, autoantibodies (including thyroid autoantibodies), and haematology/lymphoma work-up guided by history
Allergy-focused testing (specialist setting):Skin-prick/specific IgE may identify culprit allergen; avoid deliberate community re-exposure challenge due to severe reaction risk

Management

Lifestyle Modifications

  • Immediate avoidance of suspected triggers and structured trigger history review
  • Personalised emergency action plan and education on early symptom recognition
  • Prescribe and teach use of adrenaline auto-injectors for patients at ongoing risk; advise carrying two devices at all times
  • MedicAlert/medical identification and communication of drug allergies in all care settings
  • Specialist referral (allergy/immunology/dermatology) for recurrent, idiopathic, suspected hereditary, or acquired angio-oedema
  • For hereditary angio-oedema, discuss procedure-related prophylaxis (for example before dental/surgical trauma) with specialist team

Pharmacological Treatment

First-line emergency treatment for anaphylaxis

  • Adrenaline (epinephrine) 1 mg/mL (1:1000) IM into anterolateral thigh: adult and child >12 years 500 micrograms (0.5 mL), child 6-12 years 300 micrograms (0.3 mL), child 6 months-6 years 150 micrograms (0.15 mL), child <6 months 150 micrograms (0.15 mL); repeat every 5 minutes if needed

Give immediately on clinical suspicion. No absolute contraindication in true anaphylaxis. Monitor airway, oxygen saturation, ECG, blood pressure. IV adrenaline is for experts in monitored settings only due to arrhythmia risk.

Adjunctive treatment after adrenaline (anaphylaxis)

  • Chlorphenamine 10 mg slow IV or IM (adult)
  • Hydrocortisone 200 mg IV or IM (adult)
  • Salbutamol nebulised 5 mg for bronchospasm

Adjuncts do not replace adrenaline. Antihistamines improve skin symptoms but do not reverse airway or shock. Corticosteroids have delayed benefit and are not first-line rescue.

Histamine-mediated angio-oedema/urticaria (non-anaphylactic)

  • Cetirizine 10 mg orally once daily (adult)
  • Loratadine 10 mg orally once daily (adult)

Use non-sedating H1 antihistamines first-line; specialist-directed up-dosing may be used in chronic disease. Consider short oral prednisolone course only for severe flares where appropriate.

ACE-inhibitor induced angio-oedema

  • Stop ACE inhibitor permanently (for example ramipril, lisinopril, enalapril)

Symptoms may recur for weeks to months after cessation. Re-challenge is contraindicated due to risk of severe recurrence.

Bradykinin-mediated angio-oedema (specialist/emergency protocols)

  • Icatibant 30 mg subcutaneous injection for acute hereditary angio-oedema attacks (adult)
  • Human C1-esterase inhibitor concentrate 20 units/kg IV for acute attacks
  • Lanadelumab 300 mg subcutaneously every 2 weeks for long-term prophylaxis in selected patients

Antihistamines/steroids/adrenaline are often ineffective in pure bradykinin-mediated attacks, but if diagnosis is uncertain with airway compromise treat initially as anaphylaxis while securing specialist input.

Surgical / Interventional

  • Early senior airway intervention for impending obstruction (awake fibreoptic intubation where feasible)
  • Emergency front-of-neck access (cricothyrotomy) or tracheostomy if cannot intubate/cannot oxygenate

Complications

  • Upper airway obstruction with asphyxia
  • Hypoxic respiratory failure
  • Circulatory collapse/anaphylactic shock
  • Cardiac arrest and death (can occur within minutes, especially after IV drug triggers)
  • Recurrent episodes with significant anxiety and impaired quality of life
  • Diagnostic delay in hereditary/acquired angio-oedema leading to repeated severe attacks

Prognosis

Acute allergic angio-oedema is often self-limiting over 1-3 days, but recurrence is common if triggers persist. ACE-inhibitor related disease may worsen if the drug is continued and can be life-threatening. Hereditary angio-oedema usually requires lifelong specialist management; acquired disease prognosis depends on control of the underlying disorder. With prompt recognition and immediate IM adrenaline, anaphylaxis survival is generally good, but recurrence risk remains clinically important and prior mild reactions do not guarantee future mild episodes.

Sources & References

✅NICE Guidelines(1)

📖Textbook References(20)

  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1645)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 134)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1644, 1645)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 548)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 134)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 148)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 547)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1620, 1621)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 232)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1644)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 345, 346)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1645)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1621)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1645)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1833)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1644, 1645)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 133)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1686)[context]
  • David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 133, 134)[context]
  • [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 787)[context]

Sources

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