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Hives

See urticaria

Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps.

Hives may burn or sting.

The patches of rash may appear on different body parts.

Welts are raised areas surrounded by a red base, from hives can appear anywhere on the surface of the skin. 

Triggered  by a complex release of inflammatory mediators, including histamine from cutaneous mast cells, results in fluid leakage from superficial blood vessels. 

Welts may be pinpoint in size or several inches in diameter. 

Often patches of rash move around.

Hives last from minutes to days, and does not leave any long-lasting skin change.

Fewer than 5% of cases last for more than six weeks.

Hives frequently recur.

It can follow an infection, or result of an allergic reaction.

Risk factors: Hay fever, asthma.

Frequency about 20%.

Hives frequently occur following an infection or as a result of an allergic reaction such as to medication, insect bites, or food.

Psychological stress, cold temperature, or vibration may also be a trigger.

In half of cases the cause is unknown.

Risk factors include having conditions such as hay fever or asthma.

Diagnosis is typically based on the appearance. 

Patch testing may be useful to determine the allergy.

Prevention: avoiding whatever it is that causes the condition.

Treatment is typically with antihistamines such as diphenhydramine and cetirizine.

In severe cases, corticosteroids or leukotriene inhibitors may also be used.

Keeping the environmental temperature cool is also useful.

For cases that last more than six weeks immunosuppressants such as ciclosporin may be used.

About 20% of people are affected.

Hives of short duration occur equally in males and females while cases of long duration are more common in females.

Cases of short duration are more common among children while cases of long duration are more common among those who are middle aged.

Cases of short duration occur equally in males and females.

Cases of long duration are more common in females.

Cases of short duration are more common among children while cases of long duration are more common among those who are middle aged.

Angioedema is a related condition though fluid leakage is from much deeper blood vessels in the subcutaneous or submucosal layers. 

Individual hives that are painful, last more than 24 hours, or leave a bruise as they heal are more likely to be a more serious condition called urticarial vasculitis. 

Hives caused by stroking the skin, often linear, are due to a benign condition called dermatographic urticaria.

Many different substances in the environment may cause hives: including medications, food and physical agents. 

In perhaps more than 50% of people with chronic hives of unknown cause, it is due to an autoimmune reaction.

Risk factors include having conditions such as hay fever or asthma.

Drugs that have caused allergic reactions manifesting as hives include: codeine, morphine, dextroamphetamine, aspirin, ibuprofen, penicillin, clotrimazole, sulphonylurea glimepiride, sulfonamides, anticonvulsants, cefaclor, piracetam, vaccines, and antidiabetic drugs. 

The most common food allergies causing hives  in adults are shellfish and nuts. 

The most common food allergies in children are shellfish, nuts, eggs, wheat, and soy. 

Balsam of Peru, present in many processed foods, is one of the  most common cause of immediate contact urticaria.

Another food allergy that can cause hives is alpha-gal allergy, which may cause sensitivity to milk and red meat. 

The exposure to certain bacteria, such as Streptococcus species or possibly Helicobacter pylori may cause hives.

Hives including chronic spontaneous hives can be a complication and symptom of a parasitic infection, such as blastocystosis and strongyloidiasis among others.

Dermatographic urticaria is marked by the appearance of weals or welts on the skin as a result of scratching or firm stroking of the skin. 

Seen in 4–5% of the population, it is one of the most common types of urticaria.

The skin becomes raised and inflamed when stroked, scratched, rubbed, and sometimes even slapped.

The skin reaction usually becomes evident soon after the scratching and disappears within 30 minutes. 

The cause of Dermatographic urticaria is unknown.

It may be preceded by a viral infection, antibiotic therapy, or emotional upset. 

Dermatographism is diagnosed by applying pressure by strokin or scratching the skin.

The hives should develop within a few minutes. 

Unless the skin is highly sensitive and reacts continually, treatment is not needed. 

Taking antihistamines can reduce the response in cases that are annoying to the person.

Pressure or delayed pressure hives can occur right away, precisely after a pressure stimulus or as a deferred response to sustained pressure being enforced to the skin. 

Such hives are not the same as those with most urticariae, but the protrusion in the affected areas is typically more spread out. 

These hives may last from eight hours to three days. 

The source of the pressure: tight fitted clothing, belts, clothing with tough straps, walking, leaning against an object, standing, sitting on a hard surface. 

The areas of the body most commonly affected are the hands, feet, trunk, abdomen, buttocks, legs and face. 

Although this appears to be very similar to dermatographism, the differences from dermatographia is that the swelled skin areas do not become visible quickly and tend to last much longer.

Cholinergic urticaria (CU) refers to urticaria that occurs during sweating events such as exercise, bathing, staying in a heated environment, or emotional stress. 

Cholinergic urticaria hives that are produced are typically smaller than classic hives and are of a generally shorter duration.

The cold type of urticaria is caused by exposure of the skin to extreme cold, damp and windy conditions.

