Chronic Urticaria: everything you need to know

Urticaria – Angioedema and chronic urticaria: what to do and what not to do

Urticaria (hives) is a very common skin condition. While it is not dangerous, is easy to recognize and reasonably straightforward to treat, the rash is often poorly understood and managed. The term ‘urticaria’ derives from the effect that contact with urtica (nettles) causes. Immediately after contact, raised, itchy and reddened patches (welts or wheals) form on the affected area of the skin. Although the term ‘angioedema’ is often synonymous with urticaria, in this condition the edema (swelling) actually begins within the blood vessels. The term ‘chronic idiopathic (spontaneous) urticaria’ means that the symptoms last for more than two weeks and do not respond to medication. There is also no apparent cause of the urticaria, hence the addition of ‘idiopathic’. Urticaria is not a disorder of the skin, but of the blood vessels. Due to faulty commands, the blood vessels allow the watery component of the blood to leak out into the dermis, which causes the swelling that is so typical of urticaria.

How to recognize urticaria: start by identifying the wheals

Urticaria is easy to recognize because of the hives (welts) that appear on the skin. Hives are bumps of the skin that can take many different forms. In their most simple form, they are reddened and itchy patches of skin. Hives may also take on a circular or ring-like appearance with a paler center and reddened, raised outer ring.

Hives may appear as clearly defined patches that spread out across a specific area, with a few isolated welts surrounding the main rash.

Alternatively, hives appear in a sort of pattern composed of curved lines.

If hives appear in areas where the skin tissue is looser (eyelids, mouth, genital area), the fluid released from blood vessels will swell the tissue, causing the area to become deformed.

In children, hives are usually milder.

Hives may be extremely or mildly itchy, but in some people, they cause no such symptoms.
When hives appear on areas of the skin that are very taut (palms of the hands, soles of the feet), it is possible that the individual won’t even notice them. They will, however, most likely experience some itching and/or pain when walking or handling objects. This is due to the compression of the liquid that has leaked from blood cells against the nerve endings in the dermis.

How to identify hives

The detection of welts is the basis for the diagnosis of urticaria and/or angioedema. A welt is classified as evanescent and migratory. To identify hives, there are two characteristics to look out for: evanescence and migration.
Hives are welts that are present at one moment, but in a few hours or days it will have disappeared, making them an evanescent lesion.
They are also migratory because hives will appear in one position of the body, before appearing somewhere else completely just a short while later.
As there are no other skin lesions that are simultaneously evanescent and migratory, a diagnosis of urticaria is extremely easy to make.

How do hives form?

Normally, the fluid that flows alongside red and other blood cells remain inside the walls of blood vessels. Some nerve and chemical signals can command the cells in the vessels to open and let out this watery fluid, which swells in the dermis and causes hives to form.
Other nerve or chemical signals are able to command the reabsorption of this fluid from the dermis, which will cause the hives to disappear and later reappear in the same spot or elsewhere.

What are the causes of Urticaria?

Urticaria can have a variety of causes, or can appear for no apparent reason whatsoever.
The known causes of urticaria are divided into three main categories:

1. Drug-induced urticaria
2. Urticaria caused by infection
3. Urticaria caused by food.

Drug-induced urticaria and pharmaceuticals to avoid

Pharmaceuticals are usually the main cause of urticaria, with the most common drugs responsible being nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol.
The former includes pharmaceuticals such as analgesics, pain relievers, anti-inflammatory drugs and antifebrile drugs. Urticaria as a result of taking these pharmaceuticals is not an allergic reaction, meaning allergy tests are not necessary. Instead, urticaria is the result of a hypersensitivity to the drug and can occur even if just one dose is taken. In the table below, pharmaceuticals that often induce urticaria are listed and should be avoided by those who have or who have had urticaria. The table also includes the names of active ingredients that cause urticaria and the group to which they belong

Urticaria caused by infection

Although different infectious diseases can trigger urticaria, the most common infectious cause is streptococcal pharyngotonsillitis.
In pediatric patients, this is a frequent cause of urticaria.

