Plastic bronchitis during childhood: Diversity of presentation, etiology, treatment, and outcomes.

OBJECTIVE: Plastic bronchitis (PB) is a rare disease in children, and reliable data are scarce. Here, we aimed to analyze the clinical features, management, and outcomes in children with PB. METHODS: The medical data of patients who were followed up with a diagnosis of PB between January 2010 and March 2022 were retrospectively analyzed. RESULTS: The median age of 15 patients was 9 (interquartile range: 4-10) years with a male/female ratio of 12/3. Initial symptoms included recurrent pneumonia (33.3%), persistent atelectasis (33.3%), cast expectoration (26.6%), and intense, persistent cough (6.6%). The most common underlying diagnosis was asthma (n = 12, 80%), and six of the patients were newly diagnosed. The most common radiological findings were atelectasis as a consequence of major airway obstruction on chest X-ray or computed tomography. Five patients, all diagnosed as having asthma, had recurrent PB and required multiple airway procedures for treatment and diagnosis. During a median 7-year follow-up of five patients, occasionally cast expectoration was observed in one patient with asthma who had poor compliance with inhaled corticosteroids. CONCLUSION: PB is a common reflection of the different underlying etiologies in the pediatric age group, and treatment and outcomes are closely related to these. It should be kept in mind that asthma can be a predisposing factor for the development of PB.

Comparison of miRNA expression in patients with seasonal and perennial allergic rhinitis and non-atopic asthma.

BACKGROUND: MicroRNAs (miRNA) are small non-coding molecules that play a significant regulatory role in several allergic diseases. However, their role in allergic rhinitis is still not clearly understood. The aim of this study was to identify the candidate miRNAs that can discriminate between different forms of allergic rhinitis and also differ in and out of the allergen season. METHODS: The study included 20 healthy children, 20 patients with seasonal allergic rhinitis (SAR), 20 non-atopic asthmatics (NA-A), and 12 patients with perennial allergic rhinitis (PAR). Patients with SAR were evaluated comparatively in and outside the allergen season. The changes in the expressions of selected miRNAs (miR- 125b, miR-126, miR-133b, miR-181a, and miR-206) that were found related to the allergic diseases according to the literature were determined using quantitative polymerase chain reaction. RESULTS: In the SAR group, expression levels of miR-125b (p=0.040) and miR181a (p=0.014) were lower than in the controls outside of the allergen season. Expression levels of miR-181a were different between patients with SAR and NA-A (p=0.003), also between the SAR and PAR (p=0.001) groups in multiple comparisons. In contrast, the expression of miR-206 was found to be decreased in patients with NA-A and PAR compared with the controls (p=0.005 and p=0.024, respectively). In correlation analysis, expression levels of miR-125b and peak expiratory flow (PEF) values were found to be negatively correlated in the SAR (p=0.013) and PAR (p=0.029) groups. The expression level of miR-206 was positively correlated with total IgE levels in PAR (p=0.007). Receiver operating characteristic analysis revealed that miR-125b and miR-181a predicted the risk of SAR (p=0.040 and p=0.014, respectively), and miR-206 for NA-A and PAR (p=0.005 and p=0.024, respectively). CONCLUSIONS: Our study showed that expression levels of miRNAs were different according to the type of allergic diseases and the presence of allergens. miR-181a and miR-125b can be candidate biomarkers for SAR, and miR-206 for NA-A and PAR.

The common triggers of urticaria in children admitted to the pediatric emergency room.