Cold urticaria it occurs in two forms: rare form is hereditary and becomes evident as hives all over the body 9 to 18 hours after cold exposure. 

The common form of cold urticaria demonstrates itself with the rapid onset of hives on the face, neck, or hands after exposure to cold. 

Cold urticaria lasts for an average of five to six years. 

The population most affected by cold urticaria is young adults, between 18 and 25 years old. 

Many patients with cold urticaria also have dermographism and cholinergic hives.

Severe reactions can be seen with exposure to cold water.

Swimming in cold water is the most common cause of a severe hive reaction, caused by a massive discharge of histamine, resulting in low blood pressure, fainting, shock and even loss of life. 

People with cold urticaria need to protect themselves from a rapid drop in body temperature. 

Regular antihistamines are not generally efficacious in cold urticaria.

One antihistamine, cyproheptadine is useful, as is the tricyclic antidepressant doxepin being effective blocking agents of histamine. 

Ketotifen keeps mast cells from discharging histamine, has also been employed with widespread success.

Solar urticaria occurs on areas of the skin, within moments of exposure to the sun.

Aquagenic urticaria is rare and occurs upon contact with water. 

Aquagenic urticaria is not temperature-dependent and the skin appears similar to the cholinergic form of the disease. 

Hives appear within one to 15 minutes of contact with the water and can last from 10 minutes to two hours. 

Aquagenic urticaria is not stimulated by histamine discharge like the other physical hives. 

Aquagenic urticaria is actually skin sensitivity to additives in the water, such as chlorine.

Aquagenic urticaria is treated with capsaicin (Zostrix).

Antihistamines are of questionable benefit in this instance.

People with exercise urticaria (EU) experience hives, itchiness, shortness of breath and low blood pressure five to 30 minutes after beginning exercise. 

Exercise urticaria can progress to shock and even sudden death. 

Jogging is the most common exercise to cause exercise urticaria.

In some cases of exercise urticaria, exercise within 30 minutes of eating particular foods, such as wheat or shellfish prompt the process: exercising alone or eating the injuring food without exercising produces no symptoms.

The immediate symptoms of this type are treated with antihistamines, epinephrine and airway support. 

Antihistamine use prior to exercise may be effective. 

Ketotifen is acknowledged to stabilise mast cells and prevent histamine release, and has been effective in treating this hives disorder. 

Avoiding exercise or foods that cause symptoms is important.

The skin lesions of urticarial disease are caused by an inflammatory reaction in the skin, causing leakage of capillaries in the dermis, and resulting in an edema which persists until the interstitial fluid is absorbed into the surrounding cells.

Hives are caused by the release of histamine and other mediators of inflammatory cytokines from cells in the skin. 

This process can be the result of an allergic or nonallergic reaction, differing in the eliciting mechanism of histamine release.

Allergy hive: Histamine and other proinflammatory substances are released from mast cells in the skin and tissues in response to the binding of allergen-bound IgE antibodies to high-affinity cell surface receptors. 

Basophils and other inflammatory cells are also seen to release histamine and other mediators, and are thought to play an important role, especially in chronic urticarial diseases.

Over half of all cases of chronic idiopathic hives are the result of an autoimmune trigger. 

Approximately 50% of patients with chronic urticaria develop autoantibodies directed at the receptor FcεRI located on skin mast cells. 

This chronic stimulation of this receptor leads to chronic hives. 

People with hives often have other autoimmune conditions, such as autoimmune thyroiditis, celiac disease, type 1 diabetes, rheumatoid arthritis, Sjögren’s syndrome or systemic lupus erythematosus.

Hive-like rashes commonly accompany viral illnesses, such as the common cold, appearing three to five days after the cold has started, and may even appear a few days after the cold has resolved.

Processes other than allergen-antibody interactions are known to cause histamine release from mast cells. 

Many drugs can induce direct histamine release not involving any immunoglobulin molecule (morphine).

Neuropeptides are involved in emotionally induced hives. 

Porphyrias (porphyria cutanea tarda, hereditary coproporphyria, variegate porphyria and erythropoietic protoporphyria) are associated with solar urticaria. 

With scombroid food poisoning. Ingestion of free histamine released by bacterial decay in fish flesh may result in a rapid-onset, allergic-type symptom complex which includes hives. 

The hives produced by scombroid is reported not to include wheals.

Evidence demonstrates an association between this condition and stress, poor emotional well-being and reduced health-related quality of life.

Studies have demonstrated an association between stressful life events and chronic idiopathic urticaria and also an association between post-traumatic stress and chronic idiopathic hives.

Diagnosis is typically based on the appearance, and the cause of chronic hives can rarely be determined.

Patch testing may be useful to determine the allergy.

No evidence shows regular allergy testing results in identification of a problem or relief for people with chronic hives, and testing for people with chronic hives is not recommended.

