Publications by authors named "Bulent Enis Sekerel"

73 Publications

Food protein-induced enterocolitis syndrome: Current practices in oral food challenge.

Allergy Asthma Proc 2021 07;42(4):343-349

Oral food challenges (OFC) in food protein-induced enterocolitis syndrome (FPIES) are performed to confirm a diagnosis, test for development of tolerance, and find safe alternatives. We aimed to define OFC outcomes and identify safer test strategies. OFCs performed in children with FPIES over a 5-year period were reviewed. A total of 160 OFCs were performed in 59 children (median age, 2.3 years). The most commonly tested foods were hen's egg, fish, and cow's milk. Sixty-six OFC results (41.3%) were positive. Twelve (18.2%) reactions were mild, 18 (27.3%) were moderate, and 36 (54.5%) were severe. Intravenous fluid, ondansetron, and corticosteroids were administered in 83.3, 72.7, and 66.7% of the patients, respectively; one patient required hospitalization. A reaction was most likely with fish (odds ratio [OR] 2.878 [95% confidence interval {CI}, 1.279-6.473]; = 0.011), and least likely with cow's milk (OR 0.268 [95% CI, 0.082-0.872]; = 0.029). Of the 36 OFCs with egg yolk, 23 patients had a failed OFC, and of the 17 OFCs with egg white (all tolerant to egg yolk), only 2 patients had a failed result. Interestingly, two patients tolerated baked whole egg but not egg yolk. In cow's milk FPIES, two patients could consume fermented milk but not fresh milk. Of the 11 patients with anchovy-triggered FPIES, 6 tolerated sea bass, and 5 tolerated trout, whereas 4 patients with sea bass FPIES tolerated trout. The search for alternative food species, processing, or subdivision of a trigger food is common practice in FPIES, which reflects the expectations of children and their families. The experience gained can be put into practice and will contribute to the understanding of the disease mechanism.
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http://dx.doi.org/10.2500/aap.2021.42.210042DOI Listing
July 2021

Health-related quality of life in children with hereditary angioedema compared with patients with histaminergic angioedema.

Allergy Asthma Proc 2021 07;42(4):325-332

From the Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, Ankara, Turkey; and.

Hereditary angioedema (HAE) is a potentially life-threatening disease that remarkably impacts patients' health-related quality of life (HRQoL). This study evaluated the HRQoL in children with HAE and compared it with healthy controls and patients with histaminergic angioedema (HA). Fifty-nine children with HAE (median [interquartile range {IQR}], ages, 8.9 years [5.4-12.6 years]), 60 children with HA (median [IQR] ages, 10.3 years [8-15.4 years]), and 72 healthy controls (median [IQR] ages, 10.3 years [6.6-13.9 years]) were recruited. All the children and their families completed the age-adapted KINDL generic instrument for assessing health-related quality of life in children and adolescents. The total HRQoL score and other subscales scores of both the patients with HAE and patients with HA, and the parent-proxy reports were significantly lower than those of the healthy children (p < 0.05). In the patients with HAE, the age at symptom onset was positively correlated with physical well-being (r = 0.335; = 0.043) and negatively correlated with self-esteem ( = -0.324; = 0.049). In addition, the physical well-being scores were affected by the site of attacks, which was significantly lower in the patients with abdominal pain attacks ( = 0.045). The family scores and total scores were statistically significantly higher in the HA group than the HAE group ( < 0.001 and = 0.009, respectively). A significant correlation was found between self-report and parent-proxy HRQoLs in total and all subscales scores in the patients with HAE. For HA, there were no significant correlations for family scores. HAE caused significant impairment of the HRQoL of children and their families, and affected their lifestyle and quality of life. In pediatric patients with HAE, the HRQoL is mainly related to age at symptom onset and the site of attacks. Although patients with HAE are affected more negatively than the patients with HA, HA affected the quality of life as well.
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http://dx.doi.org/10.2500/aap.2021.42.210019DOI Listing
July 2021

An Algorithmic Approach for Allergy Testing in Exclusively Breastfed Infants with Atopic Dermatitis.

Int Arch Allergy Immunol 2021 Jun 1:1-2. Epub 2021 Jun 1.

Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

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http://dx.doi.org/10.1159/000516603DOI Listing
June 2021

Clinical phenotypes of childhood food allergies based on immune mechanisms: A multicenter study.

Allergy Asthma Proc 2021 05;42(3):e86-e95

The affiliations of the members of the writing committee and the names of all the authors are provided in the online appendix.

Food allergies (FA) are an important public health concern that place a major burden on the lives of children and their families. The complex pathogenesis of FAs results in multisystemic and heterogenous clinical presentations. To evaluate, according to immune mechanisms, the characteristics and risk factors of childhood FA in Turkey. This descriptive multicenter study included 1248 children with FA, aged < 18 years,, who were evaluated by pediatric allergists in 26 different centers. Immune mechanisms of FA were immunoglobulin E (IgE) mediated in 71.8%, non-IgE mediated in 15.5%, and mixed IgE/non-IgE mediated in 12.7% of the patients. An episode of anaphylaxis had occurred in 17.6% of IgE-mediated FA. The most common food allergens were classified into five categories (in order of decreasing frequency): cow's milk, egg, tree nuts and/or peanut, wheat, and seafood. Allergies to cow's milk and egg declined significantly with age, whereas tree nuts and/or peanut allergies increased with age. The 0-2 year age group accounted for 62.5% of the cases. The most frequent cause of FA and food anaphylaxis was cow's milk before age 13 years and tree nuts and/or peanut during adolescence (ages 13-18 years). Compared with other phenotypes, male sex (odds ratio [OR] 1.486; p = 0.032), sibling(s) (OR 1.581; p = 0.021), and maternal atopy (OR 1.531; p = 0.045) increased the likelihood of IgE-mediated FA, whereas high household income (OR 1.862; p = 0.026) increased the likelihood of non-IgE-mediated FA in multivariate regression analysis. This study showed that the clinical findings of FA were highly variable, depending on age and underlying immune mechanism. Knowing the population characteristics will enable better management of FA in children.
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http://dx.doi.org/10.2500/aap.2021.42.210005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143922PMC
May 2021

Oral food challenge in IgE mediated food allergy in eastern Mediterranean children.

