What are the causes and treatment options for hives (urticaria)?

Causes and Treatment of Hives (Urticaria)

Hives (urticaria) are most commonly idiopathic, but can be caused by medications, foods, infections, physical stimuli, or autoimmune processes, and should be treated with non-sedating H1 antihistamines as first-line therapy.

Causes of Urticaria

Urticaria can be classified based on duration and triggers:

Acute Urticaria (lasting <6 weeks)

• Medications:

  • NSAIDs including aspirin 1
  • Antibiotics
  • Codeine and other drugs that directly degranulate mast cells 1
  • Radiocontrast media 1

• Foods and Food Components:

  • IgE-mediated allergic reactions (nuts, fish, shellfish, etc.) 1
  • Food additives, preservatives, and dyes (salicylates, azo dyes) 1

• Infections:

  • Viral infections (most common infectious cause in children) 2
  • Bacterial infections (including H. pylori - resolution of urticaria more likely when antibiotic therapy is successful) 1

• Contact Urticaria:

  • Percutaneous absorption of allergens (e.g., latex) 1
  • Can progress to anaphylaxis in highly sensitized individuals 1

Chronic Urticaria (lasting >6 weeks)

• Autoimmune Causes:

  • Functional autoantibodies against high-affinity IgE receptor or IgE (30-40% of chronic cases) 3
  • Associated with thyroid autoimmunity (14% vs 6% in general population) 1

• Physical Urticarias:

  • Delayed pressure urticaria
  • Symptomatic dermographism
  • Cholinergic urticaria
  • Cold contact urticaria
  • Solar urticaria
  • Aquagenic urticaria 1

• Systemic Diseases:

  • Thyroid disorders (particularly autoimmune hypothyroidism) 3
  • Celiac disease (higher prevalence in children with severe chronic urticaria) 1
  • Urticarial vasculitis (presents with urticaria clinically but shows small vessel vasculitis histologically) 1

• Hereditary Causes:

  • Hereditary angioedema (C1 esterase inhibitor deficiency) 1
  • Autoinflammatory syndromes 1

Diagnostic Approach

The diagnosis of urticaria is primarily clinical 1. Investigations should be guided by history and not performed in all patients:

• For Acute Urticaria:

  • No investigations required except where suggested by history 1
  • For suspected allergic triggers: skin-prick testing or CAP fluoroimmunoassay 1

• For Chronic Urticaria:

  • For mild cases responding to antihistamines: no investigations required 1
  • For severe or resistant cases:
    • Complete blood count with differential
    • Erythrocyte sedimentation rate
    • Thyroid autoantibodies and function tests
    • Consider autologous serum skin test (ASST) for autoimmune urticaria 1

• For Angioedema Without Wheals:

  • Serum C4 as initial screening for C1 inhibitor deficiency
  • If C4 is low, confirm with quantitative and functional C1 inhibitor assays 1

Treatment Approach

First-Line Treatment

• Non-sedating H1 antihistamines are the mainstay of therapy 1, 4
  • Options include cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and mizolastine
  • Start with standard dosing

For Inadequate Response

• Increase dose of non-sedating H1 antihistamines up to four times the standard dose 1

Second-Line Options

• Combination therapy:
  • Add H2 antihistamines to H1 antihistamines 1, 2
  • Add sedating antihistamine at night 1
  • Add leukotriene receptor antagonists (may benefit a small subgroup) 1, 2

For Refractory Cases

• Omalizumab (anti-IgE monoclonal antibody) for uncontrolled chronic urticaria 4
• Short courses of oral corticosteroids for severe acute urticaria or angioedema affecting the mouth 1
• Cyclosporine or tacrolimus for resistant chronic urticaria 2

For Angioedema

• Epinephrine (IM) for angioedema associated with anaphylaxis - acts on both alpha and beta-adrenergic receptors to reduce vascular permeability and relieve angioedema 5, 2
• For hereditary angioedema: specific treatments including C1 inhibitor concentrate, anabolic steroids, or tranexamic acid 1

Special Considerations

• Physical triggers should be identified and avoided when possible 1
• Medications that can worsen urticaria (aspirin, NSAIDs, ACE inhibitors, codeine) should be minimized 1
• Cooling antipruritic lotions such as calamine or 1% menthol in aqueous cream can provide symptomatic relief 1
• Prognosis: 50% of patients with chronic urticaria with wheals alone clear by 6 months, while those with both wheals and angioedema may have a more prolonged course 1

Common Pitfalls to Avoid

• Don't perform extensive testing in all patients with urticaria - investigations should be guided by history 1
• Don't overlook autoimmune causes in chronic urticaria, particularly thyroid autoimmunity 1, 3
• Don't continue ACE inhibitors in patients with angioedema without wheals 1
• Don't assume all urticaria is allergic - many cases remain idiopathic despite thorough evaluation 1
• Don't use sedating antihistamines as first-line therapy due to cognitive impairment 6