Emine Dibek Misirlioglu

Evaluation of inhaler technique, adherence to therapy and their effect on disease control among children with asthma using metered dose or dry powder inhalers

Abstract Objective: To address the problems about correct use of inhaler devices, adherence to inhaler corticosteroid treatment and the effects of these problems on the control of asthma. Methods: Children with asthma were evaluated for the correct use of inhaler devices and adherence to therapy using a questionnaire. Effect of these on control of asthma was defined. Results: A hundred and seventy-one patients and/or their families were interviewed. The mean age was 8.29 ± 4.65 years (1–19) and 62.6% were male. Metered dose inhaler (MDI) with spacer was used by 119 (69.5%) patients and 52 (30.5%) used dry powder inhalers (DPIs). The devices were used correctly by 68.1% of patients using MDI and 34.6% of patients using DPI (p < 0.001). The most common improper step was “breathe in from the spacer 5–6 times or 10 s” for MDI (24.4%) and “exhale to residual volume” for DPI (51.9%). Frequency of correct use was higher in patients trained 3 times (p < 0.001). Asthma was controlled more frequently among correct users (p < 0.001). Partial or poor adherence was showed 22.8% of patients. Patients with mothers who had lower educational status had higher frequency of incorrect use of inhaler device (p = 0.007). Conclusion: It was found that asthma control was better among correct users. Repetitive training about using devices may contribute improving inhaler technique. Especially children whose mothers had low education level and patients using DPI should be evaluated more carefully.

Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics

Skin testing has a limited role in the diagnosis of non‐immediate beta‐lactam hypersensitivity in children. The aim of this study was to report the results of oral provocation tests performed without skin tests in children with non‐immediate mild cutaneous reactions without systemic symptoms caused by beta‐lactam antibiotics.

Characteristics and Prognosis of Allergic Proctocolitis in Infants.

Objectives: The dietary protein proctocolitis, also known as allergic proctocolitis (AP), is characterized by the presence of mucoid, frothy, and bloody stools in an otherwise healthy infant. The aim of this study was to describe a group of children with AP, diagnosed according to the criterion-standard method, food challenge to provide clinicians with more information on typical presentation, and an overview on nutritional management strategies and prognosis. Methods: We collected data on infants with AP in our allergy and gastroenterology outpatient clinics. Any other conditions that may cause bloody diarrhea were ruled out. Skin prick tests and atopy patch tests were performed for diagnosis, and patients were studied for resolution. To the patients whose rectal bleeding did not recover with oligoantigenic maternal diet in addition to amino acid–based formula, endoscopic evaluation was performed to confirm the diagnosis and to exclude other reasons of rectal bleeding. Results: Sixty patients were diagnosed as having AP. The age of onset was 1.7 ± 1.32 months. All of the patients were triggered by milk, 6.6% with milk and egg, 3.3% with milk and chicken, 1.7% with milk and wheat, 1.7% with milk and potato, and 3.3% had multiple food allergy. 53.3% (n = 32) acquired tolerance by age 1, 25.0% (n = 15) by 2 years, 5% (n = 3) by 3, and 1.7% (n = 1) by 4 years. Conclusions: Milk was a triggering factor for all of the patients. Resolution of AP is usually within 1 year but symptoms of some patients may continue even longer. An extension of the follow-up period is required according to our study.

Negative predictive value of drug provocation tests in children

The negative predictive value of the drug provocation test is important for both the patient and the physician. However, in children, this predictive value is unresolved.

Clinical and etiologic evaluation of the children with chronic urticaria.

BACKGROUND Chronic urticaria (CU) is a skin disorder defined as daily or almost daily exhibition of pruritic and transient wheals that last for >6 weeks. CU is divided into two subtypes: chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). OBJECTIVES To evaluate the clinical features, possible causes, associated findings, and laboratory results of different subtypes of CU in children according to a new classification. METHODS In this study, we evaluated the clinical features, laboratory investigations, and provocation tests of children with different subtypes of CU according to a new classification. RESULTS Two hundred and twenty-two children (59.9% girls) were enrolled in the study. Of the study patients, 59.9% and 40.1% were diagnosed as having CSU and CIndU, respectively. Antithyroid antibody levels were positive in 7.1% of the patients with CSU, 32.8% of the children had positive 14C-urea breath test results, and 6.5% of the patients had positive stool examination results for parasites. Autologous serum skin test results were positive in 53.5% of the patients with CSU. Of the patients with CIndU, 77.5% had symptomatic dermographism, 16.8% had cold urticaria, 2.2% had cholinergic urticaria, 2.2% had solar urticaria, and 1.1% had aquagenic urticaria. CONCLUSION Children with CSU represent the majority of patients with CU, and more than a half of these patients might have autoimmune urticaria. Symptomatic dermographism was the most common type of CIndU.