Allergol Immunopathol (Madr) 2021 1;49(3):185-192. Epub 2021 May 1.

Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, Ankara, Turkey;

Background: The oral food challenge (OFC) in IgE mediated food allergy causes anxiety both in parents and in patients due to its inherent risks.

Objective: Documentation of the rate, spectrum, and predictors of positive reactions is instructive.

Methods: Children, who underwent OFC between January 1, 2017 and December 31, 2019 were analyzed.

Results: A total of 1361 OFCs in 613 cases were reviewed. Most of them were performed in preschool children (≤2 years 50%) and 55% of them had more than one OFC. Mainly considered food groups were cow's milk (31.8%), hen's egg (28.5%), tree nuts (20%), legumes (7%), seeds (4.9%), and wheat (2.7%). The overall OFC positivity was 9.6%, whereas 6.7% with cow's milk, 4.9% with hen's egg, 16.1% with tree nuts, 21.6% with wheat, and 32.8% with seeds. The severity scoring revealed grade I (24.4%), II (45.8%), and III (29.7%) reactions. Fifty (38%) cases required epinephrine and four cases required hospitalization. OFCs with sesame seeds (odds ratio [OR]: 7.747, [confidence interval (CI) 95%: 4.03-14.90]), wheat (OR: 3.80, [CI: 1.64-8.84]), and tree nuts (OR: 2.78, [CI: 1.83-4.23]) predicted a positive OFC while a concomitant asthma (OR: 3.61 [CI: 1.27-10.28]) was more likely to elicit anaphylaxis.

Conclusion: In OFC practice, priority is given to basic nutritional sources and the most frequent food allergens, where preschool children with multiple sensitizations are the primary subjects. Increased risks of positive reactions with sesame, tree nut, and wheat and increased risk of anaphylaxis with concomitant asthma should be considered while performing OFC.
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http://dx.doi.org/10.15586/aei.v49i3.189DOI Listing
May 2021

Infantile atopic dermatitis: Serum vitamin D, zinc and TARC levels and their relationship with disease phenotype and severity.

Allergol Immunopathol (Madr) 2021 1;49(3):162-168. Epub 2021 May 1.

Division of Allergy, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey;

Background: Several markers that influence the clinical course of atopic dermatitis (AD) have been investigated so far. Thymus and activation regulated chemokine (TARC) - a Th2-related cytokine - increase in various atopic diseases. It has been shown that vitamin D affects Treg cells and immune responses. Zinc as an essential trace element for cell-cell interactions, cellular differentiation, and proliferation. However, the effect of these markers on infantile AD and disease severity are mostly unknown.

Objective: The aim of this study was to investigate the relationship between TARC, vitamin D, zinc levels, and the disease severity in infants with AD.

Method: AD patients (n = 160) with age and sex that matched healthy controls (n = 79) were included in the study. The diagnosis of AD was made based on the Hanifin-Rajka criteria. The objective SCORAD index was used for the assessment of disease severity.

Results: A total of 160 patients (male 71.9%) with AD were included in the study. The median age of onset of symptoms was 2 (1.0-3.5) months. The lesions initially started on face 76.9%, neck 6.9%, extremities 7.5%, and body 8.8%. Nearly 40% of the patients were found to be atopic. Food allergy was found in 39.4%. The median of objective SCORAD index was 27.5 (17.5-40) in the study group. The TARC levels of AD patients were higher than control group [1803 pg/ml (1006- 3123) vs 709 pg/ml (504-1147), p < 0.001] There was a significant correlation between objective SCORAD scores and TARC values in subjects with AD (r = 0.363, p < 0.001). As the severity of AD increased, vitamin D levels decreased (p for trend 0.015) and TARC values increased (p for trend < 0.001). Serum zinc levels did not change with the severity of the disease. The presence of atopy did not have an influence on serum TARC, zinc, and vitamin D levels.

Conclusion: In infants with AD, disease severity is positively related with TARC levels; and inversely proportional to vitamin D levels. TARC levels differ between patients and healthy controls. The presence of atopy has not been shown to affect these markers. © 2021 Codon Publications. Published by Codon Publications.
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http://dx.doi.org/10.15586/aei.v49i3.191DOI Listing
May 2021

Psychological burden of asthma in adolescents and their parents.

J Asthma 2021 Mar 27:1-6. Epub 2021 Mar 27.

Division of Adolescent Medicine, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Introduction: Asthma, a common chronic disease in adolescents is impacted by factors affecting quality of life. This study aimed to determine the psychosocial factors of adolescents with asthma and their parents.

Methods: The study included 122 adolescents with asthma, 82 healthy controls, and their parents who completed the Asthma Control Test (ACT), Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Brief Symptom Inventory (BSI).

Results: The mean age was 14.2 ± 1.9 years. ACT score was high and depression was low in patients with good treatment compliance. As the age of the first asthma symptoms/diagnosis increased, somatization, anxiety, hostility and general psychopathology scores increased, as did the somatization score of parents. Parental anxiety score was not related with adolescent BSI scores in the controls but in the study group when it was higher, the anxiety, depression, somatization, and general psychopathology scores were higher. PAQLQ showed that anxiety, negative self-esteem, somatization, depression, and general psychopathology were higher in patients concerned about asthma. Depression and somatization scores were higher in the parents of patients who perceived that "Treatment does not contribute to asthma control." Somatization scores were higher among parents of patients who noted: "Asthma will not pass in the long-term" and "I cannot control asthma."

Conclusion: Higher scores of asthma patients who were anxious about the disease and families who were despondent about treatment demonstrate that health care providers should spend more time informing patients and caregivers. Increasing patient treatment compliance during early adolescence will lessen the psychological burden of the disease.
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http://dx.doi.org/10.1080/02770903.2021.1903916DOI Listing
March 2021

Oral health status of asthmatic children using inhaled corticosteroids.

