Urticaria

Urticaria occurs when skin cells called mast cells become activated and release substances such as histamine and other inflammatory mediators. This leads to itching with redness and the appearance of hives, or angioedema when the inflammation affects deeper layers of the skin. In addition to mast cells, other immune system cells (lymphocytes, eosinophils, neutrophils, basophils, and macrophages) are involved, contributing to inflammation and itching.

This activation can be triggered by multiple factors, and in many cases, no clear cause is identified.

Symptoms

What do the lesions look like and how do they differ?

• Hives: well-defined superficial swelling, variable in size and shape, pink or reddish in color, which can appear anywhere on the skin. They usually cause itching and, in some cases, a burning or stinging sensation. These lesions are transient: they appear and disappear within minutes or hours without leaving any marks on the skin.
• Angioedema: sudden-onset deep swelling, pink or skin-colored, affecting the deep dermis, subcutaneous tissue, or mucous membranes. It is usually accompanied by tingling, stinging, a feeling of tightness, or pain, with itching being less common. Its course is slower than that of hives and it may take up to 72 hours to resolve.

Causes

This activation can be triggered by multiple factors such as infections (often respiratory), medications (especially anti-inflammatory drugs), physical stimuli (cold, heat, pressure), foods, or stress. However, in many cases, no clear cause is identified.

In other cases, persistent infections, thyroid diseases, or other inflammatory processes may play a role, although this is less common. There are also factors that are not a direct cause but can worsen symptoms, such as certain medications, stress, or specific foods.

Classification

Acute: duration of less than 6 weeks.

Up to 20% of the population may experience at least one episode of urticaria during their lifetime. In some cases, these episodes may be due to a true allergy (to foods, medications, insect stings, etc.). However, most cases of acute urticaria are not due to an allergy, but rather to a combination of multiple factors.

Chronic: duration of more than 6 weeks with daily (or almost daily) symptoms, or intermittent/recurrent symptoms.

Chronic urticaria is classified into:

• Chronic spontaneous urticaria

It is the most common type of chronic urticaria and is characterized by symptoms that appear without an identifiable trigger.

In more than 50% of patients, the underlying mechanism is autoimmune; that is, the immune system itself activates mast cells through antibodies (IgE or IgG) directed against the body’s own structures. In some cases, persistent infections, thyroid diseases, or other inflammatory processes may play a role, although this is less common. There are also factors that are not a direct cause but may worsen symptoms, such as certain medications (especially non-steroidal anti-inflammatory drugs), stress, and hormonal changes.

In 30–50% of cases, it is a self-limiting condition, meaning it may resolve spontaneously within approximately 12 months.

• Chronic inducible urticaria

Wheals appear at the site where an external stimulus has been applied.

Depending on the external trigger, several types can be distinguished:

• Dermographism (factitious urticaria): appearance of hives due to friction or scratching.
• Cholinergic urticaria: micropapular lesions triggered by an increase in body temperature (exercise, sweating, hot baths).
• Cold or heat urticaria: lesions in areas exposed to cold or heat.
• Solar urticaria: lesions in areas exposed to sunlight.
• Aquagenic urticaria: after contact with water (very rare).
• Delayed pressure urticaria: lesions appearing hours after sustained pressure.
• Vibratory angioedema: swelling induced by vibratory stimuli.
• Contact urticaria: due to direct contact with substances (e.g., nettles).

Diagnosis

The diagnosis is mainly clinical, based on the patient’s history and physical examination. A detailed interview is essential to identify possible triggers, understand the course of symptoms, and assess the impact on quality of life.

As lesions are transient, reviewing photographs provided by the patient is very helpful.

• In isolated cases of urticaria or angioedema, allergy testing is only recommended if there is a clear clinical suspicion.
• In inducible urticaria, provocation tests may be performed to reproduce the stimulus.
• In some cases, this is complemented with laboratory tests (complete blood count, CRP, ESR, total IgE, anti-thyroid antibodies, etc.) to detect autoimmune or infectious causes.
• If the clinical picture is atypical, such as lesions leaving marks after resolution, skin biopsy or specific tests such as the autologous serum skin test may be performed in cases of chronic autoreactive urticaria.

Treatment

The aim of treatment is to achieve disease control, taking into account patient safety and quality of life.

First-line treatment consists of second-generation H1 antihistamines (non-sedating), which may be increased up to fourfold doses if necessary, always under medical supervision.

In addition, in patients where triggers are identified, avoidance is important (non-steroidal anti-inflammatory drugs, cold, pressure, or other physical stimuli, etc.).

Disease control and treatment response are assessed using tools such as:

• Urticaria Control Test (UCT) or Angioedema Control Test (AECT)
• Urticaria Activity Score (UAS, UAS7) or Angioedema Activity Score (AAS)
• Quality of life questionnaires (CU-QoL, AE-QoL)

In case of inadequate response to antihistamines, other treatments should be considered by the physician (omalizumab, ciclosporin A, dupilumab, BTK inhibitors, or other immunomodulators).

The use of systemic corticosteroids is only recommended for short periods during acute exacerbations of chronic spontaneous urticaria. It is not possible to predict how long the patient will require ongoing medication. The goal is to control symptoms with a safe treatment for as long as needed, which may be between one and five years and, exceptionally, longer. Some patients experience recurrent episodes of chronic urticaria throughout their lifetime.