What are hives and how are they diagnosed. How can hives be treated effectively. What are the best antihistamines for managing hive symptoms. Are there natural remedies for hives relief. How can chronic hives be managed long-term. What lifestyle changes can help prevent hive outbreaks. When should you seek medical attention for hives.

Understanding Hives: Causes, Symptoms, and Types

Hives, medically known as urticaria, are a common allergic skin reaction affecting approximately 20% of people at least once in their lifetime. These itchy, red, raised welts can appear anywhere on the body and vary in size and shape. While often harmless, hives can be uncomfortable and distressing for those experiencing them.

What Causes Hives?

Hives can be triggered by various factors, including:

• Allergens (e.g., pollen, pet dander, mold spores)
• Insect stings or bites
• Food allergies (e.g., milk, peanuts, eggs, fish)
• Medications (e.g., NSAIDs, antibiotics)
• Infections
• Emotional stress
• Physical stimuli (e.g., cold, heat, pressure)
• Autoimmune disorders

Types of Hives

There are two main types of hives:

1. Acute Hives: These last for less than six weeks and are often allergy-related.
2. Chronic Hives: Persisting for more than six weeks, these are often autoimmune-related and may have no identifiable cause.

Diagnosing Hives: Key Indicators and Medical Approaches

Diagnosing hives typically involves a thorough examination of the skin and a detailed medical history. Healthcare providers may look for the following characteristics:

• Raised, red welts with pale centers
• Welts that change shape and location within hours
• Itching, stinging, or burning sensations
• Swelling around eyes, lips, feet, or throat (angioedema)

In some cases, additional tests may be necessary to identify underlying causes or rule out other conditions. These may include:

• Allergy tests (skin prick tests or blood tests)
• Blood work to check for infections or autoimmune disorders
• Skin biopsy in rare cases

Effective Treatments for Hives: From OTC Options to Prescription Medications

While hives often resolve on their own within a few hours, treatment can provide relief from symptoms and prevent recurrence. The most common and effective treatments include:

Antihistamines: The First Line of Defense

Antihistamines are the primary treatment for hives, helping to relieve itching, reduce swelling, and prevent new hives from forming. Over-the-counter options include:

• Cetirizine (Zyrtec)
• Levocetirizine (Xyzal)
• Fexofenadine (Allegra)
• Loratadine (Claritin)
• Diphenhydramine (Benadryl)

Are some antihistamines more effective than others for hives? While all antihistamines can be effective, second-generation antihistamines like cetirizine, levocetirizine, fexofenadine, and loratadine are often preferred due to their long-lasting effects and minimal drowsiness.

Additional Treatment Options

For severe or persistent hives, healthcare providers may recommend:

• Oral corticosteroids for short-term use
• Topical corticosteroids or anti-itch creams
• Immune-modulating drugs for chronic hives
• Epinephrine auto-injectors for severe allergic reactions

Natural Remedies and Lifestyle Changes for Hives Management

In addition to medical treatments, several natural remedies and lifestyle changes can help manage hives:

Natural Remedies

• Cold compresses to reduce itching and inflammation
• Oatmeal baths to soothe irritated skin
• Aloe vera gel for its anti-inflammatory properties
• Chamomile tea applied topically or consumed
• Witch hazel as a natural astringent

Lifestyle Changes

Making certain lifestyle modifications can help prevent hive outbreaks and manage symptoms:

• Identifying and avoiding triggers
• Wearing loose, comfortable clothing
• Managing stress through relaxation techniques
• Maintaining a cool, humidity-controlled environment
• Following a balanced diet rich in anti-inflammatory foods

Managing Chronic Hives: Long-Term Strategies for Symptom Control

Chronic hives, lasting more than six weeks, require a comprehensive management approach. Key strategies include:

Medication Management

For chronic hives, healthcare providers may recommend:

• Higher doses of antihistamines
• Combination therapy with different types of antihistamines
• Omalizumab, an injectable medication for severe cases
• Cyclosporine or other immunosuppressants in resistant cases

Lifestyle Adjustments

Long-term management of chronic hives often involves:

• Keeping a symptom diary to identify patterns or triggers
• Regular follow-ups with an allergist or dermatologist
• Joining support groups for emotional support and coping strategies
• Exploring stress reduction techniques like meditation or yoga

When to Seek Medical Attention: Recognizing Severe Symptoms

While most cases of hives are not life-threatening, certain symptoms warrant immediate medical attention. Seek emergency care if you experience:

• Difficulty breathing or swallowing
• Swelling of the tongue or throat
• Dizziness or fainting
• Rapid pulse or heart palpitations
• Severe abdominal pain or vomiting

These symptoms may indicate anaphylaxis, a severe allergic reaction requiring immediate treatment.