BACKGROUND: Urticaria frequently causes pediatric emergency department (PED) admissions. Children with urticaria may unnecessarily avoid suspected allergens. We aimed to investigate the possible and exact triggers of urticaria in children admitted to the PED. METHODS: Medical records of children admitted to the PED within a 1-year period were evaluated for the International Classification of Diseases 10 (ICD-10) L50 urticaria code, noting symptoms, and possible triggers of urticaria. We performed telephone interviews to complete the missing data and further diagnostic tests for IgE-mediated allergies to identify the exact triggers of urticaria. RESULTS: Among 60,142 children, 462 (0.8%) with the L50 code were evaluated. Possible triggers based on the history and physical examination could be identified in 46%: infections (18%), drugs (11%), foods (8%), infections and drugs (3%), insects (3%), pollen (1%), blood products (0.4%), and vaccines (0.4%). The most frequent infections related to urticaria were upper respiratory tract infections (74.5%), urinary tract infections (13.2%), gastroenteritis (8.2%), and otitis media (4.1%). After a diagnostic workup, IgE-mediated allergic diseases were diagnosed in 6% of patients. Twenty-two percent of the patients had multiple PED admission for the same urticaria flare. Urticaria severity was found to be the most important risk factor for readmissions to the PED (odds ratio: 3.86; 95% confidence interval: 2.39-6.23; p < .001). No relationship between urticaria severity, duration, and the triggers was present. CONCLUSIONS: Despite detailed diagnostic tests, IgE-mediated allergic triggers were rarely the cause of urticaria in children admitted to the PED. Infections are the most frequent trigger. Severe urticaria causes more frequent readmissions to the PED.

Obesity is a risk factor for decrease in lung function after COVID-19 infection in children with asthma.

INTRODUCTION: It is not clear whether asthma, the most frequent chronic disease in childhood, is a risk for severe SARS-CoV-2 infection in the pediatric population and how SARS-CoV-2 infection affects the lung functions in these patients. PURPOSE: We aimed to investigate the course and the consequences of SARS-CoV-2 infection among children with asthma and determine the risk factors for the decline in lung function tests (LFTs). METHODS: In this retrospective study, asthmatic children with coronavirus disease 2019 (COVID-19) were compared with a random control group of asthmatic patients without COVID-19. In addition, the clinical course and the effect on LFTs of COVID-19 among children with asthma were also evaluated. RESULTS: One hundred eighty-nine patients who had COVID-19, and 792 who did not were included in the study. Fever, fatigue, and cough were the most frequent symptoms during COVID-19. Regarding the severity of COVID-19, 163 patients (87.6%) had a mild clinical condition, 13 (7%) had moderate disease, 1 (0.5%) had severe disease, and 2 had (1.1%) critically ill disease. Two patients were diagnosed with multisystem inflammatory syndrome in children (MIS-C), one patient suffered from pneumothorax. LFTs of the patients before and after COVID-19 infection were analyzed; no significant differences were found in FEV1 % (91.7% vs. 90.9%, p = 0.513), FVC% (89.8% vs. 90.8%, p = 0.502) and FEV1 /FVC (103.1% vs. 100.6%, p = 0.056), while FEF25%-75% values (107.6% vs. 98.4%, p < 0.001) were significantly lower after the COVID-19 infection. Obesity (odds ratio [OR]: 3.785, 95% confidence interval [CI]: 1.152-12.429, p = 0.028] and having a family history of atopy (OR: 3.359, 95% CI: 1.168-9.657, p = 0.025] were found to be the independent risk factors for ≥25% decrease in FEF25-75 after COVID-19 infection. CONCLUSION: COVID-19 infection leads to dysfunction of the small airways in asthmatic children and obesity is an independent risk factor for a ≥25% decrease in FEF25-75. The long-term effects of COVID-19 infection especially on small airways require close monitoring in children with asthma.

Subcutaneous Allergen Immunotherapy in Children: Real Life Compliance and Effect of COVID-19 Pandemic on Compliance.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma, and venom allergy. Compliance is essential for SCIT to obtain maximal benefit as it is a long-term treatment. OBJECTIVES: This study aimed to determine the level of real-life SCIT compliance in pediatric patients and the associated factors. Additional aims were to determine how SCIT compliance was affected by the COVID-19 pandemic and why some patients dropped out SCIT. METHOD: Pediatric patients diagnosed with allergic rhinitis, allergic asthma, or venom allergy that received SCIT between September 2012 and July 2020 were analyzed. RESULTS: The study included 201 children (66.7% male) with a median (interquartile range) age of 12.8 years (9.4-15.2) at the time of the first SCIT injection. The overall compliance rate before COVID-19 pandemic was 86.1%. Short SCIT follow-up time and venom anaphylaxis were found to be risk factors for drop out. The leading causes of drop outs were moving to another city/country (32.1%), symptom improvement (17.8%), treatment ineffectiveness (14.2%), and adverse reactions (14.2%). Among the 108 patients that were still receiving SCIT during the COVID-19 pandemic, 31 (28.7%) dropped out the therapy. The most frequent reasons for drop-out were fear of being infected with COVID-19 (35.4%) and thinking that the AIT practise stopped due to COVID-19 pandemic (29%). Male gender and older age were found to be the independent risk factors for drop-out of SCIT. CONCLUSIONS: Real life compliance in children was found 13.9% and it was higher than adults. Nearly one-third of children dropped out during the CO-VID-19 pandemic. Male gender and older age are associated with SCIT drop-out during the COVID-19 pandemic.