The evaluation of drug provocation tests in pediatric allergy clinic: a single center experience.

Drug provocation tests (DPTs) are gold standard to diagnose drug allergy. Our goal was to evaluate the results and safety of diagnostic methods including DPTs during childhood. Between January 2010 and February 2013 DPTs were performed and evaluated, prospectively, in children who attended our pediatric allergy clinic with a suspected drug hypersensitivity reaction. One hundred ninety-eight suspected drug reactions in 175 patients (88 boys and 87 girls) were evaluated. The median age of the subjects at the time of the suspected drug-induced hypersensitivity reaction and at the time of the study was 56 (interquartile range [IQR] = 24-120 months) months and 76 (IQR = 35-149 months) months, respectively. Suspected drugs were beta-lactam antibiotics in 108 cases (54.5%), non-beta-lactam antibiotics in 22 cases (11.1%), and nonsteroid anti-inflammatory drugs in 52 cases (26.3%). The history was compatible with immediate-type reactions in 69 cases (34.8%). Skin-prick tests were not positive in any of the cases. Intradermal tests were positive in three cases (4%). DPTs were positive in 13 (6.8%) of 191 provocation cases, which were performed with culprit drugs. Our results suggest that a positive clinical history is not enough to make a diagnosis of drug allergy, which highlights the significance of undertaking further diagnostic evaluation especially for DPTs.

Serum Sickness–Like Reaction in Children Due to Cefditoren

Abstract:  We describe the case of a 7‐year‐old boy with urticaria, fever, and arthritis that appeared 10 days after starting cefditoren therapy for acute tonsillopharyngitis, which was diagnosed as a serum sickness‐like reaction due to this medication.

Food protein-induced enterocolitis syndrome in two exclusively breastfed infants.

To the Editor, Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E (IgE)-mediated gastrointestinal food hypersensitivity characterized by profuse and repetitive vomiting, severe diarrhea, leading to dehydration and lethargy in infants (1). Although cow’s milk and soy protein are the most common triggers, FPIES can be triggered by other proteins, such as rice or oat, particularly in infants who have had a previous reaction to cow’s milk or soy (1). It has been reported that 0.34% of infants were diagnosed with FPIES in a birth cohort (2). FPIES to cow’s milk in exclusively breastfed infants is rare. A few cases of FPIES have been reported in exclusively breastfed infants so far (3, 4). Here, we report two cases of FPIES described even in exclusively breastfed infants in which symptoms occurred after maternal ingestion of cow’s milk. The first patient, a 15-day-old boy, reporting fever, intermittent vomiting, and diarrhea was admitted to neonatal intensive care unit with a pre-diagnosis of sepsis and dehydration. The patient was exclusively breastfed and did not gain weight due to diarrhea 10–15 times and sometimes more per day. After hospitalization, an intravenous fluid resuscitation therapy was implemented. Blood tests showed elevated white blood cell count with mild neutrophilia (white blood cells, 16840/ll; neutrophils, 13790/ll). C-reactive protein and procalcitonin were negative. Patient’s investigations (blood, urine, and stool cultures) for infection were negative. The patient was tried breastfeeding the next day; however, he suffered repetitive vomiting and pallor. Intravenous rehydration treatment was then given. Repetitive vomiting, lethargy, and marked pallor arose immediately after the patient was introduced with milk-based formula. Henceforth, FPIES due to cow’s milk allergy was suspected. Milk and dairy products were removed from mother’s diet, and the infant’s formula was switched from milk-based to exclusively amino acidbased formula. All symptoms disappeared within a few hours after intravenous fluid resuscitation, and the patient started to gain weight. After 2 weeks, provocation with milk-based formula resulted in reappearance of repetitive vomiting, lethargy, and pallor, confirming FPIES. Atopy patch test with milk was positive. The patient was then recommended breastfeeding with maternal strict avoidance of milk and dairy products mixed with amino acid-based formula if required. To determine the prognosis, open oral provocation test was implemented at the age of 12 months but the test was interrupted and the patient was then admitted to the intensive care unit as a result of profuse vomiting and diarrhea. Restriction diet was continued, and the patient tolerated milk at age two. The second patient had been breastfed since the neonatal period and had complaints of failure to thrive and bloody diarrhea. He was admitted to the intensive care unit when 2,5 months old with symptoms of diarrhea, dehydration, and shock. Sepsis work-up was negative for the patient. All symptoms disappeared, and the patient started to gain weight when the mother’s diet was eliminated from milk and dairy products, and in addition, amino acid-based formula was added to infant’s diet. The patient was then diagnosed with FPIES. In that period, provocation was implemented with milk-based formula and the patient developed profuse vomiting and diarrhea symptoms. Patch test for milk was negative. A milk provocation was implemented for resolution and tolerated without any problems when the patient was 15 months old. Specific IgE measurement and skin prick test for milk were negative for both patients. Symptoms of classic FPIES usually begin in early infancy, within one to 4 weeks following introduction of cow’s milk or soy protein. Studies reported that FPIES presented with symptoms within the first 6 months of life (5, 6). Delayed introduction of cow’s milk or soy in breastfed infants may result in later onset. Rarely, symptoms may begin within the first days of life as reported here. Breastfeeding is generally considered to be protective from FPIES, but recently, there were two case reports of infants who developed FPIES symptoms while taking only breast milk (3, 4). These data suggest that not only proctocolitis but also FPIES can develop even in children who are exclusively breastfed. However, the exact underlying mechanisms of FPIES are not clearly understood. It is postulated that ingestion of food allergens causes local inflammation mediated by T cells, leading to increased intestinal permeability and fluid shift (7). Activated peripheral blood mononuclear cells, increased tumor necrosis factor-alpha (TNF-alpha), and decreased expression of transforming growth factor-beta (TGF-beta) receptors in the intestinal mucosa may be involved in the intestinal inflammation (7, 8). Diagnosis of FPIES through breast milk is not easy. The disease is quite rare, and symptoms are vague, not striking and not well defined, at least in the milder forms. In our two cases, the diagnosis was made based on a two-week cow’s milk elimination from mother’s diet, followed by a supervised oral food challenge as suggested by guidelines (1). It is reported that specific IgE to cow’s milk may be present in 4–25% of FPIES patients but specific IgE measurement and skin prick test were negative in our patients. A diagnosis of FPIES should be kept in mind in infants who had severe gastrointestinal symptoms when other common etiologic factors could not be displayed. The diagnosis must be suspected even when the infant is exclusively breastfed. When specific IgE and skin tests are inconclusive, restriction diet followed by a careful oral provocation test may help the diagnosis.

