Urticaria (hives)

Clifton O Bingham, III, MD

UpToDate performs a continuous review of over 375 journals and other resources. Updates are added as important new information is published. The literature review for version 15.2 is current through April 2007; this topic was last changed on April 13, 2007. The next version of UpToDate (15.3) will be released in October 2007.
INTRODUCTION — Urticaria is the medical term for hives. Hives are distinct, raised areas of the skin that itch intensely and are red with a pale center (show picture 1). Hives are a very common condition: about 25 percent of all people experience an eruption of hives at some time during their life.
Hives result from a reaction that activates immune cells in the skin, called mast cells. When activated, these cells release natural chemicals. One important chemical is histamine, which causes itching, redness, and swelling of the skin in a localized area - a hive. In most cases, hives appear suddenly and disappear within several hours. Some people are more susceptible to hives than others.
Hives usually respond well to treatment that includes the avoidance of known triggers and drugs that counter symptoms. However, medications for hives do not cure the problem or prevent future hives. Rather, the medication controls the severity of the symptoms.
CLASSIFICATION OF HIVES — Hives are usually classified based upon how long the problem persists. According to this classification, hives can be acute (brief) or chronic (long-standing). Although these two types of hives have an identical appearance, they may have different causes. When a person first develops hives, it is not possible to predict how long the problem will last or determine whether the hives are acute or chronic.
There is also a group of hive conditions that are called "physical urticarias" because they are triggered by certain types of physical stimulation. Physical triggers may affect a person only a few times, or cause hives on a chronic basis. However, once a person recognizes the triggers that cause their hives and is better able to avoid these conditions, the problem is much more easily managed.
Acute urticaria — Acute hives appear suddenly and resolve within a few hours. This may happen daily or on a few days each week, but the problem spontaneously resolves within 6 weeks. More than two-thirds of all cases of hives are acute. Some of these cases may be the result of an allergic reaction or from other causes, listed below.
Chronic urticaria — Chronic hives occur daily or almost daily for a period longer than 6 weeks, and sometimes persist for years. Individual outbreaks usually last for 2 to 24 hours. About one-third of all cases of hives are chronic. Chronic hives are rarely caused by allergies.
Physical urticarias — Hives can be triggered by a variety of physical factors: Exposure to cold (the hives often appear as the cold-exposed skin rewarms) Changes in body temperature/sweating (these hives are often tiny and numerous and appear on a background of reddened skin (show picture 4).) Vibration (palms may become red, swollen, and itchy after holding onto the steering wheel of a car while driving) Pressure (hives on the palms or the soles of the feet that occur hours after carrying heavy objects or walking long distances and that cause a burning sensation. Because the skin on the palms and soles is thick, these areas may appear reddened and swollen without clear hives) Exercise (hives that appear during exercise can be a sign of dangerous condition called exercise-induced anaphylaxis) Sunlight (this is rare) Water (this is rare)
Finally, there is a common condition called "dermatographism," (literally "skin writing") in which the skin welts if it is stroked firmly or scratched (show picture 3). These welts usually appear as reddened, raised lines after scratching. This may also be a form of physical urticaria, although some people with this condition never break out in obvious hives.
FEATURES OF HIVES
Skin appearance — Hives are distinct raised areas that itch intensely and are sometimes red with a pale center (show picture 1). In some cases of hives, the inflamed areas enlarge and merge together (show picture 2). Itching is usually the most distressing symptom of hives, and it may be severe enough to interfere with work and sleep.
Significant pain, the appearance of blood-blister like spots, and residual bruising of the skin where the hive was are NOT typical symptoms of hives. The presence of persistent fever and joint pain is also NOT part of typical hives. These symptoms suggest a different condition called urticarial vasculitis, an inflammation of blood vessels that is associated with hives; this usually requires a different type of treatment. (See "Patient information: Vasculitis").
Angioedema — In up to one-half of all cases of hives, a condition called angioedema also develops. This is a similar to hives, but occurs in the deeper layers of skin. Angioedema most commonly causes puffiness of the face, eyelids, ears, mouth, hands, feet, and genitalia. The swelling usually affects only one side of the body, or affects the two sides unevenly. Angioedema may or may not itch, may cause a sensation of fullness and discomfort in the area of the swelling, and the skin may appear normal or be slightly red.
TRIGGERS FOR ACUTE HIVES — There are many possible triggers for acute hives, including allergic-type reactions to the following:
Drugs — Many types of drugs can trigger hives, including antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or naproxen. The antibiotics that are most likely to be associated with hives are the penicillins, cephalosporins, quinolone antibiotics (eg, ciprofloxacin) and the sulfa antibiotics (eg, sulfamethoxazole). (See "Patient information: Allergy to penicillin and other antibiotics").
Hormones can cause hives in some people, including the hormones present in oral contraceptives and hormone replacement therapy. Painkillers (eg, codeine and morphine), muscle relaxants used in anesthesia, and contrast solutions given into a vein during x-ray procedures can also trigger hives.