The impact of skin prick testing on pain perception and anxiety in children and parents

Background Skin prick testing (SPT) is a major diagnostic tool in patients with allergic symptoms. The testing process may involve pain, anxiety, and stress on children and parents. Objective We aimed to measure the level of pain and anxiety before and after SPT in children and parents, and tried to identify predictive factors. Methods The children underwent SPT and parents completed the State Trait Anxiety Inventory (STAI) S-Anxiety before and after SPT, T-Anxiety before SPT. The study nurse completed Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) scores (<5 years) or Wong-Baker FACES Pain Rating Scale (VAS), (≥5 years) after the SPT, in order to quantify pain. Results A total of 523 children (5.3 [2.8–9.1] [median, interquartile range] years old, 59.5% male) were evaluated. Parent gender was a predominant factor for anxiety, as mothers had a higher pre-test STAI (S-Anxiety) score, STAI (T-Anxiety), and post-test STAI (S-Anxiety) score than fathers (p < 0.001). Pre-test STAI (S-Anxiety) scores of parents decreased with increasing age (for 0–<5 years, 5–<12 years, and ≥12 years; [p for trend = 0.016]). The children tested on the back had higher VAS scores compared with the ones tested on the forearm [2[0–4] vs 2[0–2], [p = 0.005]). Risk factors determining higher general anxiety STAI (T-Anxiety) scores above the median were female sex for the parent (OR = 1.68; 95% CI [1.10–2.57]; p = 0.017), and parent’s education level being greater than or equal to high school level (OR = 1.83; 95% CI [1.27–2.64]; p = 0.001). Conclusion SPT may cause anxiety and pain in a subgroup of children particularly in younger age, and if performed on the back. Anxiety levels were higher in mothers, and in parents with high education levels (AU)

The impact of skin prick testing on pain perception and anxiety in children and parents.

BACKGROUND: Skin prick testing (SPT) is a major diagnostic tool in patients with allergic symptoms. The testing process may involve pain, anxiety, and stress on children and parents. OBJECTIVE: We aimed to measure the level of pain and anxiety before and after SPT in children and parents, and tried to identify predictive factors. METHODS: The children underwent SPT and parents completed the State Trait Anxiety Inventory (STAI) S-Anxiety before and after SPT, T-Anxiety before SPT. The study nurse completed Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores (<5 years) or Wong-Baker FACES Pain Rating Scale (VAS), (≥5 years) after the SPT, in order to quantify pain. RESULTS: A total of 523 children (5.3 [2.8-9.1] [median, interquartile range] years old, 59.5% male) were evaluated. Parent gender was a predominant factor for anxiety, as mothers had a higher pre-test STAI (S-Anxiety) score, STAI (T-Anxiety), and post-test STAI (S-Anxiety) score than fathers (p < 0.001). Pre-test STAI (S-Anxiety) scores of parents decreased with increasing age (for 0-<5 years, 5-<12 years, and ≥12 years; [p for trend = 0.016]). The children tested on the back had higher VAS scores compared with the ones tested on the forearm [2[0-4] vs 2[0-2], [p = 0.005]). Risk factors determining higher general anxiety STAI (T-Anxiety) scores above the median were female sex for the parent (OR = 1.68; 95% CI [1.10-2.57]; p = 0.017), and parent's education level being greater than or equal to high school level (OR = 1.83; 95% CI [1.27-2.64]; p = 0.001). CONCLUSION: SPT may cause anxiety and pain in a subgroup of children particularly in younger age, and if performed on the back. Anxiety levels were higher in mothers, and in parents with high education levels.

