What are the different types of hypersensitivity urticaria and their management options?

Types of Hypersensitivity Urticaria and Management

Urticaria is classified into distinct clinical subtypes based on duration and triggering mechanisms, not by traditional Gell-Coombs hypersensitivity types, with management tailored to each specific pattern.

Clinical Classification Framework

The British Association of Dermatologists provides the primary classification system for urticaria based on clinical presentation rather than immunologic mechanisms 1:

Acute or Episodic Ordinary Urticaria

• Individual wheals last 2-24 hours before resolving without scarring 2
• Most common form in pediatric populations 3
• Often triggered by viruses, allergic reactions to foods and drugs, contact with chemicals, or physical stimuli 3
• No routine investigations required except where history suggests specific triggers 1
• IgE-mediated reactions to environmental allergens (latex, nuts, fish) can be confirmed by skin-prick testing and CAP fluoroimmunoassay when clinically indicated 1

Chronic Ordinary (Spontaneous) Urticaria

• Wheals lasting 2-24 hours per lesion, occurring for more than 6 weeks 2, 4
• Idiopathic in 80-90% of cases 5
• Approximately one-third have circulating functional autoantibodies against high-affinity IgE receptors or against IgE itself 3

Management approach:

• No investigations needed for mild disease responding to H1 antihistamines 1
• For nonresponders with severe disease, screening should include: full blood count with differential, erythrocyte sedimentation rate, thyroid autoantibodies, and thyroid function tests 1, 2
• Autologous serum skin test (ASST) offers reasonable sensitivity and specificity for histamine-releasing autoantibodies in experienced centers 1, 2

Physical Urticarias

• May occur alone or coexist with ordinary urticaria 1
• Usually resolve within 1 hour, except delayed pressure urticaria 2
• Cholinergic urticaria is classified as thermal physical urticaria, triggered by stimuli that induce sweating (acetylcholine release) rather than overheating per se 6
• Delayed pressure urticaria develops in 2-6 hours and fades within 48 hours 2
• Contact urticaria typically lasts up to 2 hours 2

Urticarial Vasculitis

• Distinguished by wheals persisting for days, not just 24 hours 2
• Lesional skin biopsy is essential to confirm small-vessel vasculitis histologically (leucocytoclasia, endothelial damage, perivascular fibrin deposition, red cell extravasation) 1, 2
• Requires full vasculitis screen including serum complement (C3, C4) to distinguish normocomplementemic from hypocomplementemic disease, which carries worse prognosis 1

Angioedema Without Wheals

• Serum C4 is the initial screening test for hereditary and acquired C1 inhibitor deficiency 1
• Low C4 (< 30% mean normal) has very high sensitivity but low specificity 1
• If C4 is low, confirm with quantitative and functional C1 inhibitor assays 1, 2
• Type I hereditary angioedema: both immunochemical and functional C1 inhibitor are low 1
• Type II hereditary angioedema: only functional activity is low 1
• Acquired C1 inhibitor deficiency: C1q is also reduced 1

Autoinflammatory Syndromes

• Present with spontaneous wheals, pyrexia (fever), and malaise 7
• Include hereditary syndromes like Cryopyrin-associated periodic syndromes (CAPS) and Muckle-Wells syndrome 7
• Acquired syndromes like Schnitzler syndrome 7
• Recurrent unexplained fever alongside urticarial lesions should prompt consideration of autoinflammatory disease rather than chronic spontaneous urticaria 7

Management Algorithm

First-Line Treatment (All Types)

• Second-generation H1 antihistamines are the mainstay, which can be titrated to greater than standard doses 5, 4, 8
• Avoid nonspecific aggravating factors: overheating, stress, alcohol, aspirin, codeine 1
• NSAIDs should be avoided in aspirin-sensitive patients 1
• ACE inhibitors should be avoided in angioedema without wheals and used cautiously if angioedema is present 1
• Oestrogens should be avoided in hereditary angioedema 1
• Cooling antipruritic lotions (calamine or 1% menthol in aqueous cream) can be soothing 1

Second-Line Treatment for Chronic Urticaria

• First-generation H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists as adjunctive treatment 5
• Brief corticosteroid bursts for acute exacerbations 5
• Omalizumab (monoclonal anti-IgE antibody) for refractory chronic urticaria 8
• Cyclosporine or tacrolimus for cases resistant to all other treatments 3

Critical Pitfall

When urticaria is associated with anaphylaxis, intramuscular epinephrine must be used immediately, together with antihistamines and steroids (plus fluids and bronchodilators if required) 3. More than one-half of patients with chronic urticaria will have resolution or improvement within one year 5.