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.

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.

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.

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.

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.

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 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.

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.

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.

Challenge-proven aspirin hypersensitivity in children with chronic spontaneous urticaria.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) exacerbated cutaneous disease is defined as the exacerbation of wheals and/or angioedema in patients with a history of chronic spontaneous urticaria (CSU). The objective of this study was to define 'aspirin-hypersensitive' children and adolescents in a clearly defined group of patients with CSU and to describe their clinical features. METHODS: Eighty-one children with a history of CSU were enrolled over a 3-year period. The daily or almost daily (>4 days a week) presence of urticaria was defined as 'chronic persistent urticaria' (CPU), while the presence of urticaria for 2-4 days a week was defined as 'chronic recurrent urticaria' (CRU). Single-blind, placebo-controlled provocation tests (SBPCPTs) with aspirin were performed for children with CSU. RESULTS: Patients with CRU had a longer duration of cutaneous symptoms [1.6 (0.5-4) vs 0.6 (0.3-1.5) years], and stress was less frequently experienced as an eliciting factor in patients with CRU compared with the patients with CPU (P < 0.016, P = 0.024, respectively). SBPCPTs with aspirin revealed that 14 of 58 patients (24%) with CPU and one of 10 patients with CRU (10%) were aspirin hypersensitive. Aspirin hypersensitivity rate was 26.5% in patients <12 years of age. All of the 15 aspirin-hypersensitive patients (aged between 6.6 and 17.4 years), except for three, experienced an unequivocal angioedema of the lips as a positive reaction in SBPCPT. CONCLUSIONS: Nearly a quarter of children and adolescents with CSU were hypersensitive to aspirin. For children with chronic urticaria, determination of NSAID hypersensitivity in a well-controlled clinical setting will help to avoid severe drug hypersensitivity reactions.

Different Phenotypes of Non-Steroidal Anti-Inflammatory Drug Hypersensitivity during Childhood.

BACKGROUND: Although non-steroidal anti-inflammatory drug hypersensitivity (NSAID-H) has been widely studied in adults, there is still a lack of data regarding the features and phenotypes of NSAID-H in children. Our aim was to define risk factors and different phenotypes according to clinical patterns. METHODS: Patients with a history of reaction to any NSAIDs referred between January 2012 and October 2014 were included. After completing a European Network for Drug Allergy (ENDA) questionnaire, initial skin and/or oral provocation tests (OPTs) were performed for the offending drug. Additional OPTs were done with aspirin in case of NSAID-H to determine cross-reactivity. NSAID-hypersensitive patients were defined as being either a selective responder (SR) or cross-intolerant (CI) and further categorized according to either the ENDA/GA2LEN classification or an alternative scheme by Caimmi et al. [Int Arch Allergy Immunol 2012;159:306-312]. RESULTS: Among 121 patients [58.7% male, average age 7.8 years (4.7-10.8)] with 161 NSAID-related reactions, 110 patients with 148 reactions were assessed. NSAID-H was diagnosed in 30 (27%) patients with 37 (25%) reactions. Multivariate regression analysis revealed that an immediate-type reaction and respiratory symptoms during the reaction increased the risk of a reproducible NSAID-related reaction (OR 3.508, 95% CI 1.42-8.7, p = 0.007; OR 3.951, 95% CI 1.33-11.77, p = 0.014, respectively). Additional OPTs revealed 13 SRs and 14 CIs. A family history of allergic disease was more frequent in CIs compared to SRs (57.1 vs. 15.4%, p = 0.031). Reactions belonging to CIs were more frequently characterized by angioedema compared to those of SRs (81.3 vs. 46.2%, p = 0.019). SRs and CIs were further classified as single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 13), NSAID-induced urticaria/angioedema (n = 7), NSAID-exacerbated cutaneous disease (n = 2) and NSAID-exacerbated respiratory disease (n = 1). Four CIs could not be categorized according to either classification system. One SR could not be categorized according to ENDA/GA2LEN. CONCLUSION: During childhood, NSAID-H exhibits different phenotypes and the majority of them can be categorized with current classification systems; however, classifications based on adult data may not exactly fit NSAID-H in paediatric patients.

