PDF
ePub
Citation
Print
INTRODUCTION
Urticaria is a common cutaneous disease characterized by pruritic, edematous and erythematous papules or wheals. Of the entire population, approximately 15%~25% experience this problem at least once in their lives1. As identifying eliciting factors may critically influence the duration of urticaria and patient compliance with treatment, it is crucial in the diagnosis and treatment of urticaria. However, identifying the exact cause is often difficult because there are many possible causative factors.
Immunoglubulin E (IgE)-mediated allergic reaction is considered in the pathogenesis of acute urticaria. Thus, an elevated serum IgE level is expected in patients with acute urticaria. While not all chronic immunological urticaria is IgE-mediated and its relationship with IgE level is less significant than that with acute urticaria, in-vitro and in-vivo methods for identifying total or specific IgE levels can be recommended as diagnostic tests and frequently adapted for the diagnosis of acute/chronic urticaria in addition to a detailed history taking and physical examination2. The skin prick test has been commonly performed, but it is invasive and is affected by drugs such as antihistamines. For the detection of specific IgE in serum, several laboratory tests are currently used. The radioallergosorbent test has been used, but its drawbacks include high cost and the need for radioactive agents during the test. Alternatively, the multiple allergen simultaneous test (MAST), especially the MAST-chemiluminescentassay (CLA), is a widely used tool for identifying serum allergens3, because it does not use a radioactive agent or high-cost equipment, and enables the simultaneous examination of multi-allergens with acceptable cost. Recently, the MAST-immunoblot assay was introduced; it is an upgraded MAST assay, that is simpler and faster, and requires less amount of blood sample than the MAST-CLA. The MAST-immunoblot assay has shown similar or better detection performance than the already existing ImmunoCAP (Pharmacia Diagnostics, Uppsala, Sweden) specific IgE and skin prick tests45.
While the MAST-immunoblot assay has been widely used for the diagnosis and identification of causative factors of acute/chronic urticaria, studies have rarely been reported on the effect of specific IgE screening test results on patients with urticaria regarding their subsequent avoidance behavior against positive allergens. The purpose of this study was to analyze the effect of MAST-immunoblot assay results on the avoidance behavior against positive allergens of patients with urticaria, and to evaluate patient assessment results on the usefulness of the test.
MATERIALS AND METHODS
Patient enrollment
Among the patients with urticaria who underwent the MAST-immunoblot assay under the diagnosis of urticaria at the dermatology outpatient clinic of Hallym University Sacred Heart Hospital, those with at least one positive allergen were requested to answer a self-reported questionnaire (Table 1) at least 1 month after their visit. For patients younger than 12 years old, the questionnaire was completed by the parents because the avoidance behaviors of children primarily depend on the parents. Patients with physical urticaria for whom the causative factors were relatively obvious (e.g., cold urticaria, dermatographic urticaria, cholinergic urticaria and solar urticaria), were excluded. Based on a chart review, patients with a history of atopic diseases, for which an IgE-mediated pathomechanism was likely, were also excluded.
The enrollment period was from June 2013 to February 2015, and 101 subjects completed the questionnaire. The study was approved by the Institutional Review Board of Hallym University Sacred Heart Hospital (IRB No. 2012-I004). Written informed consent was obtained from all participants.
MAST-immunoblot assay
The MAST-immunoblot assay was performed using a food panel of the AdvanSure Allergy Screen kit (LG Life Sciences, Seoul, Korea), which is composed of 24 types of food allergens, 6 types of pollen allergens, and 11 types of aeroallergens such as mites, animals, and molds. The test was performed according to the manufacturer's recommendations4. For each patient, 50 µl of serum was pipetted into the reaction trough that contained an allergen-coated membrane and incubated at room temperature for 45 minutes. Non-bound material was removed by washing. After this, biotin-tagged anti-human IgE antibody was added, and the mixture was incubated at room temperature for 30 minutes. After washing to remove unbound antibodies, streptavidin conjugated with alkaline phosphatase was also added, and the mixture was incubated at room temperature for 30 minutes. Non-bound conjugates were removed by washing. After adding the substrate and incubating the mixture at room temperature for 20 minutes, an enzymatic color reaction resulted in the formation of precipitates on the test strips. After complete drying of the test strips, test results were read by using allergy screen reader (AdvanSure AlloScan; LG Life Sciences, Daejeon, Korea). The results were classified into 7 levels ranging from class 0 to 6. Reactions equal or more than class 2 (≥0.7 IU/ml) were considered positive.
