What is chronic hives

Hives (urticaria) are common red, itchy welts (weals or wheals) that result from a skin reaction. A welt (or weal) is a superficial skin-colored or pale skin swelling that is very slightly raised above the skin surface, usually surrounded by erythema (redness) that lasts anything from a few minutes to 24 hours. Usually very itchy, it may have a burning sensation. The welts vary in size and appear and fade repeatedly as the reaction runs its course. The welts tend to be pale pink or flesh-colored; they can be as small as fingertip size or can run together and cover very large areas. During the course of an attack of hives, the welts can come and go and change quite rapidly. When large welts occur deeper under the skin or mucous membranes, the medical term is angioedema. This can occur with hives, and often causes the eyelids and lips to swell. It resolves within 72 hours. Angioedema may be itchy or painful but is often asymptomatic.

There are 2 kinds of hives: acute hives, in which the welts last less than 6 weeks, and chronic hives, in which the welts last longer than 6 weeks. The condition is considered chronic hives if the welts appear for more than six weeks and recur frequently over months or years. Chronic hives are less understood and may have more complicated triggers than acute hives, often, the cause of chronic hives is not clear. Some examples of common triggers include anything that the affected person is allergic to, including foods (especially peanuts and shellfish), drugs, and environmental exposures. Less common triggers include extreme body heat (such as a hot shower) or cold (such as outdoor temperature), some medications, pressure or scratching of the skin, and exercise. Very rare triggers include sunlight, water, and a reaction to adrenaline. Because there are so many triggers for hives, it can be very difficult to identify the correct trigger, and many cases of hives are called “idiopathic,” meaning the diagnosis is uncertain. However, because the development of hives may indicate an allergic process, it is important to keep your doctor aware of your hives so that you can be counseled about allergy safety.

Anyone of any age can develop hives, but chronic hives seen most often in adult women.

Chronic hives can be very uncomfortable and interfere with sleep and daily activities. For many people, antihistamines and anti-itch medications provide relief.

Figure 1. Skin hives

Figure 2. Angioedema is the rapid swelling (edema) of the deeper layers of skin usually caused by an IgE-mediated allergic reaction

Chronic hives causes

What causes chronic hives

The welts that come with hives are due to release of chemical mediators from tissue mast cells and circulating basophils. These chemical mediators include histamine, platelet-activating factor and cytokines. The mediators activate sensory nerves and cause dilation of blood vessels and leakage of fluid into surrounding tissues. Bradykinin release causes angioedema.

Several hypotheses have been proposed to explain urticaria. The immune, arachidonic acid and coagulation systems are involved, and genetic mutations are under investigation.

Chronic spontaneous urticaria is mainly idiopathic (cause unknown). An autoimmune cause is likely. About half of investigated patients carry functional IgG autoantibodies to immunoglobulin IgE or high-affinity receptor FcεRIα.

Doctors often can’t identify the reason for chronic hives or why acute hives sometimes turn into a long-term problem.

Chronic hives may be triggered or aggravated by:

• Pain medications
• Insects or parasites
• Infection
• Scratching
• Heat or cold
• Stress
• Sunlight
• Exercise
• Alcohol or food
• Pressure on the skin, as from a tight waistband
• Heat
• Viral infection
• Tight clothing
• Drug pseudoallergy—aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), opiates
• Food pseudoallergy—salicylates, azo dye food coloring agents such as tartrazine (102), benzoate preservatives (210-220) and other food additives

In some cases, chronic hives may be related to an underlying illness, such as a thyroid disease or, rarely, cancer.

Chronic spontaneous hives has also been associated with:

• Chronic underlying infection, e.g., Helicobacter pylori, bowel parasites
• Chronic autoimmune disease, e.g., systemic lupus erythematosus, thyroid disease, celiac disease, vitiligo and others
• Lymphoma

Inducible urticaria is a response to a physical stimulus.