Turk J Pediatr 2021 ;63(1):77-85

Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Background: Due to the increase in the prevalence of asthma, especially in childhood, oral health problems arising from the use of asthma medications have become a major health concern. Inhaled corticosteroids are widely used since they are the cornerstone of asthma management. This study aimed to investigate the effects of inhaled corticosteroids on oral health and various factors regarding active ingredients in inhalers, inhaler-spacer device use, rinsing the mouth after administration of inhaler, oral hygiene practices and parents` education on dental caries susceptibility in young children with asthma.

Methods: Children with asthma who were treated with inhaled corticosteroids for at least 6 months were included in the study. A questionnaire related to demographic characteristics and oral health practices of children was conducted with parents and the children were examined using a dental mirror and probe under dental unit lighting after air-drying the teeth.

Results: Oral health status was evaluated in 115 children, 54 (42-66) months old, 61% male and 39% female with determination of dmft-dmfs, DMFT-DMFS, ICDAS II, plaque index and gingival index. No statistically significant difference was found between sugar-containing and sugar-free inhalers, duration of inhaled corticosteroid use, inhaler-spacer device use, rinsing the mouth after administration of inhaler and dmft-dmfs, DMFT-DMFS, plaque and gingival index (p > 0.05). Long-term inhaled corticosteroid use was significantly associated with oral candidiasis (p=0.029). Also, the results showed that mothers` educational level had a significant effect on children`s oral health (p < sub > dmft/dmfs < /sub > < 0.001; p < sub > gingival index < /sub > =0.049; p < sub > plaque index < /sub > =0.005).

Conclusion: Due to the effect of immunosuppression, long-term use of inhaled corticosteroids enhances the risk of development of the opportunistic pathogen candida. Regular dental visits and preventive dental treatments are needed in these patients for healthy oral status.
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http://dx.doi.org/10.24953/turkjped.2021.01.009DOI Listing
January 2021

Perioperative hypersensitivity reactions during childhood and outcomes of subsequent anesthesia.

Paediatr Anaesth 2021 Apr 11;31(4):436-443. Epub 2021 Feb 11.

Division of Pediatric Allergy and Asthma Unit, Department of Pediatrics, School of Medicine, Hacettepe University, Sıhhiye, Ankara, Turkey.

Background: Pediatric perioperative hypersensitivity reactions are rare, and possibly life-threatening. Identification of precise etiology is crucial to circumvent future re-exposures.

Aims: We aim to evaluate the clinical features and triggers of perioperative hypersensitivity reactions in children, and determine the outcomes of subsequent general anesthesia.

Methods: A retrospective study was performed with patients who underwent skin testing for general anesthesia between 2007 and 2019. We noted demographic features and skin tests (neuromuscular blocking agents, induction agents, and antibiotics). We also recorded specific immunoglobulin Es or provocation results of drugs or substances (latex, chlorhexidine, and ethylene oxide) that patients were exposed to antecedent to the reaction. Telephone interviews were performed to determine the current status of the participants and reconsider subsequent anesthesia.

Results: We enrolled 50 children (58% male) with a suspected perioperative hypersensitivity reaction. The median age was 6.67 (4.4-11.5) years, and the median time between the reaction, and skin tests was 4 (1-36) months. The most common potential causative agents were neuromuscular blocking agents (n = 8), midazolam (n = 3), ketamine (n = 2), and propofol (n = 1). Three children exhibited hypersensitivity to more than one general anesthetics, and three patients were allergic to latex. Thirty-one patients received subsequent anesthesia, and only one patient had a hypersensitivity reaction. A previous history multiple of general anesthesia administration (≥2) increased the risk of reaction to neuromuscular blocking agents.

Conclusion: Data on perioperative hypersensitivity reactions during childhood are rare due to limited diagnostic procedures. Different preference of general anesthetics may change the causative agent. Meticulous evaluation is necessary to safely administer subsequent anesthesia.
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http://dx.doi.org/10.1111/pan.14126DOI Listing
April 2021

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

Allergy 2021 03 29;76(3):816-830. Epub 2020 Dec 29.

Urticaria Center of Reference and Excellence (UCARE), Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Introduction: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.

Aim: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19.

Materials And Methods: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.

Results: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19.

Conclusions: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
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http://dx.doi.org/10.1111/all.14687DOI Listing
March 2021

Recurrent angioedema in childhood: hereditary angioedema or histaminergic angioedema?

Pediatr Dermatol 2021 Jan 4;38(1):143-148. Epub 2020 Dec 4.

Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Background: Recurrent angioedema is a rare entity during childhood. This study aimed to clarify differences between hereditary angioedema (HAE) and histaminergic angioedema (HA) in children.

Methods: Fifty-seven children with HAE (male 36.8%, 8.9 years [5.4-12.5]) and 42 children with recurrent HA (male 42.9%, 11.5 years [8.1-16.8]) were analyzed.

Results: The median age at symptom onset (6 [3-10]; 7.8 [4.5-13] years), frequency of angioedema episodes within last year (3 [2-5]; 5 [2-10]), and duration of symptoms (48 [24-48]; 24 [12-48] hours) were similar in the HAE and HA group, respectively. Recurrent urticaria was observed in 7.3% (n = 3) of patients in the HAE group and in 45.2% (n = 19) of the HA group (P < .001). While angioedema episodes involving the lips (n = 30; 71.4%; P = .035) and eyelids (n = 28; 66.7%; P = .012) were observed more frequently in the HA group, gastrointestinal involvement/abdominal pain (n = 15; 36.6%) was more common in HAE (P < .001). Itching as a prodromal symptom was detected in 47.6% (n = 20) of HA patients versus 14.6% (n = 6) of those with HAE (P = .002). In the logistic regression analysis for the diagnosis of HAE, a family history of angioedema (OR = 58.289 [95% CI 10.656-318.853], P < 001) and trauma (OR = 35.208 [95% CI [4.368-283.794]], P = .001) as a triggering factor were determined to be independent variables.

Conclusion: A family history of angioedema, trauma as a triggering factor, and abdominal pain should suggest the diagnosis of HAE and the need for further investigation.
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http://dx.doi.org/10.1111/pde.14467DOI Listing
January 2021

Phenotypes and natural history of food protein-induced enterocolitis syndrome in the east Mediterranean region.