Questionnaires
The patients completed the questionnaire, which included their demographic data such as age, sex, educational level, monthly household income, and living environment; avoidance behavior against positive allergens; and self-assessment on the usefulness of the MAST-immunoblot assay. Possible avoidance behaviors that might be performed by patients were listed as answer options for patients to select. The "avoidance success" group consisted of patients who answered that they tried to avoid positive allergens. The 'avoidance failure" group consisted of patients who answered that they did not try or tried but failed to avoid positive allergens.
Statistical analysis
We divided the patients into 3 groups (food allergen, pollen allergen, and aeroallergen-positive groups) according to their test results. In order to determine the factors associated with the success/failure of avoidance against positive allergens, a statistical analysis using a generalized estimating equation was performed. All statistical analyses were performed with IBM SPSS Statistics software (Windows version 21.0; IBM Co., Armonk, NY, USA). p-values<0.05 were considered statistically significant.
RESULTS
Demographic data of the patients
One hundred and one patients (45 men and 56 women) with urticaria were included in the study. The mean age of the patients was 31.5±15.9 years. Owing to the existence of multiple positive allergens in one patient, 144 different data, which were divided into 3 subgroups (n=51, food allergens; n=17, pollen allergens; and n=76, aeroallergens) according to the positive allergens, were analyzed. The demographic data of the subjects are shown in Table 2.
Patients' self-assessment of the usefulness of the MAST-immunoblot assay
The survey included questions concerning the patients' belief in the reliability of the test. The participants were asked whether they believed that avoidance against positive allergens affected the course and prognosis of their disease. Among the participants, 13.9% responded that there was a strong correlation between avoidance success and disease prognosis. On the other hand, 16.7% answered that avoidance against positive allergens had no effect on the prognosis. Patients' willingness to recommend the MAST to other patients seeking the cause of their disease was also determined. Among the participants, 44.6% answered that they were willing to recommend the test to other patients with urticarial.
Avoidance behavior against positive allergens
The success or failure of avoidance against positive allergens after MAST was determined. The patients who answered that they succeeded in avoiding positive allergens accounted for 63.9%, whereas the rest responded that they failed. The patients who showed positivity to pollen allergens showed significantly higher avoidance failure rate than those who showed positivity to food allergens or aeroallergens (p<0.05, Table 3).
Relevant determining factors of success or failure of avoidance against positive allergens
We statistically analyzed the determining factors of avoidance success or failure against positive allergens with a generalized estimating equation (Table 3). The educational level and severity of urticaria were associated with avoidance success or failure. Patients with a higher educational level avoided positive allergens more successfully (p<0.05). Furthermore, the patients with more severe urticaria were likely to avoid positive allergens successfully (p<0.05). Household income level and reliability on the test showed borderline correlations in terms of their relevance to avoidance success/failure (p=0.057 and p=0.075, respectively).
DISCUSSION
The association between IgE level and allergic diseases has been well studied. In-vitro laboratory tests to detect serum IgE are frequently performed for the diagnosis of allergic diseases. Allergen-specific IgE level has a significant value because it is directly associated with occurrence and exacerbation of allergic diseases 67. In the last few decades, many of the pathomechanisms involved in urticaria have been discovered and evidence of the heterogeneity of urticaria has been accumulated8. In spite of the heterogeneous pathogenesis of urticaria, IgE-mediated allergic reaction is frequently considered, especially in acute urticaria. Identifying causative factors is crucial for the diagnosis and treatment of urticaria because it can greatly influence the duration of and patient compliance with treatment. If careful history taking and physical examination are not sufficient to reveal the possible eliciting factors, searching for IgE-mediated allergy is known to be helpful in determining eliciting factors of patients with urticaria and is actually widely adapted by physicians when they treat patients with urticaria2.
