What causes urticaria?

Causes of Urticaria

Urticaria is most commonly idiopathic (80-90% of chronic cases), but can be caused by immunological and non-immunological triggers that lead to mast cell activation and histamine release, resulting in characteristic wheals and sometimes angioedema. 1, 2

Classification of Urticaria Causes

Physical/Mechanical Triggers

• Delayed pressure urticaria: Develops 2-6 hours after pressure application, lasts up to 48 hours
• Symptomatic dermographism: Wheals appear after stroking or scratching skin
• Vibratory angioedema: Triggered by vibration
• Thermal triggers:
  • Cholinergic urticaria: Induced by sweating stimulus
  • Cold contact urticaria: Triggered by cold exposure
  • Localized heat urticaria: Triggered by heat exposure
• Other physical triggers:
  • Aquagenic urticaria: Triggered by water contact
  • Solar urticaria: Triggered by sun exposure
  • Exercise-induced anaphylaxis 1

Immunological Mechanisms

• IgE-mediated reactions:
  • Food allergens (common in acute urticaria)
  • Medications
  • Insect stings/venom
  • Latex and other contact allergens 1, 3
• Autoimmune mechanisms:
  • Functional autoantibodies against high-affinity IgE receptor or IgE (found in ~30-40% of chronic urticaria cases) 3, 4
  • Associated with autoimmune thyroid disease (Hashimoto's) 4

Non-immunological Mechanisms

• Direct mast cell degranulation:
  • Certain drugs (e.g., codeine, opiates)
  • Radiocontrast media
• Leukotriene pathway activation:
  • Aspirin
  • NSAIDs
  • Dietary pseudoallergens (salicylates, azo dyes, food preservatives) 1
• Kinin pathway:
  • ACE inhibitors causing angioedema (inhibition of kinin breakdown) 1

Infections

• Viral infections: Common trigger for acute urticaria, especially in children
• Bacterial infections: Including H. pylori (meta-analysis shows resolution more likely when antibiotic therapy successful) 1, 3
• Parasitic infections 3

Systemic Diseases

• Urticarial vasculitis: Small vessel vasculitis presenting with urticaria-like lesions that persist for days
• Autoinflammatory syndromes:
  • Hereditary: Cryopyrin-associated periodic syndromes (CAPS)
  • Acquired: Schnitzler syndrome 1
• Other associated conditions:
  • Thyroid autoimmunity (14% in chronic urticaria vs 6% in general population)
  • Celiac disease (higher prevalence in children with severe chronic urticaria)
  • Collagenopathies
  • Endocrinopathies
  • Tumors
  • Hemolytic diseases 1, 3

Pathophysiological Mechanism

The fundamental pathophysiology involves:

1. Mast cell and basophil activation through various triggers
2. Release of histamine and other inflammatory mediators
3. Increased vascular permeability of postcapillary venules
4. Development of edema, erythema, and pruritus 4, 5

Duration-Based Classification

• Acute urticaria: Lasts <6 weeks, often identifiable trigger
• Chronic urticaria: Lasts >6 weeks, often idiopathic (80-90% of cases) 2, 5
  • Chronic spontaneous urticaria: No specific trigger
  • Chronic inducible urticaria: Specific identifiable triggers

Clinical Pearls

• Individual wheals typically last 2-24 hours in ordinary urticaria
• Contact urticaria wheals last up to 2 hours
• Physical urticaria wheals typically resolve within an hour (except delayed pressure urticaria)
• Urticarial vasculitis wheals persist for days
• Angioedema may last up to 3 days without treatment 1

Despite thorough evaluation, many cases of urticaria remain unexplained or "idiopathic," particularly in chronic urticaria where a specific cause is identified in only about 20% of cases 3, 2.