Adverse drug reactions affecting treatment adherence in first-line treatment of asthma: An observational study.

BACKGROUND: Asthma is the most common chronic lung disease among children. International guidelines recommend inhaled corticosteroids (ICS) as the first-line daily controller therapy for children with asthma and leukotriene receptor antagonists (LTRA) as the second alternative therapy. Adherence to treatment is the most significant component to optimize the benefits of therapy in asthma. OBJECTIVE: This study aims to investigate the frequency of drug discontinuation due to adverse drug reactions (ADRs) that affect adherence to treatment in children with asthma or asthma and allergic rhinitis using LTRA or ICS as monotherapy. METHODS: The subjects aged 4-18 years with asthma or asthma and allergic rhinitis and using montelukast or ICS as monotherapy were included in the study. They were evaluated in terms of ADRs affecting adherence to treatment in the first and third months of treatment. RESULTS: A total of 468 cases, 356 of whom received montelukast monotherapy and 112 of whom received ICS treatment, with a mean age of 9.10 ± 3.08 (4-17) years, were included in the study. Males constituted 65.6% of the total cases (n = 307). In the first month of follow-up of the cases, it was observed that 4.8% (n = 17) of the patients in the montelukast group could not continue the treatment due to ADR. It was determined that the drug discontinuation rate in the montelukast group in the first month was significantly higher than in the ICS group (P = 0.016), and the risk of drug discontinuation due to ADR in the montelukast group was 1.333 (95% CI, 1.26-1.40) times higher. CONCLUSIONS: As a result, it was observed that the drug was discontinued due to ADR at a higher rate in children with asthma who received montelukast monotherapy compared to those who received ICS monotherapy.

CD4+CD25+CD127loFOXP3+ cell in food allergy: Does it predict anaphylaxis?

BACKGROUND: Food allergy (FA), hence the incidence of food anaphylaxis, is a public health problem that has increased in recent years. There are still no biomarkers for patients with FA to predict severe allergic reactions such as anaphylaxis. OBJECTIVE: There is limited information on whether regulatory T (Treg) cell levels are a biomarker that predicts clinical severity in cases presenting with FA, and which patients are at a greater risk for anaphylaxis. METHODS: A total of 70 children were included in the study: 25 who had IgE-mediated cow's milk protein allergy (CMPA) and presented with non-anaphylactic symptoms (FA/A-), 16 who had IgE-mediated CMPA and presented with anaphylaxis (FA/A+) (a total of 41 FA cases), and a control group consisting of 29 children without FA. The study was conducted by performing CD4+CD25+CD127loFOXP3+ cell flow cytometric analysis during resting at least 2 weeks after the elimination diet to FA subjects. RESULTS: When the FA group was compared with healthy control subjects, CD4+CD25+CD127loFOXP3+ cell rates were found to be significantly lower in the FA group (p < 0.001). When the FA/A- and FA/A+ groups and the control group were compared in terms of CD4+CD25+CD127loFOXP3+ cell ratios, they were significantly lower in the FA/A- and FA/A+ groups compared to the control group (p < 0.001). CONCLUSIONS: Although there was no significant difference between the FA/A+ group and the FA/A- group in terms of CD4+CD25+CD127loFOXP3+ cells, our study is important, as it is the first pediatric study we know to investigate whether CD4+CD25+CD127loFOXP3+ cells in FA predict anaphylaxis.

The quantity of unheated milk tolerated as a predictor of tolerance to baked milk.

