What is the best course of action for intermittent urticaria (hives) with fever and vomiting lasting 3 months?

Evaluation and Management of Intermittent Urticaria with Fever and Vomiting Lasting 3 Months

This presentation requires urgent evaluation to rule out systemic disease, as hives lasting 3 months with constitutional symptoms (fever and vomiting) is atypical for ordinary urticaria and suggests either chronic urticaria with concurrent illness, urticarial vasculitis, or an underlying systemic condition.

Critical Initial Assessment

The combination of chronic urticaria with fever and vomiting is a red flag that demands investigation beyond typical chronic spontaneous urticaria 1. You must immediately assess for:

• Duration of individual wheals: If wheals last longer than 24 hours, suspect urticarial vasculitis and obtain a skin biopsy for confirmation 1
• Signs of systemic disease: Fever with urticaria suggests infection, autoimmune disease (collagenopathies, endocrinopathies), or rarely malignancy 2
• Anaphylaxis features: Check for respiratory symptoms, hypotension, or severe gastrointestinal symptoms that would indicate anaphylaxis rather than simple urticaria 1

Diagnostic Workup

Unlike typical chronic spontaneous urticaria where extensive testing is unnecessary, this presentation with fever and vomiting mandates targeted investigation 2:

• Basic laboratory evaluation including complete blood count, inflammatory markers (ESR/CRP), liver and kidney function
• Consider autoimmune screening (ANA, thyroid antibodies) given the 20% association with autoimmune thyroiditis in chronic urticaria 3
• Rule out infectious causes given the fever component 2
• If wheals last >24 hours, perform skin biopsy to evaluate for urticarial vasculitis 1

Treatment Algorithm

First-Line: High-Dose Second-Generation Antihistamines

Start with a second-generation H1 antihistamine (cetirizine, fexofenadine, loratadine, or levocetirizine) and rapidly escalate to 4 times the standard dose if inadequate response after 2-4 weeks 1, 4, 5. This approach is superior to standard dosing, with approximately 40% of patients achieving partial or complete response 3.

• Offer at least two different antihistamine options, as individual responses vary significantly 1
• The dose escalation exceeds manufacturer recommendations but is guideline-supported when benefits outweigh risks 1, 5

Adjunctive Therapy for Persistent Symptoms

If high-dose antihistamines are insufficient:

• Add a sedating antihistamine at night (chlorphenamine or hydroxyzine) to address sleep disruption 1, 4
• Consider a short corticosteroid burst: Prednisolone 50 mg daily for 3 days only for severe exacerbations 4, 5
• Add montelukast (leukotriene receptor antagonist) as it benefits a subset of chronic urticaria patients 4, 2

Managing the Vomiting Component

The vomiting requires separate attention 6:

• Ensure adequate fluid and electrolyte replacement
• Use antiemetics targeting the suspected pathway: serotonin antagonists (ondansetron) or dopamine antagonists (metoclopramide) for shortest duration necessary 6
• Small, frequent meals and avoidance of trigger foods 6

Critical Pitfall to Avoid

Do NOT use long-term oral corticosteroids for chronic urticaria 4. This is a firm contraindication (Strength of recommendation A) due to cumulative toxicity and poor risk-benefit ratio 4. Short courses of 3-10 days are acceptable for severe acute exacerbations only 4, 5.

Second-Line Treatment for Refractory Cases

If symptoms persist despite maximized antihistamines after 4-6 weeks:

• Omalizumab (anti-IgE monoclonal antibody) is the guideline-recommended second-line treatment 4, 3. However, at least 30% of patients have insufficient response, particularly those with IgG-mediated autoimmune urticaria 3
• Cyclosporine 4 mg/kg daily for up to 2 months is effective in 54-73% of severe cases unresponsive to antihistamines and omalizumab, especially in autoimmune urticaria 4, 3. Monitor for kidney dysfunction and hypertension 3

Follow-Up and Prognosis

• Schedule follow-up visits within 2-4 weeks to assess treatment response 1
• Approximately 50% of patients with chronic urticaria clear within 6 months, though those with both wheals and angioedema may have over 50% still active after 5 years 1
• More than half of chronic urticaria patients will have resolution or improvement within one year 7

Emergency Considerations

Provide an emergency action plan and consider prescribing self-injectable epinephrine if there is any history of severe reactions or concern for progression to anaphylaxis 1, 5. Intramuscular epinephrine is life-saving for severe laryngeal angioedema 5.