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Urticaria and Angioedema in Children: Treatment and Complications

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Definitions

• Urticaria: Vascular leak in the superficial dermis producing transient, pruritic, edematous wheals/welts. Individual lesions come and go within 24 hours.
• Angioedema: Larger edematous areas involving the deeper dermis and subcutaneous tissue; less well-demarcated plaques.
• Acute: Duration < 6 weeks. Chronic: Duration > 6 weeks (can persist for years).

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Common Triggers in Children

• In children, milk, egg, and peanut are the most commonly implicated foods in acute urticaria (Goldman-Cecil Medicine).
• NSAIDs/aspirin are the most common causes of non-immunologic urticarial reactions; they alter prostaglandin metabolism, enhancing mast cell degranulation. NSAIDs may also exacerbate chronic urticaria (Andrews' Diseases of the Skin).

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Treatment

Step 1 - Trigger Identification and Removal

• Identify and eliminate the causative agent or aggravating factor - this is the most fundamental step.
• In food allergy: implement strict allergen avoidance. Nutritional counseling and growth monitoring are recommended (Harriet Lane Handbook, 23rd ed.).

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Step 2 - Pharmacologic Management (Stepwise Approach)

A. First-Line: Second-Generation (Non-Sedating) H1 Antihistamines

• Long-acting, non-sedating antihistamines lessen new lesions and control pruritus.
• Important paediatric note: First-generation antihistamines (e.g., diphenhydramine, chlorphenamine) are no longer recommended as first-line - they cause carry-over sedation and may produce paradoxical excitation or possibly epilepsy in children (Fitzpatrick's Dermatology, 9th ed.).
• First-generation agents (diphenhydramine, hydroxyzine) remain useful for breakthrough and nighttime pruritus (Tintinalli's Emergency Medicine).

B. Second-Line: Up-titrated Antihistamines

• For cases resistant to standard antihistamine doses, increase to up to fourfold the standard dose, as recommended by EAACI guidelines and AAAAI/ACAAI practice parameters.
• A meta-analysis confirms high-dose antihistamines significantly improve control of pruritus.

C. Add-on Options

• H2 blockers (e.g., ranitidine): Can be used as an adjunct with H1 blockers in chronic urticaria, but not as monotherapy.
• Doxepin (10-25 mg at night): Has combined H1 and H2 blocking properties; sedating, so restricted to bedtime use.
• Antileukotrienes: Added before omalizumab in some guidelines (BSACI, American consensus).

D. Third-Line: Omalizumab

• Omalizumab (anti-IgE monoclonal antibody) is approved for chronic spontaneous urticaria unresponsive to antihistamines.
• Recommended dose: 300 mg/month regardless of serum IgE level (meta-analysis data).
• Clinical effect may appear within 1 week despite taking 2+ months for full FcεRI downregulation.
• The Harriet Lane Handbook (23rd ed.) confirms omalizumab is approved for chronic urticaria in children.

E. Systemic Corticosteroids

• Reserved for severe angioedema and widespread urticaria with acute onset.
• Dose: Prednisone 1 mg/kg/day up to 60 mg PO daily (Tintinalli's), or 40-60 mg/day for 5-7 days.
• Continuous use > 10 days is NOT recommended due to significant side effects.
• Note: A double-blind RCT of 100 adults with acute urticaria found no clinical improvement with prednisone added to an H1 antihistamine (levocetirizine) - reassurance and antihistamines alone may suffice for mild-moderate acute cases.

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Step 3 - Management of Angioedema Specifically

• If associated with anaphylaxis: Epinephrine (adrenaline) is the first-line drug - IM injection, dose 0.01 mg/kg of 1:1000 solution.
• Prescribe an epinephrine autoinjector for all at-risk patients.
• Families must be counseled to always have two autoinjectors available and to call emergency services if used.
• An Anaphylaxis Action Plan should be developed and shared with the school.
• ACE inhibitor-induced angioedema: Antihistamines, corticosteroids, and adrenaline are all ineffective; the drug must be stopped.
• Hereditary angioedema (HAE - C1 esterase inhibitor deficiency): Antihistamines, corticosteroids, and adrenaline are also largely ineffective; specific HAE therapies (C1-INH concentrate, icatibant, ecallantide) are required.

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Complications

1. Anaphylaxis (Most Serious)

• Urticaria, especially extensive disease around the face or mouth, may be part of a severe anaphylactic reaction.
• Features: bronchospasm, laryngospasm, hypotension, cardiovascular collapse.
• Requires immediate epinephrine administration.

2. Laryngeal/Upper Airway Angioedema

• Angioedema involving the lip, throat, tongue, or larynx can cause life-threatening airway obstruction and asphyxiation.
• More than 50% of patients with hereditary angioedema experience a laryngeal attack in their lifetime.
• May require intubation (up to 18% of severe ACE inhibitor-related angioedema required intubation in case series).

3. Progression from Acute to Chronic Disease

• Patients who have had one episode of angioedema have a 10-fold risk of a second episode, and recurrent episodes may be more severe (Andrews' Diseases of the Skin).
• Chronic urticaria defined as recurrent episodes > 6 weeks; can persist 2-5 years on average.

4. Gastrointestinal Involvement

• In hereditary angioedema, mucosal swelling of the gastrointestinal tract can present as acute abdomen, sometimes leading to unnecessary surgical intervention.
• Can cause severe abdominal pain and colicky episodes.

5. Recurrent/Biphasic Reactions

• Symptoms may recur after initial resolution (biphasic anaphylaxis) - families must be counseled about this possibility and may need a second epinephrine dose.

6. Quality of Life Impact

• Chronic urticaria has a high impact on quality of life - problems with sleep, anxiety, and (in papular urticaria from insect bites in children) social stigma and bullying.

7. Skin Superinfection

• Severe excoriation from pruritus can lead to secondary bacterial skin infection.

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Special Considerations in Paediatrics

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Sources

• The Harriet Lane Handbook, 23rd ed. (Johns Hopkins Hospital) - Paediatric allergy management
• Tintinalli's Emergency Medicine: A Comprehensive Study - Urticaria/angioedema treatment tables
• Goldman-Cecil Medicine, International Ed. - Pathobiology, classification, treatment algorithm
• Fitzpatrick's Dermatology, 9th ed. - First-line/second-line/third-line therapy framework; paediatric antihistamine cautions
• Andrews' Diseases of the Skin, Clinical Dermatology - Drug-induced urticaria and angioedema complications