BACKGROUND: Tolerance of baked milk indicates a good prognosis in IgE-mediated cow's milk allergy. OBJECTIVE: The present study aims to investigate the predictors of baked milk tolerance, particularly the amount of milk tolerated in the first oral food challenge (OFC) test, in children with IgE-mediated cow's milk allergy. METHODS: The study included 35 cases who were diagnosed with IgE-mediated cow's milk allergy upon open OFC testing in the Pediatric Allergy Clinic. Four weeks after the diagnosis, skin prick test (SPT) and OFC were performed with baked milk. Cases who did and did not develop reactions during OFC with baked milk were compared regarding clinical and laboratory parameters. RESULTS: Twelve cases (33.3%) did not develop a reaction during OFC with baked milk. Those who had low levels of casein sIgE, ß-lactoglobulin sIgE, and ß-lactoalbumin sIgE; small SPT wheal diameter for baked milk and ß-lactoalbumin; and a large amount of unheated milk tolerated in the first OFC were found to be tolerant to baked milk (p < 0.05). For predicting baked milk tolerance, a cut-off level of the amount of unheated milk tolerated in OFC was calculated as 620 mg [with the area under the curve (AUC) 0.88 (95% confidence interval 0.77-0.99) in ROC curve analysis]. CONCLUSIONS: If a child with cow's milk allergy is able to tolerate more than 620 mg of milk protein during challenge with unheated milk, this may show that this child will tolerate baked milk, meaning that the child will be able to tolerate cow's milk in the future.

Food-induced anaphylaxis in early childhood and factors associated with its severity.

Background: Several factors that increase the risk of severe food-induced anaphylaxis have been identified. Objective: We aimed to determine the demographic, etiologic, and clinical features of food-induced anaphylaxis in early childhood and also any other factors associated with severe anaphylaxis. Methods: We carried out a medical chart review of anaphylaxis cases from 16 pediatric allergy and immunology centers in Turkey. Results: The data of 227 patients with 266 food-induced anaphylaxis episodes were included in the study. The median (interquartile range) age of the first anaphylaxis episode was 9 months (6-18 months); 160 of these patients were boys (70.5%). The anaphylaxis episodes were mild in 75 cases (28.2%), moderate in 154 cases (57.9%), and severe in 37 cases (13.9%). The most frequent food allergens involved were cow's milk (47.4%), nuts (16.7%), and hen's egg (15.8%). Epinephrine was administered in only 98 (36.8%) of these anaphylaxis episodes. A logistic regression analysis revealed two statistically significant factors that were independently associated with severe anaphylaxis: the presence of angioedema and hoarseness during the anaphylactic episode. Urticaria was observed less frequently in patients who developed hypotension. In addition, confusion and syncope were associated with 25.9- and 44.6-fold increases, respectively, in the risk of concomitant hypotension. Conclusion: Cow's milk, nuts, and hen's egg caused the majority of mild and moderate-to-severe anaphylaxis episodes. The presence of angioedema and hoarseness in any patient who presents with a history of food-induced anaphylaxis should alert clinicians that the reaction may be severe. In addition, the presence of confusion, syncope, or stridor probably indicates concomitant hypotension.

Serum osteoprotegerin levels in school-aged children with asthma.

BACKGROUND: Various inflammatory biomarkers have been used in asthma cases for evaluating inflammation, however it has been determined that the majority of these biomarkers are insufficient for putting forth the course and severity of the disease. Osteoprotegerin is a glycoprotein mediator in the lung and macrophages. As far as we know, there are no studies about the role played by osteoprotegerin in child patients with asthma. OBJECTIVE: It was planned to examine the relationship between osteoprotegerin levels in childhood asthma and respiratory functions and airway inflammation and to assess its use as a biomarker. METHODS: The study included patients aged 6-16 years who were diagnosed with asthma at the pediatric allergy outpatient clinic of Bagcilar Training and Research Hospital in Turkey. The correlation analyses for the osteoprotegerin levels of asthma patients and their respiratory functions were examined. RESULTS: The age average of asthma cases was 10.61±3.04 years and 51.2 % were female. No statistically significant difference was observed between the osteoprotegerin levels of the groups (p>0.05). A negative and statistically significant correlation was observed between the FEV1 and FVC values and osteoprotegerin levels (p=0.015, p=0.003). CONCLUSIONS: This was the first study to examine the relationship between osteoprotegerin levels and airway inflammation in children with asthma. We believe that there is a need for wider scale studies in which clinical symptoms and more parameters are evaluated for defining the role played by osteoprotegerin level in children with asthma and for determining its usability as a biomarker.

Is Oral Food Challenge (OFC) test safe for preschool children?

