What is Urticaria?
Urticaria is a common disorder. It can occur at any age, from infancy to old age. Twenty-five percent of all people are affected by it once in their lives. In most cases, it is acute. According to conservative estimates, 1.0% of the European population currently suffers from chronic urticaria. Unlike in children, in whom no gender-specific incidence of urticaria (hives) could be detected to date, urticaria in adults occurs more commonly in women. With regard to chronic urticaria, the ratio is about 2:1. Persons between the ages of 30 and 50 are often affected. Among persons 70 years of age or older, it occurs relatively rarely. In contrast, hives in newborns, which usually last only a few days, are not uncommon.
Urticaria is characterized by the sudden onset of itchy wheals and/or angioedema. The skin of the entire body or only a portion may be affected. The wheals may occur only in response to certain stimuli (e.g. cold, pressure, or sunlight) or spontaneously, i.e., apparently for no particular reason.
A wheal has three typical characteristics:
- a superficial swelling of the skin of different sizes, almost always surrounded by a redness
- itching or burning
- volatility – the appearance of the skin usually returns to normal within 1-24 hours.
In their appearance, these bumps resemble the skin swelling induced by the stinging hairs of nettle (Lat. Urtica dioica). The affected area of the skin swells and is initially red and later paler red to white in the center and red all around. The wheals seem to persist sometimes or to “migrate”. This impression arises from the fact that the individual wheal indeed disappears, but right next to it there is a new one. Not infrequently there is a deep swelling of the skin—so-called angioedema—in addition to hives (sometimes without hives).
Urticaria is one of the most common diseases of the skin. It is also known under the name of hives or nettle rash. Approximately one in four people gets urticaria in the course of her or his life. Most of these episodes last only a few days or weeks and are unproblematic. This is called acute urticaria. Much more difficult (to endure and to treat) are those cases that last for several months or years (sometimes decades). The name derives from the stinging nettle (Lat. Urticaria dioica or Urticaria urens, urere = burn) – doubtless because the skin looks the same in a case of hives as if one had been “burned” by stinging nettles.
Symptoms of Urticaria
Problem itching
Itching is the biggest problem for patients with urticaria. Especially night itching can be extremely stressful, because it disturbs sleep, and it represents a dramatic restriction of quality of life.
Itching is particularly severe for patients who suffer from so-called urticaria factitia. Here scratching and rubbing the skin leads to the appearance of new hives and to further itching. The slightest irritation of the skin, e.g. unconscious rubbing of the skin during sleep can cause severe attacks of itching.
Emergence of itching
The release of histamine from mast cells leads directly to itching.
Many substances can trigger itching. The common feature of these substances is that they release the neurotransmitter histamine into the tissue, which plays a key role in triggering itching. The so-called mast cells of the immune system release certain neurotransmitters (particularly histamine). Almost all of the histamine that occurs in the skin is stored in the so-called mast cells. If these cells are activated, i.e. these cells are triggered by a stimulus, then this is the starting signal for a localized or diffuse spreading inflammation of the skin. As a result, the capillaries widen, the skin swells and becomes red and itchy, and wheals form.
However, histamine also stimulates nerve fibers in the skin, which then release certain itch-inducing substances (neuropeptides). These neuropeptides not only cause itching but in turn activate mast cells, so that a vicious circle begins, ending only when no further mast cells and nerves can be activated. Mast cells are predominantly located in the immediate vicinity of blood vessels and nerves. Therefore, the communication between mast cells, vascular cells, and nerve fiber is excellent.
After an insect bite or after contact with nettles, we feel the itch-inducing effect of histamine most strongly. In addition to substances that release endogenous histamine, the venom of many insects and also the poisons produced by itch-inducing plants contain histamine, which penetrates the skin and irritates it. This stimulus causes us to scrape or rub the skin and allows more blood to get to this point, so the irritants can be removed faster.
What helps against itching?
For patients itching is often the biggest problem and degrades the quality of life enormously. You should avoid scratching, and this is easier said than done. “How can I stop scratching when it itches so?” asked a patient.
- Keep your fingernails cut very short, and stroke the itching area with the dorsal (top) side of the hand.
- Cooling relieves the itching. You can use cool packs that you store in the refrigerator, but taking a cool to cold shower can also be very helpful. If you suffer from cold urticaria, you should of course avoid these measures.
- Stirring half a cup of bicarbonate (e.g. baking powder) into cool bath water and bathing for 10 minutes can relieve the itching.
- Rubbing the skin with vinegar water (one tablespoon of vinegar to one quart of water) can bring temporary relief.
- Creams and gels containing antihistamines combine the local antihistaminic effect with a cooling effect.
- A cream/lotion containing 5% to (maximum) 10% polidocanol, possibly with the addition of urea, can mitigate the itching quite effectively.
- The use of onion or drops (curds)will hardly help.
- Cortisone oinments have no effect on the itching.
