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Allergology and immunology - Mucocutaneous reactions

Angioedema

Angioedema (also spelled angioedema) is a sudden, deep swelling of the subcutaneous or submucosal tissues, caused by a localized accumulation of fluid in the deep dermis, hypodermis or mucous membranes. It most often affects the face, lips, tongue, throat, hands, feet or genitals, and can occur in isolation or accompany generalized urticaria. Its prevalence in the general population is between 10 and 20 %, the majority of episodes being of allergic or idiopathic origin. Hereditary angioedema is rarer, affecting around 1 in 50,000 people, and results from a C1-esterase inhibitor deficiency. The clinical importance of this condition lies in its potential to rapidly evolve into upper respiratory tract obstruction, a life-threatening medical emergency. Rigorous medical assessment is essential to distinguish benign from high-risk forms, and to establish an appropriate treatment and prevention plan.
Medical emergencies

Rapid swelling of the tongue, larynx or throat can cause airway obstruction within minutes. If you experience difficulty swallowing, a muffled voice, a choking sensation, stridor or respiratory distress, call 9-1-1 immediately.

Don't wait. Don't drive yourself. Anaphylaxis requires an injection of epinephrine and immediate hospital treatment.

What is angioedema?

Unlike urticaria, which affects the superficial layers of the skin and causes raised, itchy patches, angioedema involves the deeper layers of cutaneous and subcutaneous tissue. The visible result is diffuse, often asymmetric swelling, which may not be itchy, but frequently causes a sensation of tension, burning or localized pain. An episode usually lasts from a few hours to 72 hours, depending on its origin.

ℹ️ Angioedema and urticaria coexist in around 40-50 % of cases. In the presence of both simultaneously, an IgE-mediated allergic cause is more likely. Isolated angioedema without urticaria is more likely to be hereditary, drug-induced (ACE inhibitors) or idiopathic.

Types and main causes

Type Mechanism Common causes Distinctive features
Allergic (IgE-mediated) Histamine release by mast cells Food (peanuts, seafood, milk), medicines, insect bites, latex Onset in minutes, often with urticaria, risk of anaphylaxis
Medicinal Inhibition of bradykinin degradation ACE inhibitors (e.g. ramipril, lisinopril), sartans (more rarely), ASA, NSAIDs May occur months or years after the start of treatment; no associated urticaria
Hereditary (AEH) C1-esterase inhibitor deficiency (C1-INH) Autosomal dominant genetic mutation (types I, II, III) Recurrent episodes since childhood, associated abdominal pain, family history
Acquired C1-INH consumption or malfunction Lymphomas, autoimmune diseases, infections Onset after age 40, no family history
Idiopathic Unknown No cause identified despite assessment Diagnosis of exclusion; often recurrent
Physical / non-allergic Mechanical, thermal or vibratory stimuli Pressure, cold, heat, exercise Reproducible by the specific stimulus

Symptoms and clinical presentation

Angioedema typically manifests as sudden, asymmetric, non-erythematous or slightly pink swelling, affecting one or more of the following areas. Speed of onset and location are important diagnostic clues.

  • Swelling of the lips, cheeks or eye area (eyelids)
  • Swelling of the tongue or floor of the mouth
  • Sensation of tightness, tension or burning in the affected area
  • Swelling of hands, feet or genitals
  • Intense crampy abdominal pain (common in AEH)
  • Hoarseness, muffled voice or stridor (laryngeal swelling, emergency)
  • Nausea, vomiting or diarrhea in case of digestive tract damage
  • Hypotension, dizziness or syncope (anaphylactic component)

Diagnosis

The diagnosis of angioedema is based first and foremost on a detailed clinical history, including medications taken, dietary exposures, family history and chronology of episodes. A targeted physical examination completes the initial evaluation. Biological investigations are indicated according to the clinical profile.

  • Complete medical history: medications, foods, exposures, triggers
  • Basic blood tests: blood count, liver and kidney function tests
  • Complement assay: C3, C4, C1q, C1-inhibitor (level and function)
  • Serum tryptase (ideally measured within 1-3 hours of the episode)
  • Allergic skin tests or specific IgE according to suspected allergens
  • Autoimmune test if acquired angioedema suspected
  • Allergology or clinical immunology consultation for recurrent cases
ℹ️ A collapsed C4 level between attacks, in the absence of any acute episode, is a highly sensitive marker of hereditary angioedema or acquired C1-inhibitor deficiency. This simple assay rapidly guides the diagnostic process and justifies a reference in the specialty.

Acute treatment

Management of an acute episode depends directly on the cause, severity and location of the edema. Laryngeal angioedema, or angioedema associated with anaphylaxis, is an emergency requiring intramuscular epinephrine without delay.

Clinical situation First-line treatment Notes
Anaphylaxis or laryngeal damage Epinephrine IM (0.3-0.5 mg, outer thigh), call 9-1-1 Don't wait; antihistamines alone are insufficient
Allergic, moderate (no respiratory involvement) Second-generation H1 antihistamines, short-term oral corticosteroids Diphenhydramine or cetirizine; avoid identified trigger
Medicated (iECA) Immediate discontinuation of the drug responsible Resolution in 24 to 96 h; do not substitute with another iECA
Hereditary angioedema (AEH) Icatibant, C1-INH concentrate or tranexamic acid depending on availability Antihistamines and corticoids are ineffective in AEH
Idiopathic recurrent High-dose H1 antihistamines, evaluation in allergology Background treatment to be discussed if frequent episodes

Prevention and long-term management

Preventing recurrences is a central objective of management, particularly for hereditary forms or allergic angioedemas with identified triggers. A written action plan, given to the patient, improves response in emergency situations.

  • Strict, documented avoidance of the identified trigger(s)
  • Wearing a medical alert bracelet in case of severe allergies or AEH
  • Prescription of an epinephrine auto-injector (EpiPen) and training in its use
  • Background prophylaxis in AEH: danazol, tranexamic acid, lanadelumab or berotralstat according to Canadian guidelines
  • Review of drug prescription to eliminate any iECA or other suspect agent
  • Regular allergology or clinical immunology follow-up for recurrent forms
  • Patient and family education on recognizing warning signs
ℹ️ ACE inhibitors are responsible for almost 30 % of angioedemas seen in emergency departments. This type of angioedema can occur after years of good tolerance to the drug. Complete discontinuation is essential; switching to a different class of antihypertensive is recommended in consultation with the prescribing physician.

Angioedema in children

In children, angioedema is more frequently of allergic or infectious origin (post-viral reaction). Hereditary angioedema often manifests itself in adolescence, with a marked worsening during episodes of stress, trauma or menstruation. If a first-degree relative is diagnosed, a family history is warranted. Pediatric management requires dose adjustment and careful monitoring, given the small size of the upper respiratory tract.

Consult at Clinique Omicron

Clinique Omicron offers a complete medical evaluation for patients with recurrent angioedema or angioedema of undetermined origin, at its points of service in Quebec. Our physicians take a detailed clinical history, prescribe the appropriate blood and immune work-up (including C4 and C1-inhibitor assays), and refer patients to specialists in allergology or immunology when required. If you've experienced an episode of angioedema and would like to identify the cause, or if you're looking to establish an appropriate prevention plan, book an appointment at one of our South Shore locations or at one of our branches in Quebec. Our team is also available by teleconsultation for initial medical triage.

The content of this page is provided for informational purposes only and is not intended to replace the advice of a qualified healthcare professional. Consult a physician for any symptoms, questions or decisions you may have regarding your health.

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