BACKGROUND: Oral food challenges (OFCs) are performed for diagnosis of a food allergy in cases where the allergy is not supported by patient history, or when a newly developed tolerance level needs to be established. OBJECTIVE: We aimed to investigate the prevalence and severity of reactions during OFCs in preschool children. METHODS: A retrospective study was conducted on children younger than 5 years, for whom OFC had been performed with milk, egg white and egg yolk. All children had been admitted to the Department of Pediatric Allergy at Behçet Uz Children's Hospital between 1 January 2010 and 31 December 2014. Any symptoms developed during the OFC were classified and recorded. RESULTS: A total of 122 patients who underwent an OFC were included in this study. The patients included 85 males (69.7%), and 50.8% of patients (n = 62) had a history of IgE-mediated food allergy. Co-existing allergies were found for 57.4% (n = 70) of patients. Of the OFCs performed, tests for milk, egg white and egg yolk made up 46.5, 30.5 and 23.0%, respectively. Of these, 19% (n = 33) were mild and 4.5% (n = 7) were moderate allergies in terms of symptom development. It was determined that the skin prick test (SPT) wheal size and the food-specific IgE levels did not effect in determining whether the allergic reaction would develop by OFC if the SPT wheal size and the food-specific IgE levels were below the cut-off point of a 95% positive predictive value (p > 0.05). CONCLUSION: The severity of egg and milk allergy symptoms resulting from the frequently used OFC in preschool children are generally mild and easy to manage, particularly if the OFC is only conducted if serum-specific IgE or SPT wheal size is below the cut-off point.

Tuberculosis masked by immunodeficiency: a review of two cases diagnosed with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a genetically heterogeneous primary immunodeficiency that is characterized by recurrent and life-threatening infections resulting from defects in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system and granuloma formation due to increased inflammatory response. The most commonly involved organs are the lungs, skin, lymph nodes, and liver due to infection. It may present with recurrent pneumonia, hilar lymphadenopathy, empyema, abscess, reticulonodular patterns, and granulomas due to lung involvement. In recent years, mycobacterial disease susceptibility has been reported in CGD cases. This article presents two male cases, one of whom is aged 18 months and the other is aged 5 years, who were diagnosed with CGD and tuberculosis during examination due to extended pneumonia. This report is presented because CGD should be considered not only in the presence of skin abscesses and Aspergillus infections, but also in the differential diagnosis for cases with BCG-itis and/or tuberculosis. It should be kept in mind that mycobacterial infections can occur during the course of the disease.

Does raising awareness in families reduce environmental tobacco smoke exposure in wheezy children?

INTRODUCTION: Environmental tobacco smoke (ETS) is thought to increase the severity and number of attacks in wheezy children. Objective assessments are needed to change the behavior of families to reduce the exposure of wheezy children to ETS. AIM: To determine whether informing families about their children's urinary cotinine levels curtailed the exposure of children to ETS. MATERIAL AND METHODS: A survey was used to determine the ETS exposure level, and the urinary cotinine level of each patient was tested. Children with positive urinary cotinine levels were included in the second part of the study. The families were randomly divided into two groups: an intervention group that was advised about urinary cotinine levels by telephone and a non-intervention group that was not so advised. The groups were followed-up 2 months later, and urinary cotinine levels were measured once again. RESULTS: The intervention group contained 65 children of average age of 24.4 ±8.9 months, of whom 46 (70.8%) were male. The non-intervention group contained 69 children of average age of 25.3 ±9.8 months (p > 0.05), of whom 52 (75.4%) were male. The urinary cotinine levels at the time of the second interview were lower in both groups. The number of cigarettes that fathers smoked at home decreased in the intervention group (p = 0.037). CONCLUSIONS: Presenting objective evidence on ETS exposure to families draws attention to their smoking habits. Measurement of cotinine levels is cheap, practical, and noninvasive. Combined with education, creating awareness by measuring cotinine levels may be beneficial.

Local and systemic reactions to subcutaneous allergen immunotherapy: Ten years' experience in a pediatric clinic.

