What is the treatment for recurrent urticaria (hives) accompanied by systemic symptoms?

Treatment of Recurrent Urticaria with Systemic Symptoms

If recurrent hives occur with respiratory symptoms, hypotension, or gastrointestinal symptoms after known allergen exposure, treat immediately as anaphylaxis with intramuscular epinephrine first, not as simple urticaria. 1

Immediate Assessment and Risk Stratification

The critical first step is distinguishing isolated urticaria from anaphylaxis, as management differs fundamentally:

• Systemic hives with organ involvement (upper/lower airway compromise, gastrointestinal symptoms, neurologic changes, cardiovascular instability, oxygen desaturation, or seizures) requires epinephrine injection as first-line therapy 2
• Systemic hives without organ involvement can be managed with antihistamines alone 2
• Cardiovascular symptoms including syncope and hypotension are more common in drug-induced anaphylaxis and indicate severe disease 3

First-Line Pharmacotherapy

Second-generation, non-sedating H1-antihistamines represent the mainstay of therapy for both acute and chronic urticaria. 4

Antihistamine Dosing Strategy

• Begin with standard-dose second-generation H1-antihistamines 5
• If inadequate response, titrate up to 4× the standard dose before considering alternative therapies 1, 5
• H2-antihistamines and leukotriene receptor antagonists may be added as adjunctive treatment, though benefits are not clearly established 6, 5

Corticosteroid Use

• Brief corticosteroid bursts may be used for acute exacerbations 5
• Keep the period of initial suppressive dosing as brief as possible (usually 4-10 days for allergic diseases) 7
• Regular steroid use suggests need for subspecialty referral 2

Trigger Identification and Avoidance

Systematically inquire about specific exposures:

• Foods: particularly peanut, tree nuts, milk, shellfish, and fish 1
• Medications: NSAIDs, aspirin, codeine, and ACE inhibitors can trigger or worsen urticaria through non-IgE mechanisms and should be avoided in all urticaria patients 1, 2
• Physical factors: exercise, temperature changes, pressure, sunlight, vibration, and water account for 20-30% of chronic urticaria cases 8
• Infections: H. pylori eradication shows benefit when antibiotic therapy is successful 2

When to Refer for Subspecialty Care

Referral to an allergist-immunologist is indicated for:

• Chronic urticaria unresponsive to high-dose (up to 4× standard) second-generation antihistamines 1
• Need for regular steroid use to control symptoms 2
• Suspected autoimmune urticaria (approximately one-third of chronic urticaria cases have circulating functional autoantibodies) 6
• Individual wheals persisting >24 hours (requires biopsy to rule out urticarial vasculitis) 1, 2
• Chronically recurring angioedema without urticaria (may indicate hereditary or acquired C1 esterase inhibitor deficiency) 2

Advanced Therapies for Refractory Disease

Omalizumab (Second-Line)

• Omalizumab 300mg subcutaneously every 4 weeks is the established second-line treatment for chronic urticaria uncontrolled by antihistamines 9, 4
• Must be administered in a healthcare setting with anaphylaxis preparedness due to 0.2% risk of anaphylaxis 9
• Observe for 2 hours after each of the first 3 injections and 30 minutes for subsequent injections 9
• Also effective for unprovoked anaphylaxis and Hymenoptera venom- or food-induced anaphylaxis in patients with negative specific IgE testing 2

Immunosuppressive Therapy (Third-Line)

• Ciclosporin 4 mg/kg daily is the best-studied immunosuppressive drug, effective in approximately two-thirds of patients with severe autoimmune urticaria unresponsive to antihistamines 10
• Treatment duration of 16 weeks shows fewer therapeutic failures than 8 weeks 10
• Tacrolimus and mycophenolate mofetil have shown similar overall responses in open studies 10
• Methotrexate has only anecdotal evidence and should be reserved as a last-resort option for steroid-dependent cases unresponsive to antihistamines, ciclosporin, and omalizumab 10

Common Pitfalls to Avoid

• Do not delay epinephrine if systemic symptoms suggest anaphylaxis—antihistamines alone are insufficient for organ involvement 2, 1
• Avoid NSAIDs in all urticaria patients as they can trigger or worsen symptoms through non-IgE mechanisms 1, 2
• Do not perform extensive laboratory workups unless the history or physical examination suggests specific underlying conditions; chronic urticaria is idiopathic in 80-90% of cases 5
• Do not use first-generation antihistamines as first-line therapy; second-generation agents are preferred due to better safety profile 4, 5