What is the recommended evaluation and step‑by‑step management for a patient with acute or chronic urticaria, including antihistamine use, dose escalation, and emergency treatment?

Management of Urticaria

Second-generation non-sedating H1-antihistamines at standard doses are first-line therapy for both acute and chronic urticaria, with dose escalation up to four times the standard dose recommended for inadequate responders before considering alternative agents. 1, 2, 3

Evaluation and Diagnosis

Acute Urticaria (Duration <6 weeks)

• No routine laboratory testing is required unless the history points to a specific trigger such as food allergens (nuts, fish, eggs), latex, or medications. 1, 2, 4
• The diagnosis is entirely clinical, based on the characteristic appearance of pruritic wheals that resolve within 2-24 hours without scarring. 2
• When IgE-mediated allergy is suspected, skin-prick testing or specific IgE (CAP) assays may confirm sensitization, but results must be interpreted in clinical context. 1, 2

Chronic Urticaria (Duration ≥6 weeks)

• Minimal investigation is needed for patients responding to antihistamines. 1
• For severe or refractory cases, a focused screening panel includes: complete blood count with differential, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), thyroid autoantibodies (anti-TPO), and thyroid function tests. 1, 2
• The autologous serum skin test (ASST) can screen for histamine-releasing autoantibodies in experienced centers, as approximately 30% of chronic urticaria cases have an autoimmune etiology. 1
• Extensive laboratory workups are not cost-effective and should be avoided unless clinical features suggest specific autoimmune diseases. 2, 5

Red Flags Requiring Further Investigation

• Wheals persisting beyond 24 hours suggest urticarial vasculitis and require lesional skin biopsy to confirm small-vessel vasculitis histologically. 1, 2
• Angioedema without wheals mandates serum C4 screening for C1 inhibitor deficiency; if low (<30% mean normal), confirm with quantitative and functional C1 inhibitor assays. 1, 2
• Recurrent angioedema should prompt evaluation for ACE inhibitor or NSAID use, as these drugs are common culprits. 5

Step-by-Step Pharmacologic Management

First-Line: Standard-Dose Second-Generation H1-Antihistamines

• Initiate cetirizine, loratadine, fexofenadine, or desloratadine at manufacturer-recommended daily doses for 2-4 weeks. 1, 5, 3
• These agents are the cornerstone of therapy, with approximately 40-44% of patients achieving adequate control. 1, 2
• First-generation sedating antihistamines (hydroxyzine, diphenhydramine) are not recommended as they disrupt REM sleep patterns and learning curves without superior efficacy in head-to-head trials. 6, 7

Second-Line: Dose Escalation

• If symptoms persist after 2-4 weeks, increase the second-generation H1-antihistamine dose up to four times the standard dose. 1, 5, 3
• This practice has become standard despite exceeding manufacturer-licensed recommendations, as the benefits outweigh risks in most patients. 1
• Continue the escalated dose for an adequate trial period before advancing to third-line options. 5

Third-Line: Adjunctive Therapies

When high-dose antihistamines fail to achieve at least 50% symptom control, consider:

• Adding an H2-antihistamine (e.g., ranitidine, famotidine) may provide modest benefit in some patients, though evidence is limited. 1, 7
• Leukotriene receptor antagonists (montelukast) can be useful for resistant cases, though response is unpredictable. 1
• A sedating antihistamine at bedtime may be added for nocturnal symptoms, though this is no longer strongly recommended given the evidence against first-generation agents. 1

Fourth-Line: Omalizumab

• Omalizumab 300 mg subcutaneously monthly is the strongest evidence-based alternative for chronic spontaneous urticaria refractory to high-dose antihistamines. 7
• It is effective in approximately 70% of antihistamine-refractory patients. 7
• High cost may limit accessibility in resource-limited settings. 5

Fifth-Line: Immunomodulating Therapies

• Cyclosporine 4 mg/kg daily for up to 2 months is effective in about 65-70% of patients with severe autoimmune urticaria unresponsive to antihistamines and omalizumab. 1, 7
• Monitor blood pressure and renal function closely due to potential side effects. 7
• Longer treatment duration (16 weeks vs. 8 weeks) reduces therapeutic failures. 1
• Other agents such as tacrolimus, mycophenolate mofetil, methotrexate, or dapsone may be considered in highly refractory cases under specialist supervision. 1

Role of Corticosteroids

Acute Urticaria

• Short courses of oral prednisolone (e.g., 50 mg daily for 3 days in adults, lower doses in children) may shorten episode duration in severe acute urticaria. 1, 2
• Parenteral hydrocortisone is an adjunct for severe laryngeal edema, though its action is delayed. 1, 2

Chronic Urticaria

• Long-term oral corticosteroids should not be used except in very selected cases under regular specialist supervision (e.g., delayed pressure urticaria, urticarial vasculitis). 1, 2
• Brief steroid bursts (3-10 days) can be employed for severe exacerbations but should be infrequent due to cumulative toxicity. 7

Emergency Treatment

Anaphylaxis and Severe Laryngeal Angioedema

• Intramuscular epinephrine is life-saving and should be administered immediately. 1, 2
• For adults and adolescents >12 years: 0.5 mL of 1:1000 (500 µg) epinephrine intramuscularly. 1
• For children 15-30 kg: fixed-dose 150 µg epinephrine autoinjector. 2
• If no significant relief after the first dose, administer a second dose. 1, 2
• Use with caution in hypertension and ischemic heart disease. 1
• Prescribe an epinephrine autoinjector for home use when the patient's history indicates risk of recurrent life-threatening attacks. 1, 2
• Epinephrine is not helpful for C1 inhibitor deficiency-related angioedema. 1

Non-Pharmacologic Measures

• Avoid known triggers: overheating, emotional stress, alcohol, hot showers, scrubbing, and excessive sun exposure. 2, 5
• Discontinue aspirin and NSAIDs, as they can trigger mast cell degranulation and worsen urticaria. 1, 2
• Topical cooling agents (calamine lotion, 1% menthol in aqueous cream) provide symptomatic itch relief. 2
• Prevent skin drying to minimize hyperresponsive skin. 5

Prognosis

• Approximately 50% of patients with chronic urticaria presenting with wheals alone are 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
• More than half of patients with chronic urticaria will experience resolution or improvement within one year. 3
• Chronic urticaria remains idiopathic in 80-90% of cases despite thorough evaluation. 2, 3

Common Pitfalls

• Do not perform extensive laboratory workups for typical acute urticaria—they are unnecessary and not cost-effective. 2, 5
• Avoid chronic corticosteroid use due to cumulative dose- and time-dependent toxicity. 1, 2, 7
• Do not use first-generation sedating antihistamines as first-line therapy—they lack superior efficacy and impair cognitive function. 6, 7
• H2-antihistamines and leukotriene antagonists add little benefit and are no longer strongly recommended as routine adjuncts. 7