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What are Hives (Urticaria)?
Hives, also known as urticaria are a common disorder affecting about 20 percent of the general population. Hives are red or white raised or swollen patches on the skin and usually accompanied by uncomfortable itching. Hives are caused by release of histamine from mast cells and can be worsened by scratching, alcoholic beverages and daily exercise. Depending on the duration of symptoms they can be classified as acute or chronic hives or acute or chronic urticaria.
Acute Hives: In general it lasts up to 6 weeks or less and may resolve after treating the underlying cause. Acute hives are likely caused by close contact with allergens such as food, medications, pollen and insect bites. Common infection such as strep throat or urinary tract infections have also been identified as common causes of acute hives.
Chronic Hives: People suffering from long-term hives may have symptoms that last longer than six weeks and in some cases even more than a year. Although it could be caused by the immune system, hormonal problems or thyroid disease, the true underlying cause of most chronic hives may not be clearly identified.
Here is a review of medications used for treating hives.
H1 Antihistamines Used in Treatment of Hives
Oral antihistamines block histamine release resulting in relieve of symptoms of urticaria. They consist of two different categories, 1st generation (older) antihistamines such as;
• Benadryl (diphenhydramine)
• Vistaril (hydroxyzine)
• Chlophen (chlorpheniramine)
And 2nd generation (newer) antihistamines such as;
• Claritin (loratadine)
• Allegra (fexofenadine)
• Zyrtec (cetirizine)
Second generation antihistamines are considered the first-line treatment of hives and work by blocking histamine (H1) receptor on cells. Histamine is a chemical released from cells called mast cells and attaches to the histamine receptors on other cells resulting in initiation of signs and symptoms of hives such as itching or redness. Compared to 1st generation antihistamines, 2nd generation antihistamines will have fewer drug-drug interactions, can be dosed less frequently, and will cause less drowsiness. Some of the possible side effects of 2nd generation antihistamines include;
• Drowsiness (Allegra causes the least drowsiness amongst 2nd generation antihistamines)
• Dry mouth
Patients diagnosed with hives, especially chronic hives, should begin a two-week treatment of a non-sedating H1 antihistamine. If the symptoms still persist, the dose of the antihistamine may be increased above standard doses. The efficacy of using a 2nd generation antihistamine has been studied in number of clinical trials and there has been an overall improvement in symptoms of urticaria such as redness, itching, and swelling in 50 to 95% of patients.
Claritin (loratadine) 5 mg and 10 mg Tablets
Claritin is used for treatment of symptoms of chronic urticaria and upper respiratory allergies (seasonal allergies) in patients older than 6 years of age. It is a long acting selective 2nd generation H1 antihistamine and considered less potent when compared to other agents such as Allegra or Zyrtec. Claritin 5 mg dose is given to children between the ages of 2 to 5 and for patients with renal or hepatic impairment where the standard dose is given every other day.
Allegra (fexofenadine) 30, 60 and 180 mg Tablets or 30 mg/5 ml Suspension
Allegra is indicated for chronic urticaria and seasonal allergies in patients older than 12 years of age. It is best taken without food and especially drinks such as orange, apple, or grapefruit juice. The standard dosing for urticaria is 60 mg twice daily or 180 mg once a day. The recommended dosing adjustment in renal impairment is 60 mg once a day.
Zyrtec (cetirizine) 5 mg and 10 mg Tablets
Zyrtec is indicated in treatment of symptoms due to chronic urticaria and upper respiratory allergies in patients over the age of 6. Compared to other 2nd generation antihistamines, Zyrtec has a rapid onset of action. Although the standard dose is 10 mg a 5 mg dose is also used depending on the severity of the symptoms. Lower doses of Zyrtec (2.5-5 mg) may be given to children between the ages of 2 to 5.
Leukotriene Receptor Antagonist (antileukotrine) for Hives
If symptoms of hives persist after 4 weeks of using non-sedating antihistamine, using an antileukotrine such as Singulair is suggested as 2nd line treatment. An antileukotrine acts by blocking leukotrienes, chemicals that cause inflammation and symptoms of hives, especially drug induced hives. Although antileukotrines are not as effective as antihistamines for treatment of hives, they are an alternative treatment or add on medication in patients who do not respond to antihistamines alone.
