ABSTRACT
The aim of our study is to evaluate the count of eosinophils in peripheral blood in atopic dermatitis (AD) patients over 14 years of age and to compare it with the occurrence of food hypersensitivity (FH) reactions. Complete allergological and dermatological examination was performed in 212 patients included in the study (90 men, 122 women, average age 26.7 years, average SCORAD 32.9). According to our results, in AD patients the difference in count of eosinophils in patients with and without FH reactions is not statistically significant. When evaluating the occurrence of FH reactions to single foods, the count of eosinophils is significantly higher only in patients suffering from reactions to carrot.
Introduction
Atopic dermatitis (AD) is a chronic noncontagious inflammatory skin disease with specific immune and inflammatory mechanisms; it is an inflammation of the epidermis and dermis with characteristic clinical and dermatopathological signs (Liu, Goodarzi, & Chen, Citation2011).
Food hypersensitivity (FH) reactions are a common finding in AD patients – in 78–83% (Celakovska & Bukac, Citation2015; Celakovska, Bukac, & Ettler, Citation2015). The term FH reaction represents the umbrella term for food allergy (IgE-, cellular-, and mixed IgE- and cell-mediated disorders) and for food intolerance (non-allergic FH) (Bindslev-Jensen et al., Citation2004; Li et al., Citation2001). Food intolerance is a non-allergic hypersensitivity to food that does not include the immune system even though the symptoms are similar to those of IgE-mediated allergic reactions. An impaired histamine degradation based on reduced diaminooxidase activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction (Maintz & Novak, Citation2007; Maintz et al., Citation2006). The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block diaminooxidase activity may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Dermatologic sequels can be rashes, itch, urticaria, angioedema, and AD. In addition to histamine-rich food, many foods such as citrus foods are considered to have the capacity to release histamine directly from tissue mast cells even if they themselves contain only small amounts of histamine (Maintz & Novak, Citation2007; Maintz et al., Citation2006). The occurrence of food intolerance, food allergy, and the occurrence of other atopic diseases and parameters in patients suffering from AD were evaluated in several studies (Breiteneder & Mills, Citation2005; Celakovska & Bukač, Citation2011; Celakovska, Citation2015; Celakovska & Bukač, Citation2015; Celakovska, Ettlerová, Vaněčková, & Ettler, Citation2011; Celakovska, Ettlerova, Ettler, Vaněčkováa, & Bukačc, Citation2015a; Celakovska, Ettlerova, Ettler, Vaněčkováa, & Bukačc, Citation2015; Celakovska, Ettlerova, Ettler, & Bukačc, Citation2015).
Eosinophilia (more than 500 eosinophils per microliter of blood) has been shown to be present in most patients with AD and correlates with the disease activity (Celakovska et al., Citation2015b).
However, the diagnostic importance of eosinophilia has been unclear. Since increased blood eosinophils may exist due to any other allergic processes and some AD patients have normal blood eosinophil levels, blood eosinophil levels are not commonly used for diagnostic purposes (Kagi, Joller-Jemelka, & Wuthrich, Citation1992). More recent studies suggested that peripheral blood eosinophilia could be used as a diagnostic tool in differentiating atopic AD from non-atopic AD and that AD patients with other symptoms of atopy have increased blood eosinophilia. Recent studies in both adults and children have indicated a more prominent role of eosinophils in sensitized patients than in those not sensitized (Akdis et al., Citation1999; Borres & Bjorksten, Citation2004; Jenerowicz, Czarnecka-Operacz, & Silny, Citation2007; Noh et al., Citation2010; Park et al., Citation2006; Uehara, Izukura, & Sawai, Citation1990). There are also studies underlining the relation of eosinophil count, eosinophil-associated cytokines, and disease severity (Kondo, Yazawa, & Jimbow, Citation2001; Wu, Li, Chen, Cheng, & Wang, Citation2011). Regarding these results, it seems that eosinophils indicate both severity of disease and allergic sensitization. Eosinophils are also closely associated with the pathogenesis of other atopic diseases, specifically the development of allergic asthma in the respiratory tract and the development of eosinophilic esophagitis in gastrointestinal tract (Bochner & Busse, Citation2005; Cianferoni & Spergel, Citation2016).
But there are no studies evaluating the eosinophil count in AD patients with and without FH reactions.
The aim of our study is the evaluation of peripheral blood eosinophilia in AD patients with and without FH reactions.
