A new Luminex-based peptide assay to identify reactivity to baked, fermented, and whole milk.

BACKGROUND: The majority of children with cow's milk allergy (CMA) tolerate baked milk. However, reactivity to fermented milk products such as yogurt/cheese has not been previously evaluated. We sought to determine whether children with CMA could tolerate yogurt/cheese and whether a patient's IgE and IgG4-binding pattern to milk protein epitopes could distinguish clinical reactivity. METHODS: Four groups of reactivity were identified by Oral food challenge: baked milk reactive, fermented milk reactive, whole milk reactive, and outgrown. sIgE and sIgG4 binding to milk protein epitopes were assessed with a novel Luminex-based peptide assay (LPA). Using machine learning techniques, a model was developed to predict different degrees of CMA. RESULTS: The baked milk reactive patients demonstrated the highest degree of IgE epitope binding, which was followed sequentially by fermented milk reactive, whole milk reactive, and outgrown. Data were randomly divided into two groups with 75% of the data utilized for model development (n = 68) and 25% for testing (n = 21). All 68 children used for training were correctly classified with models using IgE and IgG4 epitopes. The average cross-validation accuracy was much higher for models using IgE plus IgG4 epitopes by LPA (84.8%), twice the performance of the serum component proteins assayed by UniCAP (41.9%). The performance of the model on "unseen data" was tested using the 21 withheld patients, and the accuracy of IgE was 86% (AUC = 0.89) while of IgE+IgG4 model was 81% (AUC = 0.94). CONCLUSION: Using a novel high-throughput LPA, we were able to distinguish the diversity of IgE/IgG4 binding to epitopes in the varying CMA phenotypes. LPA is a promising tool to predict correctly different degrees of CMA.

Flow-volume curve in the diagnosis and follow-up of intrathoracic airway obstruction.

Spirometry is an easy method to measure lung function and to show pathophysiology. It assists not only to determine the severity of bronchial obstruction in asthma but also to differentiate the characteristics of the intrathoracic diseases narrowing the central airways. Different types of benign and malignant tumors of the trachea may cause emergence of symptoms of airway obstruction. Herein a patient who had been initially diagnosed with asthma but later on shown to have intratracheal myofibroblastic tumor is presented. The importance of flow-volume curve in both initial diagnosis of the mass and in the detection of recurrence is discussed.

Final diagnosis of children and adolescents with musculoskeletal complaints.

BACKGROUND: Musculoskeletal complaints (MSCs) are one of the leading causes of outpatient admissions. However, analytical and epidemiological data are limited. The aim of this study is to identify the etiology of MSCs (excluding acute traumatic conditions) in children and adolescents, and to identify clues for the differential diagnosis. METHODS: Children and adolescents presenting with musculoskeletal pain, swelling or limitation of movement were enrolled in a prospective design. Demographic, clinical and laboratory features were recorded. RESULTS: Four hundred and twenty-two children (48.2% female) with a mean age of 7.90±3.95 years were enrolled. Etiology was identified in 97.2% of the cases: non-inflammatory and mechanical conditions (NIMC; 42.2%), rheumatic diseases (RD; 31%), infection-related disorders (IRD; 21.6%) and malignancy (M; 2.4%). NIMC was characterized by longer duration of complaints, a higher rate of non-articular complaints, a lower rate of joint involvement and limping and lower levels of leukocytes, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The prevalence of RD was higher in the age group of >12 years; younger age was associated with higher prevalence of IRD. Small-joint involvement was highest in the RD group. Median ESR in RD and M groups was higher; compared to the other groups; the frequency of patients with ESR ≥ 60 mm/hr was higher in the M group; compared to the RD group. In the RD group familial Mediterranean fever (9.7%), juvenile idiopathic arthritis (8.3%) and Henoch-Schönlein purpura (5.7%) were the leading causes of MSCs. CONCLUSIONS: RD accounted for one-third of the etiologies for MSCs. Age, duration of complaints, pattern of joint involvement and acute phase reactants are practical tools that may guide the pediatrician for diagnosis.

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.

Modulation of immune responses by immunotherapy in allergic diseases.

Allergen immunotherapy (AIT) has been used for 100 years and until now different immunoregulatory pathways have been shown to take place in its mechanisms of action. It is characterized by administration of the causative allergen and is shown to be clinically efficient even after discontinuation of therapy particularly in allergic respiratory diseases, bee venom allergy, and food allergy. Generation of antigen/allergen-specific peripheral tolerance is the key mechanism during immunotherapy. It is mediated by development of T and B regulatory cells, IgG4 isotype allergen-specific antibodies and the involvement of multiple suppressor factors, which lead to decreased tissue inflammation, early and late phase responses. Describing novel regulatory mechanisms in the process of immune tolerance induction will help to identify treatment modalities not only for allergic disorders, but also for autoimmune diseases, organ transplantation, chronic infections, and cancer.