BACKGROUND: Local and especially systemic reactions are important problems in subcutaneous immunotherapy (SCIT). Local and systemic reactions develop in 0.7% to 4% and 0.2% of all injections, respectively. OBJECTIVE: To evaluate the frequency of and risk factors for reactions developing in pediatric patients undergoing SCIT. METHODS: Local and systemic reactions developing after 14,308 injections between 2003 and 2013 were retrospectively evaluated in the current study using the Subcutaneous Immunotherapy Systemic Reaction Grading System, as recommended by the World Allergy Organization. The type of allergic disease, allergens producing a sensitivity, allergen immunotherapy content, adjuvant content, and the effects of treatment phase on the frequency of adverse effects were investigated. RESULTS: Of 319 patients, local reactions occurred in 11.9%, wide local reactions occurred in 5%, and systemic reactions occurred in 4.7%. A local reaction was observed in 0.38% of all injections, whereas a systemic reaction was observed in 0.1% of all injections. Local reactions were most frequent in the build-up phase, and systemic reactions were most frequent in the maintenance phase (P = .01). Side reactions were more common in patients undergoing SCIT with multiple allergens (P = .002) and house dust mite (P = .001). No statistically significant difference was found between adjuvant content and adverse effect frequency (P = .32). CONCLUSIONS: The frequencies of local and wide local reactions during SCIT were lower than expected. Although systemic reactions were frequently seen, no fatal reaction was observed in the current study. House dust mite SCIT and multiple allergen use increased the risk of reaction.

Can mean platelet volume be used as a biomarker for asthma?

INTRODUCTION: Platelets play important roles in airway inflammation and are activated in inflammatory lung diseases, including asthma. AIM: We evaluated the mean platelet volume (MPV), used as a marker of platelet activation, in asthmatic patients during asymptomatic periods and exacerbations compared to healthy controls to determine whether MPV can be used as an indicator of inflammation. MATERIAL AND METHODS: Our patient group consisted of 95 children with exacerbation of asthma who were admitted to our allergy clinic. The control group consisted of 100 healthy children matched for age, gender, and ethnicity. Mean platelet volume values of the patient group obtained during exacerbation of asthma were compared to those of the same group during the asymptomatic period and with the control group. We investigated factors that can affect the MPV values of asthma patients, including infection, atopy, immunotherapy treatment, and severity of asthma exacerbation. RESULTS: The patient group consisted of 50 (52.6%) boys and 45 (47.4%) girls with a mean age of 125 ±38 months old. Mean MPV values in the exacerbation period, the healthy period, and in the control group were 8.1 ±0.8 fl, 8.1 ±1.06 fl, and 8.2 ±0.9 fl, respectively; there were no significant differences between groups (p > 0.05). The severity of asthma, severity of asthma exacerbation, immunotherapy, coinfection, eosinophil count, and IgE level also had no effect on MPV (p > 0.05). CONCLUSIONS: Although platelets play a role in the pathophysiology of asthma, MPV measurement is insufficient to detect inflammation through platelets.

DRESS syndrome associated with type 2 diabetes in a child.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started. Hyperglycemia, commencing on the first dose of the steroid given, persisted even after the discontinuation of steroids and improvement of other signs. There were no signs of pancreatitis or type 1 diabetes clinically in laboratory tests. Her blood glucose levels were regulated at first with insulin and later with metformin. Within 1 year of follow-up, still regulated with oral antidiabetics, she has been diagnosed with type 2 diabetes. Formerly, long-term sequelae related to "drug rash with eosinophilia and systemic symptoms syndrome" such as hepatic and renal failure, type 1 diabetes mellitus, Grave's disease, autoimmune hemolytic anemia, and lupus have also been reported. However, up to date, no cases with type 2 diabetes have been reported as long-term sequelae. To our knowledge, this is the first case in the literature presenting with type 2 diabetes as long-term sequelae.

Pulmonary and ventricular functions in children with repaired tetralogy of Fallot.