Aim of the study
The aim is the evaluation of the correlation between the eosinophil count in the peripheral blood and the occurrence of FH reactions in AD patients.
Methods
In the period 2008–2013, 212 patients suffering from AD at the age of 14 years or older were included in the study. The diagnosis of AD was made with the Hanifin-Rajka criteria (Hanifin & Rajka, Citation1980). Exclusion criteria were long-term therapy with cyklosporin or systemic corticoids, pregnancy, or breastfeeding. Patients with AD having other systemic diseases were excluded from the study as well. Complete dermatological and allergological examination was performed in patients included in the study. This study was approved by Ethics commitee of Faculty Hospital Hradec Králové, Charles University of Prague, Czech Republic.
The count of eosinophils – it included differential white blood cell count with eosinophils. We used the standard microscopic cytology (with a manual review, May-Grünwald- and Giemsa – Romanowsky-type staining, microscop Olympus BX41 – product of Olympus, Hamburg, Germany) and flow cytometry (using Sysmex XE-5000, product of Sysmex, Kobe, Japan). About 5% of peripheral blood eosinophils and more was considered a higher count.
The diagnosis of FH reactions
All the patients were asked by the physician during the dermatological examination to complete the questionnaire concerning the food reactions. The answers concerning the possible adverse food reactions reflect the patients’ history and are not based on the results of examinations (as specific IgE, skin prick tests [SPTs]). The patients were asked to describe only these reactions with clinical symptoms that had been repeteadly observed in their history and are reproducible after a casual ingestion. The most frequent food allergens were mentioned in the questionnaire (egg, cow milk, wheat flour, soy, celery, nuts, fish, different kinds of fruits and vegetables, spices, different kinds of meat, and alcohol) and patients answered if they had experienced some reactions to these foods such as pruritus, worsening of AD, erythema, urticaria, oral allergy syndrome (= burning of the mouth), gastrointestinal, or respiratory problems. Patients also described the time of these reactions (two hours after ingestion or later). The results of examinations, together with the patient’s answers, were collected and processed by the dermatologist.
Statistics
We evaluated the difference in the count of eosinophils between AD patients with and without the occurrence of FH reactions. We also evaluated the difference in the count of eosinophils in AD patients suffering from FH reactions in general and in patients with FH reactions to single foods. Mann–Whitney test was used for comparison, because the underlying distributions are not normal (Gauss).
Results
Patients and tested parameters
About 212 patients suffering from AD at the age of 14 years or older were examined – 90 men and 122 women, the average age 27. 1 years (s.d. 9.5 years), the average SCORAD 32.9 (s.d. 14.1) points. The average count of eosinophils in this group of patients is 5.4%; 166 patients (78%) suffer from FH reactions, in these patients the count of eosinophils is 5.8%; no FH reactions are in 46 patients (22%) and the count of eosinophils is in these patients 4%. The difference is not statistically significant.
The characteristics of 212 patients with AD and FH reactions are shown in .
Table 1. Characteristics of patients.
The occurrence of FH reactions with the clinical reactions and the count of eosinophils in these patients with FH reactions is shown in the . The FH reactions after the ingestion of nuts are described in 69 patients (32%), tomatoes in 41 patients (19%) kiwi in 35 patients (16%), apples in 35 patients (16%), spices in 42 patients (20%), tangerines in 30 patients (14%), oranges in 25 patients (12%), capsidum in 28 patients (13%) fish in 19 patients (9%), celery in 20 patients (9 %), and carrots in 14 patients (7%). In another 4–0.5% patients, the FH reactions were recorded after ingestion of these foods: strawberries, alcohol, chocolate, milk, almond, cherry, honey, potatoes, wine, apricots, garlic, poppy-seeds, cacao, pine-apple, banana, egg, gherkin, cucumbers, pears, pulses, beer, chees, beef, gooseberry, currants, melon, spinach, plum, rice, kohlrabi, ketchup, mustard, parsley, camomile, couliflower, chicken, ray flour, and maize. More than one kind of reactions were described in some patients (for example pruritus or oral allergy syndrome).
Table 2. The occurrence of FH reactions, clinical reactions and the peripheral blood count of eosinophils in these patients with FH reactions.