Allergic reactions during childhood vaccination and management.

BACKGROUND: Vaccination is one of the most effective public health tools to prevent a variety of infectious diseases. However, concerns about vaccine related adverse effects cause difficulties in clinical practice. METHODS: This review was prepared based on the latest literature available in the PUBMED database in English language (as of March 2021), and all articles with the keywords pediatric vaccine, allergy, hypersensitivity, adverse reaction were evaluated to prepare the article. RESULTS: Vaccine related confirmed allergic reactions are rare in children, ranging between 0,65-1.45 cases per million vaccine doses. Most of the allergic reactions are self-limited local reactions although in some cases severe anaphylaxis with multisystem involvement can be observed. Allergic reactions may occur because of either the active component (the antigen) of the vaccine, or additional components, such as preservatives, adjuvants, antimicrobials, stabilizers and other substances. Finding the culprit allergen is necessary to prevent future exposure to the allergen and to use alternative vaccines if possible. Diagnosis is largely based on a detailed history and clinical manifestation; also in vivo and in vitro tests may be helpful. CONCLUSIONS: In this review we provide information about hypersensitivity reactions to allergen components of childhood vaccines along with the diagnosis and management of vaccine allergy. Besides the tremendous benefits of vaccination for the health of children, we emphasized that the risk of adverse effects is rare and poses a negligible threat.

Food-induced anaphylaxis in infants, as compared to toddlers and preschool children in Turkey.

BACKGROUND: The literature includes scarce data on infants with food-induced anaphylaxis (FIA). MATERIALS AND METHODS: Medical records of the patients diagnosed with FIA aged 0-6 years between 2015 and 2020 were retrospectively analyzed. RESULTS: During the study period, there were 451 instances of FIA in 314 patients, of which 175 (38.8%) occurred in 160 infants (50.9%). The median (IQR) age of infants was 7 months (6-9 months) with a male predominance (67.5%), of which 7.5% had multiple instances (≥2) and 60% atopic dermatitis. The most common triggers were cow's milk (51.4%), tree nuts (16.6%), and hen's egg (15.4%), whereas tree nut was the most common trigger in toddlers (35.8%) and preschool children (35.2%). Skin and neurologic symptoms, and nausea-vomiting occurred more frequently (P = .003, P ≤ .001, and P = .003, respectively), whereas respiratory symptoms occurred less commonly in infants compared to toddlers and preschool children (P ≤ .001). In infants, 65 (37.1%) mild, 92 (52.6 %) moderate, and 18 (10.3%) severe episodes of anaphylaxis were detected. History of recurrent wheezing (OR: 6.837 [95% CI: 1.940-24.097], P = .003) and tree nut allergy (OR: 2.849 [95% CI: 1.056-7.688], P = .039) were found to be independent risk factors for moderate-to-severe anaphylactic reactions. 40.6% of the infants received adrenaline, which was lower than the toddlers (49.7%) and preschool children (57.6%) (P = .005). CONCLUSION: There is no doubt that food-induced anaphylaxis is a medical emergency, specifically in young children. Pediatricians should be aware of the distinct features of infant anaphylaxis, particularly gastrointestinal and neurologic symptoms to provide effective treatment as soon as possible.

Phenotypic and Molecular Characterization of Risk Loci Associated With Asthma and Lung Function.