Physical contact with allergens — Hives can occur after a person has direct physical contact with certain substances. These substances include animal saliva, plant products and resins, raw fish or vegetables, and latex. Latex is present in many medical and household products, including gloves, balloons, and condoms.
Insects stings — Stings from certain insects (bees, wasps, hornets, fire ants) can cause hives localized to the area of the sting. The eruption of hives all over the body after an insect sting may be a sign of a more serious reaction called anaphylaxis, which includes difficulty breathing, swelling of the throat, and a sometimes loss of consciousness.
Food allergies — Food allergy may cause acute hives in some people. Food-associated hives typically appear within 30 minutes of eating the offending food. The foods most likely to cause hives in children include milk, eggs, peanuts other nuts, soy, and wheat. The foods most likely to cause hives in adults include fish, shellfish, peanuts, and other nuts.
Infections — Infections with viruses are sometimes associated with hives. In fact, viral infections are the cause of more than 80 percent of all cases of acute hives in children. A variety of viruses can cause hives, even routine cold viruses. The hives seem to appear as the body is making an immune response to clear the infection, sometimes a week or more after the illness. Hives associated with viral infections usually affect people for a week or two, and then spontaneously disappear. The affected person may not even realize that they are sick with an infection at the time.
More serious viruses that have been associated with hives include hepatitis B or C, the human immunodeficiency virus (HIV, the virus that causes AIDS), Epstein-Barr virus (which causes mononucleosis), and herpes viruses.
Infection with parasites is a rare cause of hives inthe Western world, although this possibility should be considered in travelers.
CHRONIC HIVES — Chronic hives are defined as lasting for more than 6 weeks. However, in some people, chronic hives last for months or years. About one-half of people who have chronic hives will see resolution of the condition within a year.
In most cases, the cause of chronic hives cannot be determined, although researchers suspect that abnormalities of the immune system play a role.
Hives can be a sign of several other medical or autoimmune conditions, including thyroid disease, chronic infections, systemic lupus erythematosus, or Sjögren syndrome. Usually a person with one of these conditions will have other symptoms, apart from the hives. Further evaluation is needed in these cases.
DIAGNOSIS — There is no specific test for the diagnosis of acute or chronic hives. The diagnosis is usually based on a person's medical history and a physical examination. Occasionally, tests may be needed to identify triggers or underlying conditions.
Medical history and physical examination — In many cases, the results of a medical history and physical examination are all that is needed for the diagnosis of hives. It is helpful to note when the problem began, how long it has lasted, and any recent exposures to new medications, including antibiotics, NSAIDS, and hormones, non-prescription medications and supplements (eg, vitamins, herbs), recent travel, infections, changes in health, and other allergic conditions (eg, eczema, nasal allergies, asthma ). (See "Patient information: Dermatitis").
It is also important to mention other symptoms, including fever, weight loss, joint pain or inflammation, sensitivity to cold or heat, abdominal pain, or bone pain.
Testing — In most people with acute hives, further testing is not needed because the symptoms go away. Skin testing for food and drug sensitivities may be recommended if there are concerns about specific allergies as the cause of symptoms. Blood tests are sometimes performed in patients when hives persist for several weeks (chronic hives) to determine if there are signs of underlying diseases, such as liver or thyroid problems or an autoimmune disease.
Blood tests Complete blood count (CBC) — A complete blood count can identify an elevated number of immune cells called eosinophils, which may signal the presence of an allergic disorder or infection with parasites. A CBC can also identify anemia associated with other medical and autoimmune conditions. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) — The erythrocyte sedimentation rate and C-reactive protein are is a nonspecific measures of inflammation. An elevated level may indicate an autoimmune or other inflammatory conditions. Blood tests for allergies — Blood tests can sometimes identify a specific allergy. For example, people who develop hives upon exposure to foods, latex, or insects may be candidates for this type of testing. These tests measure blood levels of antibodies and are called IgE immunoassays or RAST tests. These tests may be ordered in addition to or instead of skin tests. Thyroid autoantibodies — A blood test can identify the presence of antibodies against the thyroid gland. The presence of these abnormal antibodies suggests that a person may have autoimmune thyroid disease, which has been associated with urticaria.
Skin biopsy — A skin biopsy (when a small sample of skin is removed) may help identify uncommon causes of hives. A skin biopsy may be recommended for people who have persistent fever, painful hives, individual hives that last for days at a time, or hives associated with bruising of the skin. A skin biopsy may also be recommended for people who have other symptoms or abnormalities on blood tests.
TREATMENT
Identify and avoid triggers — The initial treatment of hives involves identifying and discontinuing exposure to any potential outside triggers. In most cases, hives will disappear over days or weeks, as mentioned above. Medications may be given to control itching and decrease the severity of the outbreaks.
In patients with chronic urticaria, long-term medications are usually required to minimize symptoms. Fortunately, in most cases the hives eventually resolve, with or without treatment.
Hives can generally be managed by a pediatric, internal medicine, family practice, or other primary healthcare provider. If treatment with antihistamines is not effective, referral to an allergy/immunology or dermatology specialist is recommended.
