How should I manage a pediatric patient who develops urticaria months after COVID‑19 infection?

Management of Post-COVID Urticaria in Pediatric Patients

Treat this pediatric patient with chronic urticaria developing months after COVID-19 infection using standard urticaria management protocols: start with second-generation H1-antihistamines at standard doses for 2-4 weeks, escalate to 4-fold dosing if needed, and reserve short-course corticosteroids (prednisolone 50 mg daily for 3 days maximum) only for severe acute exacerbations unresponsive to antihistamines. 1, 2

Understanding the Post-COVID Context

Chronic urticaria is a recognized manifestation of long COVID in children, with evidence showing that children with long COVID were more likely to have had chronic urticaria and allergic rhinitis before being infected. 3 The proposed mechanisms include immune dysregulation, autoimmunity from molecular mimicry, and mast cell activation syndrome, which substantially increases in severity in patients with long COVID compared to pre-COVID controls. 3

First-Line Treatment Algorithm

Initial Management (Weeks 1-4)

• Start with second-generation non-sedating H1-antihistamines (cetirizine, loratadine, desloratadine, fexofenadine, or levocetirizine) at standard doses for 2-4 weeks as the foundation of treatment. 1, 4, 5
• More than 40% of patients respond to antihistamines alone at standard dosing. 1
• First-generation sedating antihistamines should not be used as first-line monotherapy due to sedating properties and lack of proven advantage over non-sedating antihistamines. 1, 5

Dose Escalation (Weeks 4-8)

• If inadequate response after 2-4 weeks, increase the antihistamine dose up to 4 times the standard dose before considering any corticosteroid use. 1, 4, 2
• Approximately 75% of patients respond to dose escalation, making this a highly effective strategy. 1
• Continue the escalated dose and reassess response every 2-4 weeks. 4

Corticosteroid Use: Critical Restrictions

Acute Severe Exacerbations Only

• For severe acute urticaria unresponsive to antihistamines, use prednisolone 50 mg daily for 3 days maximum—this is the guideline-recommended regimen, not methylprednisolone. 1, 2
• Lower doses are frequently effective and should be considered to minimize corticosteroid exposure. 1, 2
• Short courses of 3-10 days maximum are appropriate for severe acute exacerbations only. 1, 2

Absolute Contraindication for Chronic Use

• Long-term oral corticosteroids should NOT be used in chronic urticaria except in very selected cases under regular specialist supervision (Strength of recommendation A). 1, 2
• This is a firm contraindication due to cumulative toxicity and unfavorable risk-benefit ratio. 1, 2
• Chronic corticosteroids are contraindicated in chronic spontaneous urticaria—this is the most critical error to avoid. 2

Treatment Duration and Monitoring

• Continue antihistamines indefinitely until complete disease control is achieved for at least 3 consecutive months, at which point careful step-down can be attempted. 4
• Treatment duration is determined by disease activity rather than a fixed time period. 4
• When stepping down, reduce the daily dose by no more than 1 tablet per month. 4
• Use the Urticaria Control Test (UCT) score to guide treatment, with complete control defined as UCT >16. 4

Natural History Considerations in Post-COVID Context

• Approximately 50% of patients with chronic urticaria presenting with wheals alone achieve remission by 6 months. 4
• However, patients with both wheals and angioedema have significantly worse prognosis, with over 50% still having active disease after 5 years. 4
• Many pediatric patients will require antihistamine therapy for months to years, not weeks, due to the natural history of the disease. 4

Escalation for Refractory Cases

Second-Line Options

• If standard and high-dose antihistamines (up to 4x standard dose) fail after adequate trial, add H2 antihistamines (ranitidine or famotidine) for refractory chronic urticaria. 1
• Consider leukotriene receptor antagonists (montelukast) for refractory chronic urticaria. 1

Third-Line Options

• Omalizumab 300 mg subcutaneously every 4 weeks is effective for antihistamine-refractory chronic urticaria, allowing up to 6 months for full response assessment. 1, 4, 6
• Omalizumab is FDA-approved for chronic spontaneous urticaria in pediatric patients aged 12 years and older who remain symptomatic despite H1 antihistamine treatment. 6
• Safety and effectiveness in pediatric patients with chronic spontaneous urticaria below 12 years of age have not been established. 6

Fourth-Line Options

• Cyclosporine 4 mg/kg daily is effective in approximately two-thirds of severe autoimmune urticaria cases unresponsive to antihistamines, used for up to 2 months. 1, 2

Evidence from COVID-19 Urticaria Studies

• Management of urticaria in COVID-19 patients involves antihistamines as the primary treatment. 7
• Low-dose prednisolone should be considered on an individualized basis only for severe cases. 7
• Skin lesions in COVID-19-associated urticaria resolved from less than 24 hours to up to 2 weeks following treatment with antihistamines and/or steroids. 7
• There have been no cases of recurrent urticaria or cases nonresponsive to steroids in the acute COVID-19 setting. 7
• Quadruple doses of antihistamines have been successfully used in allergic patients with COVID-19-associated urticaria. 8

Mast Cell Activation Syndrome Connection

• Histamine receptor antagonists result in improvements in the majority of patients with long COVID and mast cell activation syndrome symptoms. 3
• The number and severity of mast cell activation syndrome symptoms substantially increased in patients with long COVID compared with pre-COVID and control individuals. 3

Common Pitfalls to Avoid

• Never use corticosteroids as first-line treatment when antihistamines are sufficient. 1
• Never continue corticosteroids beyond 3-10 days due to cumulative toxicity. 1, 2
• Never use chronic corticosteroids for chronic spontaneous urticaria. 1, 2
• Avoid aspirin and NSAIDs in patients with urticaria, as they can exacerbate symptoms. 1
• Do not discontinue antihistamines prematurely—continue until at least 3 consecutive months of complete disease control. 4

Emergency Situations

• Administer epinephrine 0.5 mL of 1:1000 (500 µg) intramuscularly immediately for anaphylaxis or severe laryngeal angioedema. 1
• This is critical as patients with mast cell disorders or urticaria may be at risk for anaphylaxis. 9