Factors associated with the course of egg allergy in children.

BACKGROUND: The risk factors that affect persistence of egg allergy are under investigation. OBJECTIVE: To investigate the factors associated with the course of egg allergy and anaphylaxis in children. METHODS: Children who had been diagnosed as having an IgE-mediated egg allergy and followed up until 6 years of age were enrolled. IgE-mediated egg allergy was diagnosed by a positive skin prick test result, specific IgE (sIgE) level of 0.35 kU/L or greater, and clear-cut history of egg-related symptoms or positive challenge test results. RESULTS: A total of 203 (56%) of 363 egg allergic children were followed up until 6 years of age. Egg allergy resolved in 92 children (45%) at 2 years of age, 134 children (66%) at 4 years of age, and 145 children (71%) at 6 years of age. The resolution of egg allergy was associated with baseline egg sIgE level of 6.2 kU/L or less and the absence of anaphylaxis (hazard ratio, 0.32; 95% CI, 0.21-0.49; P < .001; and hazard ratio, 0.38; 95% CI, 0.21-0.69; P = .001, respectively). Baseline factors, including cut-off level of egg sIgE level greater than 6.2 kU/L, egg sIgE level, gastrointestinal symptoms after egg exposure, anaphylaxis with egg, and concomitant cow's milk allergy, were significantly associated with later resolution of egg allergy. The multivariate logistic regression determined that the natural logarithm for egg-white sIgE (odds ratio, 1.44; 95% CI, 1.09-1.91; P = .01) and the baseline gastrointestinal symptoms with egg (odds ratio, 6.86; 95% CI, 2.93-16.06; P < .001) were significantly related to a higher risk of anaphylaxis with egg. CONCLUSION: Baseline egg white sIgE levels, baseline gastrointestinal system involvement, concomitant cow's milk allergy, and anaphylaxis with egg may predict a more severe course of egg allergy with late resolution. Moreover, egg white sIgE levels and gastrointestinal symptoms after egg exposure seem to increase the risk of anaphylaxis with egg.

Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use.

The possible risk of adverse effects due to regular use of inhaled corticosteroids (ICS) is a real concern. Our aim was to describe the factors that have an impact on hypothalamic-pituitary-adrenal axis suppression (HPA-AS) in children and adolescents taking ICS regularly. The HPA axis status of patients who were on moderate-to-high-dose ICS [>176 and >264 µg/day fluticasone propionate-hydrofluoroalkane (FP-HFA) for patients 0-11 and ≥12 years, respectively] was investigated. Various types of ICS were converted to FP-HFA equivalent according to National Asthma Education and Prevention Program (NAEPP) guidelines. Participants with a baseline (8 a.m.) serum cortisol <15 µg/dL underwent a low-dose ACTH stimulation test (LDAT) to diagnose HPA-AS. Among 91 patients, 60 (75.9 %) participants underwent LDAT, and seven (7.7, 95 % CI 3.5-15.3 %) were diagnosed with HPA-AS. Ciclesonide was more frequently used by the participants with HPA-AS compared to patients with a normal HPA axis (42.9 vs. 4.8 %, p = 0.009). Use of ICS at moderate-to-high doses for at least 7 months distinguished participants with HPA-AS from those with a normal HPA axis. Among the duration, type, and dose of ICS, solely the use of ICS with a body mass index (BMI)-adjusted daily dose of ≥22 µg FP was found to increase the risk for HPA-AS (odds ratio (OR) 7.22, 95 % confidence interval (CI) 1.23-42.26, p = 0.028). The receiver operating characteristics (ROC) curve analysis revealed a cutoff value of 291 µg/day FP (area under the curve (AUC) = 0.840, p = 0.003) for predicting HPA-AS Conclusion: The prevalence of HPA-AS was found to be 7.7 % in children taking not only high-dose ICS but also moderate-dose ICS. Dose alone was found to be an actual risk factor for HPA-AS.

What we miss if standard panel is used for skin prick testing?