The number of patients with FH reactions to single foods and the count of eosinophils is recorded in . The difference in count of eosinophils is not statistically significant in patients with FH reactions to nuts, spices, tomatoes, kiwi, apple, tangerines, capsidum, oranges, fishes, celery, alcohol, strawberries, or chocolate in comparison to patients without these reactions. The difference is statistically significant only in patients suffering to FH reactions to carrot: 14 patients (7%) suffer from reactions to carrot, in these patients the count of eosinophils is 9.2%; 198 patients (94%) suffer from no reactions to carrot and the count of eosinophils is in these patients 5.1% ().
Table 3. Number of patients with and without FH reactions to single foods and the peripheral blood count of eosinophils.
Discussion
We perfomed this study to evaluate the count of eosinophils in peripheral blood in AD patients older 14 years of age and to compare this count of eosinophils according to the occurrence of FH reactions. There are no similar studies dealing with this question in AD patients.
In our study, we have not distinguished between food intolerance and food allergy, although the mechanisms leading to symptoms are very different, as mentioned in the introduction. Food intolerance reactions may cause numerous symptoms mimicking allergic reactions. The recorded early allergic reactions in our study have a high diagnostic importance because the early symptoms after ingestion of foods have a clear diagnostic connection with the ingested foods. The patients eliminate these foods but they describe that these reactions are reproducible after a casual ingestion. The aim of our study was to evaluate the occurrence of both types of food reactions in patients with AD and to compare the eosinophil count in AD patients with and without these reactions. Eosinophil numbers as well as eosinophil granule protein levels in the peripheral blood are elevated in most AD patients and appear to correlate with disease activity (Ring, Przybilla, & Ruzicka, Citation2006). These observations point to a potential important role of eosinophils in the pathogenesis of AD (Ring et al., Citation2006). Some patients exhibit normal blood eosinophil counts despite active AD and increased eosinophil numbers might be the consequence of additional allergic disorders. Recent studies in both adults and children have indicated the more prominent role of eosinophils in sensitized patients than in those not sensitized (Akdis et al., Citation1999; Borres & Bjorksten, Citation2004; Jenerowicz et al., Citation2007; Park et al., Citation2006; Uehara et al., Citation1990). Our paper shows that in AD patients suffering from FH reactions the blood eosinophilia is higher in comparison with patients without these reactions although the difference is not statistically significant. When evaluating the occurrence of FH reactions in general, the eosinophils count in patients with FH reaction is 5.8% (higher than normal count) and in patients without these reactions it is 4% (normal count), but the difference is not statistically significant. When evaluating the single foods, the most prominent eosinophilia is recorded in patients suffering to FH reactions to carrots; the count of eosinophils in these patients is 9.2%, and in the patients without reactions to carrot the eosinophil count is 5.1%; this difference is statistically significant. In patients with FH reactions to celery, tangerines, capsidum, oranges, and kiwi, the count of eosinophils is higher in comparison with patients without these reactions, but the difference is not statistically significant. On the other hand, in patients suffering from FH reactions to spices, apples, fishes, alcohol, and chocolate the count of eosinophils is under 5% and it is lower in comparison to patients without these reactions. Regarding the nuts and tomatoes, the eosinophils count is similar in patients with and without the reactions to these foods.
The statistically important difference was found only in patients with reactions to carrots. Regarding the described reactions to carrots in 14 patients (7%) in our study, all these patients suffer from pruritus after ingestion of carrot and oral allergy syndrome is recorded in four patients. In patients with FH reactions to carrot, the FH reaction to apple, capsidum, and nuts is recorded in the majority of them and 15 from 20 patients with FH reaction to carrots suffer from pollen allergy (Celakovska & Bukac, Citation2015; Celakovska et al., Citation2015).
According to Balmer-Webber, allergic reactions to carrot affect up to 25% of food-allergic subjects. In their study, double-blind placebo-controlled food challenges (DBPCFCs) were performed in 26 subjects with histories of allergic reactions to carrot. This study confirmed the allergenicity of carrot by means of DBPCFC. DBPCFC-positive patients had exclusively specific IgE antibodies to birch pollen-related carrot allergens, Dau c 1 being the major allergen. The lack of inhibition of IgE binding to Dau c 1 by birch allergens in a subgroup of patients might indicate a secondary immune response to new epitopes on the food allergen that are not cross-reactive with Bet v 1 (Ballmer-Weber et al., Citation2001). Patients sensitized to birch pollen frequently suffer from a food allergy to plant foods such as celery, carrots, or hazelnut. One of the main manifestations of birch pollen-related food allergy is the oral allergy syndrome. Skin tests and specific IgE determinations are poor predictors of such reactions when assessed by DBPCFC (Ballmer-Weber, Weber, Vieths, & Wüthrich, Citation2008; Breiteneder & Mills, Citation2005; Skypala et al., Citation2011; Breiteneder & Radauer, Citation2004; Sánchez-Monge, Lombardero, García-Sellés, Barber, & Salcedo, Citation1999; Sinha et al., Citation2014).
