1st July 2023

Urticaria and Angioedema

Urticaria

Background

Mast cells release histamine which causes superficial skin swellings (wheals). Wheals are itchy, may sometimes have a burning sensation, and last for less than 24 hours.

Clinical features

Urticaria can present as discrete linear, round or ring-shaped wheals or swellings. They may be skin coloured, red or white, with or without an erythematous flare.

Erythematous wheals on the arm

Image Source: Wikimedia Commons (2010). EMminor2010, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:EMminor2010.JPG (Accessed on: 1 February 2022).

Wheals on the chest wall

Image Source: Wikimedia Commons (2010). Hives2010, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Hives2010.JPG (Accessed on: 1 February 2022).

Classification/Causes

Urticaria is classified as acute (< 6 weeks duration) or chronic (>6 weeks duration).

Acute urticaria can be triggered by infection, allergy to drugs and/or food (IgE mediated type 1 hypersensitivity reaction), stings and vaccinations. However, it can often be idiopathic.

Chronic urticaria can be spontaneous or inducible. Spontaneous is often idiopathic however associations with systemic conditions include thyroid disease, vitiligo, H. pylori infection and coeliac disease. Autoantibodies are also sometimes seen – anti-IgE or anti-FceRI antibodies.

Inducible causes:

• Symptomatic dermographism – scratching the skin
• Cold urticaria – exposure to cold, cold water on the skin
• Cholinergic urticaria – sweating after exercise
• Contact urticaria – substances that trigger an IgE mediated allergic response, e.g. cosmetics, latex, fabrics 
• Delayed pressure urticaria – pressure on the skin, e.g. carrying a heavy object
• Solar urticaria – sun exposure
• Heat urticaria – exposure to heat
• Vibratory urticaria – handling a vibrating object
• Aquagenic urticaria – exposure to water

Assessment

Activity of urticaria is assessed using an Urticaria Activity Score (UAS7). The number of wheals (<20, 20-50, >50) and severity of itch (mild, moderate, intense) are scored every 24 hours for 7 days, giving a maximum score of 42.

The Dermatology Life Quality Index (DLQI) can also be used to measure the impact of the rash on quality of life.

Investigations

• Normally a clinical diagnosis
• Skin biopsy – histology may reveal oedema in the dermis, dilated blood vessels, and mixed inflammatory infiltrate
• If indicated, blood tests to rule out a systemic cause: e.g. full blood count and autoimmune screen
• Skin prick testing if suspected food allergy

Treatment

• Avoid triggers if known/identified
• Antihistamines (2nd generation)
• Short course of oral steroids
• Chronic spontaneous urticaria: Ciclosporin, Omalizumab
• Epipen if there is cardiovascular compromise or breathing difficulties

Angioedema

Background

Angioedema is characterised by a sudden, localised, deep swelling of the subcutaneous tissue of the skin and mucous membranes, caused by increased endothelial permeability and plasma extravasation in the dermis and submucosa. It varies in severity and can be life threatening.

Classification and Pathophysiology

• Histaminergic – histamine and other vasoactive molecules are released. This type of angioedema can present with associated urticaria, anaphylaxis and bronchospasm.
• Non-histaminergic – bradykinin and complement derived mediators are released.

Aetiology

• Acute allergic
• Hereditary – C1 inhibitor deficiency (type I) or low activity (type II) causes an increase in bradykinin levels
• Acquired C1 inhibitor deficiency– secondary to autoimmune disease, malignancy or infection
• Iatrogenic – NSAIDs, ACE inhibitors (non-allergic)

Clinical Features

• Skin coloured or pale red swellings of the skin or submucosal tissue
• Lesions vary in size and are asymmetrical
• Generally affects the face or genital skin, however limbs, airways and abdomen can also be affected
• Associated urticaria in 1/3 of cases

Angioedema causing periorbital swelling

Image Source: Wikimedia Commons (2008). Angioedema2010, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Angioedema2010.JPG (Accessed on: 1 February 2022).

Investigations

• Routine blood tests: full blood count, liver function tests, renal function, c-reactive protein
• Other blood tests: thyroid stimulating hormone, tryptase, IgE, thyroid antibodies, C1 inhibitor concentration and function, complement, ANA, ANCA
• Skin biopsy

Treatment

• Stop triggering factor
• Keep the airways patent
• Treat any underlying infection
• Antihistamines
• Corticosteroids
• C1INH concentrate (for non-histaminergic angioedema)
• Prophylaxis: Danazol

Prognosis

Self-limiting after a few hours or days.