Allergy Asthma Proc 2020 11;41(6):420-427

From the Department of Pediatric Allergy, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Food protein-induced enterocolitis syndrome (FPIES) is a rare non-IgE mediated food allergy. To delineate the differences in the spectrum of culprit foods, remission patterns, and predictors among varying cultures. We reviewed demographics, culprit foods, outcomes, and predictors in 81 children with a diagnosis of FPIES who were followed up between 2015 and 2020. Eighty-one patients (55.6% boys) were enrolled, including 72 with acute FPIES and 9 with chronic FPIES. Hen's egg was the most common culprit food (36.6%), followed by fish (26.9%), and cow's milk (21.5%). Interestingly, cow's milk was significantly prevalent in chronic FPIES cases (p = 0.006). The most common clinical symptoms were vomiting (100%), pallor (63.4%), and lethargy (55.9%). Emergency department visits were noted in 39 patients (41.9%), of whom 37 (39.8%) were treated with intravenous (IV) fluid. The subjects were followed up for a median (interquartile range) of 19.4 months (12.3-41.2 months), and 26 subjects (32.1%) achieved tolerance. The median (interquartile range) age at tolerance was 2.5 years (2.1-3.2 years). With regard to the culprit foods, hen's egg was observed more frequently in the subjects with resolved FPIES cases (p = 0.008), whereas fish FPIES cases were high in the persistent group (p = 0.001). IgE sensitization of the culprit food was found to be an independent risk factor for the persistence of FPIES (odds ratio 4.855 [95% confidence interval, 1.131-20.844]; p = 0.034). In our cohort, unlike other published series, hen's egg and fish were the two most common culprit foods. Fish differed from other culprit foods, with significantly delayed onset and persistence, and may create a model that allows for the understanding of the disease.
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http://dx.doi.org/10.2500/aap.2020.41.200078DOI Listing
November 2020

The experiences, perceptions and challenges of mothers managing asthma in their children: a qualitative study.

Turk J Pediatr 2020 ;62(5):734-745

Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Background: Despite the fact that childhood asthma poses an important burden, especially on the families, little is known about the emotional experiences of mothers. This article describes the predominant emotional challenges and experiences reported by mothers of children with asthma.

Methods: Individual, semi-structured, in-depth interviews with a qualitative study method was used in collection of the data. Face-to-face interviews with mothers of children with asthma were conducted using sociodemographic data form and semi-structured interview forms developed by the investigators. The transcribed interview texts were analyzed according to a qualitative content analysis.

Results: A total of 20 mothers were interviewed. We found that the experience of mothers of the children with asthma was a strenuous journey of overriding an emotional rollercoaster, that is, from being thrown into a chaotic situation to later processing the difficult situation affected by the asthma. First moment at diagnosis, relaxation against uncertainties, anxiety, fear, truly acceptance, sadness were the predominant emotions. Mothers described experiences and challenges of frequent admission to emergency, administration of medication and treatments, school problems, limitations in physical activity and spouse relationship problems. Experiences of problems contributed to hopelessness, abandoned, angry and burnout. Mothers had concerns about the chronic nature of the disease, side effects of medications, complications that might develop, factors influencing the disease, and future plans.

Conclusions: Mothers of children with asthma described complex emotional journeys. This has implications for healthcare providers who need to be aware of the complexity of these emotional journeys to support parents more effectively, thereby helping improve patient outcomes. Parents should be trained for symptoms and disease management with a written action plan. It is imperative to realize multi-disciplinary team collaboration and to regularly review training and information. Future research should concentrate on promoting awareness, education, advocacy, and support for parents of asthmatic children.
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http://dx.doi.org/10.24953/turkjped.2020.05.004DOI Listing
January 2020

Change in Allergy Practice during the COVID-19 Pandemic.

Int Arch Allergy Immunol 2021 15;182(1):49-52. Epub 2020 Oct 15.

Division of Allergy and Clinical Immunology, Department of Chest Diseases, Faculty of Medicine, Ankara University, Ankara, Turkey,

Background: International guidelines in asthma and allergy has been updated for COVID-19 pandemic and pandemic has caused dramatic changes in allergy and immunology services. However, it is not known whether specialty-specific recommendations for COVID-19 are followed by allergists.

Objectives: By conducting this study, we aimed to determine the attitudes and experiences of adult/pediatric allergists on allergy management during COVID-19.

Method: We used a 20-question survey to elicit data from allergists (residents and pediatric and adult allergists registered to the Turkish National Society of Allergy and Clinical Immunology) across Turkey via e-mail. We analyzed the data statistically for frequency distributions and descriptive analysis.

Results: A total of 183 allergists participated in the survey. Telemedicine was used for management of asthma (73%), allergic rhinitis (53%), atopic dermatitis (51%), chronic urticaria/angioedema (59%), drug hypersensitivity (45%), food allergy (48%), venom allergy (30%), anaphylaxis (22%), and hereditary angioedema (28%). Thirty-one percent of the respondents discontinued subcutaneous immunotherapy (SCIT) during the COVID-19 pandemic. Thirty-four percent of the physicians reported interruption of systemic steroid use in asthma patients, and 25% of the respondents discontinued biological therapy.

Conclusions: Allergists in Turkey have been using telemedicine at a high rate during the COVID-19 pandemic for asthma and rhinitis. The continuation rate of SCIT was low while the discontinuation rate of biologicals and systemic steroid use in asthma was high in Turkey.Our study results and learning from the experiences of other countries and specialties may help to optimize allergy practice and compatibility with international guidelines.
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http://dx.doi.org/10.1159/000512079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649687PMC
January 2021

Improving the diagnostic utility of lip dose challenges to diagnose tree nut allergy.

J Allergy Clin Immunol Pract 2021 01 16;9(1):534-536.e2. Epub 2020 Sep 16.

Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.08.061DOI Listing
January 2021

Food protein-induced allergic proctocolitis may have distinct phenotypes.

Ann Allergy Asthma Immunol 2021 01 25;126(1):75-82. Epub 2020 Aug 25.

