Food oral immunotherapy: Any distinguishing factors predicting the need of anti-IgE?

Oral immunotherapy (OIT) has gained popularity recently for IgE-mediated food allergy. Omalizumab (OMZ) has been used in patients (10-20%) who have too severe/frequent allergic reactions (AR) to continue OIT, to reduce these reactions. In this study, it was aimed to compare two groups of patients who completed OIT with and without OMZ and to seek determinants predicting the need of this treatment. It was also aimed to share the clinical findings regarding the long-term use of OMZ and the withdrawal process. Forty-one patients were started OIT and 93% could be desensitized. Two groups were similar in means of demographic characteristics, and clinical and laboratory findings. The patients who needed OMZ during OIT had also lower reaction doses during oral challenge (p = 0.037). Higher AR rate in this group declined after starting OMZ (p < 0.001). The injection intervals of OMZ were gradually extended. Most patients were able to discontinue OMZ (81%). There were no severe reactions during drug withdrawal attempts. The low reaction thresholds during oral food challenge may give a clue about OMZ requirement during OIT. It may be an option to start the treatment before OIT if reaction was seen in the first few steps of the oral food challenge. For the sake of safety, extension of injection intervals should be preferred instead of abruptly stopping OMZ.

Cut-Off Values of Specific IgE and Skin Prick Test to Predict Oral Food Challenge Positivity in Children with Cow's Milk Allergy.

OBJECTIVE: The cut-off values for the skin prick test diameters and cow's milk-specific IgE measurements are used to predict the result of the oral food challenge test for the diagnosis of cow's milk allergy. This study aimed to determine the diagnostic values of skin prick test and cow's milk-specific IgE according to age groups and compare the diagnostic powers of these 2 methods. MATERIALS AND METHODS: In total, 153 children who had a preliminary diagnosis of cow's milk allergy were evaluated. Group A (n = 90) consisted of cow's milk allergy patients whose diagnosis was confirmed by a positive oral food challenge or a history of anaphylaxis. Group B (n = 63) was composed of patients with a negative oral food challenge. The demographic, clinical, and laboratory findings of 2 groups were compared. RESULTS: The cut-off points for cow's milk-specific IgE and cow's milk-skin prick test were determined as >2.12 kUA/L and >5 mm, respectively. The area under the curve was 0.844 for cow's milk-skin prick test (sensitivity 73%, specificity 84%) and 0.745 for cow's milk-specific IgE (sensitivity 67%, specificity 86%). The diagnostic power of skin prick test was determined to be higher when compared to cow's milk-specific IgE (P = .02). According to the predicted probability curves, decision points for cow's milk-specific IgE and cow's milk-skin prick test with 95% probability were determined as follows, respectively: for ≤24 months: 22 kUA/L, 11.3 mm; for >24 months: 44.1 kUA/, 15.1 mm. The lowest cut-off value with a positive predictive value of 95% and a specificity of 96% was found in patients 3.3 kUA/L) Conclusion: The use of high probability diagnostic values of communities for specific IgE and skin prick test along with a significant clinical history may provide accurate and rapid diagnosis of cow's milk allergy and facilitate patient follow-up.

Evaluation of the Impact of Environmental Changes on Asthma Control in Children, Access to Health Care, and Treatment Adherence in Early COVID-19 Lockdown.

OBJECTIVE: During the coronavirus disease 2019 pandemic, lockdown measures and difficulties in accessing healthcare have impacted asthma management in children. This study aimed to determine the evaluation of the impact of environmental changes on asthma control in children, access to health care, and treatment adherence in early coronavirus disease 2019 lockdown. MATERIALS AND METHODS: The study included children with asthma aged 6-11 years. A survey form was administered to the patients who visited the pediatric allergy outpatient clinic between June 1 and 30, 2020. The survey acquired demographic information about the children and their families as well as information about their asthma symptoms, how they reached healthcare services, and adherence. The childhood asthma control test was administered. The P values <.05 were considered significant. RESULTS: The study included a total of 123 children (female/male : 48/75) with a mean age of 8.4 ± 1.9 years. According to the mothers' self-report, it was found that 78% of the patients were not able to follow-up routinely, 19.5% were non-adherence to treatment, and 16.2% were poorly controlled asthma. It was found that, based on childhood asthma control test scores, asthma control was better during the pandemic lockdown period (P = .001). Asthma symptoms were better in 41.5% of the patients compared to the previous months and in 53.7% compared to the same period last year. CONCLUSION: Our study found that the children's asthma was controlled although most of them did not have their follow-up visits, and poorly controlled asthma was higher in older children in early coronavirus disease 2019 lockdown.

Anxiety Levels and Changes in Health and Hygiene Behaviors in Mothers of Children with Asthma in Early COVID-19 Lockdown in Turkey.

