What is the treatment for unexplained urticaria (hives)?

Treatment of Unexplained Urticaria (Hives)

Start with second-generation non-sedating H1 antihistamines as first-line therapy, and if symptoms persist after 2-4 weeks at standard dosing, increase the dose up to 4-fold before considering additional treatments. 1

Initial Management Approach

First-Line Treatment: H1 Antihistamines

• Begin with a second-generation non-sedating H1 antihistamine (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, or mizolastine) at standard licensed doses 1, 2
• Offer patients a choice of at least two different antihistamines, as individual responses and tolerance vary significantly 1
• Continue treatment for 2-4 weeks to assess response 1

Dose Escalation Strategy

• If standard doses fail to control symptoms, increase the antihistamine dose up to 4 times the manufacturer's licensed recommendation 1
• This practice has become standard when potential benefits outweigh risks, though it exceeds official licensing 1
• Cetirizine may cause sedation at higher doses, which should be considered when escalating 1

Second-Line Interventions

Additional Pharmacologic Options

• Add an H2 antihistamine to the H1 antihistamine regimen for resistant cases 1
• Add a sedating antihistamine at bedtime if nocturnal symptoms are problematic 1
• Consider antileukotrienes (typically montelukast) as add-on therapy, particularly for aspirin-sensitive patients or those with positive autologous serum skin test, though evidence for monotherapy is limited 1

Short-Term Corticosteroids

• Use oral prednisolone (50 mg daily for 3 days in adults, though lower doses often work) only for severe acute exacerbations 1
• Long-term oral corticosteroids should NOT be used in chronic urticaria except in very selected cases under specialist supervision 1
• Short tapering courses over 3-4 weeks may be necessary only for urticarial vasculitis or severe delayed pressure urticaria 1

Lifestyle Modifications and Trigger Avoidance

Nonspecific Aggravating Factors to Minimize

• Overheating, stress, and alcohol consumption 1
• Aspirin and NSAIDs (avoid completely in aspirin-sensitive patients due to cross-reactivity) 1
• Codeine and other opioids that directly degranulate mast cells 1
• ACE inhibitors should be avoided if angioedema is present 1

Symptomatic Relief Measures

• Apply cooling antipruritic lotions such as calamine or 1% menthol in aqueous cream for itch relief 1

Minimal Investigation Approach

When to Investigate

• No investigations are required for mild disease responding to H1 antihistamines 1
• For nonresponders with more severe disease, consider a screening profile including: 1
  • Full blood count with differential (to detect eosinophilia from parasites or leucopenia from lupus)
  • Erythrocyte sedimentation rate (usually normal in chronic ordinary urticaria)
  • Thyroid autoantibodies and thyroid function tests (14% of chronic urticaria patients have thyroid autoimmunity) 1

What NOT to Do

• Do not perform extensive allergy testing or food panels routinely, as most chronic unexplained urticaria remains idiopathic despite thorough evaluation 1
• Investigations should be guided by specific historical clues, not performed reflexively in all patients 1

Special Considerations

Medication Adjustments for Specific Populations

Renal impairment: 1

• Avoid acrivastine in moderate renal impairment
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine
• Avoid cetirizine and levocetirizine in severe renal impairment

Hepatic impairment: 1

• Mizolastine is contraindicated
• Avoid alimemazine due to hepatotoxicity risk

Pregnancy: 1

• Avoid all antihistamines if possible, especially in first trimester
• Chlorphenamine is often chosen when treatment is necessary due to long safety record
• Loratadine and cetirizine are FDA Pregnancy Category B

Prognosis and Patient Education

• Explain that a specific cause is unlikely to be found in most cases, but prognosis for eventual recovery is excellent 1
• Approximately 50% of patients with chronic urticaria and wheals alone clear by 6 months 1
• Patients with both wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years 1
• Over 40% of patients show good response to antihistamines 1

Common Pitfalls to Avoid

• Do not pursue extensive allergy workups in chronic unexplained urticaria without specific historical triggers 1
• Do not use long-term oral corticosteroids as maintenance therapy 1
• Do not assume food allergies are the cause without clear temporal relationship 1
• Do not stop treatment prematurely—give adequate trial periods before declaring treatment failure 1