Urticaria caused by food

Food is not as common a trigger of urticaria as people asume.
Urticaria as a result of food or beverages is most commonly a response to either an additive or preservative, or a response to food that has not been well preserved.
In such cases, urticaria will appear immediately after consuming the food in question, but will usually disappear on its own after a few hours.

Other causes of urticaria and physical urticaria

Urticaria can also be triggered by intense emotions, or by stimuli caused by stress. It can appear following exposure to heat, cold, sunlight or UV rays, or during exercise and sweating. All of these urticaria triggers are referred to as ‘physical urticaria’.
Contact urticaria also exists, which appears as soon as the skin comes into contact with certain chemical or plant-derived substances.

Diet and urticaria

Individuals with chronic urticaria are often prescribed a restrictive diet that limits some foods containing histamine or those that release histamine.
It is true that histamine is only one of the many chemical mediators of inflammation that can cause hives. However, while eating foods rich in histamine or histamine liberators, there is no direct increase in histamine in the blood. This is likely because any histamine contained within the foods is digested before it can be released into the bloodstream, meaning there is no clinical benefit in avoiding these foods in an attempt to reduce urticaria.

Is urticaria the result of an allergy?

No, urticaria is not the result of an allergy, meaning allergy tests are not useful.

Can urticaria be the symptom of an illness?

Very rarely, urticaria can be a sign of an infection (usually dental or related to the heart valve, etc.) that the person does not know he or she has. In even rarer cases, urticaria may be a sign of a developing neoplasm, usually in the intestines.

Acute and chronic urticaria

Urticaria – Angioedema is a very common condition, especially in young people.
It manifests with the sudden onset of wheals in various parts of the body.
Sometimes, the cause can be traced back to medications, infections, or food, but it can also occur without any apparent cause.
The wheals of acute urticaria are bothersome for the individual for a few hours or days before subsiding.
Chronic urticaria, on the other hand, behaves differently: after the initial onset, even in cases where the apparent causes have been removed, it tends to persist for weeks, months, or even years.

When urticaria becomes chronic

Oftentimes, acute urticaria can turn into chronic urticaria. This phenomenon can occur spontaneously, but is usually the result of cortisone. This can happen to individuals who have developed urticaria and try to treat it with cortisone, before finding they can no longer get rid of the hives.

How cortisone transforms acute urticaria into chronic urticaria

Regardless of the cause, when urticaria occurs, the body triggers factors that will block the effect of histamine and, therefore, hives. If cortisone is introduced at this point, pro-urticaria and anti-urticaria are both blocked, which will put urticaria into remission. When cortisone is reduced or discontinued, the pro-urticaria factors reappear, as does urticaria.

Why cortisone should not be used in urticaria treatment

As in cases of atopic dermatitis and psoriasis, cortisone also has an illusory therapeutic effect in urticaria and eventually ends up worsening the disease. In addition to its well-known negative effects (blood pressure, blood sugar, glaucoma, weight gain, etc.), cortisone makes urticaria more unstable, more aggressive and less manageable. Tachyphylaxis and rebound are other negative side effects that cortisone can trigger in cases of urticaria. Where tachyphylaxis occurs, it is necessary to gradually increase doses of cortisone in order to control urticaria. At this point, the high levels of cortisone administered becomes dangerous and the urticaria will have been completely destabilized.
Instead, rebound refers to the return of urticaria upon discontinuation of cortisone, usually in a more aggressive form than before.

Why cortisone is prescribed for urticaria

Although cortisone is unsuitable and contraindicated for urticaria treatment, it is still prescribed. One reason probably lies in the confusion that many physicians have in distinguishing urticaria and symptoms of anaphylactic shock, a condition where cortisone use is indicated. This confusion may occur if patients have angioedema in the oral cavity which may cause them difficulty breathing. Unlike anaphylactic shock, angioedema will not cause suffocation and will regress within about an hour with rest. Cortisone should not, therefore, be administered even in cases of urticaria with respiratory distress.