PURPOSE: Respiratory diseases have a highly multifactorial etiology where different mechanisms contribute to the individual's susceptibility. We conducted a deep characterization of loci associated with asthma and lung function by previous genome-wide association studies (GWAS). METHODS: Sixteen variants were selected from previous GWAS of childhood/adult asthma and pulmonary function tests. We conducted a phenome-wide association study of these loci in 4,083 traits assessed in the UK Biobank (n = 361,194 participants). Data from the Genotype-Tissue Expression (GTEx) project were used to conduct a transcriptomic analysis with respect to tissues relevant for asthma pathogenesis. A pediatric cohort assessed with the International Study of Asthma and Allergies in Children (ISAAC) Phase II tools was used to further explore the association of these variants with 116 traits related to asthma comorbidities. RESULTS: Our phenome-wide association studies (PheWAS) identified 206 phenotypic associations with respect to the 16 variants identified. In addition to the replication of the phenotypes tested in the discovery GWAS, we observed novel associations related to blood levels of immune cells (eosinophils, neutrophils, monocytes, and lymphocytes) for the asthma-related variants. Conversely, the lung-function variants were associated with phenotypes related to body fat mass. In the ISAAC-assessed cohort, we observed that risk alleles associated with increased fat mass can exacerbate allergic reactions in individuals affected by allergic respiratory diseases. The GTEx-based analysis showed that the variants tested affect the transcriptomic regulation of multiple surrounding genes across several tissues. CONCLUSIONS: This study generated novel data regarding the genetics of respiratory diseases and their comorbidities, providing a deep characterization of loci associated with asthma and lung function.

Desensitisation overcomes rituximab- and tocilizumab-related immediate hypersensitivity in childhood.

OBJECTIVES: Biologic drugs (BD) have been game-changers in rheumatic diseases; however, severe hypersensitivity reactions concerning anaphylaxis may limit their use. Desensitisation is a crucial option that is safe and effective to maintain patients on the preferred drug. Herein we report 84 Rapid Drug Desensitisation (RDD) procedures with rituximab and tocilizumab in children with rheumatic diseases. METHODS: The study was conducted as a retrospective chart review of patients who received tocilizumab or rituximab therapy between January 2010 and December 2018. The results of RDD with tocilizumab and rituximab were documented. RESULTS: The study group consisted of 53 patients (11.6±4.5 years, 67.9% female) with rheumatic disease who had used tocilizumab (64.1%, 1007 infusions) or rituximab (35.8%, 73 infusions). Five patients (14.7%) had experienced anaphylaxis with tocilizumab and two patients (10.5%) with rituximab. Anaphylaxis was grade II in four cases whereas it was grade III in the remaining three children. Skin testing with the culprit BD performed in five children yielded positive results. We performed 65 RDDs with tocilizumab in 3 patients and 19 RDDs with rituximab in two patients. No reactions were recorded in 97.6% of the procedures. We observed one anaphylaxis during the 5th RDD of tocilizumab. After modifying the protocol, this patient continued tocilizumab RDD uneventfully. CONCLUSIONS: RDD is a groundbreaking innovation which ensures giving the full target doses while protecting the patient against severe hypersensitivity reactions (HSRs) and anaphylaxis. As BD use increases in childhood, management of HSRs to BD will become more complicated, necessitating an increased need for RDD in clinical practice.

Factors Affecting Food Allergy-Related Quality of Life From Parents' Perception in Turkish Children.

PURPOSE: Food allergy (FA) affects the daily lives of children and parents in varying degrees. The Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) is a valid and reliable instrument to assess the quality of life (QoL) of children from parents' perception. The aim of this study was to validate and determine the reliability of the Turkish FAQLQ-PF and to assess QoL in food-allergic children. METHODS: Children aged between 0 and 12 years and diagnosed with immunoglobulin E (IgE)-mediated FA for at least 1 month were enrolled. The English FAQLQ-PF was translated into Turkish according to the World Health Organization guidelines. The Food Allergy Independent Measure and the Turkish Child Health Questionnaire-Parent Form 50 were used for construct validity. RESULTS: One hundred and fifty-seven patients participated. The median age of patients and FA duration were 2.4 years (1.2-5.2 years, interquartile-ranges) and 2 years (0.8-5.1), respectively. Ninety-six (61.1%) patients had anaphylaxis. The Cronbach's alpha coefficient and intra-class correlation coefficient for test-retest reliability was good for all age groups of children (<4, 4-6, and 7-12 years). Patients with either asthma or anaphylaxis had worse scores than others. Total scores of FAQLQ-PF tended to increase with age. Patients aged 7-12 had the highest total scores among all patients (2.2±0.1, 3.0±0.2, and 3.3±0.3 for <4, 4-6, and 7-12 years, respectively, P<0.001, P for trend <0.001). Other factors causing the poor QoL were cow's milk allergy, sibling allergy, mother's age over 30 years, mother's high education level and lower number of persons in household. CONCLUSIONS: The Turkish FAQLQ-PF is a valid and reliable scale. FA-related QoL was significantly worse with age. Coexistent asthma, anaphylaxis regardless of its severity, cow's milk allergy, sibling allergy and the older and educated mothers seem to poorly affect QoL.