Division of Pediatric Allergy and Asthma Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Sıhhiye, Ankara, Turkey. Electronic address:

Background: Food protein-induced allergic proctocolitis (FPIAP) is a non-immunoglobulin E (IgE)-mediated food allergy, which presents with bloody mucoid stool in infants. Although IgE-mediated allergy and sensitizations to offending foods have been described in other non-IgE-mediated food allergies, it has not been investigated in FPIAP.

Objective: To investigate IgE-mediated allergy and sensitization to offending foods in FPIAP.

Methods: Patients (n = 204) were retrospectively recruited and grouped as FPIAP (n = 180; FPIAP with or without the symptoms of IgE-mediated food hypersensitivity to offending and nonoffending foods at initial consultation), FPIAP-IgE sensitization to offending foods (n = 17), and FPIAP-transition to IgE-mediated allergy to offending foods (n = 7). The study was performed in accordance with the protocol approved by the local ethical committee of the Hacettepe University.

Results: The median age of onset of symptoms and the development of tolerance was 2 months (interquartile range [IQR], 1.0-3.0) and 12 months (IQR, 10.0-14.0), respectively, and of the patients with skin prick test or serum specific IgE tests (n = 196), 38 (19.4%) had evidence of IgE sensitization to offending foods at the initial consultation or during follow-up; 17 (8.6%) had IgE sensitization, 7 (3.6%) indicated a transition to IgE-mediated allergy to FPIAP-induced foods. The median age of tolerance development of the FPIAP-transition group (19 months, IQR, 18.0-29.0) was significantly later than that of the FPIAP group (11 months, IQR, 10.0-14.0; P < .001) and the FPIAP-IgE sensitization group (11.0 months, IQR, 9.5-12.0; P < .001). Tolerance was observed within the study period in almost all the patients.

Conclusion: Children with FPIAP may have sensitization or develop IgE-mediated allergy over time to offending foods. In addition, IgE sensitization in FPIAP does not have an unfavorable effect on tolerance development; however, the transition to an IgE-mediated phenotype may delay tolerance for a brief time.
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http://dx.doi.org/10.1016/j.anai.2020.08.021DOI Listing
January 2021

Chronic inducible urticaria subtypes in children: Clinical features and prognosis.

Pediatr Allergy Immunol 2021 01 24;32(1):146-152. Epub 2020 Aug 24.

Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Background: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria induced by a physical stimulus.

Objective: To evaluate the clinical features, prognostic factors, and natural course of childhood CIndU subtypes.

Methods: Patients (1-18 years old, n = 117) diagnosed with CIndU between March 2011 and March 2019 were analyzed. Patients (n = 101) were re-evaluated for the status of their CIndU at least 6 months after the initial evaluation.

Results: The study population comprised of 117 children with a median (inter-quartile range) age of 10.3 (6-14.8) years at admission and a male predominance (53%). Symptomatic dermographism was the most common type of CIndU, affecting 65% of the group, followed by cold urticaria and cholinergic urticaria, which affected 17% and 15.4%, respectively. Baseline serum tryptase levels in cholinergic urticaria and cold urticaria were higher than those in symptomatic dermographism [7.0 (3.3-10.7) μg/L, 4.2 (2.8-9.3) μg/L, and 2.7 μg/L (1.8-5.9), respectively; P = .020]. Recovery was observed in 9.6%, 25.3%, and 34.7% of the CIndU children after 12, 36, and 60 months, respectively. Of the patients with symptomatic dermographism, 40% had remission in 5 years, whereas this rate was only one-fifth in patients with cold urticaria. The worst prognosis was observed in patients with cholinergic urticaria.

Conclusion: This study concluded that nearly one-third of children with CIndU recovered within 5 years and symptomatic dermographism has the best prognosis. Cholinergic urticaria is the CIndU type with the worst prognosis, male dominance, and highest baseline serum tryptase levels.
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http://dx.doi.org/10.1111/pai.13324DOI Listing
January 2021

Economic Burden of Pediatric Asthma in Turkey: A Cost of Illness Study from Payer Perspective.

Turk Thorac J 2020 Jul;21(4):248-254

Department of Health Care Management, Başkent University Faculty of Health Sciences, Ankara, Turkey.

Objectives: To estimate economic burden of pediatric asthma in Turkey from payer perspective.

Materials And Methods: This cost of illness study was based on identification of per patient annual direct medical costs for the management of pediatric asthma in Turkey from payer perspective. Average per patient direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations and interventions, drug treatment and equipment, and co-morbidities/complications.

Results: Based on total annual per patient costs calculated for outpatient admission ($113.14), laboratory-radiological tests ($35.94), hospitalizations ($725.92), drug treatment/equipment ($212.90) and co-morbidities/complications ($144.62) cost items, total per patient annual direct medical cost related to management of pediatric asthma was calculated to be $1,232.53 from payer perspective. Hospitalizations and interventions (58.9%) was the main cost driver. Direct cost for managing controlled and uncontrolled pediatric asthma were calculated to be $530.17 [key cost driver: drugs/equipment (40.0%)] and $1,023.16 [key cost driver: hospitalization/interventions (59.0%)], respectively.

Conclusion: Our findings indicate that managing patients with pediatric asthma pose a considerable burden to health economics in Turkey, with hospitalizations identified as the main cost driver and two-fold cost increment in case of uncontrolled disease.
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http://dx.doi.org/10.5152/TurkThoracJ.2019.19025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371397PMC
July 2020

Rare occurrence of common filaggrin mutations in Turkish children with food allergy and atopic dermatitis

Turk J Med Sci 2020 12 17;50(8):1865-1871. Epub 2020 Dec 17.

Department of Pediatric Allergy, Faculty of Medicine, Koç University, İstanbul, Turkey

Background/aim: Filaggrin is a protein complex involved in epidermal differentiation and skin barrier formation. Mutations of the filaggrin gene (FLG) are associated with allergen sensitization and allergic diseases like atopic dermatitis (AD), allergic rhinitis, food allergy (FA), and asthma. The aim of the study is to reveal the frequency of change in the FLG gene and determine the association between FLG loss-of-function (LOF) mutations and FA and/or AD in Turkish children.