How to treat urticaria

Acute urticaria usually needs no treatment. This is because it will usually resolve by itself, or steps to remove the trigger can be easily taken (e.g. discontinuation of certain medications, abstention from certain foods, suspension of specific antibiotics etc.).
Chronic urticaria, instead, should be treated according to the situation. In cases of chronic urticaria where cortisone has not been used, antihistamines can be administered. Antihistamines can block the H1 receptor for histamine that is present on cells. There are first, second and third generation antihistamines available, each with its own mechanism of action, duration and side effects. In general, antihistamines that are prescribed to treat urticaria are well tolerated, free of major side effects, and can be used for long periods. The exact choice of antihistamine, dosage, and any secondary measures needed to regress urticaria should be determined on a case-by-case basis.
If, however, the case of chronic urticaria does not respond to antihistamines and/or cortisone has been used, the treatment is more complex.
It should be taken into account that, upon discontinuation of cortisone, there will inevitably be a rebound whereby the urticaria will become more unstable and aggressive. In such cases, the most suitable drug is flunarizine. Flunarizine belongs to the calcium antagonist pharmacological class and also possesses antihistamine activity on H1 receptors.
(http://www.drugbank.ca/drugs/DB04841) Flunarizine can also cause serious side effects, but if taken in cycles (e.g. with a withdrawal period) these can usually be avoided. Before taking flunarizine, it is important to consult a doctor.
Therefore, based on years of clinical experience gained in many dermatology centers, flunarizine is used in cycles to treat chronic urticaria. A cycle of flunarizine consists of taking a 5mg dose twice per day for 21 days per month, followed by a pause of seven days. Cycles of flunarizine should be repeated until urticaria symptoms disappear, which will usually happen after three or four consecutive cycles. If remission does not occur at this point, other urticarial drugs should be considered.

Flunarizine plus antihistamine

In cases where, despite the use of flunarizine significant welts still appear, antihistamines may be added to treatment. First-generation antihistamines are taken in the evening to avoid any risk of daytime drowsiness, while more modern antihistamines can be taken during the day in combination with flunarizine.
As antihistamines only cure symptoms and not the urticaria itself, they should be used as and when needed.
Examples of possible treatment patterns:

1. Flunarizine

Follow treatment for 21 days, followed by a seven day suspension

2. Flunarizine and antihistamine

3. Antihistamines during flunarizine suspension, if hives appear

According to the indications of the dermatologist, other treatment plans may be recommended.
Other drugs that have been shown to have positively treated urticaria include sodium cromoglycate, cyproheptadine hydrochloride and montelukast, all of which belong to different pharmacological classes.
The decision whether to use these drugs alongside Flunarizine or not is at the discretion of the dermatologist who may use them variably according to individual cases.

Two particular forms of hives: dermographism and aquagenic urticaria

Dermographism is a particular form of urticaria whereby any mechanical pressure on the skin causes a welt to appear. The name of the condition is derived from the fact that, for those suffering from dermographism, passing a blunt-tipped object over the skin and exerting slight pressure results in a pattern formed by a linear welt with a white, raised center and bright red outlines.

Those who suffer from dermographism often complain of discomfort and itching in areas of the body that are often rubbed, touched or constricted by clothing (e.g. bra, stockings).
As the causes of dermographism are the same as those that cause hives, the treatment for both conditions is also the same.
Aquagenic urticaria is common and occurs on contact with water such as when taking a shower, bathing or swimming in the sea etc.
After a few minutes of contact with water, itchy hives that last for 20 to 30 minutes form, before regressing.
Aquagenic urticaria has no known cause, but can be treated like hives.

Omalizumab to cure hives

Omalizumab is a recombinant humanized murine monoclonal antibody that binds to free IgE, preventing it from binding to receptors on mast cells and basophils The newly formed IgE-homalizumab complexes are removed by phagocytosis, and serum concentrations of free IgE are reduced by 95-99% within a few days of administration. This drug has been used in severe forms of asthma and more recently has also been approved to treat cases of chronic hives. Omalizumab is a drug that can only be prescribed by a hospital dermatologist. It is important to note that, in Italy, experiences with this drug have been very mixed. While some have responded positively to the drug and have seen a stable regression of hives, most patients have had a transient remission with relapse. Others, instead, have not responded well to the drug, or the hives have considerably worsened. This is to be slightly expected, as the administration of this drug was not exclusively reserved for patients with elevated IgE.