Prevention Strategies: Minimizing the Risk of Hive Outbreaks

While not all hive outbreaks can be prevented, several strategies can help reduce their frequency and severity:

Allergen Avoidance

If specific triggers have been identified, avoiding them is crucial. This may involve:

• Reading food labels carefully
• Using hypoallergenic skincare products
• Minimizing exposure to known environmental allergens
• Being cautious with new medications

Skin Care

Maintaining healthy skin can help prevent hive outbreaks:

• Use gentle, fragrance-free soaps and moisturizers
• Avoid hot showers and pat skin dry instead of rubbing
• Protect skin from extreme temperatures and direct sunlight
• Stay hydrated to maintain skin health

Stress Management

Since stress can trigger hives in some individuals, incorporating stress-reduction techniques can be beneficial:

• Practice regular exercise
• Engage in mindfulness or meditation
• Ensure adequate sleep
• Consider counseling or therapy if needed

Emerging Treatments and Research: The Future of Hives Management

The field of hives treatment is continuously evolving, with ongoing research into new therapies and management approaches. Some promising areas include:

Biologics

Biologic drugs, which target specific components of the immune system, are showing promise in treating chronic hives. Omalizumab is already approved for this use, and other biologics are in clinical trials.

Immunotherapy

While traditionally used for allergies, researchers are exploring the potential of immunotherapy in managing chronic hives, particularly for cases with identifiable triggers.

Gut Microbiome Research

Emerging evidence suggests a link between gut health and chronic hives. Studies are investigating how modulating the gut microbiome might impact hive occurrence and severity.

Personalized Medicine

Advances in genetic testing and biomarker identification may lead to more personalized treatment approaches, allowing healthcare providers to tailor therapies to individual patients based on their specific hive triggers and immune responses.

As research progresses, individuals with hives can look forward to potentially more effective and targeted treatments in the future. However, it’s important to note that while these emerging treatments show promise, they are still in various stages of research and development. Patients should always consult with their healthcare providers for the most current and appropriate treatment options based on their individual cases.

In conclusion, while hives can be uncomfortable and sometimes distressing, a wide range of effective treatments and management strategies are available. From over-the-counter antihistamines to prescription medications and lifestyle modifications, most people can find relief from hive symptoms. By working closely with healthcare providers, identifying triggers, and staying informed about new developments in hives research, individuals can effectively manage this common skin condition and maintain a good quality of life.

Best Antihistamines for Hives (Urticaria) – Curist

By Deni Hui, The University of Texas at Austin College of Pharmacy

Curist delivers FDA-approved allergy medicines to your door at half the price of traditional brands. We hope everyone stays safe and healthy during this time.

Have you ever broken out in hives and felt the itchy red bumps on your skin? For most people, hives are usually more than just a temporary nuisance. Read along to learn more about what hives are and what you need to know about them!

Hives (also known as urticaria) are a common skin reaction to an allergen (a substance that causes allergies). About 20% of people will develop hives at least once in their lifetime. Though uncomfortable, It is a harmless skin condition marked by spots on the skin that are itchy, red, and raised. Hives are usually a temporary condition, and there are two different types of hives, acute hives (acute urticaria) and chronic hives (chronic urticaria).

• Acute Hives (Urticaria): Short term, most likely allergy-related rash that fades in 2-3 hours but could hold on for as long as six weeks.
• Chronic Hives (Urticaria): Long term, auto-immune related rash that lasts longer than six weeks.

Hives are the classic sign of an allergic reaction, although hives can erupt for other reasons including:

• Allergens (contact urticaria) like pollen, ragweed, mold spores or pet dander
• Insect stings or bites
• Poisonous plants (e.g. poison ivy, poison oak)
• Foods (e.g. milk, peanuts, eggs, fish or shellfish)
• Chemicals
• Medications (e.g. NSAIDs like ibuprofen, aspirin; codeine, blood pressure medicine)
• Infections (e.g. Strep throat or urinary tract infections)
• Emotional stress
• Autoimmune disorders
• Physical causes (physical urticaria) such as cold (cold urticaria), sweating (cholinergic urticaria), water, or sun exposure.

Hives can appear anywhere on your body and can vary in appearance depending on the person and the situation, but the main sign of hives is the hallmark red raised welts. The welts from hives can:

• have a pale center (turns white when pressed)
• appear in clusters
• change shape and location in a matter of hours
• be tiny or as big as a dinner plate
• itch, sting, or cause a burning sensation
• swelling (or angioedema) around eyes, lips, feet or throat

It is important to note that rarely, a person with hives and angioedema can also get anaphylactic shock which include signs of trouble breathing, a drop in blood pressure, or a loss of consciousness. If this situation ever occurs, make sure to seek medical attention immediately.

The main differences between acute and chronic hives (urticaria) are how long the symptoms last and what their respective triggers are. Acute hives are short-term; they can last for less than a day or up to six weeks. They can be triggered by coming into contact with an allergen such as food, animal dander, insect bite, latex or pollen. Acute hives can also occur from non-allergic causes such as heat, exercise or stress. Being able to identify and avoid these triggers can help prevent this allergic reaction from occurring.

Chronic hives, on the other hand, can stick around for a longer period of time (more than 6 weeks). Most chronic hives are idiopathic, meaning that the exact cause is unknown. Only a small percentage of chronic hives are due to an allergic reaction.