Materials And Methods: Four FLG loss-of-function (LOF) mutations known to be common in European populations were analyzed in 128 healthy children, 405 food-allergic children with or without atopic dermatitis, and 61 children with atopic dermatitis. PCR-RFLP was performed for genotyping R501X, 2282del4, and R2447X mutations; S3247Xwas genotyped using a TaqMan-based allelic discrimination assay. Results were confirmed by DNA sequence analysis in 50 randomly chosen patients for all mutations.

Results: A total of 466 patients [(67% male, 1 (0.7–2.8) years] and 128 healthy controls [59% male, 2.4 (1.4–3.5) years)] were included in this study. Two patients were heterozygous carriers of wild-type R501X, but none of the controls carried this mutation. Three patients and one healthy control were heterozygous carriers of wild-type 2282del4. Neither patients nor controls carried R2447X or S3247X FLGmutations. There were no combined mutations determined in heterozygous mutation carriers.

Conclusions: Although R501X, 2282del4, R2447X, and S3247X mutations are very common in European populations, we found that FLG mutations were infrequent and there is no significant association with food allergy and/or atopic dermatitis in Turkish individuals.
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http://dx.doi.org/10.3906/sag-1910-162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775701PMC
December 2020

Hypersensitivity Reactions to Biologicals: from Bench to Bedside.

Curr Treat Options Allergy 2020 18;7(1):71-83. Epub 2020 Jan 18.

Department of Pediatric Allergy, Hacettepe University School of Medicine, 06100 Ankara, Turkey.

Purpose Of Review: Biologic agents are new treatment options for chronic inflammatory diseases and cancers. As a result of their unique mechanism of action, they are more effective and less toxic treatment option and their clinical usage is increasing. While they are more commonly used, various adverse effects have been observed including life-threatening ones including anaphylaxis. The aim of this review is to distinguish the anaphylaxis from other hypersensitivity reactions (HSR) and provide a management algorithm for the anaphylactic reactions induced by biological agents.

Recent Findings: Many case reports and series have been published regarding anaphylaxis and other hypersensitivity reactions (concerning cytokine release syndrome, acute infusion-related reactions) due to biologic agents. Although acute treatment of HSR varies according to the clinical presentation, desensitization with the drug is the major management option for subsequent administrations in the case of anaphylactic reactions.

Summary: Anaphylaxis and other immediate onset hypersensitivity reactions are occasionally difficult to differentiate from each other, and mixed-type reactions may be observed. Immediate management of anaphylaxis includes discontinuation of infusion, immediate administration of adrenaline, antihistamines, corticosteroids, and other treatment options depending on the symptoms. After 30-120 min of the reaction, a blood sample for serum tryptase level should be obtained and after 4-6 weeks skin testing with the culprit drug should be performed for decision of long-term management via either graded challenge or desensitization.
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http://dx.doi.org/10.1007/s40521-020-00242-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222858PMC
January 2020

Fine-tuning the use of a skin prick test device.

World Allergy Organ J 2020 May 8;13(5):100122. Epub 2020 May 8.

Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, 06100, Ankara, Turkey.

Background: Skin prick tests (SPTs) are the gold standard for the diagnosis of IgE-mediated allergic diseases. Newly introduced devices have different results in performance. This study aimed to provide data for sensitivity, reproducibility, and acceptability of a new SPT device by using different techniques.

Methods: The study was conducted in 4 sections. Different application techniques were evaluated. In the first section, a drop of histamine/saline was put by vial (V). In the second section, it was taken from a well via the test device (W). ALK® Lancet served as a reference in both sections. The techniques were as follows; 1) apply vertical pressure (VP/WP), 2) apply vertical pressure and rotate 90° clockwise (VC/WC), 3) apply vertical pressure and rotate 90° clockwise and then counter-clockwise (VCC/WCC). Pain assessment was performed by using the Wong-Baker FACES Pain Rating Scale. Different histamine concentrations were transferred from the well by the Oryum device and applied as WC in section 3. Lancet and Oryum-WP were compared in terms of time and allergen adequacy in section 4.

Results: In the first section the sensitivity of all techniques for Oryum and lancet were 100%. The false positivity of Oryum-VP, WP and lancet were found 0%. The Oryum-VP technique was found the best for intrapatient coefficient of variation (CV) (10.72%) (p < 0.001). The interpatient CV was similar in the Oryum-VP, VC, VCC and lancet techniques and was different from the Oryum-WP (p < 0.001). In the second section, all Oryum techniques yielded high sensitivities (100%). False-positive results were obtained more in Oryum-WC and WCC. Oryum-WP technique had the lowest pain score. In the 3rd section, the high positive correlation between histamine concentrations was observed (r = 0.731). In terms of time and allergen adequacy, Oryum-WP was superior to the lancet.

Conclusion: Oryum-VP and WP techniques are reliable, tolerable and comparable with the lancet technique.
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http://dx.doi.org/10.1016/j.waojou.2020.100122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218071PMC
May 2020

Systemic and large local reactions during subcutaneous grass pollen immunotherapy in children.

Pediatr Allergy Immunol 2020 08 27;31(6):643-650. Epub 2020 May 27.

Division of Pediatric Allergy and Asthma Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: Subcutaneous immunotherapy (SCIT) is the allergen-specific curative treatment of allergic rhinitis. Adverse effects, most of which are local, can be observed during the immunotherapy. These adverse effects have been reported more frequently during the pollen season. The purpose of this study was to estimate the rate of local, large local, and systemic reactions during the treatment, to determine the relationship between adverse reactions and the season in which these reactions occur, as well as the risk factors for adverse reactions during the grass pollen-specific SCIT treatment in children.

Methods: We retrospectively collected and analyzed the data of 261 children who administered grass pollen SCIT between 2008 and 2018.

