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

Treatment of Autoimmune Urticaria

Begin with second-generation H1-antihistamines at standard doses, escalate up to 4-fold if needed after 2-4 weeks, then add omalizumab 300 mg subcutaneously every 4 weeks for refractory cases, reserving cyclosporine 4 mg/kg daily as fourth-line therapy for severe disease unresponsive to omalizumab. 1

First-Line: Antihistamine Monotherapy

• Start with second-generation H1-antihistamines (cetirizine, loratadine, fexofenadine, levocetirizine) at standard FDA-approved doses, as over 40% of patients with autoimmune urticaria achieve good symptom control with this approach alone 1
• Continue standard-dose antihistamines for 2-4 weeks before escalating, allowing adequate time to assess response 1

Second-Line: Antihistamine Dose Escalation

• If symptoms persist after 2-4 weeks, increase the H1-antihistamine dose up to 4 times the standard dose before considering additional therapies 1
• This dose escalation has become standard practice when potential benefits outweigh risks, though it represents off-label use 1
• Consider adding H2-antihistamines (ranitidine, famotidine) to the H1-antihistamine regimen for additional histamine receptor blockade 1
• Leukotriene receptor antagonists (montelukast 10 mg daily) can be added as adjunctive therapy, particularly useful in resistant cases, though evidence as monotherapy is limited 1, 2

Corticosteroids: Short-Term Use Only

• Restrict oral corticosteroids to short courses of 3-10 days maximum (prednisolone 50 mg daily for 3 days) for severe acute exacerbations or angioedema affecting the mouth 1, 3
• Never use long-term oral corticosteroids for chronic autoimmune urticaria except in very selected cases under regular specialist supervision, as cumulative toxicity is dose and time dependent 1, 3
• The most critical error in management is using chronic corticosteroids, which leads to significant morbidity (hypertension, hyperglycemia, osteoporosis, gastric ulcers) without sustained benefit 4, 3

Third-Line: Omalizumab for Antihistamine-Refractory Disease

• Add omalizumab 300 mg subcutaneously every 4 weeks for patients who remain symptomatic despite maximized antihistamine therapy (up to 4-fold standard dose) 4, 5
• Omalizumab demonstrates excellent efficacy with 36% of patients achieving complete symptom resolution (no itch, no hives) at 12 weeks in clinical trials 5
• The safety profile is favorable with minimal adverse events (primarily mild headache and upper respiratory infections), making it preferable to long-term corticosteroids 4
• Anaphylaxis risk is 0.2%, requiring 2-hour observation for the first 3 doses, then 30-minute observation for subsequent doses 4
• All patients must be prescribed epinephrine autoinjectors and trained in their use, with administration occurring only in settings equipped to treat anaphylaxis 4
• Continue omalizumab until spontaneous remission occurs, with periodic reassessment of disease activity 4
• For breakthrough symptoms during therapy, consider updosing to 450 mg every 4 weeks, then to 600 mg if needed (maximum dose is 600 mg every 14 days) 4

Fourth-Line: Cyclosporine for Severe Refractory Disease

• Reserve cyclosporine exclusively for patients with disabling autoimmune urticaria who have failed optimal antihistamine therapy and omalizumab 1
• Use cyclosporine at 4 mg/kg daily (or up to 5 mg/kg/day), which achieves efficacy in approximately 65-70% of severe autoimmune urticaria cases 1, 6
• Low-dose cyclosporine (starting at 2.5 mg/kg, tapering to 0.55 mg/kg) can be effective with minimal side effects, with 88% improvement after 5 months of treatment 6
• Treatment duration is typically up to 2 months, with 78.3% of patients showing negative autologous serum skin test after 3-6 months and 87% remaining symptom-free at one-year follow-up 1, 6

Diagnostic Confirmation of Autoimmune Etiology

• At least 30% of patients with chronic ordinary urticaria have an autoimmune etiology with histamine-releasing autoantibodies against the high-affinity IgE receptor (FcεRIα) 1, 7
• Use the autologous serum skin test (ASST) as a reasonably sensitive and specific screening test for histamine-releasing autoantibodies in centers with experience performing it 2, 1
• The basophil histamine release assay remains the gold standard for functional autoantibodies but is only available in specialized centers 2
• Combined ASST, autologous plasma skin test (APST), and anti-FcεRIα antibody testing reveals 100% sensitivity and specificity for autoimmune urticaria diagnosis 8
• Check thyroid autoantibodies and thyroid function tests, as thyroid autoimmunity occurs in 14% of chronic urticaria patients versus 6% of controls 2, 9

Essential Investigations

• Perform full blood count with differential and erythrocyte sedimentation rate for patients with severe disease not responding to antihistamines 2
• The ESR is usually normal in chronic ordinary urticaria but may be raised in urticarial vasculitis (which requires skin biopsy if lesions persist >24 hours) 2, 1
• Consider testing for Helicobacter pylori, as successful antibiotic eradication is associated with resolution of chronic urticaria in meta-analyses 2
• Avoid extensive routine investigations, as most chronic urticaria remains idiopathic and extensive testing is not warranted 1

Critical Pitfalls to Avoid

• Do not delay omalizumab while continuing to increase antihistamine doses beyond 4-fold standard dose, as this provides diminishing returns and delays effective therapy 4
• Never use corticosteroids as first-line treatment when antihistamines are sufficient—always attempt antihistamine dose escalation first 3
• Distinguish urticarial vasculitis by lesion duration >24 hours and residual bruising, which requires skin biopsy and different management 1
• Do not use hydrocortisone as routine treatment for urticaria; prednisolone is the preferred corticosteroid formulation 3

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 1
• The appropriate duration of omalizumab therapy has not been definitively determined, but continue until underlying disease remits with periodic reassessment 4, 5