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Epidemiology of urticaria in Poland – nationally representative survey results

Introduction The prevalence of urticaria is 15–20%. Women are twice as likely to be affected. Aim To present the epidemiology of urticaria and angioedema in Poland. Material and methods A questionnaire-based survey was conducted on a representative group of 4,897 individuals, aged 15–74 years. Results A total of 11.2% of respondents reported at least one episode of urticaria symptoms in their life, and the frequency was higher in females (OR = 1.46; p < 0.001). Single episodes accounted for 34.8%, while repeated episodes accounted for 65.2%. Acute urticaria was observed in 10.6% (more frequent in females; OR = 1.41; p < 0.001), chronic in 0.6%. Median age of the first episode was 15 years. Angioedema was observed in 3.2%. The last episode of urticaria symptoms and/or angioedema occurred within the previous week in 0.7% of subjects, the last month in 1%, and the last year in 2.2%. 8.8% had experienced urticaria symptoms or angioedema over 1 year prior to the survey. The impact of urticaria symptoms on patients’ daily activities was rated with 3.8 points on a scale of 0–10. In addition, chronic urticaria was rated 6.5, and acute urticaria 3.6. Angioedema and urticaria had a negative impact of 5.7 points. Conclusions Urticaria and angioedema are serious health problems in Poland, although their prevalence is below the mean rate for the global population. Females are more likely to suffer from these diseases. People affected by urticaria most frequently report contact with plants and substances, insect bites/stings, and food as the provoking factors.


Introduction
Urticaria is a very common skin disease characterized by a rapid onset of itchy wheals and in 40% of cases is accompanied by angioedema [1,2]. Classical urticarial wheals resolve within a period of 24 h. Urticaria constitutes a heterogeneous group of variants, classified as types and subtypes. According to the Urticaria Consensus Meeting, urticaria is classified as acute (not exceeding 6 weeks) or chronic (more than 6 weeks). Chronic urticaria is further divided into spontaneous and induced [2]. Furthermore, two variants of chronic spontaneous urticaria are distinguished: chronic continuous urticaria (wheals appear and thereafter disappear every day or almost every day) and chronic recurrent urticaria (with symptom-free periods, lasting for a few days or weeks) [1,3].
There are no nation-wide data available on the prevalence of urticaria or angioedema in the general Polish population. Previous studies were based on a different methodology and included a selected group and/or a particular geographical area. Most epidemiological estimates on Poland are based on data from other countries and/or regional studies.
Angioedema is characterized by edema of the subcutaneous or submucosal tissue resulting from dilatation of blood vessels and their increased permeability. Its clinical features consist of rapid onset, significant severity, pain sensation within the area of skin lesions, commonly affected mucous membranes, and slower regression in comparison to urticarial wheals (up to 72 h) [3]. In approximately 33-67% of chronic spontaneous urticarial cases, urticarial wheals and angioedema appear simultaneously, as compared to 29-65% reporting isolated wheals, and in 1-13% only angioedema [4,5,10,13].
Worldwide epidemiological studies on urticaria may be divided into two main categories: outpatient based studies and questionnaire-based surveys. There are also combined protocols used in the trials, such as outpatient studies supplemented by questionnaire-based surveys (e.g. those concerning the quality of life of patients with urticaria) and vice versa, being performed in order to verify the preliminary diagnoses. Epidemiological data on urticaria may also be obtained from various medical registers -however, these are "nonreactive studies"carried out without participation of the study individuals and therefore of different characteristics. There are reliable and specifically constructed questionnaires used for epidemiological studies on urticaria available in the worldwide literature [14][15][16].

Aim
However, the primary aim of this study is to present the epidemiology of urticaria and angioedema in the Polish population and to analyze the factor/s possibly inducing urticarial episodes. Additionally, assessment of the negative impact of urticaria or angioedema for the respondent is also evaluated.