Proven Non-β-Lactam Antibiotic Allergy in Children

Background: Parallel to the increasing use of non-β-lactam (NBL) antibiotics, allergic reactions to this drug group seem to increase. Data about NBL antibiotic hypersensitivity in children are limited. The aim of this study is to evaluate characteristic reactions to NBL antibiotics in children. Method: Patients with suspected NBL allergy were assessed between 2011 and 2015. Characteristics of the reactions and results of skin and drug provocation tests (DPTs) were recorded. Results: In total, 96 patients aged 75.15 ± 56.77 months (range: 3-208) were assessed. Clarithromycin (63.6%) was the most common cause of reactions reported. After ingestion of NBL antibiotics, maculopapular rash, urticaria/angioedema and anaphylaxis presented in 48.9, 40.7 and 10.4% of the patients, respectively. Tests were performed in 85 patients. Intradermal tests were positive in 3 patients (clarithromycin, ciprofloxacin and cotrimoxazole) and DPT was positive in 1 patient (clarithromycin). Eleven patients could not be tested. Seven patients had severe anaphylaxis, and 4 patients with urticaria/angioedema had to take their medications at the time of the reaction so desensitization was performed. When only patients confirmed by tests were evaluated, NBL allergy was 4.7% (4/85) in our study group. However, when patients who could not be tested, but were regarded as suffering from drug hypersensitivity according to clinical findings, were included, the frequency of NBL allergy was 15.6% (15/96). Conclusion: Most of the children with suspected NBL do not have true hypersensitivity. The frequency of confirmed hypersensitivity is low, and thus a detailed history should be taken from patients with suspected NBL hypersensitivity and DPTs should be performed in patients without contraindications.

Anaphylaxis/angioedema caused by honey ingestion

Honey allergy is a very rare, but serious health condition. In this study, we presented six patients who described systemic allergic reactions after ingestion of honey. Three of the six patients had suffered from anaphylaxis. Honey-specific IgE was measured and skin-prick tests for honey were performed to diagnose honey allergy. The results of honey-specific IgE of all patients were positive. Four patients had high serum-specific IgE for honey bee venom and two of five patients had also experienced anaphylaxis due to bee stings. Skin-prick tests with honey and pollens were positive in five patients. Honey is one of the foods that can cause severe systemic reactions. Specific IgE and skin-prick tests are helpful for the diagnosis of honey allergy.