OBJECTIVE: This study aimed to evaluate biventricular function, brain natriuretic peptide levels, respiratory function test and 6 minute walking test (6MWT) in children with repaired tetralogy of Fallot (TOF), and analyse the correlation between these variables and clinical status. METHODS: Twenty-five children (14 boys, 11 girls; aged 6 to 17 years) with repaired TOF (Group 1) and 25 age-sex matched healthy controls (Group 2) were enrolled in the study. Tissue Doppler echocardiography, respiratory function test, 6MWT distance and brain natriuretic peptide levels were measured. RESULTS: Mean ages of the children at TOF corrective surgery and at study time were 5.1±3.5 years and 11.6±2.7 years respectively. The duration between palliative operation and corrective surgery was 4.3±2.0 years, and the follow-up period after corrective surgery was 6.3±3.0 years. The right ventricular and left ventricular myocardial performance indices (MPIs), and isovolumic relaxation and contraction times were significantly higher in Group 1 than in Group 2 (p<0.01). Spirometry displayed significantly reduced forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow 25-75% (FEF25-75) and inspirational capacity in Group 1 compared to Group 2 (p<0.01). In Group 1, 6MWT distances were significantly lower than in Group 2 (p=0.001). Right ventricular MPI is correlated with FEV1, FVC and 6MWT distance in the current study. CONCLUSION: The children with repaired TOF had impaired ventricular and pulmonary functions. Hence, right ventricular MPI along with FEV1, FVC and 6MWT distance may be useful in the follow-up of children with repaired TOF.

Eosinophilic cellulitis (Wells' syndrome) caused by a temporary henna tattoo.

Eosinophilic cellulitis (Wells' syndrome) is an uncommon condition of unknown etiology. Wells' syndrome is usually seen in adulthood but very rare in childhood. Although pathogenesis of the disease is not very clear, it is a hypersensitivity reaction developing against a variety of exogenous and endogenous antigenic stimuli. Paraphenylenediamine is a strong allergen frequently used as a temporary henna tattoo, which makes the color darker. Here, a 9-year-old male patient with Wells' syndrome is presented, which developed following a temporary henna tattoo and shown by the patch test sensitivity to paraphenylenediamine.

Acute generalized exanthematous pustulosis induced by ceftriaxone use.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous rash characterized by the abrupt onset of a generalized pustular rash often accompanied by fever. There is a history of drug use in 90% of the cases. Here we have reported a 15-year-old male patient with sickle cell anemia who developed AGEP after the use of ceftriaxone. Our patient was hospitalized because of vaso-occlusive crisis and on the third day of ceftriaxone treatment, erythematous pustular lesions accompanied with fever were observed on the body and extremities. Resolution of symptoms followed discontinuation of ceftriaxone. Sensitivity to ceftriaxone was shown with a patch test. The AGEP was considered due to clinical and histopathological findings. This is the first pediatric case of AGEP due to ceftriaxone.

The association between urinary tract infection and idiopathic hypercalciuria in children.

BACKGROUND: Identifying the risk factors is important in prevention of urinary tract infections (UTIs) in children. The aim of this study is to evaluate the association of UTI and idiopathic hypercalciuria (IHC). METHODS: Two hundred and twenty-four children aged between 1 month and 16 years and diagnosed to have UTI were evaluated for urinary calcium excretion. The children were diagnosed to have IHC if their urinary calcium/creatinine ratios in at least two different spot urine samples were >0.6 between 0-1 year old and ≥0.21 over 1 year or daily calcium excretion >4 mg/kg. RESULTS: The frequency of IHC was found to be 16.7%. Family history of urolithiasis, parental consanguinity, presentation with abdominal pain, loss of appetite, and discomfort were found to be significantly higher in the IHC group. No association was found between IHC and the recurrence of UTI, presence of vesicoureteral reflux, renal scar formation, and the prognosis. CONCLUSIONS: IHC should be considered among the risk factors for UTI and should be investigated particularly in patients with family history of urinary stones and suggestive complaints of IHC.

Over restrictive elimination of foods in children with food allergy.