Singulair 10 mg once daily is suggested as an addition to the treatment with antihistamines for up to 4 weeks. In a 4-week long clinical trial newly diagnosed patients with urticaria received antileukotrine plus non-sedating H1 antihistamine treatment (Group A) or a sedating plus non-sedating antihistamine treatment (Group B). At the end of 4 weeks, there was 63.3% response to treatment in Group A compared to 23.3% response to treatment in Group B based on severity of itching and redness. Some of the side effects of Singulair include, headache, dizziness, and tiredness.
Calcineurin Inhibitor for Chronic Hives
Calcineurin inhibitor such as Gengraf are another alternative or 2nd line treatment used when symptoms of urticaria persist after 4 weeks of using non-sedating antihistamines. Calcineurin inhibitor acts by directly affecting the mast cells and inhibiting the release of histamine, a chemical that causes the symptoms of urticaria. High incidence of side effects and high cost are two main reasons why Gengraf is considered as an alternative agent used only in patients that do not respond to any dose of antihistamine.
Gengraf (cyclosporine A)
Cyclosporine A is an immunosuppressant most often used for preventing organ rejection after transplantation. A dose of 3 to 5 mg/kg may be added to a regimen of non-sedating antihistamine treatment of chronic urticaria. The efficacy of cyclosporine in addition to a non-sedating H1 antihistamine has been studied in a clinical trial comparing 8 weeks and 16 weeks of cyclosporine A therapy. A 62% improvement in severity of urticaria was observed in both durations compared to 23% improvement on placebo. The most common side effects of cyclosporine include, high blood pressure, nausea, diarrhea, urinary tract infection, and kidney problems.
Anti-IgE Antibodies Used in Treatment of Chronic Urticaria
On March 2014, the FDA approved Xolair an anti-IgE antibody for 2nd line treatment of urticaria. Anti-IgE antibody acts by binding to antibodies called IgE and causes a decrease in free IgE antibodies. IgE is responsible for the release of histamine in chronic urticaria resulting in outbreak of symptoms such as itch, redness and swollen patches. Although Xolair is the first biologic agent approved in chronic urticaria its high cost and lower efficacy makes it an alternative treatment for patients who do not respond to antihistamines.
Xolair 150 or 300 mg injection may be given subcutaneously every 4 weeks as an addition to antihistamine treatment if the patient is not responding to antihistamines alone for treatment of chronic urticaria. In a 12-week long trial, the efficacy of different dosages of Xolair in the treatment of chronic urticaria was studied in comparison to a placebo. At the end of week 12, it was reported that 36% of the patients treated with Xolair 300 mg, 15% of the patients treated with Xolair 150 mg, 12% of the patients treated with Xolair 75 mg, and 9% of the patients treated with a placebo had no symptoms of urticaria such as itch or hives. The most common side effects of Xolair include, nausea, headache, sinus infection (sinusitis), sore throat (pharyngitis), upper respiratory tract infection, and cough.
Corticosteroids for Acute Hives
If 4 weeks of antihistamine treatment alone does not relieve symptoms of urticaria, especially acute urticaria, a short-term corticosteroid treatment such as prednisolone may be added. A Corticosteroid such as Orapred acts as an anti-inflammatory agent in treatment of symptoms of urticaria. Although the addition of corticosteroids may benefit patients by decreasing the course of symptoms, if used long-term, they may weaken the immune system and increase risk of infections.
Prednisolone 20 mg twice a day by mouth may be used for 3 to 7 days in addition to non-sedating antihistamine treatment. In a clinical trial comparing the effectiveness of prednisolone and loratadine in the treatment of acute urticaria, significant improvement in redness was seen after 3 days in 93.8% of the patients on prednisolone compared to 65.9% of the patients on loratadine. Some of the side effects of Orapred may include, increased blood pressure, low potassium, high sodium (salt) levels, headache, and muscle weakness.
For treatment of hives (urticaria), non-sedating antihistamines are recommended as first line treatment. Over the counter antihistamines are low in cost and are also safer and more effective compared to other medications for hives. Second generation antihistamines cause minimal sedation and drug-drug interactions. Antihistamines may be combined with other agents. Xolair, cyclosporine, montelukast are used when antihistamines fail.
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