The MAST-immunoblot assay, an in-vitro test for identifying multiple allergens simultaneously, was recently introduced and is being used with increasing frequency by virtue of its convenience9. As a part of diagnosing and identifying the causes of urticaria, clinicians frequently check whether patients have associated allergens with a MAST in addition to history taking and physical examination. However, how patients with urticaria avoid positive allergens in real life after obtaining MAST results about possible susceptible allergens is controversial, and no studies have been conducted to investigate this issue. In this study, we analyzed the avoidance behavior of patients with urticaria against positive allergens after a MAST to identify variables that determine the success or failure of avoidance after patients obtain information about the allergens to which they are susceptible.
Several of the findings in the present study will likely be useful for clinicians treating patients with urticaria. First, the types of allergen were divided into food allergens, pollen allergens, and aeroallergens. Patients who had positivity for pollen allergens showed a significantly higher avoidance failure rate than those with positivity for food allergens or aeroallergens, which largely seems to be due to the practical difficulties of avoiding an air-borne ubiquitous allergen. Pollens can be categorized into tree pollens (e.g., birch and oak) and weed pollens (e.g., mugwort, ragweed, and Humulus japonicus). They display seasonal distributions depending on their flowering period. Recently, changes in climate such as global warming appear to have altered the spatial distribution of pollens, and contributed to an increased risk of allergic diseases1011. It also seems that pollens interact with air pollution and, this increases the rate of pollen-induced allergic diseases10. Methods to avoid pollen allergens may include refraining from going outside during seasons in which causative allergens commonly occur, closing windows to prevent allergens from entering, or not going to mountains or parks. However, avoidance is not easy in reality.
Second, patients with a higher educational level were likely to avoid positive allergens more successfully (p<0.05). This result seems to be based on the difference in the patients' understanding about the disease and allergen-specific IgE screening test depending on the educational level, which allows us to conclude that clinicians should provide detailed explanations about the disease and avoidance methods after the test for patients with lower educational levels.
Lastly, self-reported severity of urticaria appeared to be relevant to avoidance success/failure. The patients with more severe urticaria tended to more successfully avoid positive allergens (p<0.05). Kim et al.12 reported no correlation between MAST results and the clinical severity of chronic urticaria. However, we can assume that patients who think they have a more severe disease are more motivated to rely on the MAST results to improve their symptoms, irrespective of the subsequent outcome.
Although not reaching the statistical level of significance, patients with a higher household income and greater belief in the reliability of the MAST results were more likely to avoid positive allergens. On the question to evaluate how much the patients believe in the usefulness of the allergen-specific IgE screening test, only 13.9% of the patients responded that they believed there was a correlation between their avoidance behavior and prognosis of their urticaria. This means that the self-assessment by patients regarding the usefulness of the allergen-specific IgE screening test was low, which allows us to assume that improving the reliability of the test would improve patients' avoidance behavior against susceptible allergens. Furthermore, this result is attributed to the fact that while allergy to a particular antigen may become a cause of urticaria, other various pathogenic factors can also cause urticaria, and the causes are uncertain in many cases.
This study has several limitations that should be considered when interpreting the results. The responses to the questionnaires depended on patient recall. For children who might not have been able to understand the questionnaire, their parents completed the questionnaire, potentially creating a gap between the responses and real avoidance behaviors. Finally, because the study was performed in a single center, the results might not reflect local differences such as residential environment or economic level.
In conclusion, the authors conducted a survey of 101 patients diagnosed with urticaria and showed positive allergens in the MAST-immunoblot assay. The avoidance behavior against each positive allergen, and the determining factors of avoidance success or failure were analyzed. The results of this study showed a difference in avoidance behavior depending on the type of allergen, patient educational level, and severity of urticaria. This research is meaningful in that it is the first study to evaluate the effect of an allergen-specific IgE screening test on patient avoidance behavior against positive allergens in real life, and to analyze relevant determining factors of avoidance success/failure among the multiple patient-related variables. We expect that this study can be used as a source to which clinicians can refer when they treat patients with urticaria and perform allergen-specific IgE screening tests in the future. Further multi-center studies involving a larger population and additional variables are required to verify our findings.
XML Download