BACKGROUND: Previous studies demonstrated critical deficits in diagnosis and management of childhood food allergy (FA), and recent developments in FA research support adopting a proactive approach in FA management. Our objective was to describe FA knowledge and management patterns of pediatricians. METHOD: We applied a 24-item survey to 170 general pediatricians, pediatric allergists and pediatric gastroenterologists practicing in Turkey. RESULTS: Some IgE-mediated symptoms of FA such as cough, urticaria, wheezing and anaphylaxis were falsely recognized as symptoms of non-IgE-mediated FA by 30%, 29%, 25% and 19% of the participants, respectively. By contrast, 50% of the participants falsely recognized bloody stool, a finding of IgE-mediated FA. Most frequently and least frequently used diagnostic tools were specific IgE (30.5%) and oral food challenge test (1.7%), respectively. Maternal diet restrictions and infant diet restrictions were advised by 82% and 82%, respectively. Percentages of physicians eliminating only 1 food were 21%, 19%; 2 foods were 15%, 11%; 3 foods were 7%, 8%; 4-5 foods were 8%, 11%; 5 to 10 foods were 21%, 26%; and > 10 foods were 28%, 25% from the maternal and infant diet, respectively. Cow`s milk, cheese, butter, yoghurt, baked milk products and hen`s egg were the most commonly restricted items. CONCLUSION: Overall, FA knowledge of pediatricians was fair. Pediatricians utilize an overly restrictive approach when advising diet eliminations in FA. Recent developments favor a more proactive approach to induce immune tolerance and need to be encouraged in pediatric clinical practice. Future educational efforts should focus on emphasizing the deleterious effects of injudicious and extensive eliminations.

Are infants with food allergy candidates for respiratory allergy?

AIM: Allergic sensitization in infancy generally develops against food allergens. We aimed to investigate the frequency of aero-allergens sensitization at older ages in infants with food allergy. MATERIAL AND METHODS: This retrospective cross-sectional study was conducted in Dr. Behçet Uz Children's Allergy Clinic. Infants with confirmed IgE-mediated food allergy between January 1st, 2004, and December 31st, 2016, were evaluated for aero-allergen sensitivities through skin prick tests (SPT) after at least two years after diagnosis, and the data were compared with a healthy control group. RESULTS: A total of 187 cases, 87 of which were patients, were included in the study. The cause of food allergies was cow's milk only in 24 (27.6%) cases, egg only in 26 (29.9%) cases, both cow's milk and egg in 33 (37.9%) cases, fish only in two cases (2.3%), and both fish and egg in two (2.3%) cases. The mean age at which the aero-allergen SPT was performed was 65 (46-180) months in the patient group and 72 (48-132) months in the healthy control group. In the patient group, 39 (44.8%) had aero-allergen sensitization, whereas, in the healthy control group, five (5%) had aero-allergen sensitization. Aero-allergen sensitization was more frequent in the patient group (p<0.05). There was no statistically significant difference in the type and number of food allergies and the development of aero-allergen sensitization (p>0.05). CONCLUSION: In infants with food allergies, sensitization may develop with aero-allergens at an early age. Clinical follow-up of these patients may be important in terms of allergic respiratory diseases.

Angioedema Due to Lamiaceae Allergy.

We present a 13-year-old male childallergic to three different plants (Salvia officinalis, Mentha piperita and Origanum onites L.) of Lamiaceae family. The patient developed angioedema 20-30 minutes after eating chicken meat with cheddar cheese. There was no history of allergy. Oral food challenge (OFC) with both cheddar cheese and chicken meat was negative. Skin tests for inhalant allergens were negative. 3 weeks later, the patient was admitted with angioedema after drinking sage tea. OFC with sage was applied and angioedema was observed. It was recognized that the first trigger, chicken meat with cheddar cheese, included oregano (Origanum onites L.). OFC for oregano was positive. Prick to prick test for Lamiaceae herbs (oregano, sage, mint) was performed. A positive reaction was observed only to mint. OFC was repeated with fresh mint and angioedema developed after 16 hours. Diagnose of Lamiaceae allergy is complicated and cross-sensitivity is common. Skin prick test (prick to prick)revealed a positive response only to mint but not to oregano and sage. Commercial radioallergosorbent (RAST) tests are available only for a few members of the family. Finally, thediagnose is based mainly on OFC. Spices from Lamiaceae group should be considered as potential triggers of allergic reactions.