Characteristics of drug-induced anaphylaxis in children and adolescents.

BACKGROUND: Although data on anaphylaxis in the general population exist for different allergens, there is still lack of detailed etiologic data on drug-induced anaphylaxis (DIA), particularly in children. OBJECTIVE: To define the etiology of DIA, to determine the accuracy of drug-related anaphylaxis histories, along with the severity and culprit drug associations among individuals <18 years old. METHODS: Patients with a history of drug hypersensitivity reaction (DHR) referred to our center between January 2012 and February 2016 were included. After the collection of European Network for Drug Allergy questionnaire results, initial skin tests and/or provocation tests were performed for the offending drug. RESULTS: Among 561 children and adolescents referred due to a suspected DHR, 113 (19%) (median age [interquartile range], 9.6 years [5.4-13.8 years]; 55% boys) had anaphylaxis in their history. At the end of diagnostic evaluation of the patients, 84 (74% of the patients with a history of DIA) were actually hypersensitive to the offending drug. Major drugs that resulted in DIA were antibiotics (33%), nonsteroidal anti-inflammatory drugs (25%), and chemotherapeutics (19%). The majority of patients reported grade 2 (moderate) (45%) and grade 3 (severe) (33%) anaphylactic reactions. A history of systemic illness (41.7 versus 7.1%; p = 0.001), concomitant intake of other drugs regularly (36.9 versus 10.3%; p = 0.007), and the use of chemotherapeutics as the culprit drug (19 versus 0%; p = 0.011) were more frequent, whereas the use of antibiotics was less frequent (34.5 versus 75.9%; p < 0.001) among patients with actual DIA compared to drug tolerant patients. CONCLUSION: Three-fourths of the children and adolescents referred due to a suspected history of DIA were found to actually be drug hypersensitive. Prediagnosed systemic illness and different types of drugs would have an impact on the risk of DIA; however, atopic disease or a family history of drug hypersensitivity did not have an impact on actual DIA.

The persistence of chronic spontaneous urticaria in childhood is associated with the urticaria activity score.

BACKGROUND: There is little information regarding the etiology and natural course of chronic spontaneous urticaria (CSU) in childhood. OBJECTIVE: To investigate the etiology, prognosis, and the factors associated with the prognosis of CSU in children. METHOD: Data from children with CSU who had been diagnosed between 1992 and 2015 were analyzed. A telephone interview was done to assess the current status of these patients. Remission was defined as the disappearance of urticaria for >6 months. RESULTS: A total of 222 children with CSU were evaluated. The median age of symptom onset was 8.8 years (interquartile range [IQR], 4.6-12.3 years), median duration of urticaria was 23 months (IQR, 7-48 months), and the median sum of the daily urticaria activity score of 7 consecutive days (UAS7) was 28 (IQR, 21-42). Accompanying angioedema was reported by 107 patients (48.2%), whereas 27.1% of the study population had autoantibody positivity. Autologous serum skin testing results were positive in 43 (34.1%); skin-prick testing results revealed atopy in 55 children (27.9%). Parasites (4.8%), pollen sensitization (1.5%), food allergy (0.9%), urinary tract infection (0.9%), and Hashimoto thyroiditis (0.5%) were determined as etiologic factors of CSU. The patients were followed up for a median time of 15 months (IQR, 5-36.5 months). Remission was observed in 10.6, 29.3, and 44.5% of the patients in 1, 3, and 5 years, respectively. In multivariate regression analysis, a UAS7 of >28 at admission was found to be a risk factor for persistence of urticaria (odds ratio 6.22 [95% confidence interval, 1.54-25.15; p = 0.010). CONCLUSION: The etiology of CSU in children was mostly idiopathic despite detailed investigation. In childhood, the natural course of CSU was favorable, and nearly half of the patients recovered after 5 years of disease duration. A high UAS7 at admission seemed to be a significant risk factor for the persistence of symptoms.