Regardless of whether you have acute or chronic hives (acute or chronic urticaria), antihistamines will be your mainstay of treatment options to help relieve symptoms.

Hives (urticaria) are a particular type of skin rash. They are raised, itchy red bumps that can be large or small in size. Skin rash, on the other hand, can take many other forms often characterized by changes in color or texture of the skin. They can cause your skin to feel rough and look scaly or cracked. Unlike hives, rashes don’t always itch. Sometimes, they hurt or make your skin feel irritated, scratchy or uncomfortable.

Hives are often a temporary skin reaction that can go away in 2 to 3 hours without treatment. However, in some people, hives can persist for weeks or months.

Even though hives typically resolve in a couple of hours, over-the-counter (OTC) antihistamines are recommended as treatment options because they provide the quickest route to symptom relief. Anti-itch lotions, creams as well as topical anesthetics can provide instant relief from the pain and itchiness of hives, but they will not relieve the swelling or redness. Thus, antihistamines are best recommended for quick overall symptom relief.

For acute cases of hives (acute urticaria), some of the best antihistamines are well-known over-the-counter antihistamines such as Curist Allergy Relief (levocetirizine), (fexofenadine (brand Allegra), diphenhydramine (brand Benadryl), loratadine (brand Claritin), and cetirizine (brand Zyrtec) can help reduce swelling, redness, itching, and other problems such as wheezing or difficulty breathing. Chronic hives (chronic urticaria) are usually treated with a three to six month regimen of antihistamines. For chronic hives, it’s recommended to use a newer antihistamine like levocetirizine which does not have the same sedating side effects like Benadryl.

If none of the antihistamines work, consult your doctor or pharmacist as they may also add a different type of antihistamine called an histamine-2-receptor blocker, such as ranitidine or cimetidine. These medications are usually used to treat acid reflux but can also help with reducing hives.

Yes, there are non drowsy antihistamines for treating hives, for instance Curist Allergy Relief (levocetirizine) which is minimally drowsy! Fexofenadine (brand Allegra), loratadine (brand Claritin) and cetirizine) (brand Zyrtec) are all considered newer antihistamines because they were designed to be safer than first generation antihistamines like Benadryl (diphenhydramine) as they do not cause drowsiness, or have very limited drowsiness. These newer antihistamines are non drowsy and can provide ample symptomatic relief for as long as 24 hours.

There is not a single best antihistamine for hives, it depends on which antihistamine works for you. Commonly, people often try Benadryl for hives and while it is effective, it has a significant tradeoff – Benadryl is very sedating. So Benadryl may be effective for acute hives, Benadryl is not appropriate for chronic hives. Instead, a newer antihistamine with less sedating side effects like Curist Allergy Relief (levocetirizine), would be better antihistamine for treating hives.  

The most common side effect of antihistamines is drowsiness, but this is less of a problem with the non-sedating antihistamines used to treat hives. Other possible side effects may include headache, mood changes, nausea or dry mouth. If you are concerned about the drug interactions caused by hives medications with the other medicines you are currently taking, make sure to consult your doctor or pharmacist first.

Hives generally go away in a few hours, but some people may live with chronic hives or regular episodes. Here are a few proven home remedies that can help soothe your itchy skin:

• Use a cold compress: Apply an ice pack or washcloth soaked in cold water to your skin for 10 minutes to provide rapid relief from pain and itchiness. You may repeat it several times throughout the day until symptoms subside.
• Use anti-itch cream: Calamine lotion, menthol, capsaicin or hydrocortisone creams are the most effective in quickly relieving skin discomfort. Other topical anesthetics such as lidocaine cream can provide relief against long term itching or pain.
• Take a cool bath: Heat can make itching worse; while cool water can soothe the skin.
• Avoid triggers: If you are repeatedly experiencing episodes of hives, keep a symptom diary to help you identify foods, allergens (pollen or pet dander), chemicals, activities or medications that might be provoking allergic reactions. Avoid any triggers that you discover in your diary.

Lastly, to learn more about itchy skin and hives, read Curist team member Waverly’s story about her experiences diagnosing chronic hives and treating itchy skin.

Hives: Diagnosis and treatment

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Antihistamines in the treatment of chronic urticaria | Nenasheva N.M.

The article is devoted to the possibilities of using antihistamines in the treatment of chronic urticaria. Pharmacological and clinical studies of levocetirizine

Urticaria (lat. Urtica – nettle) is a disease manifested by urticarial, blistering elements on the skin, similar to those after a nettle burn. The basis of the blister is a limited swelling of the superficial layers of the dermis. The blister is usually pale pink in color with redness around the periphery, is accompanied by intense itching and resolves within 24 hours, usually without any marks. In some patients, urticaria is accompanied by the development of angioedema, characterized by a sudden onset, spreading to the lower layers of the dermis and subcutaneous layer with rapid involvement of the submucosal membrane, while sometimes pain prevails over itching. Angioedema resolves more slowly than a blister – up to 72 hours.