Study evaluating the blood eosinophilia in AD patients was done in Japan (Kagi et al., Citation1992; Nishimoto, Numahara, Nakashima, & Yoshida, Citation1998). It was suggested that disease severity and personal or family history of respiratory atopy are important factors in determining high blood eosinophil levels in AD (Kagi et al., Citation1992). Akan evaluated the risk factors of disease severity to facilitate better management of children with severe AD (Akan et al., Citation2014). According to their results, eosinophilia may predict severe disease and allergic sensitization. Further large-scale follow-up studies are needed to improve the reliability and relevance of this relation (Akan et al., Citation2014). Accordingly, in a study in which both children and adults were enrolled, eosinophilia was found to be a predictor of food allergy in patients with AD. In this study, 303 patients with AD were studied using elimination diets and food challenge tests. An elimination diet improved clinical severity and decreased blood eosinophil levels (Celakovska, Citation2015). In the Jerenowicz’s study, in patients with positive SPT test (grass pollen, tree pollen, weed pollen, feathers, and animal dander) and detectable specific IgE in serum, and also in patients with symptoms of other atopic diseases, the peripheral blood eosinophilia was more prominent compared to patients with negative SPTs and without symptoms of other atopic diseases, but the difference was not statistically significant (Akdis et al., Citation1999).
According to Ring, clinical improvements due to therapeutic interventions are associated with markedly reduced eosinophilic inflammation. Although these observations make it likely that eosinophil plays an important pathogenic role in AD, its exact function remains to be determined (Ring et al., Citation2006).
Conclusion
Our study evaluated the role of eosinophils in AD patients suffering from FH reactions. As for the single foods, the most prominent eosinophilia is recorded in patients suffering from FH reactions to carrot and the difference is statistically significant in comparison with patients without these reactions. In patients with FH reactions to celery, tangerines, capsidum, oranges, and kiwi, the count of eosinophils is higher in comparisson to patients without these reactions, but the difference is not statistically significant.
Disclosure statement
No potential conflict of interest was reported by the authors.
Notes on Contributors
Jarmila Celakovska works as the specialist for atopic dermatitis in the Department of Dermatology and Venereology Faculty Hospital and Medical Faculty of Charles University, Hradec Králové, Czech Republic. At this Department, she works in the research of atopic dermatitis in the following of some immunological parameters such as food allergy and food sensitisation.
Josef Bukac is the mathematician, and works as a specialist for the statistical analysis at the Department of Medical Biophysic, Medical Faculty of Charles University in Hradec Králové, Czech republic.
References
- Akan, A., Azkur, D., Civelek, E., Erkoçoğlu, M., Yılmaz-Öztorun, Z., Kaya, A., … Kocabaş, C. (2014). Risk factors of severe atopic dermatitis in childhood: Single-center experience. The Turkish journal of pediatrics, 56(2), 121.
- Akdis, C., Akdis, M., Simon, D., Dibbert, B., Weber, M., Gratzl, S., … Simon, H. U. (1999). T cells and T cell-derived cytokines as pathogenic factors in the nonallergic form of atopic dermatitis. Journal of Investigative Dermatology, 113, 628–634. doi: 10.1046/j.1523-1747.1999.00720.x
- Ballmer-Weber, B., Weber, J., Vieths, S., & Wüthrich, B. (2008). Predictive value of the sulfidoleukotriene release assay in oral allergy syndrome to celery, hazelnut, and carrot. Journal of investigational allergology & clinical immunology, 18(2), 93–99.
