What is the best approach to manage a patient presenting with generalized urticaria?

Management of Generalized Urticaria

Start with a standard-dose second-generation H1 antihistamine (cetirizine, fexofenadine, loratadine, or desloratadine) taken daily, and if symptoms persist after 2-4 weeks, increase the dose up to 4 times the standard dose before adding any other therapies. 1, 2

Initial Assessment and Diagnosis

Before initiating treatment, determine the urticaria subtype and rule out life-threatening presentations:

• Individual wheals lasting 2-24 hours suggest ordinary urticaria, while lesions persisting beyond 24 hours warrant skin biopsy to exclude urticarial vasculitis 1
• Physical urticaria wheals resolve in less than 1 hour (except delayed pressure urticaria, which can last up to 48 hours) 1, 2
• Immediately administer intramuscular epinephrine 0.5 mL of 1:1000 for severe urticaria with anaphylaxis or angioedema affecting the airway 1, 3

First-Line Treatment: Antihistamine Monotherapy

Begin with a single second-generation H1 antihistamine at standard dosing for 2-4 weeks:

• Cetirizine 10 mg daily 4, 1
• Fexofenadine 180 mg daily 4, 1
• Loratadine 10 mg daily 4, 1
• Desloratadine (standard dose) 1, 2

Trial at least two different non-sedating antihistamines if the first is ineffective, as individual responses and tolerance vary significantly 1, 2

Dose Escalation for Inadequate Response

If standard dosing provides inadequate control after 2-4 weeks, increase the antihistamine dose up to 4 times the standard dose when potential benefits outweigh risks 1, 2, 5

This approach exceeds manufacturer's licensed recommendations but is supported by guideline evidence when benefits outweigh risks 5

Adjunctive Therapies for Resistant Cases

Add the following sequentially if high-dose antihistamines alone are insufficient:

• Add a first-generation antihistamine (hydroxyzine) at night for additional symptom control and to help with sleep 1, 5
• Add H2-antihistamines (ranitidine or famotidine) for resistant cases 1, 2, 5
• Add leukotriene receptor antagonists (montelukast), particularly beneficial for aspirin-sensitive and autoimmune urticaria 1, 5

Role of Corticosteroids: Use Sparingly

Restrict oral corticosteroids to short courses (3-10 days) only for severe acute urticaria or life-threatening angioedema, due to cumulative toxicity including hypertension, hyperglycemia, osteoporosis, and gastric complications 1, 5, 6

Avoid long-term oral corticosteroids in chronic urticaria except in very selected cases under specialist supervision 5

General Measures and Trigger Avoidance

Identify and minimize aggravating factors:

• Avoid overheating, stress, and alcohol 1, 5
• Avoid aspirin and NSAIDs, as they inhibit cyclooxygenase and can exacerbate urticaria 1, 5
• Avoid ACE inhibitors if angioedema is present without wheals, and use cautiously when angioedema accompanies urticaria 1
• Apply cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) for symptomatic relief 2, 5

Advanced Therapies for Refractory Cases

For patients failing high-dose antihistamines with or without adjunctive therapies:

• Omalizumab 300 mg subcutaneously every 4 weeks is recommended for chronic spontaneous urticaria unresponsive to high-dose antihistamines, with up to 6 months allowed for response 1, 5
• Cyclosporine 4 mg/kg daily for up to 2 months is effective in approximately 65-70% of patients with severe autoimmune urticaria who fail omalizumab 1, 5

Stepping Down Treatment

Use an "as much as needed and as little as possible" approach:

• Do not step down higher-than-standard antihistamine doses before completing at least 3 consecutive months of complete control 5
• Reduce the daily dose by no more than 1 tablet per month during step-down 5
• Return to the last dose that provided complete control if symptoms recur during step-down 5

Prognosis and Patient Education

• About 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months 1, 5
• Patients with both wheals and angioedema have a poorer prognosis, with over 50% still having active disease after 5 years 1
• Acute post-viral urticaria typically resolves much sooner with appropriate antihistamine therapy 1

Common Pitfalls to Avoid

• Do not use sedative antihistamines as first-line monotherapy due to sedating properties; reserve for nighttime use only 5
• Do not use crotamiton cream, topical capsaicin, or calamine lotion for generalized pruritus of unknown origin, as evidence does not support their use 4
• Do not delay omalizumab in patients with severe, refractory disease who clearly meet criteria for second-line therapy 5
• Never use montelukast as monotherapy; always maintain antihistamine therapy 5