Is systemic corticosteroid (cortisol) appropriate as first‑line therapy for urticaria?

Systemic Corticosteroids Are NOT Appropriate as First-Line Therapy for Urticaria

Systemic corticosteroids should not be used as first-line treatment for urticaria—second-generation H1-antihistamines are the definitive initial therapy, and corticosteroids should be restricted to short courses (3-10 days maximum) only for severe acute exacerbations. 1, 2, 3

First-Line Treatment: Antihistamines

• Start with a standard dose of a second-generation H1-antihistamine (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine) as the definitive first-line treatment for all forms of urticaria. 1, 2, 3

• Offer at least two different second-generation antihistamines to each patient, as individual responses and tolerance vary significantly between agents. 2, 4

• If symptoms remain inadequately controlled after 2-4 weeks, increase the antihistamine dose up to 4 times the standard dose before considering any other therapy. 1, 2, 4

Why Corticosteroids Are NOT First-Line

• Corticosteroids are not recommended for long-term treatment due to unavoidable severe adverse effects including adrenal suppression, osteoporosis, diabetes, hypertension, and Cushing syndrome. 2, 3

• In children, glucocorticoids may actually increase the risk of biphasic reactions (OR 1.55; 95% CI 1.01-2.38), though confounding by severity cannot be excluded. 1

• The evidence for corticosteroid efficacy in preventing biphasic reactions is very low, with a number needed to treat of 161 patients at a 5% baseline risk to prevent one episode—and confidence intervals include the possibility of harm. 1

• A 2024 meta-analysis found that while corticosteroids likely improve urticaria activity by 14-15% in patients with low-to-moderate antihistamine responsiveness, they also likely increase adverse events in approximately 15% more patients (OR 2.76; 95% CI 1.00-7.62). 5

Limited Role for Corticosteroids

• Restrict oral corticosteroids to short courses of 3-10 days only for severe acute exacerbations of urticaria, never for chronic maintenance therapy. 2, 4, 6

• If corticosteroids must be used, employ no more than 10 mg/day with a weekly reduction of 1 mg to minimize cumulative toxicity. 7

• Short courses of adjunctive corticosteroids may be considered as a bridge therapy to other systemic treatments in cases of acute severe exacerbations, but only after antihistamines have been optimized. 1

Algorithmic Treatment Approach

1. Start: Second-generation H1-antihistamine at standard dose 1, 2
2. After 2-4 weeks if inadequate control: Increase antihistamine up to 4-fold standard dose 1, 2
3. If still inadequate after up-dosing: Add omalizumab 300 mg subcutaneously every 4 weeks 1, 2, 4
4. If inadequate response within 6 months: Add cyclosporine (up to 5 mg/kg body weight) to the antihistamine regimen 1, 2, 4

Common Pitfall to Avoid

The most critical error is using antihistamines or corticosteroids before epinephrine in anaphylaxis. While antihistamines may treat urticaria and itching to improve comfort during anaphylaxis, if used prior to epinephrine administration, they could lead to a delay in first-line treatment of anaphylaxis. 1 Epinephrine is the only first-line medication for anaphylaxis, and secondary therapies must never interfere with early epinephrine treatment. 1

Corticosteroids have no role in preventing biphasic anaphylaxis and should not be routinely administered for this purpose. 1