Angioedema

ICD-11

idiopathic: EB04

Synonyms

Quincke edema, angioneurotic / heriditary edema.

Epidemiology

Frequent, but no statistical data available for spontaneous angioedema; prevalence heriditary angioedema 1:50.000 for types I and II, type III rare, females more commonly.

Definition

Acute or slowly progressing dermal and subdermal persistent swellings over several hours to days involving subcutis, mucosa and submucosal tissue. It may occur either as a solitary finding localized or disseminated and following or in parallel with urticaria.

Aetiology & Pathogenesis

Most of the pathogenic causes are histamine related allergic or pseudoallergic following the course of different types of urticaria. Additionally, there are forms without urticaria such as bradykinin-related HAE type I and II (INH-activity partial deficient), III (INH-activity normal). C1-esterase inhibitor deficiency type I and II: renin-angiotensin system related drugs (ACE and dipeptidylpeptidase inhibitors) or paraneoplastic causes.

Signs & Symptoms

Subcutaneous and mucosal oedema (upper and lower airways, esophageal-gastro-intestinal tract) with the sensation of tightness or swelling, sometimes itchy or painful.

Localisation

Sites of predilection: face (eyelids, lips), mucosal: tongue, larynx, genitalia.

Classification

Spontaneous and urticaria-related; acquired bradykinin driven without C1-INH deficiency; type I-II hereditary C1 –INH deficiency and type III bradykinin driven without C1-INH deficiency.

Laboratory & other workups

See urticaria for diagnostics. Allergic: IgE, specific IgE, histamine, diaminooxidase. In addition: C1-esterase inhibitor analysis and complement C4 (both concentration + activity). C1-INH and C1q autoantibodies.

Dermatopathology

Edema of the dermal, subcutaneous, submucosal and mucosal tissue without inflammatory infiltrate. Mast cell degranulation.

Course

Acute onset or progressive development. In allergic and hereditary types chronic relapsing course.

Complications

Airway obstruction, laryngeal oedema, birth delivery complications (be aware of hereditary C1-esterase inhibitor deficiency).

Diagnosis

Clinical, laboratory.

Differential diagnosis

Physical urticaria (pressure, vibration), autoimmune diseases (e.g. lupus erythematosus), lymphedema, acute phase of herpes zoster and erysipelas. Acute contact dermatitis.

Prevention & Therapy

Acute: depending on localization and acuity: systemic antihistamines; systemic corticosteroids and adrenaline. For C1-esterase inhibitor deficiency: replacement of C1-esterase inhibitor (if not available, fresh frozen plasma); concentrated C1-inhibitor infusion; bradykinin –B2-receptor antagonist infusion (lanadelumab); recombinant C1 inhibitor. (Danazol or tranexamic acid for long-term prophylaxis only).

1.1.1.2 Angioedema