Urticaria

What is it?

Urticaria (commonly known as hives) is a mast cell-driven skin condition that presents with wheals (raised, itchy, red or pink swellings that typically resolve within 24 hours), angioedema (deeper swelling of the skin and subcutaneous tissue), or both. It is one of the most common dermatological conditions, affecting approximately 1 in 5 individuals (20% lifetime prevalence) at some point in their lives. Urticaria is classified as acute when episodes last less than 6 weeks and chronic when symptoms persist beyond 6 weeks.

Who is affected?

Urticaria is a widespread condition that can affect anyone:

• Prevalence: Acute urticaria affects approximately 20% of the population at some point in life. Chronic urticaria has a point prevalence of 0.5-1%, affecting women more frequently than men (2:1 ratio)
• Age: Can occur at any age, with chronic spontaneous urticaria peaking between 20 and 40 years
• Risk factors: Atopic individuals, those with autoimmune conditions (thyroid disease in particular), and patients taking certain medications (NSAIDs, antibiotics) are at higher risk
• Impact: Chronic urticaria significantly affects quality of life, interfering with sleep, daily activities, and work performance

What causes it?

Urticaria results from mast cell activation and degranulation, releasing histamine and other mediators:

• Acute urticaria: Most commonly triggered by viral infections (especially in children), medications (NSAIDs, antibiotics), food allergies (shellfish, nuts, eggs), or insect stings. In many cases no cause is identified
• Chronic spontaneous urticaria: Autoimmune mechanisms are identified in approximately 30-50% of cases, involving IgG autoantibodies against the high-affinity IgE receptor (FcεRI) or against IgE itself. In the remaining cases the cause remains unknown
• Chronic inducible urticaria: Specific physical stimuli trigger mast cell degranulation (cold urticaria, delayed pressure urticaria, solar urticaria, dermographic urticaria, cholinergic urticaria, aquagenic urticaria)

What are the clinical features?

Urticaria presents with distinctive signs and symptoms:

Signs:

• Wheals (raised, well-defined swellings of variable size, pale centrally with a surrounding erythematous flare, each individual wheal resolving within 24 hours)
• Angioedema (deeper swelling, often affecting eyelids, lips, tongue, hands, feet, or genitalia, resolving within 72 hours)
• Dermographism (wheals appearing where the skin is scratched or stroked, in inducible urticaria)
• No residual skin changes (wheals resolve completely without bruising or pigmentation — if they leave marks, consider urticarial vasculitis)

Symptoms:

• Intense pruritus (itching is the predominant symptom, often described as burning rather than typical itch)
• Unpredictable flares (episodes may occur daily or intermittently, often with no clear trigger)
• Angioedema-related symptoms (pain, tightness, or pressure sensation rather than itching)
• Sleep disruption and psychological distress (anxiety, social withdrawal, reduced quality of life)

Classification:

• Acute urticaria (less than 6 weeks duration — most often triggered by infections, medications, or food allergies)
• Chronic spontaneous urticaria (more than 6 weeks, with no identifiable external trigger — may have autoimmune basis)
• Chronic inducible urticaria (triggered by specific physical stimuli: cold, pressure, sunlight, vibration, or skin stroking)

How is it diagnosed?

Diagnosis is primarily clinical:

• Clinical assessment: Based on the characteristic appearance of wheals and/or angioedema, their duration, and recurrence pattern
• Disease activity monitoring: The Urticaria Activity Score over 7 days (UAS7) quantifies disease severity (range 0-42, combining daily wheal and itch scores)
• Laboratory investigations (for chronic urticaria): Complete blood count, ESR/CRP, thyroid function and anti-TPO antibodies
• Provocation testing: For suspected inducible urticaria (ice cube test for cold urticaria, dermographic testing)
• Differential diagnosis: Urticarial vasculitis (wheals lasting >24 hours with bruising), drug eruptions, anaphylaxis, hereditary angioedema

What treatment options are available?

Treatment follows a stepwise approach based on the EAACI/GA²LEN/EuroGuiDerm 2022 international guideline:

• Step 1: Second-generation H1 antihistamines at standard dose (cetirizine, loratadine, bilastine, or fexofenadine — taken daily, not just when symptoms appear)

• Step 2: Updosing of second-generation antihistamines up to 4 times the standard dose (effective in approximately 60% of patients who fail standard dosing)

• Step 3: Add-on omalizumab (anti-IgE monoclonal antibody, 300mg subcutaneous injection every 4 weeks — highly effective with response rates exceeding 70%)

• Step 4: Add-on cyclosporine (for refractory cases, short-term use with monitoring for renal function and blood pressure)

• Acute flares: Short course of oral corticosteroids (up to 10 days, not for long-term use)

• Emerging treatments: Remibrutinib (BTK inhibitor, recently approved for chronic spontaneous urticaria) and dupilumab (anti-IL-4/IL-13, showing efficacy in recent phase 3 trials)

Key points for patients

• Urticaria is not an allergy in most chronic cases — extensive allergy testing is usually not helpful
• Antihistamines should be taken daily for chronic urticaria, not just during flares
• Most episodes of acute urticaria resolve within days to weeks without lasting consequences
• Chronic spontaneous urticaria, while distressing, resolves spontaneously in approximately 50% of patients within 1-5 years
• Seek emergency care immediately if urticaria is accompanied by difficulty breathing, throat swelling, dizziness, or rapid heartbeat (signs of anaphylaxis)
• Avoid known triggers (specific medications, physical stimuli) when identified
• First-generation antihistamines (diphenhydramine, chlorpheniramine) are not recommended due to sedation and short duration of action