Symptomatic dermographism

• Stroking or scratching the skin
• Tight clothing
• Towel drying after hot shower

Cold urticaria

• Cold air on exposed skin
• Cold water
• Ice block
• Cryotherapy

Cholinergic urticaria

• Sweat induced by exercise
• Sweat induced by emotional upset
• Hot shower

Contact urticaria

• Eliciting substance absorbed through skin or mucous membrane
• Allergens (IgE-mediated): white flour, cosmetics, textiles, latex, saliva, meat, fish, vegetables
• Pseudoallergens or irritants: stinging nettle, hairy caterpillar, medicines

Delayed pressure urticaria

• Pressure on affected skin several hours earlier
• Carrying heavy bag
• Pressure from seat belt
• Standing on ladder rung
• Sitting on a horse

Solar urticaria

• Sun exposure to non-habituated body sites
• Often spares face, neck, hands
• May involve long wavelength UV or visible light

Heat urticaria

• Hot water bottle
• Hot drink

Vibratory urticaria

• Jack hammer

Aquagenic urticaria

• Hot or cold water
• Fresh, salt or chlorinated water

Recurrent angioedema without urticaria can be due to inherited or acquired complement C1 esterase deficiency, or to the longterm use of an anticholinesterase inhibitor drug.

Chronic urticaria outlook (prognosis)

Although chronic hives clears up in most cases, 15% continue to have wealing at least twice weekly after 2 years.

Chronic hives complications

Chronic hives don’t put you at any sudden risk of a serious allergic reaction (anaphylaxis). But if you do experience hives as part of a serious allergic reaction, seek emergency care. Signs and symptoms of anaphylaxis include dizziness, trouble breathing, and swelling of your lips, eyelids and tongue.

Chronic hives signs and symptoms

Signs and symptoms of chronic hives include:

• Batches of red or skin-colored welts (wheals), which can appear anywhere on the body
• Welts that vary in size, change shape, and appear and fade repeatedly as the reaction runs its course
• Itching, which may be severe
• Painful swelling (angioedema) of the lips, eyelids and inside the throat
• A tendency for signs and symptoms to flare with triggers such as heat, exercise and stress
• A tendency for signs and symptoms to persist for more than six weeks and to recur frequently and unpredictably, sometimes for months or years

Short-term (acute) hives appear suddenly and clear up within a few weeks.

Chronic hives diagnosis

Your doctor will do a physical exam and ask you a number of questions to try to understand what might be causing your signs and symptoms. He or she may also ask you to keep a diary to keep track of:

• Your activities
• Any medications, herbal remedies or supplements you take
• What you eat and drink
• Where hives appear and how long it takes a welt to fade
• Whether your hives come with painful swelling

Chronic hives is diagnosed in people with a long history of daily or episodic welts that last less than 24 hours, with or without angioedema. A family history should be elicited. A thorough physical examination should be undertaken to evaluate the cause. Inducible hives is often confirmed by inducing the reaction, e.g, scratching the skin in dermographism or applying an ice cube in suspected cold urticaria.

There are no routine diagnostic tests in chronic spontaneous hives apart from blood count and C-reactive protein (CBC, CRP), but investigations may be undertaken if an underlying disorder is suspected.

• The autologous serum skin test is sometimes carried out in chronic spontaneous hives, but its value is uncertain. It is positive if an injection of the patien’s serum under the skin causes a red weal.
• Investigations for a systemic condition or autoinflammatory disease should be undertaken in urticaria patients with fever, joint or bone pain, and malaise.
• Patients with angioedema without weals should be asked if they take ACE–inhibitor drugs and tested for complement C4; C1-INH levels, function and antibodies; and C1q.
• Biopsy of urticaria can be non-specific and difficult to interpret. The pathology shows edema in the dermis and dilated blood vessels, with variable mixed inflammatory infiltrate. Vessel-wall damage indicates urticarial vasculitis.

Chronic hives treatment

How to treat chronic hives

Your doctor will likely recommend you treat your symptoms with home remedies, such as over-the-counter antihistamines. If self-care steps don’t help, talk with your doctor about finding the prescription medication or combination of drugs that works best for you. Usually, an effective treatment can be found.

Antihistamines

The main treatment for chronic hives in adults and in children is with an oral second-generation, nondrowsy antihistamine chosen from the list below. If the standard dose (e.g., 10 mg for cetirizine) is not effective, the dose can be increased fourfold (e.g., 40 mg cetirizine daily). There is not thought to be any benefit from adding a second antihistamine.

If the nondrowsy antihistamines don’t help you, your doctor may increase the dose or have you try the type that tends to make people drowsy and is taken at bedtime. Examples include hydroxyzine pamoate (Vistaril) and doxepin (Zonalon).

Check with your doctor before taking any of these medications if you are pregnant or breast-feeding, have a chronic medical condition, or are taking other medications.

• Cetirizine
• Loratidine
• Fexofenadine
• Desloratadine
• Levocetirizine
• Rupatadine
• Bilastine

Terfenadine and astemizole should not be used as they are cardiotoxic in combination with ketoconazole or erythromycin.

