What is the recommended management for acute and chronic urticaria?

Management of Urticaria

Start all patients with urticaria on a second-generation H1-antihistamine at standard dose, and if symptoms remain inadequately controlled after 2-4 weeks, increase the dose up to 4-fold before considering any other therapy. 1, 2

Acute Urticaria Management

First-Line Treatment

• Second-generation H1-antihistamines are the definitive initial treatment for acute urticaria 1, 3
• Available options include cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and mizolastine 1, 3
• Offer patients at least two different non-sedating antihistamines, as individual responses and tolerance vary significantly between agents 1, 2
• Cetirizine reaches peak plasma concentration fastest, making it preferable when rapid symptom control is required 1, 2

Adjunctive Measures for Acute Episodes

• Short courses of oral corticosteroids (e.g., prednisolone 50 mg daily for 3 days in adults) may shorten the duration of acute urticaria 1
• Restrict corticosteroids to 3-10 days for severe acute exacerbations only—they should not be used chronically due to cumulative toxicity including adrenal suppression, osteoporosis, diabetes, hypertension, and Cushing syndrome 1, 2, 4
• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) provide symptomatic relief 1, 5

Trigger Avoidance

• Minimize nonspecific aggravating factors: overheating, stress, alcohol, aspirin, NSAIDs, and codeine 1, 5
• NSAIDs should be avoided in aspirin-sensitive patients with urticaria 1, 3
• ACE inhibitors should be avoided in patients with angioedema without wheals 1, 3

Chronic Urticaria Management (>6 weeks duration)

Step 1: Standard-Dose Second-Generation H1-Antihistamine

• Begin with a standard dose of a second-generation H1-antihistamine 1, 2, 3
• Assess disease control using the Urticaria Control Test (UCT) every 4 weeks; a score ≥12 indicates well-controlled disease 1, 2
• For patients with angioedema, use the Angioedema Control Test (AECT); a score ≥10 indicates adequate control 1, 2

Step 2: Up-Dose Antihistamines (If Inadequate Control After 2-4 Weeks)

• Increase the second-generation H1-antihistamine dose up to 4 times the standard dose 1, 2
• This up-dosing achieves sufficient response in approximately 23% of patients who failed standard dosing 2
• Schedule antihistamine dosing so peak drug levels coincide with anticipated timing of urticaria flares 2
• Consider adding a sedating antihistamine at night (chlorphenamine 4-12 mg or hydroxyzine 10-50 mg) to improve sleep quality, though this provides minimal additional urticaria control when H1 receptors are already saturated 2, 3

Step 3: Add Omalizumab (If Inadequate Control Despite Up-Dosing)

• Add omalizumab 300 mg subcutaneously every 4 weeks 1, 2, 5, 3
• Omalizumab is effective in approximately 70% of antihistamine-refractory patients 4
• Allow up to 6 months for patients to demonstrate a response before considering alternative therapies 1, 2, 5, 3
• If insufficient response at standard dosing, increase to 600 mg every 2 weeks as the maximum recommended dose 5

Step 4: Add Cyclosporine (If Inadequate Control After 6 Months of Omalizumab)

• Add cyclosporine up to 5 mg/kg body weight daily to the antihistamine regimen 1, 2, 5, 3
• Cyclosporine is effective in approximately 65-70% of patients with severe urticaria unresponsive to antihistamines and omalizumab 2, 3, 4
• A treatment duration of 16 weeks is superior to 8 weeks for reducing therapeutic failures 5
• Monitor blood pressure and renal function every 6 weeks due to potential nephrotoxicity and hypertension 1, 2, 5, 3

Treatment Monitoring and Step-Down

• Once complete symptom control is achieved, maintain the effective dose for at least 3 consecutive months before considering step-down 2
• When stepping down, reduce the daily dose by no more than 1 tablet per month 2
• If symptoms recur during step-down, return to the last effective dose that provided complete control 2

Special Considerations and Pitfalls

Distinguishing Urticaria Subtypes

• Individual wheals lasting 2-24 hours indicate chronic spontaneous urticaria 1, 2
• Lesions persisting >24 hours suggest urticarial vasculitis and warrant skin biopsy for confirmation and different management 1, 2
• Presence of ecchymotic or purpuric residues, pain/burning sensations, fever, arthralgia, or general malaise should prompt specialist referral 2

Diagnostic Workup for Chronic Spontaneous Urticaria

• Perform differential blood count, C-reactive protein level/erythrocyte sedimentation rate, total IgE level, and IgG-anti-thyroid peroxidase (TPO) level 1
• Serum C4 should be used as an initial screening test for hereditary and acquired C1 inhibitor deficiency in patients with angioedema without wheals 1
• No routine testing is recommended in acute urticaria unless the patient's history suggests an underlying cause requiring specific testing 1

Dose Adjustments in Special Populations

Renal Impairment: 1, 2, 3

• Avoid acrivastine in moderate renal impairment (creatinine clearance 10-20 mL/min)
• Halve the dose of cetirizine, levocetirizine, and hydroxyzine in moderate renal impairment
• Avoid cetirizine and levocetirizine in severe renal impairment (creatinine clearance <10 mL/min)

Hepatic Impairment: 1, 2, 3

• Mizolastine is contraindicated in significant hepatic impairment
• Avoid chlorphenamine and hydroxyzine in severe liver disease due to inappropriate sedating effects

Pregnancy: 1, 2, 3

• Avoid all antihistamines during pregnancy, especially in the first trimester, unless absolutely necessary
• When antihistamine therapy is required, chlorphenamine is often selected due to its long safety record
• Loratadine and cetirizine are FDA Pregnancy Category B drugs (no evidence of risk in human studies)

Anaphylaxis Recognition and Management

• Generalized acute urticaria alone is not life-threatening, but in the context of known exposure to an allergen that previously triggered anaphylaxis, inject epinephrine immediately 1
• Administer intramuscular epinephrine 0.5 mL of 1:1000 (500 µg) for adults and adolescents >12 years with severe laryngeal angioedema or anaphylaxis 1, 3
• Epinephrine must be given before any antihistamine or corticosteroid; using antihistamines or corticosteroids first can delay essential epinephrine therapy 2
• Fixed-dose epinephrine pens (300 µg for adults, 150 µg for children 15-30 kg) should be prescribed for patients at risk of life-threatening attacks 1, 3
• Systemic corticosteroids have no proven role in preventing biphasic anaphylaxis and should not be given routinely for this purpose 2

Therapies with Limited Evidence

• Adding an H2-antihistamine (e.g., cimetidine) may benefit patients with antihistamine-refractory urticaria, particularly when dyspeptic symptoms coexist, but evidence is limited 1, 2
• Adding an antileukotriene (e.g., montelukast) can be considered for resistant cases, but efficacy data are sparse 1, 2

Prognosis

• About 50% of patients with chronic urticaria presenting with wheals alone will be clear by 6 months 3
• Patients with wheals and angioedema have a poorer outlook, with over 50% still having active disease after 5 years 3