BACKGROUND: Although standard skin prick test (SPT) panels are crucial for routine investigation of sensitization in daily clinical practice, it has limitations in terms of missing allergens. OBJECTIVE: To find out sensitization rates (SR)s to additional panel of allergens and their relative contributions in allergic diseases. METHODS: SPTs with a battery of aeroallergens [tree pollen (A.glutinosa, C.arizonica, J.communis, T.platyphyllos, R.pseudoacacia), weed pollen (R.acetosa, U.dioica, A.artemisifolia), smut mix, yeast mix, storage mites (SM) (B.tropicalis, L.destructor, T.putrescentiae, A.siro), mouse and budgerigar epithelia], were performed to 318 participants (6-18 years) who were previously identified to be sensitized to at least one of the aeroallergens found in standard battery. RESULTS: Forty percent of participants were sensitized to at least one additional aerollergen. Three most frequent sensitizations were to B.tropicalis (11.3%), R.pseudoacacia (9.7%) and L.destructor (8.2%). SR for tree pollen increased from 6.9% to 19.8%, for mites increased from 26.3% to 31.6% and for moulds increased from 5.3% to 9.4% with addition of respective group of other allergens to battery. Furthermore, higher rates for additional tree pollen sensitization was found among patients with "only AR" (21%) compared to patients with "only asthma" (4.6%, p =0.006), contrarily higher rates for SM sensitization was found among patients with "only asthma" (20%) compared to patients with "only AR" (3.2%, p =0.003) CONCLUSIONS: Though some of sensitizations may occur due to cross-reactivity, almost 40% of sensitized children were also co-sensitized to the additional allergens tested. Physicians should consider further steps when a negative or inconsistent result is achieved through a standard skin test panel.

Increased osteopontin levels in children undergoing venom immunotherapy may serve as a marker of clinical efficacy.

BACKGROUND: Venom immunotherapy (VIT) has its effect by modulating various mediators resulting in immune tolerance. The aim of this study was to measure changes in plasma osteopontin (OPN) and serum basal tryptase (sBT) levels over the course of 1 year of VIT in children with venom allergy. METHODS: Children who suffered from a large local reaction (LLR) or a systemic reaction (SR) after insect stings were included along with control subjects. Measurements were performed before the initiation of VIT and 6 and 12 months after it had been started. RESULTS: A total of 58 children (24 with SR, 18 with LLR and 16 control subjects) with a median age of 9.5 years (range 6.7-12.8) were enrolled. The plasma OPN levels of patients with LLR [median 1,477 ng/ml, interquartile range (IQR) 1,123-1,772] were significantly higher than patients with SR (882 ng/ml, 579-1,086; p < 0.001) and healthy control subjects (1,015 ng/ml, 815-1,203; p = 0.002). A significant increase in plasma OPN levels in children was determined after the 1-year VIT. The sBT levels of children with SR (4.1 ng/ml, 3.6-5.8) were significantly higher than children with LLR (3.1 ng/ml, 2.5-4.0) and control subjects (3.0 ng/ml, 2.9-3.8; p = 0.001). There was no significant change in the sBT levels of the patients after the 1-year VIT. CONCLUSIONS: The results of our study showed higher baseline levels of OPN in children with LLR compared to control subjects and children with SR. In children with SR, OPN levels were increased after the 1-year VIT. Our results may suggest a possible association between OPN and successful VIT in children.

Clinical features of children with venom allergy and risk factors for severe systemic reactions.