Antihistamines — Antihistamines are typically recommended first for the treatment of hives. These drugs can relieve itching by blocking the effects of histamine. Most cases of hives respond to antihistamines, although this often requires that a person take relatively high doses or combinations of antihistamines.
Most antihistamines block either the H1 histamine receptors or the H2 histamine receptors. These drugs differ with respect to their side effects, cost, duration of action, and availability in prescription or over-the-counter form. H1 blockers — The older H1 blockers are called first-generation H1 blockers; the newer H1 blockers are called second-generation H1 blockers.
- First-generation H1 blockers — The first-generation H1 blockers include hydroxyzine (Atarax®, Vistaril®) and diphenydramine (Benadryl®), cyproheptadine (Periactin®), chlorpheniramine (Chlor-Trimeton® and others), and tripelennamine (PBZ). Chlorpheniramine and tripelennamine appear to be safe in pregnant women.
The advantages of the first-generation H1 blockers include their rapid action and effectiveness. The drawbacks of these drugs include the need for frequent dosing (typically, they must be taken once every six hours) and side effects, which may include drowsiness, dry mouth, double or blurred vision, difficulty urinating, and vaginal dryness.
Some of these side effects may interfere with driving, tasks requiring fine movements, and tasks requiring quick reactions, similar to the effects of drinking alcohol. These drugs are therefore not recommended for people who plan to drive, pilot aircraft or boats, or operate heavy machinery, or for people whose job performance may be otherwise affected. The drowsiness can be minimized by starting the drug at a low dose and gradually increasing the dose or by increasing the dose at bedtime. The side effects usually diminish with continued use.
- Second-generation H1 blockers — The second-generation H1 blockers include the over-the-counter medication loratidine (Claritin®), and the prescription medications cetirizine (Zyrtec®), desloratadine (Clarinex®) and fexofenadine (Allegra® and generic).
The second-generation H1 blockers were developed to avoid some of the side effects, especially drowsiness; they also have a longer duration of action, allowing a once or twice daily dose. They are sometimes administered a twice the usual dose to control hives, ie, fexofenadine (180 mg twice daily), loratidine (10 mg twice daily), or cetirizine (10 mg twice daily). Desloratadine (Clarinex®) is usually effective at the normal dose. H2 blockers — The H2 blockers include ranitidine (Zantac®), nizatidine (Axid®), famotidine (Pepcid®), and cimetidine (Tagamet®). The H2 blockers are sometimes added to treatment with H1 blockers if the H1 blockers alone are not effective.
The H2 blockers are usually not associated with serious side effects. However, cimetidine can interact with some other drugs. Doxepin — Doxepin (Sinequan®) is a triclyclic antidepressant and an antihistamine that blocks both H1 and H2 receptors. Doxepin may relieve hives that do not respond to routine antihistamine treatment.
Doxepin causes significant drowsiness and is not recommended when driving or working. It is usually taken in the evening. Doxepin can also have cardiac side effects when used in high doses. Ketotifen — Ketotifen keeps mast cells from releasing the chemicals that cause hives. This drug is not available in the United States, but has been used for many years in Canada, Japan, and Europe. Possible side effects include sedation and weight gain.
Oral corticosteroids — Oral corticosteroids, such as prednisone, counter inflammation, although these medications do not prevent the release of histamine from mast cells.
Oral corticosteroids may be used for some people with persistent severe attacks or chronic hives who do not respond adequately to the maximum doses of antihistamines. In this setting, the corticosteroid can help gain control over the outbreaks. Once the outbreaks have subsided, the dose is gradually lowered over several weeks and then discontinued. Hives recur in some people after stopping steroids, although others have prolonged relief.
Corticosteroids can have serious side effects when taken for prolonged periods of time; they should therefore be taken at the lowest effective dose and only when antihistamine therapy is not adequate.
Other medications — In some cases, additional drugs may be needed to effectively control the symptoms of hives, although referral to a specialist is generally recommended for hives of this severity.
SUMMARY Urticaria is the medical term for hives. Hives are distinct, raised areas of the skin that itch intensely and are red with a pale center (show picture 1). Itching can be very bothersome, and it may be severe enough to interfere with work and sleep. In most cases, hives appear suddenly and disappear within several hours (called acute hives). This may happen daily or a few days each week, but the problem usually goes away within 6 weeks. Some people have hives daily or almost daily for a longer than 6 weeks, which can continue for years (called chronic hives). There are many possible triggers for acute hives, including allergic reactions to medications, certain materials (eg, latex), insect stings, foods, and viral infections (eg, the common cold). If there is a trigger, it should be avoided completely. Medications may be given to control itching and decrease the severity of the outbreaks. Common medications include diphenhydramine (Benadryl®), chlorpheniramine (Chlor-Trimeton® and others), loratidine (Claritin®), and the prescription medications cetirizine (Zyrtec®), desloratadine (Clarinex®) and fexofenadine (Allegra® and generic). Even without treatment, hives usually disappear over days or weeks.
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(www.aaaai.org) National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html) National Institute of Allergy and Infectious Diseases
(www.niaid.nih.gov/) American Academy of Dermatology
(www.aad.org/) American College of Allergy, Asthma, and Immunology
(www.acaai.org)