Although systemic treatment is best avoided during pregnancy and breast feeding, there have been no reports that second-generation antihistamines cause birth defects. If treatment is required, loratidine and cetirizine are currently preferred.

Conventional first-generation antihistamines such as promethazine or chlorpheniramine are no longer recommended for chronic hives:

• They are short-lasting.
• They have sedative and anticholinergic side effects.
• They impair sleep, learning and performance.
• They cause drowsiness in nursing infants if taken by the mother.
• They interact with alcohol and other medications.
• Lethal overdoses are reported.

Treatment of refractory chronic hives

Patients with chronic hives that has failed to respond to maximum-dose second generation oral antihistamines taken for 4 weeks should be referred to a dermatologist, immunologist or medical allergy specialist.

There is good evidence to support treatment with omalizumab or ciclosporin, which each have a 65% response rate in antihistamine-resistant patients.

• Omalizumab is a monoclonal antibody directed against IgE, with low toxicity.
• Ciclosporin is a calcineurin inhibitor, with potential serious side effects (eg may increase blood pressure and reduce renal function).

Other treatments that are sometimes used off-label in chronic urticaria include:

If antihistamines alone don’t relieve your symptoms, other drugs may help. For example:

• Histamine (H-2) blockers. These medications, also called H-2 receptor antagonists, are injected or taken orally. Examples include cimetidine (Tagamet HB), ranitidine (Zantac) and famotidine (Pepcid).
• Anti-inflammation medications. Oral corticosteroids, such as prednisone, can help lessen swelling, redness and itching. These are generally for short-term control of severe hives or angioedema because they can cause serious side effects if taken for a long time.
• Antidepressants. The tricyclic antidepressant doxepin (Zonalon), used in cream form, can help relieve itching. This drug may cause dizziness and drowsiness.
• Asthma drugs with antihistamines. Medications that interfere with the action of leukotriene modifiers may be helpful when used with antihistamines. Examples are montelukast (Singulair) and zafirlukast (Accolate).
• Man-made (monoclonal) antibodies. The drug omalizumab (Xolair) is very effective against a type of difficult-to-treat chronic hives. It’s an injectable medicine that’s usually given once a month.
• Immune-suppressing drugs. Options include cyclosporine (Gengraf, Neoral, others) and tacrolimus (Astagraft XL, Prograf, Protopic).
• Methotrexate
• Dapsone
• Phototherapy
• Anti-TNF alpha agents, eg, infliximab, adalimumab

Long-term systemic corticosteroids are not generally recommended, as high doses are often required to reduce symptoms of urticaria and they have inevitable adverse effects that can be serious. However, a study published in 2018 has reported effective clearance and long-lasting response of chronic spontaneous urticaria to oral prednisolone.

Avoidance of trigger factors

In addition to antihistamines, the triggers for urticaria should be avoided where possible. For example:

• Treat identified chronic infections such as H pylori.
• Avoid aspirin, opiates and nonsteroidal anti-inflammatory drugs (paracetamol is generally safe).
• Minimize dietary pseudoallergens for a trial period of at least 3 weeks.
• Avoid known allergies that have been confirmed by positive specific IgE/skin prick tests if these have clinical relevance for urticaria.
• Cool the affected area with a fan, cold flannel, ice pack or soothing moisturising lotion.

The physical triggers for inducible urticaria should be minimized; see examples below. However, symptoms often persist.

• Reduce friction in symptomatic dermographism, e.g., avoid tight clothing.
• Dress up carefully in cold or windy conditions and avoid swimming in cold water in cold urticaria.
• Broaden the contact area e.g., of a heavy bag in delayed pressure urticaria.
• Dress up and use broad-spectrum sunscreens in solar urticaria.

Some patients with inducible urticaria benefit from daily induction of symptoms to induce tolerance. Phototherapy may be of benefit for symptomatic dermographism.

Lifestyle and home remedies

Chronic hives can go on for months and years. They can interfere with sleep, work and other activities. The following precautions may help prevent or soothe the recurring skin reactions of chronic hives:

• Wear loose, light clothing.
• Avoid scratching or using harsh soaps.
• Soothe the affected area with a bath, fan, cool cloth, lotion or anti-itch cream.
• Keep a diary of when and where hives occur, what you were doing, what you were eating, and so on. This may help you and your doctor identify triggers.
• Avoid known triggers.
• Apply sunscreen before going outside.