Material and methods
The study on Epidemiology of Urticaria in Poland (EUP) was a questionnaire-based survey. A total of 19 closed and semi-closed questions (developed for purposes of the study) were implemented as the basic research tool. Survey questions focused on the occurrence of urticaria and angioedema episodes in studied individuals (Appendices 1 and 2). Questions were based on existing knowledge about the symptoms of urticaria and experience from other similar epidemiological studies. The respondents were presented with the most common examples of urticaria and angioedema (two separate cards with 8 pictures of urticaria and 5 pictures of angioedema) in order to clarify signs and symptoms of the disease, and make their identification easier. Additionally, the questionnaire included definitions of urticaria and angioedema, which were verbally presented to each respondent.
We classified urticaria according to the Urticaria Consensus Meeting [2]. The negative impact of urticaria on patients' quality of life was measured by a self-assessment question. It contained a simple scale, where 0 means no negative effect and 10 is the maximum negative impact.
The main part of the study was preceded by a pilot survey (106 individuals in 4 centers), primarily for validation of the questions. As many as 52 individuals with urticaria and 54 without signs and symptoms of urticaria (27 healthy individuals, 27 with other skin diseases) were selected for the pilot study (purposive sampling).
The EUP was carried out all over Poland by two independent research centers (TNS and Millward Brown). The main survey was conducted by the pollsters with the computer-assisted personal interviewing (CAPI) method at respondents' homes during July and August, 2014. The random-quota method was used for sampling from the general population (adults). There were no inclusion criteria except age. In total, 5,017 individuals participated in the study (4,897 individuals aged 15-74 years were qualified for further analyses; 120 individuals aged 75 and more were excluded because of the age criteria). The data were weighted to the population structure (Table 1). Results were considered to be statistically significant at p < 0.05. According to the guidelines of the Bioethics Committee of the Medical University of Warsaw non-invasive studies (including surveys) do not require ethics approval.

Results
Lifetime occurrence of at least one episode of urticaria symptoms was reported by 11.2% of respondents. There was a statistically significant difference related to gender (p < 0.001). Females declared at least once in life appearance of urticaria symptoms more frequently than males (OR = 1.46; 95% CI: 1.22-1.75%). Age (grouped in 10-year categories) did not influence the prevalence of declared urticaria symptoms (p = 0.729). Similarly, there was no difference in relation to the place of living (urban vs. rural area) (p = 0.963). Detailed results are presented in Table 2.
Among individuals reporting urticaria symptoms, 34.8% (3.9% of all study subjects) experienced one single episode, and 65.2% (7.3% of all study subjects) reported many episodes. Gender was not associated with these results (p = 0.082). Among individuals reporting more than one episode of urticaria symptoms, 41.1% experienced urticarial wheals less than once a year, 17.2% once a year, 30.4% several times a year, 7.6% several times a month, and 3.7% several times a week or every day. There was no statistically significant difference in relation to gender (p = 0.236).
Acute spontaneous urticaria (symptoms lasting for less than 6 weeks) was reported by 10.6% of respondents (95% CI: 9.8-11.5%), 9.0% males and 12.2% females (p < 0.001). A total of 28 individuals (0.6%; 95% CI: 0.4-0.8%) reported suffering from chronic spontaneous urticaria (symptoms lasting for longer than 6 weeks). It was more frequently reported in females than males (0.8% vs. 0.3%; p < 0.05). Among respondents reporting urticaria symptoms, 40.7% did not remember when the first episode of the disease occurred. Among other individuals, the median age at the first episode of urticaria symptoms was 15 years, and the mean age was 19.5 years (20.7 in women, and 17.8 in men). The difference in the mean age between genders was statistically insignificant (p = 0.082). Details are presented in Figure 1.
Among the respondents who reported at least one episode of urticaria symptoms or angioedema, 5.2% reported the last episode within the previous week (0.7% of all study subjects), 7.9% (1%) within the last month, and 17.6% (2.2%) within the last year. There was no statistically significant difference in relation to gender (p = 0.927).
Respondents who reported urticaria symptoms or angioedema evaluated the negative impact of the disease on their quality of life as a mean value of 3.8 points on a scale of 0-10. There was a statistically significant difference related to gender (p < 0.001). The negative impact of chronic urticaria was assessed as 6.5 points, and in acute urticaria as 3.6 points (p < 0.001). Angioedema and urticaria symptoms (not necessarily at the same time) were characterized by a negative impact of 5.7 points (Figure 3).