BACKGROUND: Severe systemic reactions (SRs) to insect venom are rare in childhood and there are few data on this study population. The aim of our study is to analyze the clinical features and to document the risk factors for severe SRs in children with insect venom allergy. METHODS: Children with SRs after Hymenoptera sting were analyzed. The diagnosis was based on medical history, skin tests and/or specific IgE testing. RESULTS: Seventy-six children were included [57 boys (75%), mean age 9.8 ± 3.4 years]. The mean age of children at the time of SR was 8.3 ± 3.4 years. Reactions were accounted for Vespula (wasp) venom in 58 (76%) and Apis mellifera (bee) venom in 18 (24%) patients. Twenty-six percent of patients had aeroallergen sensitization and 33% had atopic disease, whereas 66% had experienced previous stings. The upper limb was the most frequent area of sting (43%), and the cutaneous system (99%) was the most frequent involved system. SRs occurred in 59% of patients. Multivariate logistic regression analysis revealed eosinophilia (>5%) [odds ratio (OR) 12.6; confidence interval (CI) 1.5-109.7; p = 0.022], female sex (OR 6.4; CI 1.5-26.9; p = 0.011) and accompanying atopic disease (OR 3.4; CI 1.2-12.3; p = 0.016) as significant risk factors for severe SRs. Ninety-seven percent of patients were admitted to the emergency department; however, epinephrine was used in only 46% of patients. CONCLUSIONS: There was a high frequency of hypersensitivity to wasp venom among the study population, and severe reactions were related to mild eosinophilia, female sex and concomitant atopic diseases. A better understanding of the risk factors may lead to effective utilization of health care sources in the future.

Validation of the Turkish version of "Test for Respiratory and Asthma Control in Kids (TRACK)" questionnaire.

BACKGROUND: Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire is the first to measure both the risk and impairment domains of the current guidelines in preschool children. We aimed to measure the reliability, validity and responsiveness of the Turkish version of the TRACK. METHODS: A total of 268 children (69.8% boys) were included in the study. Caregivers responded to three individual TRACK questionnaires, at each clinical visit (baseline, 1st month, and 3rd month). At each visit, physicians determined the control level and the treatment strategy based on the GINA guideline recommendations. RESULTS: The internal consistency reliability of the Turkish version of the TRACK questionnaire was found to be 0.74, 0.74, and 0.76 at each of the three visits, respectively (reliability statistics, Cronbach's alpha). There was a significant difference between the mean TRACK scores of the patients in different asthma control status categories (p < 0.001). The test-retest reliability in stable patients was 0.90. The optimal cut-off scores according to the Youden index were 80 and 60 points for uncontrolled and very poorly controlled children, respectively. CONCLUSION: The Turkish version of the TRACK is an accurate and reliable tool for evaluating asthma control status among preschool Turkish children. Its widespread use may help physicians correctly assess control levels among children and may improve the quality of life for both patients and their caregivers.

Predicting hospitalization in children with acute asthma.

BACKGROUND: Acute asthma is one of the most common medical emergencies in children. Appropriate assessment/treatment and early identification of factors that predict hospitalization are critical for the effective utilization of emergency services. OBJECTIVE: To identify risk factors that predict hospitalization and to compare the concordance of the Modified Pulmonary Index Score (MPIS) with the Global Initiative for Asthma (GINA) guideline criteria in terms of attack severity. METHODS: The study population was composed of children aged 5-18 years who presented to the Emergency Departments (ED) of the tertiary reference centers of the country within a period of 3 months. Patients were evaluated at the initial presentation and the 1(st) and 4(th) hours. RESULTS: Of the 304 patients (median age: 8.0 years [interquartile range: 6.5-9.7]), 51.3% and 19.4% required oral corticosteroids (OCS) and hospitalization, respectively. Attack severity and MPIS were found as predicting factors for hospitalization, but none of the demographic characteristics collected predicted OCS use or hospitalization. Hospitalization status at the 1(st) hour with moderate/severe attack severity showed a sensitivity of 44.1%, specificity of 82.9%, positive predictive value of 38.2%, and negative predictive value of 86.0%; for MPIS ≥ 5, these values were 42.4%, 85.3%, 41.0%, and 86.0%, respectively. Concordance in prediction of hospitalization between the MPIS and the GINA guideline was found to be moderate at the 1(st) hour (κ = 0.577). CONCLUSION: Attack severity is a predictive factor for hospitalization in children with acute asthma. Determining attack severity with MPIS and a cut-off value ≥ 5 at the 1(st) hour may help physicians in EDs. Having fewer variables and the ability to calculate a numeric value with MPIS makes it an easy and useful tool in clinical practice.