Medical and social significance of urticaria

The medical and social significance of urticaria is determined by its high prevalence, especially the acute form. 15-23% of adults have at least one episode of acute urticaria during their lifetime [1-3], and the prevalence of chronic urticaria (CU) varies according to different studies, from 0.5 to 5% [1, 4, 5 ]. The incidence of urticaria is most often observed in working age, worsening the quality of life (QoL). A number of studies show that the effect on QoL in patients with CU is similar and even worse than in other skin diseases, including psoriasis and atopic dermatitis [6]. Patients often suffer from severe itching, fatigue, decreased quality of sleep and activity [7, 8]. Results of an international study [9] according to a quantitative assessment of the economic, social, humanistic burden of the disease in 673 adult patients with inadequately controlled CU, which has a moderate to severe course (50%) with persistence of symptoms for ≥12 months, despite standard treatment [10], the development of angio-
edema (66%), indicate the impact of the disease on the development of anxiety and depressive disorders, sleep disturbance (Fig. 1), decreased quality of life, daily activity, and labor productivity. The study showed that HC has a high socio-economic value due to direct and indirect costs.

Classification and pathophysiology of urticaria

The spectrum of clinical manifestations of different types of urticaria is very wide. Two (or more) different subtypes of urticaria can coexist in the same patient. Acute spontaneous urticaria is defined as the occurrence of spontaneous wheals, angioedema, or both within less than 6 weeks. [eleven]. Urticaria lasting more than 6 weeks is considered chronic. There are different types of HC, presented in Table 1 [12].

All international and national guidelines emphasize that urticarial vasculitis, maculo-papular cutaneous mastocytosis (formerly called urticaria pigmentosa), autoinflammatory syndromes (eg, cryopyrin-associated periodic syndromes or Schnitzler syndrome), non-mast cell (MC) activated angioedema ( due to bradykinin) and other diseases and syndromes that may begin with skin blistering and/or angioedema are not considered subtypes of urticaria due to their distinctly different pathophysiological mechanisms [11-13].

MCs and possibly basophils are key cells in the pathogenesis of urticaria. Histamine and other mediators such as platelet activating factor (PAF) and cytokines released from activated skin MCs lead to activation of sensory nerve endings, vasodilation and extravasation of plasma, and recruitment of other cells to the skin. These effects lead to urticaria and itching. The signals activating TK are heterogeneous and diverse. MCs express many receptors (for chemokines, prostaglandins, immunoglobulins, etc.), the activation of which leads to cell degranulation. Studies show that the key MC receptor in CCS, FcεRI, is a high-affinity receptor for immunoglobulin E [14–16]. Cross-binding of these receptors on the cell surface leads to its activation and release of mediators from it, the main of which in relation to urticaria is histamine (Fig. 2). Histologically, wheals are characterized by edema of the upper and middle dermis, with dilatation and increased permeability of post-capillary venules, as well as lymphatic vessels of the upper dermis, leading to the penetration of serum into the tissue. With angioedema, such changes occur mainly in the lower layer of the dermis and subcutaneous tissue. The skin of a patient suffering from urticaria is almost always characterized by increased expression of adhesion molecules, neuropeptides and growth factors by endothelial cells. A mixed inflammatory perivascular infiltrate of varying intensity occurs, consisting of neutrophils with or without eosinophils, basophils, macrophages, and T cells, but without vascular necrosis, which is a sign of urticarial vasculitis [17, 18].

It should be noted that these changes are specific not only for urticaria and can occur in other inflammatory skin diseases, so it is necessary to search for more specific histological biomarkers for different subtypes of urticaria and for its differential diagnosis from other diseases accompanied by urticarial rashes.