Results: A total of 261 children (177, 67.8% male), who received grass pollen SCIT, with a mean (±SD) age of 12.0 ± 3.0 years at the initiation of SCIT were enrolled to the study. The number of the patients who experienced local and large local reactions was 109 and 30, respectively. In addition, the number of the patients with systemic reactions was 35. After the 12 284 injections, local reactions occurred in 357 (2.9%), and this was followed by systemic reaction as 55 (0.4%) and large local reactions as 40 (0.3%). Frequency of local (P < .001) and systemic reactions (P = .003) was higher during grass pollen season than out of the grass pollen season. In multivariate analysis, initiation of SCIT during the grass pollen season [OR:7.351, 95%CI:1.532-35.279, P = .013] and experiencing local reactions [OR:4.214, 95%CI:2.159-8.224, P < .001] were independent predictors for the development of large local and systemic reactions.

Conclusion: SCIT, in which only mild-to-moderate systemic reactions occurred, is safe for the treatment of allergic rhinitis in children. Our study revealed that previous local reactions and initiation of immunotherapy during the grass pollen season were the predictors for large local and systemic reactions during SCIT in children.
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http://dx.doi.org/10.1111/pai.13261DOI Listing
August 2020

Co-sensitization to the fruit seeds and raw potato in children with cashew nut allergy.

Allergy 2020 09 22;75(9):2366-2369. Epub 2020 Apr 22.

Division of Pediatric Allergy and Asthma Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

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http://dx.doi.org/10.1111/all.14315DOI Listing
September 2020

Immunoglobulin E-Mediated Food Allergies Differ in East Mediterranean Children Aged 0-2 Years.

Int Arch Allergy Immunol 2020 25;181(5):365-374. Epub 2020 Feb 25.

Department of Pediatric Allergy, Hacettepe University Faculty of Medicine, Ankara, Turkey,

Objective: Precise diagnosis of allergy requires knowledge of the population's food allergy (FA) spectrum and predictors.

Methods: Medical charts of Turkish children aged 0-2 years with FA and/or atopic dermatitis (AD) were reviewed.

Results: A total of 1,389 patients, 912 with FA and 1,140 with AD, were included. In the FA group, the most frequently diagnosed FAs were egg white (75.9%), cow's milk (55.7%), tree nuts (31.5%) and sesame (20.6%). The detection of FA in 99% of children with any kind of FA necessitate testing with egg white, cow's milk, hazelnut, sesame, walnut, cashew, and pistachio. In the FA group, 72.7 and 56.8% had AD and multiple FA respectively. Multiple FA (56.8 vs. 49.8%) and hen's egg allergy (85.5 vs. 50.2%, p < 0.005) were more common and cow's milk allergy (51.4 vs. 67.1%, p < 0.005) less common in the AD subgroup of the FA group than in the non-AD subgroup. Multiple FA likelihood increases parallel to the severity of AD (p < 0.05). In the AD group, 58.2% had an immunoglobulin E-mediated FA. The risk of concomitant FA increased as the age at symptom onset of AD decreased (OR 0.800 [95% CI 0.731-0.875]; p < 0.001) and the severity of AD increased (OR 2.350 [95% CI 1.898-2.911]; p < 0.001).

Conclusion: Although severe and early-onset AD is a predictor of the presence and magnitude of FA in infancy, the spectrum of FA is a reflection of cultural characteristics. The clinical presentations of both AD and FA may in fact be an expression of the extent of the immune dysregulation underlying atopy and allergy.
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http://dx.doi.org/10.1159/000505996DOI Listing
November 2020

Exercise-induced anaphylaxis: a case report and review of the literature.

Turk J Pediatr 2019 ;61(3):440-443

Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Esenboğa S, Şekerel BE. Exercise-induced anaphylaxis: a case report and review of the literature. Turk J Pediatr 2019; 61: 440-443. Exercise-induced anaphylaxis (EIAn) is a rare, unpredictable, and potentially fatal cause of anaphylaxis which occurs with physical exhaustion. To the best of our knowledge, here we report the first case of EIAn from Turkey with no prior history of allergy. A detailed patient history is the most crucial point in the diagnosis of EIAn. The triggering and co-factors should be questioned in detail to determine treatment recommendations.
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http://dx.doi.org/10.24953/turkjped.2019.03.020DOI Listing
July 2020

Predictors for late tolerance development in food protein-induced allergic proctocolitis.

Allergy Asthma Proc 2020 01;41(1):e11-e18

Food protein-induced allergic proctocolitis (FPIAP) is a non-immunoglobulin E (IgE) mediated food allergy that typically presents with blood-mixed mucoid stool. To identify the predictors that affect the tolerance development in infants with FPAIP and laboratory as well as clinical differences between patients with early and with late tolerance. A total of 185 infants with FPIAP were included. The patients were grouped and analyzed based on laboratory tests and clinical characteristics. The median (interquartile range [IQR]) age of onset of symptoms was 2.0 months (1.0-3.0 months). Symptoms began in severe cases in patients (n = 23) at a younger median (IQR) age (1.5 months [0.7-2.0 months]) than the group with nonsevere presentation (median 2.0 months [IQR 1.5-3.0 months]) (p < 0.001). The frequency of neutropenia (<1500/mm³) (p = 0.045) and eosinophilia (450 mm³) (p = 0.018) was increased in severe cases. Concomitant IgE-related food allergy (odds ratio [OR] 3.595 [95% confidence interval {CI}, 1.096-11.788], p = 0.035), non-IgE-mediated multiple food allergy (OR 3.577 [95% CI, 1.595-8.018], p = 0.002), feeding with cow's milk-based formula (at least once during infancy) (OR 2.517 [95% CI, 1.188-5.333], p = 0.016), and late complementary feeding (OR 5.438 [95% CI, 2.693-10.981], p < 0.001) were the predictors for late tolerance development. The estimated optimal cutoff value for introduction of complementary foods for the resolution of allergy was 5.5 months, with 69.4% sensitivity, 74.4% specificity, and an area under the curve of 0.737 (95% CI, 0.626-0.812) (p < 0.001). This study showed that the early introduction of complementary feeding accelerates tolerance development in FPAIP. A longer duration of an elimination diet has no impact on the resolution of allergy. Physicians should consider conservative avoidance measures and earlier introduction of complementary feeding in FPIAP.
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http://dx.doi.org/10.2500/aap.2020.41.190017DOI Listing
January 2020

Current Trends in Tolerance Induction in Cow's Milk Allergy: From Passive to Proactive Strategies.

