Urticaria: Symptoms, Causes and Diagnosis

Generality

Urticaria is a rash characterized by the sudden appearance of raised, pale, pink or decidedly red and itchy wheals. These lesions, localized or diffuse, typically develop at the superficial (epidermal) level, but sometimes they can also be associated with oedematous reactions in the deeper layers of the skin and the subcutis (in this case one speaks more correctly about angioedema).

Most episodes last less than six weeks (acute urticaria), while an eruption that lasts for a longer time characterizes the chronic form. Acute urticaria is often caused by allergic reactions, however the triggering causes can be multiple; the chronic form, on the other hand, rarely depends on an allergic cause and often recognizes an autoimmune etiology.

20% of the general population has hives at least once in their life. Many cases of urticaria do not need specific treatment, as the eruption often resolves spontaneously within a few days. Alternatively, an antihistamine may help relieve symptoms, while more severe cases may require a short course of oral corticosteroids.

Symptoms

Urticaria occurs mainly with the appearance of an itchy rash, sometimes associated with a burning or stinging sensation. In particular, the urticaria is characterized by the so-called " pomfi ", skin lesions of variable dimensions (from a few millimeters to several centimeters in diameter), in relief and reddish (like those that appear following the bite of a mosquito). These lesions change rapidly over the course of 24 hours, within which they completely regress and eventually arise elsewhere; therefore, even if the wheal itself disappears within 24 hours it is possible that the hives last longer.

The skin rash can appear anywhere and be limited to one part of the body or spread over large areas. The skin returns to its normal appearance as soon as the wheals disappear.

Acute urticaria

Cases of urticaria are mostly temporary (acute urticaria) and resolve completely within six weeks. The rash arises quickly, becomes more severe after 8-12 hours and then resolves normally within a day (although it can sometimes persist for 48 hours). It is however possible that the hives last much longer, because the regurgitating wheals are constantly replaced by new ones that are formed in other areas of the body.

Acute urticaria is a common condition and occurs more frequently in children, in women aged 30-60 years and in allergic subjects. In fact, the rash may depend on an IgE-mediated allergic reaction, with activation of the mast cells and release of chemical mediators. In a susceptible subject, the wheals become evident a few minutes after exposure to a specific allergen, but in about half the cases the trigger is unknown.

The causes of allergic urticaria can be:

Food allergies : peanuts, shellfish, eggs, nuts, kiwi, cheese etc .;
Environmental factors : pollen, dust mites, chemicals or certain fragrances;
Drug-induced : some drugs can cause hives as a side effect, including antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, antihistamines, anticonvulsants and antidiabetic drugs;
Insect bites or bites (example: bees and wasps).

Most allergies are associated with the ingestion, injection or inhalation of allergens; however, urticaria may also result from direct contact of the skin or mucous membranes with a substance, as occurs with the latex reaction. Most allergies occur in mild form, but some people may develop severe anaphylactic shock within minutes of exposure.

Histamine and other vasoactive chemicals can be released into the skin for many other reasons. Non-allergic causes of acute urticaria include:

Viral, bacterial or parasitic infections, including sinusitis, fascioliasis , Helicobacter pylori (stomach ulcers), viral hepatitis (A, B and C), mononucleosis and candida;
Cholinergic pathway alteration (excessive sweating) and emotional reaction to stress;
External physical stimuli, such as friction or pressure on the skin, water, temperature change or sunlight.

Chronic urticaria

The clinical presentation of chronic urticaria is indistinguishable from the acute form. Furthermore, the pattern with which symptoms appear in the chronic form is unpredictable: about half of the people present symptoms that last for 6-12 weeks, followed by remission phases during which the signs improve or disappear. Certain triggers such as stress or alcohol consumption can make symptoms worse.

Often, chronic urticaria is the result of autoimmune reactions: the immune system releases abnormal antibodies that mistakenly attack the body's tissues with histamine release. The reason why autoimmune urticaria develops is not clear, although it can often arise in the context of other diseases of similar etiology, such as rheumatoid arthritis, systemic lupus erythematosus or cryopirin-associated periodic syndrome. In more rare cases, chronic urticaria can also be caused by other chronic diseases and infections, such as an inactive or overactive thyroid gland, celiac disease, hepatitis or intestinal parasites. Chronic urticaria often presents a fluctuating trend.

Many people find that some events do reappear or contribute to worsening the existing urticaria symptoms:

Stress;
Alcohol and caffeine;
Prolonged pressure on the skin (for example from tight clothing);
Drugs such as NSAIDs, codeine (painkiller) and ACE inhibitors (used to treat hypertension);
Some food additives and salicylates, which occur naturally in tomatoes, orange juice and tea;
Insect bites;
Exposure to heat, cold, pressure or water.

Causes

Urticaria occurs when a certain stimulus causes the immune system to react, with the release of histamine and other mediators (such as cytokines) that regulate and control inflammatory processes. This response induces dilation of local blood vessels, with a rapid swelling due to the transfer of fluids and proteins into the extracellular spaces. The swelling persists until the reappearance of interstitial fluids in the surrounding cells. The process may represent the result of an allergic or non-allergic reaction (they differ in the mechanism of histamine release).