Urticaria diagnosis

Diagnosis of urticaria does not require special research methods, including laboratory tests, in contrast to the diagnosis of the causes of urticaria. Given the heterogeneity of urticaria, the examination should begin with a detailed history taking, physical examination, using basic laboratory methods to exclude severe systemic diseases. Sometimes special provocative tests, such as a diet containing biogenic amines or histamine liberators, and laboratory tests help to identify the causes of CSU, but they are of little information in physical and other types of urticaria caused by external factors. Extended diagnostic testing aimed at finding the cause of urticaria is warranted in patients with long-standing, severe, and/or persistent CU. The cause may be diseases and conditions often associated with CU: autoimmune diseases (eg, autoimmune thyroiditis), viral infections (hepatitis A and B, norovirus, and parvovirus B19etc.), bacterial infections (for example, diseases of the gastrointestinal tract caused by Helicobacter pylori, Yersinia spp.), parasitic infestations ( Giardia lamblia, Anisakis simplex, Entamoeba spp., Blastocystis spp. ), non-infectious chronic inflammatory processes ( gastritis, reflux esophagitis, cholecystitis), non-allergic food hypersensitivity or atopy (rare).
The experts of the Russian Association of Allergologists and Clinical Immunologists (RAACI), as well as the experts of the European Academy of Allergology and Clinical Immunology (EAACI), do not recommend intensive screening of all patients with urticaria to identify the causes of the disease [12, 13]. It is not recommended to conduct an examination in the case of acute urticaria, unless a history of a provoking factor is indicated. AT 9In 5% of cases, acute urticaria resolves on its own within 2 weeks. and is quite effectively treated with antihistamines (AHP). In severe cases, a short course of glucocorticosteroids (GCS) may be required. Examination in HC is indicated to identify the cause of the disease. In the case of CSU, a limited range of mandatory examinations (clinical blood test and determination of the level of C-reactive protein) is recommended. The range of diagnostic measures for HC, in addition to routine examination methods, is determined by the patient’s history and the specific clinical situation. This may include: tests to rule out infectious diseases (for example, Helicobacter pylori ), parasitic infestation; atopy; thyroid hormones and antibodies to thyroid structures; tests to rule out physical urticaria, with drugs, oral food; autologous serum test; tryptase level determination; D-dimer; antinuclear antibodies; C3/C4 complement components; protein fractions; skin biopsy [12, 13].
At present, the only available screening tests for the diagnosis of CRS are the autologous serum skin test (ASCT) and the basophil activation tests (BAT). ASCT is a non-specific screening test that assesses the presence of any type of serum histamine-releasing factors, not just histamine-releasing autoantibodies. There is a special EAACI article on the methodology for performing ASCT [19, 20]. BAP assesses the release of histamine or an increase in the activity of donor basophil activation markers in response to stimulation with the serum of a patient with CRS. BAT can help diagnose autoimmune urticaria [21]. In addition, BAT can be used as a marker to evaluate the response
to cyclosporine or omalizumab [22, 23].

Chronic urticaria activity assessment

There is a validated tool for assessing HC activity, the Urticaria Activity Scale (UAS 7). UAS 7 implies a total assessment of the main symptoms of the disease (the number of rashes and the intensity of itching) by the patient every 24 hours for 7 consecutive days (Table 2). This assessment is convenient for the patient and the doctor and allows an objective assessment of the patient’s condition and his individual response to therapy. Angioedema activity scale (AAS) has also been developed and validated for patients with angioedema [24]. In induced HC, it is necessary to determine the threshold of the precipitating factor to assess the activity of the disease, for example, the critical temperature and the duration of stimulation during cold provocation in patients with cold urticaria. These thresholds allow patients and clinicians to assess disease activity and response to treatment.

Treatment of chronic urticaria

The goal of HC therapy is to treat the disease until it disappears. Basic principles of HC therapy:
identification and elimination of root causes;
avoidance of provoking factors;
tolerance induction and/or
the use of pharmacological treatment to prevent the release of TA mediators and/or their effects [12, 13].
The main principle of pharmacological treatment of CU is the control or complete reduction of symptoms. Another general principle of pharmacotherapy is to use the drug as much as necessary, and at the same time as little as possible. This may mean an increase or decrease in the volume of therapy in accordance with the HC therapy algorithm (Fig. 3) [12]. Thus, the extent and choice of drug may vary depending on the disease of the patient.

The main variant of HC therapy aimed at relieving symptoms is to reduce the effect of TC mediators, such as histamine, PAF, etc. , on target organs. Many symptoms of urticaria are mediated primarily by the actions of histamine on h2 receptors,
located on endothelial cells (blister) and sensory nerve endings (pruritus).
Long-term continuous use of h2-antihistamines (H1-AHP) is essential for the treatment of CU. The need for continuous use of h2-AHP in CC is evidenced not only by the results of clinical studies [25, 26], but also by the peculiarities of the mechanism of action of these drugs, since they are inverse agonists with a predominant affinity for the inactive state of the h2-histamine receptor and stabilize it in this conformational state, shifting the equilibrium to an inactive state. In addition to histamine, other MC mediators (PAF, leukotrienes, cytokines) may also be involved in the formation of the disease, and a pronounced cellular infiltrate may be observed, including basophils, lymphocytes, and eosinophils [27]. In this case, skin rashes will most likely fully respond to a short course of corticosteroids and be relatively resistant to H1-AHP.
These general provisions regarding pharmacotherapy (continuous daily use of H1-AHP) apply to all forms of acute urticaria and CU. However, the difference between spontaneous and induced urticaria is that for some forms of physical urticaria, such as cold urticaria, on-demand use of H1-AHP may be beneficial instead of continuous treatment. If, for example, the patient is aware of a possible exposure to a causative factor (such as expected cold exposure from swimming in the summer), then taking H1-HPA 2 hours before exposure may be sufficient to prevent the development of symptoms.