Front Pediatr 2019 18;7:372. Epub 2019 Sep 18.

Division of Pediatric Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

This review addresses the current strategies of inducing tolerance development in infant and childhood cow's milk protein allergy (CMPA). The change in prevention strategies for CMPA has been emphasized based on the lack of evidence to support the efficacy of food allergen avoidance in infancy and the concept of the dual-allergen-exposure hypothesis, which suggests that allergen exposure through the skin leads to sensitization, whereas early oral consumption of allergenic food protein induces oral tolerance. The new approach is based on the likelihood of early introduction of allergenic foods to the infant's diet to reduce the development of food allergies through oral tolerance induction. The latest treatment guidelines recommend the continuation of breast feeding and the elimination of cow's milk and products from the maternal diet in exclusively breast-fed infants with CMPA, the use of an extensively hydrolyzed infant formula (eHF) with proven efficacy in CMPA as the first elimination diet in formula-fed infants with CMPA and the use of amino acid-based formula (AAF) in severe cases, such as anaphylaxis, enteropathy, eosinophilic esophagitis, and food protein-induced enterocolitis syndrome (FPIES), as well as cases of multiple system involvement, multiple food allergies, and intolerance to extensively hydrolyzed formula (eHF). In conclusion, this paper presents the current knowledge on tolerance development in infants and children with CMPA to increase the awareness of the clinicians concerning the new approaches in CMPA treatment Tolerance development is considered a relatively new concept in CMPA, inducing a shift in interventions in CMPA from a passive (avoidance of responsible allergen) toward a proactive (tolerance induction) strategy.
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http://dx.doi.org/10.3389/fped.2019.00372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760011PMC
September 2019

Phenotypical characterization of tree nuts and peanut allergies in east Mediterranean children.

Allergol Immunopathol (Madr) 2020 Jul - Aug;48(4):316-322. Epub 2019 Oct 4.

Division of Pediatric Allergy and Asthma Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Sıhhiye, Ankara, 06100 Turkey. Electronic address:

Introduction/objectives: The characteristics of tree nuts (TNs) and peanut (PN) allergies vary in different regions of the world. We aim to identify the characteristics of TNs/PN allergies in Turkish children.

Patients And Methods: A total of 227 children [4.8 (3.2-6.8) years] with TN and/or PN allergies were included. The phenotypical features of TNs/PN allergic children and the risk factors for multiple TNs/PN allergies were evaluated.

Results: Allergy to TNs/PN developed at a median age of 12.0 (10.0-18.0) months. The most common TNs/PN responsible for food allergies were the hazelnut (63.9%) and the pistachio (54.6%). Of TNs/PN allergic children, 54.2% experienced reactions with at least two types of . Current ages 6-10 years [OR:2.455, 95% CI:1.255-4.852, p=0.009] and family history of atopy [OR:2.156, 95% CI:1.182-3.932, p=0.012] were the risk factors for multiple TNs/PN allergies. Most of the patients with cashew nut and pistachio allergies exhibited co-sensitization and co-allergy to both of these TNs/PN. Although the rarest TNs/PN allergy was seen with almond, the possibility of allergy to other TNs or PN was highly increased in the patients with almond allergy compared to other TNs/PN.

Conclusions: Children with TNs/PN allergy living in an East Mediterranean region differ from the counterparts living in Western countries by an earlier age of onset of the TNs/PN allergy symptoms, increasing possibility to have multiple TNs/PN allergy at older ages, and different spectrum of TN/PN allergies (hazelnut followed by pistachio/cashew) that all indicate the consumption habits which are important determinants of TN/PN allergy development.
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http://dx.doi.org/10.1016/j.aller.2019.07.005DOI Listing
April 2021

Children with chronic spontaneous urticaria: Recurrence after remission and its predictors.

J Allergy Clin Immunol Pract 2020 Feb 16;8(2):796-798.e1. Epub 2019 Aug 16.

Faculty of Medicine, Department of Pediatrics, Division of Pediatric Allergy, Hacettepe University, Sihhiye, Ankara, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2019.08.010DOI Listing
February 2020

Severe hypersensitivity reactions to biological drugs in children with rheumatic diseases.

Pediatr Allergy Immunol 2019 12 8;30(8):833-840. Epub 2019 Sep 8.

Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey.

Background: Hypersensitivity reactions (HSR) to biologic drugs (BD) may limit their use in children with rheumatic diseases. We aimed to analyze the incidence and clinical characteristics of immediate type I (IgE/non-IgE) hypersensitivity reactions to BD and the risk factors for these reactions.

Methods: Children with rheumatic diseases using BD who were evaluated in the pediatric allergy department for possible drug hypersensitivity reaction (DHR) due to BD or any other drug were included in the study.

Results: One hundred and twenty-eight children (49.2% boys; 14.6 years [9.9-16.9 years] with juvenile idiopathic arthritis [58%], familial Mediterranean fever [14%], vasculitis [14%], and other diseases [14%]) had used eight different BD with 32 494 infusions/injections. Fifteen patients were evaluated for DHR [injection-site reactions [n = 4], adverse events [n = 2], drug hypersensitivity other than BD [n = 3], and immediate BD hypersensitivity [n = 6]). The incidence of immediate BD HSR was 4.7%, with a clinical presentation of anaphylaxis in 3.9% (tocilizumab [n = 3], rituximab [n = 2], positive skin test with culprit BD [n = 3]). Among patients with BD HSR, the median follow-up was longer (84.5 vs 54 months, P = .048), and renal (33.3% vs 4.1%, P = .002), hematologic involvement (16.7% vs 0, P < .001), and active disease (83.3% vs 13.9%, P < .001) were more common. Logistic regression analysis revealed that renal involvement, more than 14 hospitalizations per lifetime, and more than two different BD used were associated with BD hypersensitivity.

Conclusion: The frequency of severe immediate HSR due to BD was shown to be 3.9% in children with rheumatic diseases. Children with active rheumatic disease and who have exposure to multiple BD should be monitored for BD HSR, particularly during intravenous BD infusions.
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http://dx.doi.org/10.1111/pai.13114DOI Listing
December 2019
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