Characteristics of children with food protein-induced enterocolitis and allergic proctocolitis.

BACKGROUND: The aim of this study was to determine and compare the clinical and laboratory features of food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP), and to provide information about the short-term prognoses. METHOD: Children diagnosed with FPIES or FPIAP between 2010 and 2015 were enrolled in this study. RESULTS: Overall, 64 infants (37 FPIAP, 27 FPIES) were evaluated, with the average age at the onset of symptoms being significantly lower in the patients with FPIAP than in the patients with FPIES (2 months [1-3 months] versus 4 months [1.5-6 months]; p = 0.043). Fifteen of the patients with FPIAP (40.5%) and six of the patients with FPIES (22.2%) were exclusively breast-fed at the time of the onset of symptoms. Cow's milk was the most frequent trigger (100% FPIAP, 74% FPIES); solid foods caused FPIES more frequently. Forty-eight of the 64 patients were followed up until at least 2 years of age, with the resolution rates being 91.3% for FPIAP and 60% for FPIES. The solid food-induced cases of FPIES (27.3%) had a significantly lower rate of resolution than the liquid food-induced FPIES (83.3%) (p = 0.003). CONCLUSION: Cow's milk is the most common trigger of both FPIAP and FPIES. The symptom onset age seemed to be earlier in FPIAP. The resolution age was similar, however, the recovery in FPIES may be later if the trigger food is solid. To our knowledge, this was the first clinical study to compare the clinical and laboratory characteristics of patients with FPIAP and FPIES.

Parasitic Infections in Children with Chronic Spontaneous Urticaria.

BACKGROUND: Parasites have been proposed to be an underlying cause of chronic spontaneous urticaria (CSU) in childhood, but a clear causal relationship between them has not been established. This study aimed to investigate the prevalence of parasitic infection-related CSU (PIRCSU) in children and to determine the factors associated with PIRCSU. METHOD: Data from 211 children with CSU were analyzed. Information on stool examination, antiparasitic medications received, and response to treatment was recorded. The disappearance of urticaria for more than 6 months is defined as remission, and remission of urticaria after antiparasitic treatment is defined as PIRCSU. RESULTS: Parasites were detected in 21 (10%) patients. Blastocystis hominis was the most common parasite. After antiparasitic medication, all samples became normal; urticaria continued in 5, was reduced in 6, and disappeared in 10 patients. The latter 10 patients were considered as cases of PIRCSU (4.7%). The erythrocyte sedimentation rate was significantly higher in patients with PIRCSU than in those without [8.5 mm/h (3.5-14.5) vs. 2 (0-7), p = 0.011]. Gastrointestinal complaints were significantly more frequent in patients with PIRCSU than in those without. The occurrence of abdominal pain was a significant risk factor that increased the probability of PIRCSU [OR = 6.60, 95% CI = 1.35-32.23, p = 0.020]. CONCLUSION: Parasites may cause CSU even in nontropical countries, and remission may only be possible with the treatment of the parasitic infection. The occurrence of abdominal pain points to parasitic infection in patients with CSU. Therefore, we suggest that parasites should be investigated routinely, especially if the patient has gastrointestinal symptoms of CSU in childhood.

Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children.