Role of antihistamines in the treatment of urticaria

Antihistamines have been used to treat urticaria since the 1950s. There are two groups of antihistamines: 1st generation (sedative) and 2nd generation (non-sedative). The use of 1st generation antihistamines (diphenhydramine, chloropyramine, hifenadine, etc.) is limited by their side effects: pronounced sedative effect, cholinergic, adrenergic effects, short period of action, rapid development of tachyphylaxis. 2nd generation antihistamines (cetirizine, ebastine, loratadine, fexofenadine, desloratadine, levocetirizine, rupatadine, bilastine) are highly selective H1-receptor blockers that have a pronounced antiallergic effect, do not cause tachyphylaxis, and do not have clinically significant interactions with food and drugs. The antihistamine effect of these drugs manifests itself quickly (within 30–60 minutes) and lasts up to 24 hours, which makes it possible to use them 1 r./day. 2nd generation antihistamines are practically devoid of or have a slight sedative effect, which does not differ from the placebo effect, they practically do not affect cholinergic and adrenergic receptors. These drugs are highly effective in relieving the symptoms of hives, such as itching, blisters, redness, and swelling. Experimental studies have shown that the spectrum of their pharmacological activity is not limited to binding to h2-histamine receptors – they suppress the release of pro-inflammatory mediators (histamine, leukotrienes), the expression of adhesion molecules (ICAM-1 and P-selectin) and some cytokines (interleukins ( IL) -4, IL-6, IL-8, IL-13, granulocyte-macrophage colony-stimulating factor). All these data suggest that modern anti-inflammatory drugs have an anti-inflammatory effect.
Modern 2nd generation antihistamines should be considered as first-line therapy in the symptomatic treatment of urticaria (Fig. 3) due to their efficacy and good safety profile. However, to date, there are no well-designed clinical studies comparing the efficacy and safety of modern h2-AHP in the treatment of urticaria. There are studies showing the benefits of a higher dose of 2nd generation H1-HPA in patients with CU [28-30], confirming the results of previous studies in which they came to the same conclusion using 1st generation AHD [31, 32] . This benefit has been confirmed in studies in which 2nd generation antihistamines were used at doses four times higher than the recommended doses [28, 29, 33–36]. Thus, studies show that the majority of CU patients who do not respond to standard doses will experience symptomatic relief from high doses of these drugs. Therapy with modern 2nd generation antihistamines at licensed doses is the 1st line treatment for CU, and high-dose therapy is the 2nd line (Fig. 3) [12].
A recent meta-analysis evaluating the effectiveness of increased doses of antihistamines in the treatment of CSK showed that at least 40% of patients achieve control of the symptoms of urticaria as a result of treatment with standard doses of H1-AHP, 60% of patients – as a result of increasing doses of antihistamines [37].
One of the drugs that most fully meet the necessary requirements is levocetirizine .
Pharmacological and clinical studies demonstrate the rapid onset of effect and the long-term therapeutic effect of the drug. The small volume of distribution of levocetirizine leads to an increase in efficacy (longer contact with H1 receptors) and safety due to less permeability through the blood-brain barrier. The drug undergoes minimal hepatic metabolism without the participation of enzymes of the cytochrome P450 system. At the same time, levocetirizine has a high affinity and selectivity for H1 receptors.
An example of the efficacy of levocetirizine at standard and elevated doses is a double-blind study conducted in adult (19–67 years) patients with CU, who were randomized into groups (40/40) receiving treatment with levocetirizine or desloratadine [38]. According to the protocol, treatment was started with standard doses of 5 mg, then, if there was no effect, the dose was increased weekly, first to 10 and then to 20 mg. If there was no effect when taking 20 mg, the patient was transferred to 20 mg of another drug. As can be seen from figure 4,

a greater number of patients with CU responded to levocetirizine therapy (compared to the number of those who responded to desloratadine therapy), both in standard and increased doses. The authors of the study noted that increasing doses of 2nd generation antihistamines was not accompanied by an increase in unwanted side effects, in particular, drowsiness.
Another double-blind, randomized, crossover, placebo-controlled study compared levocetirizine and desloratadine for their ability to inhibit allergen-induced wheal and flushing (by skin test) in 18 allergic patients [39]. This approach mimics the situation of in vivo as mast cell degranulation and release of numerous vasoactive and pro-inflammatory mediators in addition to histamine occur in response to allergen exposure. Response was assessed at 1.5 h, 4 h, 7 h, 12 h and 24 h after administration at the appropriate therapeutic doses (5 mg). Compared with placebo, both antihistamines significantly inhibited allergen-induced wheals and flushing. However, levocetirizine showed a more pronounced effect and had a faster onset of action, most likely due to its higher occupation of H1 receptors. Indeed, H1 receptor occupancy affects the antihistamine activity of a drug more than affinity or plasma half-life. An important observation in this study was the persistence of levocetirizine’s symptom-inhibiting activity in all patients, while desloratadine was not effective in all patients. This is important to the allergist-immunologist as it indicates that most (if not all) patients are likely to improve their symptoms when taking levocetirizine.
Another open study was performed in 113 patients with CSU who received sequentially increasing doses of levocetirizine (5 mg, 10 mg, 15 mg and 20 mg/day) every week until complete control of symptoms or a dose of 20 mg/day was achieved [40]. The UAS 7, the Quality of Life Questionnaire (CU-Q2oL) and the Global Patient Assessment were used to assess treatment response. As a result, in 21 (18.58%) patients, the symptoms disappeared when taking the standard dose of levocetirizine 5 mg / day, and in 50 patients, higher doses of levocetirizine were required for complete control: 29/92 (31.52%), 6/63 (9.52%) and 15/57 (26.31%) on 10 mg, 15 mg and 20 mg/day, respectively. The proportion of patients with >75% improvement increased with increasing dose of levocetirizine: 26.54%, 53.98%, 60.17%, and 69.91% at 5 mg, 10 mg, 15 mg, and 20 mg/day, respectively. A gradual increase in the dose of levocetirizine resulted in a gradual improvement in both urticaria control and QoL without a significant increase in sleepiness.
Thus, the results of the research, as well as the experience of
Real clinical practice testifies to the efficacy and good tolerability of levocetirizine both in standard and elevated doses in patients with chronic urticaria.
Recently, a generic levocetirizine under the trade name Allerway (manufactured by Dr. Reddy’s Laboratories Ltd., India) has appeared on the domestic pharmaceutical market. Allerway has proved to be bioequivalent to the original drug and is recommended for use in children from 6 years of age, adolescents and adults for the treatment of symptoms of urticaria, other allergic dermatosis, and allergic rhinitis.