Causes of Urticaria
In the skin, histamine, responsible for itching and hives, occurs only in mast cells. Wheals arise because the skin vessels in the affected skin area begin to leak. Histamine makes the cells of blood vessels move away from each other by binding to specific structures (histamine receptors) on the vascular cells and thus indicating to vascular cells that they should move away from each other. This allows blood fluid and some blood cells to escape from the interior of the vessel into the surrounding tissue. In addition to histamine, mast cell products such as leukotrienes or other messengers (so-called cytokines) can increase the permeability of blood vessels. The effect of anti-itch drugs in cases of urticaria can be explained by the fact that these drugs specifically inhibit the binding of histamine to the histamine receptors. These drugs are therefore referred to as antihistamines. The fact that antihistamines do not help in all cases of urticaria indicates that histamine is not the only itch- and hives-inducing substance that is playing a role here.
How are mast cells activated in connection with the different types of urticaria?
This question can be answered most easily with regard to allergic urticaria, a rare subtype of chronic urticaria. The mast cell is the ultimate allergy cell and is involved in all allergies mediated by the protein immunoglobulin E (IgE) and thus responsible for the symptoms of asthma, hay fever, or eczema. The hives can cause allergic mast cell activation, that is, an activation by IgE and an allergen (a substance that can trigger an allergic reaction). In such a case, allergens enter the body along with food or air that is breathed in (e.g. tree pollen, grass pollen, house dust mite droppings) and then activate mast cells, which are loaded with corresponding IgE antibodies. Rarely the absorption of cross-reacting foods can trigger urticaria even in cases of such an allergy.
Any person can become allergic in the course of her or his life. This occurs if we become sensitized against certain pollen such as birch pollen after contact with the pollen. Sensitization refers to the production of immunoglobulins (anti-proteins) against a particular substance, in our example against birch pollen. If we are sensitized, our bodies produce various immunoglobulins with different tasks. The type E immunoglobulins (IgEs) formed by the defense cells of the immune system, for example, get stuck at specially prepared sites on mast cells (IgE receptors) on their way through the human body. Now, when our bodies again come in contact with birch pollen, the IgEs that adhere to the IgE receptors on the mast cells recognize the birch pollen and collect them. The mast cell to which the IgE with the captive birch pollen is stuck is activated and discharges its histamine. An allergic reaction occurs. This best studied pathway of mast cell activation is found only in a small proportion of all urticaria patients.
Much more often the formation of antibodies (defense protein bodies) against the IgE receptor or IgE bound to it seems to be responsible for urticaria. In up to 30 percent of patients with chronic urticaria, such antibodies against the body’s own substances can be detected. In other words, the body reacts against itself. Therefore, one also speaks of autoantibodies and autoimmune urticaria. A simple test for the existence of such autoimmune urticaria is the injection of a patient’s own blood, or the liquid portion of the blood, into the skin of the forearm. In patients with antibodies against their own IgE receptor or IgE, this results in significant wheal formation.
The complement system is an essential component in the network of the body’s immune defense. Its main responsibilities include the direct destruction of cells and agents (such as bacteria or parasites) and the activation of the immune system. The activation of the complement system, e.g. in the context of bacterial infections, leads to the release of powerful mast-cell-activating substances. Not infrequently, chronic urticaria has been caused by a chronic infection (e.g. of the paranasal sinuses, the tonsils, the gastric mucosa, or the teeth): it is known that the removal of such a chronic focus of infection can lead to the healing of chronic urticaria. This is called urticaria due to infection.
The term intolerance urticaria is used in cases in which the body cannot tolerate a particular substance. Discomfort occurs due to intolerance reactions to substances such as medicines, preservatives, or dyes in food. Avoidance of the triggering substance, e.g. by means of a diet, can bring about healing.
Urticaria Diagnosis
Prepare for the interview with your doctor about urticaria by following these steps:
- Note when your urticaria occurred for the first time and how often discomfort has occurred since then.
- What do you think is the cause? Are there triggers that aggravate your urticaria?
- Write down your previous therapies (name, duration, dose).
- Write down the medications you have taken against urticaria so far (name of the drug, duration of use, dosage).
- How well have these medications helped, and what side effects have they had?
- Write down the medications you are currently taking, even those not being taken for urticaria or that have not been prescribed by your doctor.
- Please also record the medicines you do not regularly take (e.g. headache tablets) and specify how many times a month you take medicine and when you last took it.
- If tests have already been carried out to find the cause of your hives, bring along previous findings.
Photograph your skin changes
In the mobile phone era, that should be easily possible.
In many patients, wheals do not occur daily. So you need to expect that you cannot show your doctor how your skin condition at the time of an outbreak looks.
When photographing the lesions, take care to make them appear as they do. Good lighting conditions (oblique daylight, no flash, no neon lights), a sufficient distance (at least 30 cm), and a dark background are helpful here.
Treatment for Urticaria
Treatment with medication is carried out in a similar way in connection with all cases of chronic urticaria.
In accordance with a three-stage scheme, the following medicines are used.