To dissect the role of immunogenetics in allergy and asthma, we performed a phenome-wide association study in 974 Turkish children selected from a cross-sectional study conducted using ISAAC (International Study of Asthma and Allergies in Children) Phase II tools. We investigated 9 loci involved in different immune functions (ADAM33, ADRB2, CD14, IL13, IL4, IL4R, MS4A2, SERPINE1, and TNF) with respect to 116 traits assessed through blood tests, hypertonic saline challenge tests, questionnaires, and skin prick tests. Multiple associations were observed for ADAM33: rs2280090 was associated with reduced MEF240% (i.e., the ratio of Mean Expiratory Flow after 240s of hypertonic saline inhalation with respect to the age- and ancestry-matched reference value) and with an increased risk of allergic bronchitis (p = 1.77*10(-4) and p = 7.94*10(-4), respectively); rs3918396 was associated with wheezing and eczema comorbidity (p = 3.41*10(-4)). IL4 rs2243250 was associated with increased FEV240 (Forced Expiratory Flow Volume after 240s of hypertonic saline inhalation; p = 4.81*10(-4)) and CD14 rs2569190 was associated with asthma diagnosis (p = 1.36*10(-3)). ADAM33 and IL4 appeared to play a role in the processes linked to allergic airway inflammation and lung function. Due to its association with wheezing and eczema comorbidity, ADAM33 may also be involved in the atopic march.

Basal serum tryptase is not a risk factor for immediate-type drug hypersensitivity during childhood.

BACKGROUND: High serum basal tryptase (sBT) levels have been identified as a risk factor for both venom- and food-induced severe allergic reactions. The aim of this study was to compare sBT levels in children with different severity of actual drug hypersensitivity reactions (DHRs) with those of age- and sex-matched controls without any history of DHRs. METHOD: Patients between 0 and 18 years of age with a history of immediate-type DHRs manifested in 0-6 h after the culprit drug intake were included. Following ENDA (European Network for Drug Allergy) inquiries, patients were evaluated with skin and/or provocation tests to define the actual drug-hypersensitive patients. Serum BT levels were determined for both patients and controls. RESULTS: Of 345 children, 106 patients (30.7%) [(58.5% male), median age (interquartile range) 8.0 years (4.2-12.2)] were diagnosed as drug hypersensitive. Ninety-eight controls were also included. The sBT levels of drug-hypersensitive patients with and without anaphylaxis and the control group were similar [2.6 (2.0-3.6) µg/l vs. 2.8 (1.6-4.3) µg/l vs. 2.6 (1.8-3.6) µg/l, respectively, (p > 0.05)]. The sBT levels of the patients with sole cutaneous symptoms 2.8 (1.6-4.3) µg/l, mild anaphylaxis 3.0 (1.9-4.9) µg/l, and moderate-to-severe anaphylaxis 2.6 (2.0-3.6) µg/l were also comparable (p > 0.05). The onset of DHRs [those occurring in 1 h (n = 87) or in 1-6 h (n = 19) after the drug intake], positive results with skin tests with the culprit drug, or the classification of the patients according to different age groups [(0-2 years), (2-6 years), (6-12 years), (12-18 years)] did not correlate with sBT levels. CONCLUSION: The sBT levels in children with actual drug hypersensitivity would not be a risk factor for severe systemic reactions on the contrary to children with allergic reactions to food or insect venom.

Haplotype analysis of non-HLA immunogenetic loci in Turkish and worldwide populations.

Immunogenes (i.e., genes related to the immune system and its functions) are involved in the predisposition to numerous traits and their variation contributes to the phenotypic variability observed among human groups. Turkish population presents particular genetic features since its genetic pool is an admixture of European, Middle-Eastern, and Central Asian ancestries. Here, we analyzed the haplotype structure of four immunogenetic loci (i.e., ADAM33; IL13-IL4; IL4R; MS4A2) in 482 subjects from five different regions of Turkey. Genotyping was performed using KASP technology. Turkish data were compared with the haplotype information available from the 1000 Genomes Project Phase 3 (26 human populations from 5 ancestry groups). We did not observe significant differences among Turkish groups. Comparing other ancestries, we identified haplotype similarity of Turkish subjects with European populations in IL13-IL4, IL4R, and ADAM33 loci; and with central Asians in MS4A2 region. Considering loci displaying Turkish-European haplotype similarity (i.e., IL13-IL4, IL4R, and ADAM33), we observed differences between Turkish subjects and northern/western Europeans. Conversely, no significant difference was determined in MS4A2 between Turkish and central Asian populations. Finally, we assessed the haplotypes responsible for the differences between Turkish and European samples and the potential functional effects on the immunogenetic loci investigated.