Discussion
Urticaria, a common skin disorder, is a member of the group of severe allergic diseases, which may not only cause a decline in the quality of life of affected individuals, but also in their performance at work and school (1). Symptomatic treatment, including anti-histamines, is currently the most frequently used form of management, but after discontinuation of medications a rapid relapse of symptoms commonly occurs (1). Therefore, identification of the responsible allergens prevalent in a particular region may facilitate early diagnosis and the development of strategies to prevent this disease. In the present study, the prevalence of allergen sensitization in recent years in Henan province, where no allergen profile of patients with urticaria has been reported to date, to the best of our knowledge, was investigated.
The present results indicated that 48.0% (524) of the subjects were sIgE-positive to at least one of the 19 allergens tested, which was comparable with the rates in central China (42.9%) (6), Italy (41%) (7) and northern China (52.4%) (8). These results indicated that only half of the patients with urticaria had contact sensitization. However, at present, there isn't any one biomarker with sufficient ability to reflect urticaria. As urticaria is a heterogeneous disease, other reliable indicators, including histamine and cytokines, are helpful to indicate the patients' condition in association with allergens and may be added to support a diagnosis of urticaria in the future. Compared with food allergens, inhaled allergens were the major components in patients with urticaria (the positive rate ranged from 1.4 to 34.5% vs. 0 to 8.1%). In China, the majority of patients with urticaria choose to, or rather they are instructed by their physicians, to eliminate certain foods from their diet without undergoing any further diagnostic procedures. The present results suggested that the contribution of food allergens to urticaria was limited. This was similar to the results of a study by Hsu and Li (9), which indicated that food avoidance is common among patients with CU in China but was revealed to be mostly ineffective, and part of the reason is that allergic disorders in adults generally involve environmental factors through the respiratory tract rather than through food. Furthermore, according to the present data, sensitivity to multiple allergens was more common than that to a single allergen, indicating that sensitization to multiple allergens is common in urticaria. As is known, excessive accumulation of seasonal and perennial allergens above the clinical relevance threshold may give rise to symptoms of allergy (10). It is necessary to develop comprehensive plans to avoid allergens and help patients remain below the clinical relevance threshold. Of note, although sIgE-positivity for certain allergens is likely to be a reaction from other allergic diseases, including rhinitis and asthma, patients were excluded if they were diagnosed with any other allergic diseases in the present study. Patients with known sIgE positivity avoiding those specific allergens may reduce the incidence of urticaria, as previously reported by Chen et al (11).
The present results indicated that of the 19 allergens tested, patients reacted most frequently to the inhaled allergen D. pteronyssinus, cockroach and tree pollen mix, which is similar to the results of a previous study on urticaria (8) or studies on other allergic diseases (12–14). However, cashew nut, shrimp and crab were identified to be the most common food allergens in Henan province, which was inconsistent with a previous study (8), whose results suggested that egg and cow's milk were the most frequent food allergens with positivity in northern China, but the prevalence of them was similar to commonly reported allergens worldwide (15). It is known that the climate determines the types of flora and fauna in a particular geographical area, which may affect airborne and food allergens (16). Henan is a province in the center of China characterized by a high population density and dry weather conditions, providing a relatively suitable environment for dust mite and cockroach. Moreover, the imbalanced economic development and sanitation in Henan may also have played a part. Zhengzhou, the capital of Henan Province, is commonly referred to as a ‘green city’ due to its environment with plenty of vegetation. This may explain the common sensitivity to tree pollen mix allergen. Furthermore, with the development of economy and transportation in this region in recent years, access to seafood, including shrimp and crab, has increased, which explains for the inconsistent results between the present study and traditional food allergens in northern China. However, as the tested allergen sources were not identical to those of/among previous studies, it was not possible to directly compare them. Of note, the present study indicated that positive reactions to several allergens, including D. pteronyssinus, dog hair, cockroach, mold mix, tree pollen mix and shrimp were more frequent in the CU group than in the AU group, suggesting that sensitization to allergens, particularly inhaled ones, had a crucial role in the relapse and duration of urticaria.
Among the 1,091 patients with urticaria, a difference in the sensitization to certain allergens was observed between males and females. The positive rates to 10 allergens (D. pteronyssinus, mulberry, dog hair, cockroach, amaranth, tree pollen mix, cow's milk, cowry, crab and cashew nut) were higher in males than in females. This phenomenon has been reported in several previous studies (6,17,18), but the reacting allergen types between genders were inconsistent. This may be due to different rates of contact to allergens and the difference in immune sensitivity between males and females.
In addition, certain allergens were reported to be associated with age (19,20). The rates of sIgE positivity for six allergens (D. pteronyssinus, mulberry, cockroach, amaranth, grass mix and crab) were low in the younger groups. Subsequently, they increased with age and peaked or plateaued in the 19–25-year-old group followed by a modest decline (the rate for mulberry peaked in the 26–40 year-old group), but they still remained at a relatively high level in the highest age group. For cat dander, dog hair, egg and cow's milk, the positive rates were the highest in the 0–3-year-old group and declined with age. These results were similar to those of previous studies (21–23). Regarding the high sensitization to cat dander and dog hair, one explanation may be that children are more likely to be in close contact with pets whilst playing with them or tend to crawl on the ground where pet hair/dander may accumulate (24). Furthermore, cow's milk and eggs have been reported to be the primary food allergens in children worldwide, including China. It has been indicated that avoidance of pets and breastfeeding in infants and young children were effective to prevent urticaria (25). As for whether any genetic predisposition or hormone secretion has a role in these pathological processes, further research is required in the future.
Furthermore, the present study indicated that the degree of positivity for most allergens was mainly at an ‘Intermediate’ or ‘High’ level in positive cases, indicating that the intensity of sensitization to these allergens was obvious but not extremely high in patients with urticaria. As, hypersensitivity occupied an important position in the pathological process of urticaria (7,26), it is necessary for patients in this area to identify and avoid major allergens in order to remain below the clinical relevance threshold.
The prevalence and distribution of allergens among patients with urticaria revealed by the present study provided information that may be utilized for the prevention, diagnosis and management of urticaria in Henan province. For instance, although the scoring system dividing the intensity of the positivity of sIgE into seven levels has been widely used in clinical research for allergic diseases (5,12), based on the allergen distribution data of the present study, a novel scoring system may be proposed to assist the diagnosis of urticaria, integrating the clinical symptoms of patients with urticaria, as well as histamine, cytokines and other reliable indicators with the consultation of dermatologists. However, further comprehensive, in-depth and multi-center research is still required.
Of note, the present study had certain limitations. First, the tests included a variety of allergens in the environment but the reactivity to only 19 allergens was assessed in the present study. Furthermore, the difference in tested allergen sources limits the comparability with other studies (27). In addition, due to the heterogeneity of urticaria, only part of the cases featured IgE production and type I hypersensitivity (26,28). Further studies are required to explore the pathogenic mechanism of urticaria. Furthermore, healthy controls are not included and there may be bias associated with patient selection due to the retrospective nature of the present study and the severity of this disease cannot be assessed with allergen distribution patterns in detail. Furthermore, patients with urticaria are no longer tested for allergen sensitization after treatment in clinical practice at our hospital, and whether the dynamic changes of the allergen distribution patterns reflect the treatment response still requires to be investigated in further studies.
In conclusion, the prevalence and distribution of several allergens among patients with urticaria in Henan province exhibited differences in terms of gender, age and type of urticaria (CU or AU). The characteristics of allergen sensitization revealed in the present study may facilitate the prevention, diagnosis and management of urticaria in this area, particularly in terms of allergen avoidance management for this disease.