- Antihistamines
- Leukotriene antagonists
- Cyclosporin A
- Omalizumab (new in therapy)
Antihistamines
These drugs, which counteract the effects of histamine and are well-known to allergy sufferers, are used first. Initially, a simple daily dose is recommended, such as is commonly used in connection with allergy patients. This corresponds, for example, to 5 mg of levocetirizine or desloratadine or 10 mg cetirizine or loratadine or 20 mg of bilastine or 180 mg of fexofenadine. If, after two weeks of continuous administration of the antihistamine, there is still discomfort, a prescription for a much higher dose can be issued by a doctor. Up to four times what is specified in the package leaflet as the usual dose. This is not dangerous. However, high doses cause fatigue or sleepiness in some people.
About two-thirds of all urticaria patients can live well with the disease with antihistamines and other non-pharmacological measures. However, further options are available for the remaining third.
Leukotriene antagonists
Leukotrienes are chemical messengers that are created in connection with inflammation and play a role in the development of asthma symptoms such as swelling and narrowing of the airways. This drug, too, is therefore used primarily for asthmatics, but also is also effective in treating some urticaria patients.
Leukotriene antagonists such as Montelukast enhance the effects of pro-inflammatory leukotrienes. However, they are considered to be less effective than antihistamines.
Cyclosporin A
Cyclosporin A suppresses the immune system and thus also the mast cells. It is also used for severe psoriasis, severe atopic dermatitis or in chronic arthritis / rheumatoid arthritis. It can cause—sometimes severe—side effects and therefore therapy must be closely monitored.
Omalizumab
A new drug is omalizumab. This drug, too, was originally developed to treat asthma. Its effectiveness against urticaria was discovered by chance. Omalizumab is not taken as a tablet but injected under the skin. Omalizumab is effective against immunoglobulin E (IgE). Actually, this immunoglobulin—at least this has been believed so far—plays only a minor role in most forms of urticaria. However, it is known that in the case of allergic patients IgE plays a very important role in the activation of mast cells. Presumably, the blocking of IgE by omalizumab simply hinders the activity of mast cells or the “cascade”, which leads to ever more hives and angioedema.
There are numerous clinical studies that show that omalizumab is good and safe but above all that it usually works very quickly. If discomfort cannot be controlled with this regimen during a short period, cortisone can be administered as a tablet or an injection. This solution should always be used as a single therapy or as short-term therapy. Permanent treatment with cortisone is not suitable in connection with urticaria.
Other methods
Experimental methods include, for example, symptomatic treatment with probiotics, the so-called histamine habituation therapy (with histaglobin), autologous whole blood injections, and acupuncture.
Emergency kit
In cases of severe chronic urticaria, e.g. in cases in which there is mucosal swelling that causes difficulty swallowing and shortness of breath, constant carrying of a so-called emergency kit with which severe urticaria attacks can be controlled is recommended. Most such emergency kits contain a fast-acting cortisone preparation and an antihistamine.
What can the patient do for Urticaria?
The most important step is to identify the triggers of Urticaria and determine the individual threshold. Then, the trigger must be avoided to the extent this is possible. Do continue your diary to document the course of the disease accurately. Fewer attacks or a decrease in the severity of attacks is already a success.
In connection with some forms of urticaria, habituation similar to the immunotherapy used in connection with allergic patients is possible. In part this is because the mast cells, when they have discharged their histamine, take a while until they can be activated the next time. Some patients exploit this deliberately.
For example, a daily cold (arm) bath can cause cold urticaria symptoms to disappear for the rest of the day or at least mitigate these symptoms. A person who reacts to stress with wheals may trigger wheals deliberately by means of rubbing or pressure before a stressful situation such as an exam or a job interview in order to be spared itching in the later stressful situation. But please discuss such measures with the doctor, because reactions vary greatly and no one should take the risk of a violent reaction if no help is available.
Stress, by the way, is very often a trigger or an amplifier of urticaria. It is true that “avoid stress” is much easier said than done. Again, keeping a diary will help you identify urticaria-inducing stress. Learning relaxation techniques or autogenic training can help.
Avoid taking NSAIDs (non-steroidal anti-inflammatory drugs). These include, for example, acetylsalicylic acid (in aspirin, Thomapyrin etc.), diclofenac, ibuprofen, phenylbutazone. Taking even a single dose of one of these drugs can cause an attack of hives.
Especially avoid high-proof alcoholic beverages. Alcohol can irritate the stomach lining so that specific enzymes of the gastrointestinal tract (diamine oxidases) that are required for the degradation of histamine can no longer break down the histamine ingested with food sufficiently well.
Histamine is then absorbed into the blood through the mucosa of the small intestine and can cause urticaria and associated discomfort. Alcohol can cause the mast cells, the main trigger cells of urticaria, to be more easily activated.
Spicy foods can also irritate the mucous membranes and are therefore often poorly tolerated and should be avoided by urticaria patients.
Resources
Patient & Family CU Flyer
Patient Charter CU Summaries
Useful Links
www.dermnetnz.org/reactions/urticaria.html