What is the recommended treatment approach for a patient with autoimmune urticaria?

Treatment Approach for Autoimmune Urticaria

Start with second-generation H1-antihistamines at standard doses, escalate up to 4-fold if needed, then add ciclosporin for severe refractory cases—this stepwise approach is the evidence-based standard for autoimmune urticaria. 1

First-Line Treatment: Antihistamine Therapy

• Begin with second-generation H1-antihistamines (cetirizine, loratadine, fexofenadine) at manufacturer-recommended doses as the mainstay of therapy, with over 40% of patients showing good response 1
• Escalate antihistamine doses up to 4 times the standard dose when symptoms persist after 2-4 weeks, as this has become common practice when potential benefits outweigh risks 1, 2
• Switch to a different second-generation antihistamine if one fails at high doses, as individual responses vary significantly 2

Second-Line Combination Strategies

When monotherapy with high-dose antihistamines fails:

• Add H2-antihistamines to your H1-antihistamine regimen for additional histamine receptor blockade 1, 2
• Consider adding leukotriene receptor antagonists (montelukast) as combination therapy, particularly useful in resistant cases 1, 2
• Add sedating antihistamines at night if nocturnal symptoms are problematic 1

Corticosteroid Use: Short-Term Only

• Restrict oral corticosteroids to short courses (3-10 days maximum) for severe acute exacerbations or angioedema affecting the mouth 1, 2
• Avoid prolonged corticosteroid therapy due to cumulative toxicity that is dose and time dependent 2
• More prolonged corticosteroid treatment may be necessary only for delayed pressure urticaria or urticarial vasculitis, not typical autoimmune urticaria 1

Third-Line: Immunomodulating Therapy for Severe Disease

Reserve immunosuppressive therapy exclusively for patients with disabling disease who have failed optimal conventional antihistamine-based treatments. 1

Ciclosporin: The Best-Studied Option

• Ciclosporin at 4 mg/kg daily is effective in approximately two-thirds of patients with severe autoimmune urticaria unresponsive to antihistamines 1
• Treat for 16 weeks rather than 8 weeks to reduce therapeutic failures, though optimal duration still needs definition 1
• Monitor blood pressure and renal function appropriately during ciclosporin therapy 3
• Note that only 25% of responders remain clear or much improved 4-5 months after stopping ciclosporin 1

Alternative Immunosuppressive Options

When ciclosporin fails or is contraindicated:

• Tacrolimus and mycophenolate mofetil show similar overall response rates in open studies 1
• Plasmapheresis and intravenous immunoglobulins may be effective but are expensive and not widely available 1
• Methotrexate and cyclophosphamide have anecdotal success reports 1

Diagnostic Confirmation

• At least 30% of patients with chronic ordinary urticaria have an autoimmune etiology with histamine-releasing autoantibodies 1
• The autologous serum skin test (ASST) is a reasonably sensitive and specific marker for histamine-releasing autoantibodies in autoimmune urticaria 1
• Autoantibodies to IgE and the alpha-chain of FcεRI are present in 30-50% of chronic urticaria cases and are capable of releasing histamine from basophils and mast cells 4, 5

Important Clinical Pitfalls

• Do not perform extensive investigations routinely—most chronic urticaria remains idiopathic and extensive testing is not warranted 6
• Distinguish urticarial vasculitis by lesion duration >24 hours, which requires skin biopsy and different management 6, 2
• Screen for associated autoimmune diseases including thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and celiac disease, as these comorbidities are common 7
• Avoid medications that worsen urticaria: aspirin, NSAIDs, codeine, and ACE inhibitors 2

Prognosis and Treatment Duration

• Over 50% of patients with wheals and angioedema still have active disease after 5 years, indicating a poorer outlook than those with wheals alone 1
• Continue treatment until complete symptom control is achieved and maintained for at least 3-6 months before considering dose reduction 3
• After successful ciclosporin treatment, ASST becomes negative in 78.3% of patients, with 87% remaining symptom-free at one-year follow-up 8