- Ballmer-Weber, B., Wüthrich, B., Wangorsch, A., Fötisch, K., Altmann, F., & Vieths, S. (2001). Carrot allergy: Double-blinded, placebo-controlled food challenge and identification of allergens. Journal of Allergy and Clinical Immunology, 108(2), 301–307. doi: 10.1067/mai.2001.116430
- Bindslev-Jensen, C., Ballmer-Weber, B., Bengtsson, U., Blanco, C., Ebner, C., Hourihane, J., … Werfel, T. (2004). Standardization of food challenges in patients with immediate reactions to foods – Position paper from the European academy of allergology and clinical immunology. Allergy, 59, 690–697. doi: 10.1111/j.1398-9995.2004.00466.x
- Bochner, B., & Busse, W. (2005). Allergy and asthma. Journal of Allergy and Clinical Immunology, 115, 953–959. doi: 10.1016/j.jaci.2005.02.032
- Borres, M., & Bjorksten, B. (2004). Peripheral blood eosinophils and IL-4 in infancy in relation to the appearance of allergic disease during the first 6 years of life. Pediatric Allergy and Immunology, 15(3), 216–220. doi: 10.1111/j.1399-3038.2004.00143.x
- Breiteneder, H., & Mills, E. (2005). Molecular properties of food allergens. Journal of Allergy and Clinical Immunology, 115, 14–23. doi: 10.1016/j.jaci.2004.10.022
- Breiteneder, H., & Radauer, C. (2004). A classification of plant food allergens. Journal of Allergy and Clinical Immunology, 113, 821–830. doi: 10.1016/j.jaci.2004.01.779
- Celakovska, J. (2015). Atopic march, food allergy and food hypersensitivity in children and adolescents suffering from atopic dermatitis. Food and Agricultural Immunology, 26(4), 590–600. doi: 10.1080/09540105.2014.998636
- Celakovska, J., & Bukač, J. (2011). Food adverse reactions in patients over 14 years of age suffering from atopic eczema. Food and Agricultural Immunology, 22(2), 105–114. doi: 10.1080/09540105.2010.533751
- Celakovska, J., & Bukac, J. (2015a). The severity of atopic dermatitis and analysis of the food hypersensitivity reactions. Food and Agricultural Immunology, 26(6), 896–908. doi: 10.1080/09540105.2015.1043622
- Celakovska, J., & Bukač, J. (2015b). Food allergy in patients suffering from atopic dermatitis – Association with concomitant allergic diseases. Food and Agricultural Immunology, 26(3), 325–339. doi: 10.1080/09540105.2014.914470
- Celakovska, J., Bukac, J., & Ettler, K. (2015). Food hypersensitivity reactions in atopic dermatitis patients and analysis of contomitant diseases. Food and Agricultural Immunology, 26(2), 260–270. doi: 10.1080/09540105.2014.900531
- Celakovska, J. Ettlerova, K., Ettler, K., & Bukačc, J. (2015). Food allergy, asthma bronchiale, and rhinitis in atopic dermatitis patients with total immunoglobulin E under and above 200 IU/ml. Food and Agricultural Immunology, 26(5), 671–681. doi: 10.1080/09540105.2015.1007447
- Celakovska, J., Ettlerová, K., Vaněčková, J., & Ettler, K. (2011). The peanut allergy in patients suffering from atopic dermatitis over 14 years of age. Food and Agricultural Immunology, 22(3), 195–204. doi: 10.1080/09540105.2010.549214
- Celakovska, J., Ettlerova, K., Ettler, K., Vaněčkováa, J., & Bukačc, J. (2015a). Sensitization to aeroallergens in atopic dermatitis patients: Association with concomitant allergic diseases. Journal of the European Academy of Dermatology and Venereology, 29(8), 1500–1505. doi: 10.1111/jdv.12891
- Celakovska, J., Ettlerova, K., Ettler, K., Vaněčkováa, J., & Bukačc, J. (2015b). Evaluation of food allergy to wheat, cow milk, egg, soy and peanuts in patients suffering from atopic dermatitis. Food and Agricultural Immunology, 26(1), 26–37. doi: 10.1080/09540105.2013.864603
- Celakovska, J., Ettlerova, K., Ettler, K., Vaněčkováa, J., & Bukačc, J. (2015c). Evaluation of allergy to soy in patients with atopic dermatitis older than 14 years of age. Food and Agricultural Immunology, 26(1), 60–70. doi: 10.1080/09540105.2013.864604
- Cianferoni, A., & Spergel, J. (2016). Eosinophilic esophagitis: A comprehensive review. Clinical Reviews in Allergy & Immunology, 50(2), 159–174. doi:10.1007/s12016-015-8501-z
- Hanifin, J., & Rajka, G. (1980). Diagnostic features of atopic dermatitis. Acta Dermatol Venereol, 92, 44–47.