Discussion
The EUP was conducted employing a methodology similar to that of other major global epidemiological questionnaire-based research studies. In 2004, a Spanish study was based on telephone interviews and included 5,003 adults. The methodology and diagnosis criteria were similar to our study [14]. In Greece, a study was conducted in a group of 12,396 participants using a questionnaire on the internet [16]. In Germany, an epidemiological study on urticaria by Zuberbier et al. included inhabitants of Berlin. Four thousand and ninetythree respondents answered the questionnaire-based survey. Individuals suspected of urticaria (n = 767) were additionally interviewed by phone. Respondents who reported the occurrence of urticarial signs and symptoms within the last 3 years were then invited to an outpatient study for allergy tests (double-blind study). The questionnaire used included questions concerning signs and symptoms of the disease, its duration, influence on the quality of life (sleep, entertainment, free time, etc.), probable causes of the disease, body areas affected, concomitant angioneurotic edema, and frequency of symptoms [4]. Our study, because of the similar methodology, could be compared to any one of these studies. Additionally,   the advantages of our study include a large sample size (nearly 5,000 individuals), being carried out all over the country (through representative random-quota sample), validation of the questionnaire on a group of 106 individuals before the main study, interviews conducted by renowned international research companies, and the use (as an aid for the respondents) of photos showing the most common symptoms of urticaria and angioedema. There are limited data on prevalence of urticaria in Poland, with most studies conducted on some selected subgroups of a small sample size. One multi-center, large research study (Epidemiology of Allergic Diseases in Poland -ECAP study) included 4,783 outpatients. The final diagnosis of urticaria was based on the patient's history. In 6-7 and 13-14 year-old children, urticaria was diagnosed in 5.0%, and in adults (20-44 years) in 8.0%, but the ECAP study does not reflect the population structure of Poland [6]. According to our study, 11.2% of respondents aged 15-74 years (95% CI: 10.3-12.1%) reported signs and symptoms of urticaria (3.9% one episode, 7.3% multiple episodes). In our study, there is more than a 3% higher prevalence of urticaria in comparison to the ECAP study. Similarly, Nitter-Marszalska et al., in a group of 2,050 inhabitants of Wroclaw, recorded lower incidence of urticaria in their findings (systemic reactions 8.9% with an urticarial flare in 4.7%) [17]. Another study on occupational dermatoses performed in Poland in the period 1998-2000 (145 participants, residents of 37 randomly selected arable farms) reported prevalence of urticaria of 2.8% (95% CI: 0.1-5.4%) [18].
A Turkish study from 2011-2012, performed in a group of 11,040 patients of a dermatology outpatient clinic, re-ported 8.3% of patients with urticaria, with 54.2% of the female gender. The highest incidence was recorded in the age group between 20 and 50 years [7]. Our findings are similar.
Doña et al. in a group of 1,001 Spanish patients with drug allergies observed urticarial in 82.63% of individuals [19]. The incidence of urticaria over 10% of the population, with 62.8% females, was observed in another Spanish epidemiological study (2005). Mean age of patients with urticaria was 35 years, and the maximal incidence was for the age of 49 years. The incidence of urticaria in children was 13.4%, with food as well as drugs reported to be possible triggering factors (19.7% and 9.5%, respectively). Physical urticaria constituted 5.3% of acute urticaria, with dermographism accounting for 3.2% of patients, cold urticaria 1.1%, heat urticaria 0.7%, solar urticaria 0.4%, and vibratory urticaria 1.1% [12].
Angioedema in the Danish epidemiological questionnaire-based survey (3,471 participants; 18-69 yearsold) was reported in 7.4%, while urticaria was reported in over 35% [20]. Similar results (6%) were obtained by Kalogeromitros et al., with females having more frequent episodes of both angioedema and urticaria [16]. In the present study, gender also strongly influenced prevalence of angioedema (2.5% males and 4.0% females), but in all groups we recorded a lower level than both Danish and Greek studies. There are various methods of epidemiological research on urticaria due to the large number of subtypes of urticaria. A comparison of different epidemiological studies on urticaria was presented by Śpiewak and Plichta [21].
The main limitation of our study was the research method. The study was carried out with a questionnaire-based method, so urticaria and angioedema were diagnosed based on answers of the respondents. The cards with examples of urticaria and angioedema were presented to respondents to help them distinguish the symptoms of the disease. However, Śpiewak et al. found that showing such pictures may evoke emotional responses [22] that may affect the respondents' answers. The answers given by the respondents were not verified in outpatient conditions. On the other hand, it was the only research method that allowed analysis of a representative sample of 5,000 individuals while maintaining acceptable costs. All studies quoted above are considerably different from each other as regards methodology, although they are all based on similar presumptions. They included populations of different habitats, ethnic structure and age. It needs to be stressed that all results and conclusions are based to a significant degree on answers of the respondents. Even if medical consultations have been included in methodology of the trial (as in ECAP's or Zuberbier's study), it was only related to active types of the disease. Therefore, one should not expect similarities to be obtained in terms of results from different surveys. However, all surveys significantly contribute F. Raciborski, A. Kłak, M. Czarnecka-Operacz, D. Jenerowicz, A. Sybilski, P. Kuna, B. Samoliński, EUP WG to the complex picture of epidemiology of urticaria in Europe, and we would like to add the contemporary data on the Polish part of the global 'map' of the problem within the European Union.

Conclusions
The findings of the reported study clearly demonstrate that urticaria and angioedema are a serious health problem in Poland, although its prevalence is below the mean rate for the European population. As we expected, acute urticaria was more common. We confirmed that women are more likely to suffer from acute and chronic urticaria and angioedema than men. We also found out that people affected by urticaria most frequently indicate contact with plants, insect bites/stings, skin contact with other substances or materials and eating certain foods as the provoking factors. Furthermore, urticaria has a significant impact on quality of life.