Chemical inflammation mediators are released for a wide range of reasons, including:

Allergic reaction : following exposure to an allergen, histamine and other pro-inflammatory substances are released by mast cells, activated in the skin and tissues in response to the IgE-mediated reaction. This induces an increased vascular permeability, which leads to localized swelling. Histamine and other mediators are also released by basophils and other cells found in the inflammatory process and potentially responsible for reactions in some types of chronic urticaria;
Exposure to cold or heat ;
Infection : cutaneous eruptions commonly accompany some infectious diseases, where they represent a symptom or a complication;
Direct effect of some chemicals found in some types of foods and drugs: several mechanisms, in addition to allergen-antibody interaction, are known to induce mast cell degranulation. For example, some drugs can induce the direct release of histamine from immunoglobulins (as in the case of morphine, codeine and contrast agents for imaging techniques). Urticaria induced by some non-steroidal anti-inflammatory drugs usually involves the formation of leukotrienes. Non-allergic reactions to food can be caused by salicylates in fruits, preservatives (such as benzoate) or other food additives.

However, in many cases of hives, no obvious cause can be found (idiopathic form).

Note. The eruption that characterizes hives is essentially the same as the immediate wheal-erythematosus reaction that is obtained with the inoculation of allergens in skin tests for the determination of allergy, and which can also be caused by the inoculation of histamine alone.

Classification

In addition to the duration, the hives can be classified according to the alleged etiological agent. The most common forms are:

dermographism

Touching, stroking, scratching and rubbing the skin causes swelling and inflammation of the skin surface. Dermographic urticaria causes a lot of itching, but scratching causes the further appearance of wheals. Dermographism begins suddenly and represents a form of chronic urticaria, recognized as "physical urticaria": symptoms can be induced by periods of stress, tight or abrasive clothing, watches and glasses. Even a hot or extremely cold shower followed by rubbing with a towel can cause itchy wheals.

Cholinergic urticaria

It results from an excessive sweating, application of occlusive dressings, hot baths, fever and any similar event that involves a stimulation of the cholinergic endings. In severe cases, hundreds of small itchy red spots develop after physical activity, during a moment of anxiety or concentration.

Cold urticaria-angioedema

It is caused by the skin's reaction to an extreme reduction in the ambient temperature, especially during the winter. The wheals can be spread to large areas of the skin and cause systemic symptoms, such as wheezing and fainting. Affected individuals should not expose themselves to water, wind or cold objects.

Contact urticaria

It consists in the response to the contact of a certain substance with the skin or a mucous membrane. This reaction can cause wheals confined to the contact site or spread. Contact hives can be of allergic origin (white flour, cosmetics and textiles, latex, saliva, meat, fish and vegetables) or non-allergic. Non-allergic examples include the stinging reaction to some plants, animals (like some insects) and drugs.

Vasculitic urticaria

a less common form of urticaria, called urticarial vasculitis, is associated with inflammation of the blood vessels that supply the skin and is the result of immune complex deposits. The symptoms persist for more than 24 hours and are more painful.

The cases of aquagenic urticaria (in contact with water), solar (sunlight), pigmentosa (abnormal accumulation of mast cells in the dermis), and pressure (reaction to excessive pressure on the skin) are less common.

Complications

Angioedema

About a quarter of people with acute urticaria and half of those with chronic urticaria develop a condition known as angioedema. This manifestation can be severe and sudden, and affect different parts of the body, such as eyes, lips and genitals. Edema is caused by an accumulation of interstitial fluids that occurs much more deeply (ie subcutaneously or in the submucosal layers) than in the urticarial reaction.

Angioedema usually lasts 1-3 days and can cause the following symptoms:

Burning sensation, heat and pain in swollen areas;
Narrowing of the airways which can cause breathing difficulties;
Swelling of the conjunctiva (which covers the eye).

Some medications, such as antihistamines and corticosteroid tablets, can be used to relieve swelling. In the most severe cases corticosteroid injections may be necessary.

Systemic anaphylaxis

Urticaria may be one of the first symptoms of a severe allergic reaction known as anaphylaxis. This evolves with manifestations such as dyspnea, weakness and collapse, so it should always be treated as a medical emergency.

Diagnosis

Acute urticaria is diagnosed by an accurate medical history (which includes the gathering of information regarding ingested food, medications, etc.) and the examination of the signs and symptoms associated with the appearance of skin lesions. Tests can be performed on skin or blood to show if the wheals are caused by an allergic reaction, especially if their onset appears to be determined by some specific triggers.

In most mild cases of hives, there is no need to perform specific investigations. Furthermore, if the urticaria lasts for more than six weeks it is extremely unlikely that it is due to an allergy, so allergy tests are not normally recommended.

However, in patients who do not respond to treatment or experience severe recurrent symptoms, the following investigations may be useful to assess a suspected cause and to rule out other diseases:

Complete blood count: identifies quantitative changes in blood cells and possible eosinophilia caused by allergies or infections;
Erythrocyte sedimentation rate (ESR), PCR and other inflammatory parameters: they can help identify possible autoimmune conditions;
Examination of a stool sample: it can highlight the presence of intestinal parasites;
Thyroid function test and dosage of antithyroid antibodies;
Liver and kidney function test;
If the wheals are persistent, a skin biopsy can identify a possible vasculitis.