Urticaria (Hives) and Angioedema

Urticarial (Hives) lesions are usually red, raised, itchy skin lesions. These lesions can occur anywhere on the body. The most common causes of acute hives or angioedema includes to an allergic reaction to a food, an allergic reaction to insect stings, antibiotics or other medications such as aspirin or aspirin related products or angiotensin converting enzyme (ACE) inhibitors as are used in the treatment of high blood pressure, topical agents (soaps, lotions, perfumes), or an associated viral illness. Ten to twenty percent of the population will have hives at some point in their lives. Acute hives usually last for only a few days. Chronic hives are those which recur over a 6-week period or longer. Fifty percent of patients with chronic hives continue to have hives for six months or longer, of which twenty percent have recurrent symptoms for ten years or more. The cause of recurrent hives is usually not identified. Rarely one can identify an underlying systemic cause for chronic hives such as thyroid dysfunction, inflammation in skin blood vessels (vasculitis), collagen vascular disease such as lupus, or hepatitis. The individual hive lesions, in both acute and chronic cases, last less than 24 hours and do not produce ulcer type lesions. There is not an increased incidence of hives in patients who have eczema, asthma, or hay fever.

The same process that causes hives can also result in angioedema (swelling). Angioedema occurs in the deeper skin layers than hives. Angioedema often involves the face, tongue extremities, or genitalia. While angioedema results in swelling of an area, the skin itself usually appears normal. Angioedemal lesions are generally not itchy but can have a burning or painful sensation. The lesions generally do not occur in dependent areas, are asymmetrically distributed and last less than 24 hours.

Hives and angioedema are caused by the release of chemicals from both, inflammatory cells or inflammatory pathways. The major chemical involved in the development of both hives and angioedema is histamine. Histamine in the skin produces itching, dilation of blood vessels with an increase in their permeability (leakiness), which results in swelling and redness.

Some forms of angioedema may be hereditary. Inherited forms of angioedema usually start during the teenage years. Patients do not have associated hives. The skin lesions are not itchy. Angioedemal lesions may involve the larynx with respiratory difficulty, extremities, or gastrointestinal tract with resultant abdominal complaints. Acute episodes may be triggered by trauma, dental work, or surgery. Often no cause is found. Acquired forms of angioedema can also occur in adult patients. The acquired forms are not inherited and are often associated with lymphomas or other malignancies. Both the inherited and the acquired forms of angioedema are due to reduced levels and/or function of a protein called C1-esterase inhibitor.

Physical Urticaria and Angioedema

Some types of hives or angioedema are caused by physical factors such as changes in temperature, direct stimulation of the skin such as pressure, stroking, vibration or light. In most of these instances these lesions last only 1 to 2 hours.

Cold-induced hives are due to rapid temperature changes and not necessarily the absolute temperature. Usually the lesions are confined to portions of the body in contact with the cold. Swelling of the tongue is less common and swelling of the throat is rare. Patients with cold-induced hives should take great care when swimming since total body exposure occurs and can result in a large release of inflammatory chemicals which causes low blood pressure. Cold-induced hives may peak after exposed areas are warmed up. Lesions may occur while outside on cold windy days or while holding cold objects.

Heat-induced and cholinergic hives may occur in a local area or lesions may occur all over. In cholinergic hives the lesions are often small lesions about the size of a pimple with a lot of surrounding redness. Exercise, hot showers, sweating, and anxiety can all precipitate skin lesions. Cholinergic skin lesions generally do not occur on the palms of the hands, soles of the feet or axilla. Patients generally stop having cholinergic skin lesions after several years. Some patients may have lesions which persist for more than 20 to 30 years.

Exercise induced anaphylaxis is caused by exercise and is characterized by hives and may be associated with wheezing. Ingestion of food within 3 to 4 hours of exercise has been associated with an increased risk in susceptible patients. Reactions which are associated with food may be due to ingestion of and an allergic response to a specific food. Alternatively these reactions, as associated with ingestion of foods, may not be related to eating any specific food. Patients affected with this disorder should stop the exercise activity when symptoms start and should avoid exercise within 3 to 4 hours after eating.

Dermatographism affects 2 to 5% of the population. Hive-like skin lesions are generally produced within 5 to 15 minutes of stroking the skin. This is commonly seen in patients with chronic hives.

Some patients develop hive lesions 4 to 6 hours after pressure has been applied. Symptoms therefore are often seen on skin covered by tight clothing such as waistbands, bra straps, or socks, on the hands after hammering, on the feet after walking, or even on the buttocks after prolonged sitting. This type of skin lesion is not frequently seen in patients with chronic hives.

Other rare types of hive lesions can occur due to exposure to sunlight at specific wavelengths (solar-induced hives) or after contact with water of any temperature (aquagenic hives). Patients with solar-induced hives develop lesions within 1 to 3 minutes after exposure to sunlight of the right wavelength.

Other

Some patients with recurrent hives actually have an inflammation that occurs in the blood vessels that supply the skin with blood. This is called a vasculitis. Skin lesions in patients with a vasculitis generally last longer than 24 hours, are more pronounced on the lower extremities, and often leave a residual increase in skin pigment after they resolve. Patients with a vasculitis frequently have associated general symptoms such as joint pain, gastrointestinal symptoms, low grade fevers, or respiratory symptoms. Disease which can be associated with hives and vasculitis may include lupus, viral infections such as hepatitis, Lyme disease, or serum sickness. Skin biopsy may be helpful to demonstrate the inflammation in the blood vessels of the skin.

Other diseases that can have skin lesions that look like hives include erythema multiforme, bullous pemphigoid, dermatitis herpetiformis, or urticaria pigments.

Treatment

Avoidance of things that are known to precipitate hives is ideal. Limiting exposure to things that may aggravate hives such as stress, exercise, or alcohol may also be helpful. Tepid showers or baths may help reduce itching. In severe cases the use of subcutaneous epinephrine (adrenaline) can be quite helpful. Nonsedating antihistamines such as Claritin® (Loratadine), Clarinex® (Desloratadine), Allegra® (Fexofenadine), Zyrtec® (Cetirizine), or Xyzal® (Levocetirizine) are the treatment of choice. Antihistamines may reduce itching and reduce skin lesions, thereby allowing patients to function comfortably. Older antihistamines such as Hydroxyzine (Atarax®) or Cyproheptadine (Periactin®) may be required, if the newer nonsedating antihistamines are not effective. If antihistamines are not effective, the addition of other medications may prove useful in some patients. Other medications that may prove useful include H2 antihistamines such as Cimetidine (Tagamet®) or Ranitidine (Zantac®) or tricyclic antidepressants such as doxepin. Oral corticosteroids are often very effective in the treatment of hives and angioedema. However, recurrent symptoms can occur when corticosteroids are stopped. Rarely treatment with alternate daily corticosteroids with a taper over a 3-week period may be required. Patients with delayed pressure hives often do not respond to treatment with antihistamines, but may respond to treatment with nonsteroidal anti-inflammatory medications. For patients with hereditary angioedema treatment with anabolic steroids such as stanazolol or epsilon aminocaproic acid may be useful. For acute treatment use of replacement factor, if available, is useful. Treatment of the underlying malignancy may be helpful in patients with the acquired form of angioedema.