The spectrum of aeroallergen sensitization in children diagnosed with asthma during first 2 years of life.

Aeroallergens may trigger symptoms in sensitized children with asthma. Documentation of sensitization is crucial to enable effective implementation of measures to prevent asthma exacerbations. To document the sensitization patterns of very young children (≤2 years) with asthma, we retrospectively analyzed the skin-prick test (SPT) results of the largest referral center in the country. During a 4-year period, 432 children (median age, 1.21 years; male/female, 2.35) were referred. All patients had recurrent wheezing attacks and good response to inhaled bronchodilators and were diagnosed with asthma by their referring physician. SPT with eight aeroallergens (grass mix, weed mix, tree mix, mold mix, house-dust mite, cockroach, cat, and dog) was performed in 209 patients (full panel group) and the remaining 223 were tested only with a mixture of two house-dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae; house-dust mite group). The sensitization rates in house-dust mite and full panel groups were 3.2% (7/223) and 3.3% (7/209), respectively. Univariate and multivariate modeling was unable to identify a predictor for the presence of aeroallergen sensitization. During first 2 years of life, low rates of aeroallergen sensitization and lack of predictors of sensitization in children with asthma suggest that skin testing for aeroallergens may not be a routine procedure. When there is a high index of suspicion, testing only for indoor aeroallergens including house-dust mites, molds, and pets may identify the majority of sensitized children.

Recurrent wheezing in the first three years of life: short-term prognosis and risk factors.

OBJECTIVE: It is difficult to determine if preschool children with recurrent wheezing are suffering from asthma or will suffer from asthma in the future. The aim of this study was to investigate the prognosis and risk factors of recurrent wheezing in children, beginning in the first 3 years of life. METHOD: Children who were referred because of recurrent wheezing episodes during the first 3 years of life were evaluated for the presence of asthma over a 4-year period. A child without any symptoms within the last 12 months was considered to be in remission. RESULTS: The study included 529 (male/female: 2.17) children with a median (inter-quartile) age of 0.6 years (0.3-1.0) at symptom onset. The median follow-up and symptom durations were 2.93 years (1.74-4.76) and 4.30 years (2.91-5.97), respectively. Remission/recovery was achieved in 1.7%, 8.0%, and 14.4% of the children within 12, 24, and 36 months, respectively. A negative "stringent asthma predictive index" (API) significantly shortened the time to recovery of wheezing compared to the positive API (p = .036). Maternal smoking during pregnancy (OR = 4.35; 95% CI = 1.29-14.63); p = .018) and the number of emergency room admissions within the first 3 years of life (OR = 1.10; 95% CI = 1.01-1.19); p = .031) were found to be independent risk factors for the persistence of wheezing symptoms. CONCLUSION: Most of the children who were referred with frequent wheezing remain symptomatic 3 years after the initial wheezing episodes. A negative API is related to a shorter wheezing duration. Maternal smoking during pregnancy and the severity of the wheezing episodes appeared to be significant risk factors for the persistence of wheezing symptoms.

A Case of DOCK8 Deficient Hyper-IgE Syndrome Presenting Primarily With Eczema, Food Allergy, and Asthma.

Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare and recently described immunodeficiency, which is characterized with cutaneous viral and sinopulmonary infections, eczema, and high IgE levels. A DOCK8 deficient patient who had been followed up for severe atopic dermatitis, multiple food allergies, and asthma for several years is reported and clues are given for the diagnosis of DOCK8 deficiency. A 7-year-old girl was referred due to refractory eosinophilia and eczema. She had angioedema of the lips and increase in eczematous lesions during infancy after milk and egg ingestion and during childhood after fish, hazelnut, and wheat-containing food ingestion. She had episodic wheezing attacks since she was 1-year-old, and she had recurrent pneumonia and acute otitis media in the following years. She was hospitalized for pyoderma after a zona zoster infection. Laboratory findings suggested DOCK8 deficiency and mutational analysis verified. She had stem cell transplantation from a matched unrelated donor but unfortunately she died due to pneumonia 3 months after transplantation. Even though infants have food allergy and recurrent wheezing attacks, the presence of refractory eczema should be carefully followed up by pediatricians for the presence of recurrent cutaneous infections to exclude the diagnosis of DOCK8 deficiency in which stem cell transplantation is the only option and must be done as soon as possible.