1. Signs and symptoms

2. Cause
    Medications  Food  Infection or environmental agent  Dermatographic urticaria  Pressure or delayed pressure  Cholinergic or stress  Cold-induced  Solar urticaria  Water-induced  Exercise 

3. Pathophysiology
     Allergic hives    Autoimmune hives    Infections    Nonallergic hives   Dietary histamine poisoning    Stress and chronic idiopathic hives  

4. Diagnosis
    Acute versus chronic  Related conditions  Angioedema  Vibratory angioedema 

5. Management
    Antihistamines  Systemic steroids  Leukotriene-receptor antagonists  Other 

6. Research

7. See also

8. References

9. External links

Hives frequently occur following an infection or as a result of an allergic reaction such as to medication, insect bites, or food.^[2] Psychological stress, cold temperature, or vibration may also be a trigger.^[1][2] In half of cases the cause remains unknown.^[2] Risk factors include having conditions such as hay fever or asthma.^[3] Diagnosis is typically based on the appearance. has demonstrated an association between stressful life events (e.g. bereavement, divorce, etc.) and chronic idiopathic urticaria^[26] and also an association between post-traumatic stress and chronic idiopathic hives.^[27]

Diagnosis

The cause of chronic hives can rarely be determined.^[28] In some cases regular extensive allergy testing over a long period of time is requested in hopes of getting new insight.^[29][30] No evidence shows regular allergy testing results in identification of a problem or relief for people with chronic hives.^[29][30] Regular allergy testing for people with chronic hives is not recommended.^[28]

Acute versus chronic

• {{Visible anchor|Acute}} urticaria is defined as the presence of evanescent wheals which completely resolve within six weeks.^[31] Acute urticaria becomes evident a few minutes after the person has been exposed to an allergen. The outbreak may last several weeks, but usually the hives are gone in six weeks. 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 (viral exanthem). Less common causes of hives include friction, pressure, temperature extremes, exercise, and sunlight.
• {{Visible anchor|Chronic}} urticaria (ordinary urticaria)^[32] is defined as the presence of evanescent wheals which persist for greater than six weeks.^[31] 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 sufferers and 20 years or more in 20% of them.^[33]

Acute and chronic hives are visually indistinguishable.

Related conditions

Angioedema

Angioedema is similar to hives,^[34] but in angioedema, the swelling occurs in a lower layer of the dermis than in hives,^[35] as well as in the subcutis. This 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, and is a concern in severe cases, as angioedema of the throat can be fatal.

Vibratory angioedema

This very rare form of angioedema develops in response to contact with vibration. In vibratory angioedema, symptoms develop within two to five minutes after contact with a vibrating object, and abate after about an hour. Patients with this disorder do not suffer from dermographism or pressure urticaria. Vibratory angioedema is diagnosed by holding a vibrating device such as a laboratory vortex machine against the forearm for four minutes. Speedy swelling of the whole forearm extending into the upper arm is also noted later. The principal treatment is avoidance of vibratory stimulants. Antihistamines have also been proven helpful.{{citation needed|date=August 2013}}

Management

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

Chronic hives can be difficult to treat and lead to significant disability. Unlike the acute form, 50–80% of people with chronic hives have no identifiable triggers. But 50% of people with chronic hives will experience remission within 1 year.^[36] Overall, treatment is geared towards symptomatic management. Individuals with chronic hives may need other medications in addition to antihistamines to control symptoms. Patients who experience hives with angioedema require emergency treatment as this is a life-threatening condition.

Treatment guidelines for the management of chronic hives have been published.^[37][38] According to the 2014 American practice parameters, treatment involves a step wise 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. If the individual doesn't respond to steps 1–3 then they are considered to have refractory symptoms. At this point, anti-inflammatory medications (dapsone, sulfasalazine), immunosuppressants (cyclosporin, sirolimus) or other medications like omalizumab can be used. These options are explained in more detail below.

Antihistamines

Non-sedating antihistamines that block the histamine H1 receptors are the first line of therapy. First generation antihistamines such as diphenhydramine or hydroxyzine block both central and peripheral H1 receptors and can be sedating. Second generation antihistamines such as loratadine, cetirizine, or desloratadine selectively antagonize the peripheral H1 receptors and are less sedating, less anticholinergic, and generally preferred over the first generation antihistamines.^[39][40]

People who don’t respond to the maximum dose of H1 antihistamines may benefit from increasing the dose, then to switching to another non-sedating antihistamine, then to adding a leukotriene antagonist, then to using an older antihistamine, then to using systemic steroids and finally to using ciclosporin or omalizumab.^[39]

H2-receptor antagonists are sometimes used in addition to H1-antagonists to treat urticaria, but there is limited evidence for their efficacy.^[41]

Systemic steroids

Oral glucocorticoids are effective in controlling symptoms of chronic hives however they have an extensive list of adverse effects such as adrenal suppression, weight gain, osteoporosis, hyperglycemia, etc. Therefore, their use should be limited to a couple of weeks. In addition, one study found that systemic glucocorticoids combined with antihistamines did not hasten the time to symptom control compared with antihistamines alone.^[42]

Leukotriene-receptor antagonists

Leukotrienes are released from mast cells along with histamine. The medications, montelukast and zafirlukast block leukotriene receptors and can be used as add on treatment or in isolation for patients with CU. It is important to note that these medications may be more beneficial for patients with NSAID induced CU.^[43][44]

Other

Other 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. It is helpful in therapy-refractory cases^[45] and is contraindicated in patients with G6PD deficiency. Sulfasalazine, a 5-ASA derivative, is thought to alter adenosine release and inhibit IgE mediated mast cell degranulation, Sulfasalazine is a good option for people with anemia who cannot take dapsone. Hydroxychloroquine is an antimalarial agent that suppresses T lymphocytes. It has a low cost however it takes longer than dapsone or sulfasalazine to work.

Omalizumab was approved by the FDA in 2014 for patients 12 years old and above with chronic hives. It is a monoclonal antibody directed against IgE. Significant improvement in pruritus and quality of life was observed in a phase III, multicenter, randomized control trial.^[46]

Immunosuppressants used for CU 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. They are preferred by some experts to treat severe symptoms.^[47] Sirolimus and mycophenolate have less evidence for their use in the treatment of chronic hives but reports have shown them to be efficacious.^[48][49] Immunosuppressants are generally reserved as the last line of therapy for severe cases due to their potential for serious adverse effects.

Research

See also

• Urticarial vasculitis

References

External links

• {{Commons category inline}}
• Urticaria photo library at Dermnet

• Johanna Mängel
• Johann Andre
• Johann Andreas Amon
• Johann Andreas Benignus Bergstraesser
• Johann Andreas Benignus Bergstrasser
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• Johann Anton Friedrich Fleischmann
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