Acute urticaria is defined as the presence of evanescent wheals which completely resolve within six weeks.

Acute urticaria becomes evident a few minutes after the person has been exposed to an allergen. 

Typically, the hives are a reaction to food, but in about half the cases, the trigger is unknown. 

Common foods may be the cause, as well as bee or wasp stings, or skin contact with certain fragrances. 

Acute viral infection is another common cause of acute urticaria, known as a viral exanthem.

Less common causes of hives include friction, pressure, temperature extremes, exercise, and sunlight.

Chronic urticaria is defined as the presence of evanescent wheals which persist for greater than six weeks.

Some of the more severe chronic cases have lasted more than 20 years. 

A survey indicated chronic urticaria lasted a year or more in more than 50% of those affected and 20 years or more in 20% of them.

Acute and chronic hives are visually indistinguishable.

Angioedema similar to hives, but its swelling occurs in a lower layer of the dermis than in hives, as well as in the subcutis. 

Angioedema swelling can occur around the mouth, eyes, in the throat, in the abdomen, or in other locations. 

Hives and angioedema sometimes occur together in response to an allergen.

In severe cases angioedema of the throat can be fatal.

Anngioedema rarely develops in response to contact with vibration (vibratory angioedema).

Vibratory angioedema symptoms develop within two to five minutes after contact with a vibrating object and abate after about an hour. 

The mainstay of therapy for both acute and chronic hives is, avoiding triggers and using antihistamines.

Unlike the acute hives, 50–80% of people with chronic hives have no identifiable triggers. 

But 50% of people with chronic hives will experience remission within 1 year.

Treatment for hive  is symptomatic management. 

Individuals with chronic hives may need other medications in addition to antihistamines to control symptoms. 

People who experience hives with angioedema require emergency treatment as this is a life-threatening condition.

Treatment guidelines for the management of chronic hives involves a stepwise approach.

Step 1 consists of second generation, H1 receptor blocking antihistamines. 

Systemic glucocorticoids can also be used for episodes of severe disease but should not be used for long term due to their long list of side effects. 

Step 2 consists of increasing the dose of the current antihistamine, adding other antihistamines, or adding a leukotriene receptor antagonist such as montelukast. 

Step 3 consists of adding or replacing the current treatment with hydroxyzine or doxepin. 

With refractory symptoms anti-inflammatory medications (dapsone, sulfasalazine), immunosuppressants (cyclosporine, sirolimus) or other medications like omalizumab can be used. 

Non-sedating antihistamines that block histamine H1 receptors are the first line of therapy. 

First-generation antihistamines, such as diphenhydramine or hydroxyzine, block both brain and peripheral H1 receptors, and cause sedation. 

Second-generation antihistamines, such as loratadine, cetirizine or desloratadine, selectively antagonize peripheral H1 receptors, and are less sedating, less anticholinergic, and generally preferred over the first-generation antihistamines.

Fexofenadine, a new-generation antihistamine that blocks histamine H1 receptors, may be less sedating than some second-generation antihistamines.

People who do not respond to the maximum dose of H1 antihistamines may benefit from increasing the dose/switching to another non-sedating antihistamine, adding a leukotriene antagonist, using systemic steroids and finally to using cyclosporin or omalizumab.

H2-receptor antagonists are sometimes used in addition to H1-antagonists to treat urticaria, but there is limited evidence for their efficacy.

Oral glucocorticoids are effective in controlling symptoms of chronic hives, but their use should be limited to a couple of weeks. 

Leukotrienes are released from mast cells along with histamine.

Montelukast and zafirlukast block leukotriene receptors and can be used as add on treatment or in isolation for people with  chronic urticaria.

Additional options for refractory symptoms of chronic hives include anti-inflammatory medications, omalizumab, and immunosuppressants. 

Potential anti-inflammatory agents include dapsone, sulfasalazine, and hydroxychloroquine. 

Dapsone is a sulfone antimicrobial agent and is thought to suppress prostaglandin and leukotriene activity, and is helpful in therapy-refractory cases.

Sulfasalazine, a 5-ASA derivative, is thought to alter adenosine release and inhibit IgE mediated mast cell degranulation.

Hydroxychloroquine is an antimalarial agent that suppresses T lymphocytes.

Hydroxychloroquine is an antimalarial agent that suppresses T lymphocytes. was approved for people with hives 12 years old and above with chronic hives. 

It is a monoclonal antibody directed against IgE, demonstrating significant improvement in pruritus and quality of life was observed in randomized control trial.

Immunosuppressants used for chronic urticaria include cyclosporine, tacrolimus, sirolimus, and mycophenolate. 

Calcineurin inhibitors, such as cyclosporine and tacrolimus, inhibit cell responsiveness to mast cell products and inhibit T cell activity. 

Immunosuppressants are generally reserved as the last line of therapy for severe cases due to their potential for serious adverse effects.

Opioid antagonists such as naltrexone have evidence to support their use.

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