Conclusion

HC is a burdensome disease both medically and socially. The modern goal of HC therapy is to achieve complete control of symptoms, i.e., rid the patient of skin rashes and itching. H1-HPA 2nd generation are the drugs of first choice for urticaria. Levocetirizine, as well as other 2nd generation H1-AHPs, is recommended to be used preventively, i.e. in the daily regimen until a stable improvement develops – control of symptoms of chronic urticaria. Therapy should be started with standard doses. In patients who do not respond to standard doses of 2nd generation H1-HPA within 2 weeks, it is reasonable to consider increasing the dose by 2-4 times. Considering that high doses of 2nd generation H1-AHP are not registered in the instructions for the use of drugs, each prescription should be approached individually, making a collegial decision with the participation of an expert in the treatment of urticaria and the head of the department, and it is imperative to explain to the patient the appropriateness of this therapy. . In the absence of an effect from the use of high doses of 2nd generation H1-AHP, it is reasonable to consider the addition of omali-zumab. With any HC therapy, the development of spontaneous remission (in the absence of symptoms during treatment) should be checked, temporarily canceling pharmacotherapy.

Antihistamines in the treatment of urticaria | #05/04

Urticaria is clinically characterized by the appearance of itchy urticaria on the skin. A blister, the main morphological element of urticaria, is a limited swelling of the dermis in diameter from several millimeters to several centimeters, hyperemic along the periphery and paler in the center. With the spread of edema to the deep layers of the dermis and subcutaneous tissue, as well as mucous membranes, Quincke’s edema (angioneurotic edema) is formed.

Quincke’s edema is quite common. It is estimated that 15–20% of the population has experienced at least one episode of urticaria [15]. The prevalence of all types of urticaria in children ranges from 2.1–6.7% [8].

In recent years, the classification of urticaria has been widely discussed.

A published consensus document [12, 13] categorizes urticaria into spontaneous, physical, and special types. This classification is aimed at practitioners and is convenient for clinicians.

The etiological factors of urticaria are presented in table 1 .

Spontaneous urticaria

Spontaneous urticaria according to the duration of the course is divided into acute and chronic. Acute urticaria lasts up to 6 weeks. Chronic urticaria persists for more than 6 weeks, has an undulating course with alternating relapses and remissions.

Acute urticaria . The main etiological factors of acute urticaria (UK) are foods and drugs. The development of urticaria is possible with allergies to epidermal allergens (cat, dog), house dust mites and pollen allergens, Hymenoptera venom (bees, wasps) [2, 7, 11].

Most often, the disease is caused by the development of IgE-dependent allergic reactions. Many studies have shown a high incidence of OC in patients with atopic diseases [3, 7, 12]. An analysis of clinical symptoms in children with food allergies, conducted by I. Dalal et al., made it possible to establish that OK alone or in combination with Quincke’s edema was the most common clinical symptom of food allergy and was observed in 74.4% of cases [7].

In a study conducted by T. Zuberbier et al., it was found that 50.2% of patients with acute urticaria had concomitant allergic diseases – pollinosis, bronchial asthma, atopic dermatitis [16].

The development of urticaria may be due to the direct release of histamine and other biologically active substances from mast cells without the participation of immunological mechanisms. A number of foods, drugs, and chemicals can cause mast cell degranulation. Eating foods rich in histamine can also cause urticaria ( tab. 2 ).

Chronic urticaria (HC) . According to most authors, the most common causes of spontaneous chronic urticaria are infections – hepatitis, Helicobacter pylori-associated gastritis, staphylococcal and streptococcal infections. Food products and drugs can also maintain chronic symptoms of urticaria, but, unlike acute urticaria, the role of IgE-dependent reactions in the formation of symptoms is minimal [2, 6, 11, 16].

Of great interest is the frequency of detection of autoantibodies to high-affinity IgE receptors (FceRI) and IgE in patients with CC. Autoimmune genesis of urticaria is confirmed by skin tests with autoserum. There is still no consensus on the role of autoantibodies in the formation of symptoms of urticaria, further research is needed.

