Definition:

Urticaria is a common terminology used to describe recurring wheals on the skin, with angioedema typically seen as a physical manifestation. However, it is increasingly recognized that “urticaria” is more accurately defined as a disease, which can be either acute or chronic. Consequently, urticaria may present with wheals, angioedema, or a combination of both.

Wheals are itchy, erythematous or pale swellings that occur in the superficial layer of the dermis, initially surrounded by a red flare. These lesions can range in size from a few millimeters to several centimeters, with numbers varying from a few to many. A defining feature of wheals is that each lesion appears and disappears quickly, typically within 24 hours.

In contrast, angioedema involves deeper layers of the dermis, as well as subcutaneous or submucosal tissues. Affected areas are usually normal or light pink in color, tend to be painful rather than itchy, and are generally larger and less distinct than wheals, often persisting for 2 to 3 days.

Classification of Urticaria:

Urticaria is categorized based on its duration:

Acute urticaria, lasting less than 6 weeks and frequently resolving within hours to days.
Chronic urticaria, persisting for over 6 weeks, with wheals occurring daily or intermittently.

Chronic urticaria can be either spontaneous or triggered by specific factors, and both forms may occur simultaneously.

Chronic inducible urticaria includes:

Dermographism
Cold urticaria
Cholinergic urticaria
Contact urticaria
Delayed pressure urticaria
Solar urticaria
Heat urticaria
Vibratory urticaria
Vibratory angioedema
Aquagenic urticaria

Etiology:

Many cases of urticaria are idiopathic, with various potential causes, including allergies, autoimmune responses, infections, and medications. In children, viral infections or idiopathic factors are the most common triggers, although other causes include:

Infectious: Evaluate for symptoms of urinary tract, respiratory, or gastrointestinal infections.
Allergic: Foods, medications, and environmental allergens.
Physical stimuli: Pressure, sunlight, exercise-induced (cholinergic), and cold exposure.
Arthropod bites: Can cause reactions known as “papular urticaria.”
Malignancy: Often associated with lymphoma.

The primary cell involved in urticaria is the mast cell, with basophils and eosinophils also contributing. These cells release proinflammatory mediators:

Preformed mediators: Include histamine, proteases, and heparin.
Newly synthesized mediators: Such as prostaglandin D2, leukotrienes C4, D4, E4, platelet-activating factor, and various cytokines (e.g., TNF-a, IL-1, IL-4, IL-5, IL-6, and IL-8).

Clinical features:

Urticaria is categorized based on its duration:

Acute urticaria, lasting less than 6 weeks and frequently resolving within hours to days.
Chronic urticaria, persisting for over 6 weeks, with wheals occurring daily or intermittently.

Chronic urticaria can be either spontaneous or triggered by specific factors, and both forms may occur simultaneously.

Urticarial wheals vary in size, from a few millimeters to several centimeters in diameter, and can appear white or red, with or without an erythematous flare. Each wheal may last from a few minutes to several hours, often changing shape. Wheals may be round or take on ring shapes, map-like patterns, or even form large patches.

Urticaria can affect any area of the body, typically presenting in widespread distribution, whereas angioedema tends to be more localized. Angioedema frequently involves the face (particularly the eyelids and areas around the mouth), hands, feet, and genital regions, and may extend to the tongue, uvula, soft palate, or larynx.

Serum sickness, which can occur following a blood transfusion, and serum sickness-like reactions triggered by certain medications, can lead to acute urticaria with accompanying bruising, fever, swollen lymph nodes, joint pain, and swelling.

In chronic inducible urticaria, wheals generally appear about five minutes after exposure to a trigger and may last from a few minutes to an hour. These wheals are characterized as follows:

Linear wheals in dermographism
Small wheals in cholinergic urticaria
Restricted to contact areas in contact urticaria
Diffuse in cold urticaria; in cases where large areas are involved, fainting may occur, posing a risk during cold-water swimming.

In chronic spontaneous urticaria, wheals tend to persist longer, although each individual lesion typically resolves within 24 hours and may recur at specific times of the day

Diagnosis:

Urticaria is diagnosed in individuals with a history of wheals lasting less than 24 hours, with or without angioedema. Assessment includes reviewing medication and family history, as well as performing a comprehensive physical examination.

For acute urticaria, if allergies to drugs, latex, or food are suspected, skin prick testing and specific allergen blood tests like RAST or CAP fluoroimmunoassay may be conducted. In chronic spontaneous urticaria, routine diagnostic tests are usually limited to blood counts and C-reactive protein (CBC, CRP); however, further tests may be performed if an underlying condition is suspected. Sometimes, the autologous serum skin test is used, showing a positive result if the patient’s serum injection under the skin produces a red wheal, although its effectiveness is debated.

Inducible urticaria is often confirmed by directly inducing the response, such as scratching for dermographism or applying an ice cube in suspected cases of cold urticaria. Additional tests are recommended for patients presenting with fever, joint or bone pain, or malaise to rule out systemic or autoinflammatory conditions. Patients with angioedema without wheals should be checked for ACE inhibitor usage and tested for complement C4, C1-INH levels, function, antibodies, and C1q.

Histopathological examination through biopsy may be non-specific, generally showing dermal edema, dilated blood vessels, and mixed inflammatory infiltrates. If vessel wall damage is present, urticarial vasculitis may be indicated.

Management:

The primary treatment for all types of urticaria in adults and children is an oral second-generation H1-antihistamine, like cetirizine or loratadine. If the standard dose (e.g., 10 mg of cetirizine) is ineffective, it may be increased up to four times (e.g., 40 mg daily). Antihistamines are discontinued once acute urticaria subsides, and adding a second antihistamine generally offers no additional benefit.

Systemic treatments are generally avoided during pregnancy and breastfeeding, second-generation antihistamines, particularly loratadine and cetirizine, are preferred if necessary, as they have shown no link to birth defects.

Avoidance of triggers

Avoiding known triggers can help manage urticaria. For example, avoiding allergens identified through testing can clear urticaria within 48 hours. Additionally, chronic infections, such as H. pylori, should be treated, and medications like aspirin, opiates, and NSAIDs should be avoided when possible, with paracetamol being a safer option. A temporary trial of a low pseudoallergen diet for at least three weeks may also be beneficial.

Physical triggers for inducible urticaria should be minimized, though symptoms may persist:

Symptomatic dermographism: Avoid friction and tight clothing.
Cold urticaria: Dress warmly and avoid cold-water swimming.
Delayed pressure urticaria: Broaden contact areas, such as with heavy bags.
Solar urticaria: Use protective clothing and broad-spectrum sunscreen.

Some individuals may benefit from daily, controlled exposure to triggers to build tolerance, and phototherapy can reduce itching in symptomatic dermographism.

Written by:

Mashael Alanazi, Medical Intern

Revised by:

Naif Alshehri, Medical Intern

Resources:

Bologina textbook

Review of dermatology textbook

DermNet