- Jenerowicz, D., Czarnecka-Operacz, M., & Silny, W. (2007). Peripheral blood eosinophilia in atopic dermatitis. Acta dermatovenerologica Alpina, Panonica, et Adriatica, 16, 47–52.
- Kagi, M., Joller-Jemelka, H., & Wuthrich, B. (1992). Correlation of eosinophils, eosinophil cationic protein and soluble interleukin-2 receptor with the clinical activity of atopic dermatitis. Dermatology, 185(2), 88–92. doi: 10.1159/000247419
- Kondo, S., Yazawa, H., & Jimbow, K. (2001). Reduction of serum interleukin-5 levels reflect clinical improvement in patients with atopic dermatitis. The Journal of Dermatology, 28, 237–243. doi: 10.1111/j.1346-8138.2001.tb00124.x
- Li, X., Kleiner, G., Huang, C., Lee, S., Schofield, B., Soter, N., & Sampson, H. (2001). Murine model of atopic dermatitis associated with food hypersensitivity. Journal of Allergy and Clinical Immunology, 107, 693–702. doi: 10.1067/mai.2001.114110
- Liu, F., Goodarzi, H., & Chen, H. (2011). IgE, mast cells, and eosinophils in atopic dermatitis. Clinical Reviews in Allergy & Immunology, 41(3), 298–310. doi: 10.1007/s12016-011-8252-4
- Maintz, L., Benfadal, S., Allam, J., Hageman, T., Fimmers, R., & Novak, N. (2006). Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema. Journal of Allergy and Clinical Immunology, 117(5), 1106–1112. doi: 10.1016/j.jaci.2005.11.041
- Maintz, L., & Novak, N. (2007). Histamin and histamine intolerance. American Journal of Clinical Nutrition, 85(5), 1185–1196.
- Nishimoto, M., Numahara, T., Nakashima, K., & Yoshida, T. (1998). Peripheral eosinophil counts relates the improvement of the skin lesions of atopic dermatitis patients more sensitive than serum eosinophil cationic protein levels. Arerugi, 47(6), 591–596.
- Noh, G., Jin, H., Lee, J., Noh, J., Lee, W. M., & Lee, S. (2010). Eosinophilia as a predictor of food allergy in atopic dermatitis. Allergy and Asthma Proceedings, 31, 18–24. doi: 10.2500/aap.2010.31.3312
- Park, J., Choi, Y., Namkung, J., Kim, W. S., Lee, J. H., Park, H. J., … Yang, J. M. (2006). Characteristics of extrinsic vs. intrinsic atopic dermatitis in infancy: Correlations with laboratory variables. British Journal of Dermatology, 155, 778–783. doi: 10.1111/j.1365-2133.2006.07394.x
- Ring, J., Przybilla, B., & Ruzicka, T. (2006). Handbook of atopic eczema. ISBN 3-540-23133-1. Berlin: Springer – Verlag, pp. 299, 313, 318.
- Sánchez-Monge, R., Lombardero, M., García-Sellés, F., Barber, D., & Salcedo, G. (1999). Lipid-transfer proteins are relevant allergens in fruit allergy. Journal of Allergy and Clinical Immunology, 1, 514–519. doi: 10.1016/S0091-6749(99)70479-3
- Sinha, M., Singh, R., Kushwaha, G., Iqbal, N., Singh, A., & Singh, T. P. (2014). Current overview of allergens of plant pathogenesis related protein families. The Scientific World Journal, 2014, 543195. doi:10.1155/2014/543195
- Skypala, I., Calderon, M., Leeds, A., Emery, P., Till, S., & Durham, S. (2011). Development and validation of a structured questionnaire for the diagnosis of oral allergy syndrome in subjects with seasonal allergic rhinitis during the UK birch pollen season. Clinical & Experimental Allergy, 41, 1001–1011. doi: 10.1111/j.1365-2222.2011.03759.x
- Uehara, M., Izukura, R., & Sawai, T. (1990). Blood eosinophilia in atopic dermatitis. Clinical and Experimental Dermatology, 15(4), 264–266. doi: 10.1111/j.1365-2230.1990.tb02086.x
- Wu, K., Li, T., Chen, C., Cheng, H., & Wang, T. (2011). Correlations of serum interleukin-16, total IgE, eosinophil cationic protein and total eosinophil counts with disease activity in children with atopic dermatitis. International Journal of Immunopathology and Pharmacology, 24, 15–23.