Causes of Urticaria
Urticaria is primarily caused by mast cell and basophil activation with subsequent release of histamine and other inflammatory mediators, resulting in increased vascular permeability, edema, erythema, and pruritus. 1 Despite thorough evaluation, many cases remain idiopathic, particularly in chronic urticaria where 80-90% of cases have no identifiable cause. 2
Main Categories of Urticaria Causes
Immunological Triggers
- IgE-mediated reactions:
Non-immunological Triggers
- Direct mast cell degranulation:
- Certain drugs (opiates, codeine, radiocontrast media)
- NSAIDs and aspirin (via leukotriene formation)
- Dietary pseudoallergens (salicylates, azo dyes, food preservatives) 1
Physical Triggers
- Mechanical stimuli (dermographism, delayed pressure urticaria, vibratory angioedema)
- Thermal stimuli (cold contact urticaria, cholinergic urticaria, localized heat urticaria)
- Other physical stimuli (aquagenic urticaria, solar urticaria) 1, 4
Infections
- Viral infections (especially in children with acute urticaria)
- Bacterial infections (including Helicobacter pylori)
- Parasitic infections (can cause eosinophilia) 1, 4
Autoimmune Mechanisms
- Autoantibodies against high-affinity IgE receptor or against IgE (found in approximately 40-60% of chronic urticaria cases)
- Association with thyroid autoimmunity (14% of chronic urticaria vs. 6% in controls) 1, 5
Medication-Related
- ACE inhibitors (causing angioedema through inhibition of kinin breakdown)
- Aspirin and NSAIDs (through altered arachidonic acid metabolism)
- Antibiotics
- Topical medications (antibiotics, disinfectants, anesthetics) 1, 3
Systemic Diseases
- Thyroid disorders (particularly autoimmune hypothyroidism)
- Connective tissue diseases
- Malignancies (though no statistical association has been established)
- Celiac disease (higher prevalence in children with severe chronic urticaria) 1, 4, 5
Hereditary/Genetic Causes
- Hereditary angioedema (C1 esterase inhibitor deficiency)
- Autoinflammatory syndromes (cryopyrin-associated periodic syndromes) 1
Clinical Patterns and Duration
The clinical presentation can help identify the cause:
- Acute urticaria (<6 weeks): More likely to identify a specific trigger (foods, medications, infections)
- Chronic urticaria (>6 weeks): Often idiopathic (80-90% of cases)
- Physical urticarias: Reproducibly induced by specific physical stimuli
- Contact urticaria: Occurs only with percutaneous/mucosal absorption of eliciting substance
- Urticarial vasculitis: Presents with urticaria clinically but shows small vessel vasculitis histologically 1, 2
Diagnostic Approach
The diagnosis is primarily clinical, and investigations should be guided by the history rather than performed routinely in all patients. 1 For chronic urticaria that doesn't respond to antihistamines, consider:
- Complete blood count with differential
- Erythrocyte sedimentation rate
- Thyroid antibodies and function tests 1, 6
Common Pitfalls
- Overinvestigation: Extensive laboratory workups are rarely helpful without specific clinical indications
- Missing underlying systemic disease: Watch for signs of urticarial vasculitis (lesions lasting >24 hours) or angioedema without urticaria (may indicate C1 inhibitor deficiency)
- Overlooking medication causes: Particularly NSAIDs and ACE inhibitors
- Failure to recognize physical urticarias: These require specific provocation tests for diagnosis 1, 4
Remember that while many cases of urticaria remain idiopathic despite thorough evaluation, identifying and avoiding triggers when possible remains the cornerstone of management.