In many cases, urticaria can be caused by diseases of the gastrointestinal tract, intestinal dysbacteriosis, and parasitic infestations.

Physical urticaria

Physical urticaria (FC) develops as a result of exposure to physical factors. The mechanism of the development of the disease is not well understood. An important role of mast cell degranulation in the formation of FC symptoms has been suggested. Physical urticaria includes cold urticaria, solar urticaria, heat urticaria, dermographic urticaria, vibrational urticaria, and pressure urticaria.

Special forms of urticaria – cholinergic, adrenergic, aquatic.

Urticaria treatment

Treatment of urticaria largely depends on the form of the disease and causative factors. Nevertheless, the basic principles of therapy are the same, they include the following steps.

• Exclusion or limitation of exposure to factors that cause urticaria.
• Administration of pharmacotherapy.
• Detailed examination of patients, treatment of diseases that may be the cause of urticaria.

Pharmacotherapy . Patients with acute urticaria, exacerbation of chronic or physical urticaria in order to relieve an acute condition, in most cases, the appointment of second-generation antihistamines is indicated. In a more severe course of the disease, parenteral administration of first-generation antihistamines is advisable (there are no dosage forms for parenteral administration in H ₁ second-generation blockers), as well as glucocorticosteroids.

Treatment of patients with chronic urticaria requires a lot of patience, close cooperation between doctor and patient. In patients, the quality of life is seriously affected: itching can affect daily activities, disturb sleep, rashes on the face embarrass the patient, sharply limit his communication and professional activities. Patients need frequent and long-term use of antihistamines. Antihistamines of the first generation have a number of undesirable effects that limit their use. The sedative effect, disorders of the cognitive and psychomotor functions of the central nervous system are well known [4]. Low selectivity, binding of M-cholinergic receptors are manifested in the dryness of the mucous membranes of the oral cavity, in patients with bronchial asthma, the viscosity of sputum increases, which negatively affects the course of the disease. Urinary retention, constipation, a possible increase in intraocular pressure limit the prescription of drugs to patients with concomitant diseases. No less serious disadvantage H ₁ -blockers of the first generation is a short-term effect, the need for 3-4-fold intake during the day, rather high doses. The decrease in therapeutic efficacy with long-term use dictates the need to change the drug every 10-14 days.

Antihistamines of the second generation (desloratadine, loratadine, fexofenadine, cetirizine, ebastine) do not have these disadvantages. All drugs are characterized by a high safety profile, no serious side effects, they are easy to use. New antihistamines are prescribed once a day, regardless of food intake, no change of drugs is required, since high therapeutic efficacy is maintained with prolonged use. Possible appointment H ₁ second-generation blockers for patients with concomitant diseases for whom first-generation drugs were contraindicated.

Of course, second-generation antihistamines differ from each other. Before general practitioners, dermatologists, pediatricians, the question arises: which drug to prescribe to the patient?

In recent years, a fairly large number of studies have been carried out in an attempt to determine which antihistamine is superior to others. The use of the results of the comparisons in practical work is difficult, since individual parameters were studied on selective groups of patients or healthy individuals, and adequate dosages of the compared drugs were not always used. However, most researchers conclude that the new non-sedating antihistamines are comparable in terms of efficacy, safety, and ease of use. Patient preference may be a determining factor in choosing between second-generation antihistamines [9, 10, 15].

Given the involvement of histamine in the formation of all symptoms of urticaria [1], second-generation antihistamines are the drugs of first choice. In addition to the direct antihistamine action, the new H ₁ blockers have anti-inflammatory activity. Their regular intake facilitates the course of the disease and improves the quality of life of patients.

For literature, please contact the editors .

We conducted a double-blind, placebo-controlled study of the efficacy and safety of the use of the drug kestin (ebastine) in patients with chronic urticaria. The study included 40 patients with chronic urticaria aged 16–61 years. Women – 35, men – 5.

Prior to enrollment in the study, patients had not received systemic antihistamines for 7 days or more. Throughout the study, patients did not receive macrolides (erythromycin, clarithromycin) and azoles (itraconazole, ketoconazole). Patients did not have severe comorbidities. ECG showed no prolongation of the QT interval.

For 8 weeks, 30 patients received Kestin 20 mg/day and 10 patients received placebo.

Patients daily in the evening noted in the diary the severity of itching, the number and size of urticarial rashes. The dynamics of symptoms was assessed by the doctor during visits. The doctor and patients recorded the occurrence of adverse events, their manifestations and the necessary therapy. There were 3 visits in total: the first visit was the starting one, the second visit was 4 weeks later, and the third visit was 8 weeks after inclusion in the study.

Considering that itching is the main symptom of urticaria, which significantly reduces the patient’s quality of life, tables 4 and 5 show the dynamics of the severity of itching in patients after 4 and 8 weeks of therapy. In the group treated with kestin, all patients showed a regression in the severity of this symptom. Among patients receiving placebo, the effectiveness of therapy was significantly lower – 5 (50%) patients were prematurely excluded from the study due to the lack of effect at the same time.