Background
Urticaria is a common condition defined by the development of pruritic wheals, angioedema or both [
1]. A wheal is characterised by a central swelling of variable size, almost delimited by reflex erythema, itching and a transient nature, with the skin returning normal within 30 min to 24 h. Angioedema, for its part, exhibits a sudden, pronounced erythematous or skin coloured swelling of the lower dermis and subcutis or mucous membranes, sometimes pain and a slower resolution [
1].
At the beginning of 2018, an updated version of the EAACI/GA
2LEN/EDF/WAO (European Academy of Allergology and Clinical Immunology, Global Asthma and Allergy European network, European Dermatology Forum, World Allergy Organization) urticaria guideline was published, providing new inputs regarding both the diagnosis and the treatment of patients with urticaria. This guideline, in the perspective of diagnosis, recommends that urticaria is classified based on its duration as acute (≤ 6 weeks) or chronic (> 6 weeks) [
1]. In addition, chronic urticaria is classified as spontaneous (CSU) or inducible (CIndU). CSU is characterized by spontaneous symptoms that are not elicited by apparent factors, and CIndU, on the other hand, requires specific triggers for the urticarial symptoms to occur, such as sunlight, pressure, friction, or exposure to heat or cold [
1]. Chronic urticaria is not rare, with a prevalence of at least 1% in the general population and CSU is two to three times more common than CIndU; moreover, patients may have more than one type of chronic urticaria [
2,
3]. Urticaria can occur in all age groups, including infants and young children [
1] and has similar epidemiological characteristics across different locations [
4]. Tang et al. reported that among 411 pediatric patients that visited a dermatological department in China, 314 (76.4%) had acute urticaria and that infection was the main trigger of acute urticaria in children (41%, 16/39). The accompanying symptoms of acute urticaria in children mainly included abdominal pain and diarrhoea (44%, 17/39) [
5]. Chronic urticaria is less frequent than acute in children, but it still represents a debilitating condition, always needing treatment. CU in children has a point prevalence between 0.1% and 0.3% and is diagnosed as CSU in 80% of cases. In children, prospective studies suggested that autoimmune CSU affects about half of pediatric CU cases in Europe. Resolution rate in children with CU was found to be lower than in adults (10.3% per year). The presence of certain biomarkers (CD63 level > 1.8% and basophil count) may help to predict the likelihood of resolution [
6].
In the management of urticaria, the treatment must aim at complete control of symptoms, taking into account the safety and the patient’s quality of life, as the main goals. Treatment of CU in children should be continuous [
1]. Specifically, the use of second-generation antihistamines as a first line therapy is recommended, due to the good safety profile, minimal cognitive and anti-muscarinic side effects, and a long duration of action [
1].
Many clinicians still use first-generation, sedating, H
1-antihistamines as their first choice in the treatment of children because they assume that the safety profile of these drugs is better known. In addition, recommendation about age for the first-generation H
1-antihistamines is sometimes less clear as these drugs were licensed at a time when the code of good clinical practice was less stringent [
1]. A strong recommendation was made by the panel of EAACI/GA
2LEN/EDF/WAO urticaria guideline, on the basis of current literature, to discourage the use of first-generation antihistamines in infants and children encouraging the usage of the newer non-sedating antihistamines [
1].
As understanding the pharmacological characteristics of individual drugs is essential for effective and safer use of antihistamines in clinical practice, this review summarizes the characteristics of bilastine as the most novel 2nd generation antihistamine and describes its use in children with urticaria, as newly recommended by the current guideline. Table
1 compares the safety profile of bilastine with profiles of some representative second generation H
1 antihistamines (cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine, and rupatadine); first generation drugs are not included in the table, as few data is available and clinical use is discouraged by current guidelines (Table
1) [
1].
Table 1
Safety profile of representative second generation H1 antihistamines indicated for urticaria in children.
Modified from 15
Properties |
Paediatric indication | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
T1/2 (h) | 14.5, any age | 10, in adults 6.1–7.1, in children over 4 years 5.5, in children under 4 years | 27, any age | 11–15, any age | 7.9, in adults In children 6–11 years 24% shorter than in adults | 8.4, any age | 5.9 in adults 15.9, in children 2–5 years 12.3, in children 6–11 years |
Dosage adjustment in impaired kidney function | No | In moderate to severe | In severe impairment | No | In moderate to severe | No | Not recommended in renal impairment |
Dosage adjustment in impaired hepatic function | No | If concomitant renal dysfunction | Not mentioned | No | If concomitant renal dysfunction | In severe disease | Not recommended in hepatic impairment |
Interaction with food | Yes, give on empty stomacha | No | No | Not mentioned | No | No | With grapefruit |
Clinically relevant drug interactions | No | No | No | Yes, antacids | No available data | Potential (with inhibitors of CYP3A4 and CYP2D6) | Yes, with CYP3A4 inhibitors |
Lack of sedative potential | Yes (caution, drowsiness) | Yes (in adult, check drug response when intending to drive) | Yes (caution, drowsiness) | Yes (impairment is unlikely) | Yes (in adult, check drug response when intending to drive) | Yes (caution, drowsiness) | Yes (caution, drowsiness) |
Contraindications (except hypersensitivity) | None | Severe renal impairment | None | None | Severe renal impairment | None | None |
The pediatric indication is also shown. Because of the diversities in regulation between countries worldwide, the youngest age, for which antihistamines are registered according to local resolutions, differs and it is not reported in the table.
Conclusions
Chronic urticaria has a profoundly negative impact on quality of life and everyday life of affected children, impairing sleep and school and learning performance. Long-term, continuous treatment is required to control symptoms, so that great tolerability of a pharmacologic treatment is mandatory. First generation antihistamines cannot be considered safe for lack of evidence, and for their strong sedating effect; on this basis they are not recommended.
Bilastine is a suitable tool for treatment of CU, due to its efficacy and good tolerability profile that were proven in well-controlled studies using objective indices. Specifically, lack of potential to induce sedation allows prolonged administration without impairment of performance and learning abilities.
Competing interests
Dr. Papadopoulos reports Grants from Gerolymatos International SA and Capricare; personal fees from Hal, Novartis, Menarini/Faes Farma, Mylan/Meda, Nutricia, Sanofi, Biomay, AstraZeneca, GSK, MSD and Asit Biothech, outside the submitted work.
Dr. Zuberbier reports grants or honoraria from AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, FAES, HAL, Henkel, Kryolan, Leti, L’Oreal, Meda, Menarini, Merck, MSD, Novartis, Pfizer, Sanofi, Stallergenes, Takeda, Teva, UCB. He also reports the following organizational affiliations: Committee member, WHO-Initiative “Allergic Rhinitis and its Impact on Asthma” (ARIA). Member of the Board, German Society for Allergy and Clinical Immunology (DGAKI). Head, European Centre for Allergy Research Foundation (ECARF). Secretary General, Global Allergy and Asthma European Network (GA2LEN). Member, Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO).”
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