Objective: The restrictions imposed by the coronavirus disease 2019 (COVID-19) pandemic have caused significant changes in people's lives. This study aimed to investigate anxiety levels and changes in health and hygiene behaviors in mothers of children with asthma in early COVID-19 lockdown in Turkey. Materials and Methods: This study was a cross-sectional survey conducted on children with asthma, 6 to 11 years of age, between June 1 and 30, 2020, in Turkey. A sociodemographic data form, health and hygiene behavior form, childhood asthma control test, and state-trait anxiety inventory were administered to the mothers of the children. Results: The asthma group included 123 children (Female: 39.0%) and median age, interquartile range (IQR) [minimum-maximum]: 8.0 (6) [6-12] years; the control group included 88 children (Female: 47.7%) median age, IQR [minimum-maximum]: 8.0 (7) [5-12] years. Increased hygiene behaviors and high compliance with social isolation measures were recorded in the early lockdown, with no difference between the groups. Before the pandemic, the most frequently used cleaning products were general-purpose cleaners. During the early lockdown, however, the most frequently used product was disinfectants and was similar in both groups. In both groups, the rate of using nutritional supplements increased during the pandemic period, but the rate was higher in children with asthma both before and during the early lockdown (P < 0.001). The anxiety levels of the mothers in asthma and control groups were similar. Conclusion: This study is the first in Turkey demonstrating that, in mothers of children with asthma, lifestyle changes related to health and hygiene and anxiety levels are similar to those of other children and their mothers during the early lockdown period of COVID-19 pandemic.

Effects of Cow's Milk Components, Goat's Milk and Sheep's Milk Sensitivities on Clinical Findings, and Tolerance Development in Cow's Milk Allergy.

OBJECTIVE: Cow's milk (CM) contains some proteins capable of causing an allergic reaction in a sensitized individual and one of the most common causes of food allergy in childhood. Most of the patients will develop tolerance by the age of 3. In this study, we aimed to evaluate sensitivity to CM allergen components as well as goat's milk (GM) and sheep's milk cross reactions in cow's milk allergic (CMA) patients and to figure out the risk factors for tolerance non-development. METHODS: This is a retrospective cross-sectional study including 66 patients for IgE-mediated CMA with mean age of 38 months. We evaluated the patients in two groups: Group 1 (n=50): Patients who have no tolerance in oral food challenge test; Group 2 (n= 16): Patients who were found tolerant to CM after elimination diet. Cow's milk-spesific IgE(sIgE), α-lactalbumin(ALA)-sIgE, ß-Lactoglobulin(BLG)-sIgE, casein-sIgE, goat's milk-sIgE, sheep's milk-sIgE, skin prick tests(SPTs) with CM and GM, eosinophils in peripheral blood were all compared between two groups. RESULTS: In the whole group, goat's milk-sIgE and sheep's milk-sIgE were positive in 84.8% and ALA-sIgE, BLG-sIgE, casein-sIgE were positive in 69.7%, 62.7%, 77.3% of the patients, respectively. Two groups were similar in terms of age at onset and diagnosis, gender, median elimination period, total IgE levels, cow's milk-sIgE and eosinophilia (p>0.05). Mean wheal diameters of CM and GM in SPT (p<0.001), goat's milk-sIgE (p=0.03), sheep's milk-sIgE (p=0.01) were significantly higher in Group 1. Cow's milk-sIgE showed a positive correlation with total IgE (p=0.001), eosinophilia percentage (p=0.04), CM wheal diameter in SPT (p=0.001), casein-sIgE (p<0.001), goat's milk-sIgE (p<0.001), sheep's milk-sIgE (p<0.001) in Group 1. Patients with respiratory symptoms and history of anaphylaxis had higher cow's milk-SPT, cow's milk-sIgE, casein-sIgE, goat's milk-sIgE, sheep's milk-sIgE levels(p<0.05). Gastrointestinal and skin symptoms showed no relation with laboratory findings. Any patient with a history of anaphylaxis did not develop tolerance. CONCLUSIONS: As with cow's milk-sIgE levels and high induration diameters in SPT; high casein-sIgE, sheep's milk-sIgE and goat's milk-sIgE levels are also risk factors for persistence of CMA. Anaphylaxis, as a first reaction, may also be a risk factor. High cow's milk-sIgE, casein-sIgE, sheep's milk-sIgE, goat's milk-sIgE levels are associated with respiratory symptoms.

Correction to: the IL1RN Mutation Creating the Most-Upstream Premature Stop Codon Is Hypomorphic because of a Reinitiation of Translation.

The original version of our manuscript, entitled, " The IL1RN mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translation" unfortunately contained mistakes in Fig. 1a and d legends. The text should read as follows.

Successful management of colchicine resistant familial Mediterranean fever patients with a standardized canakinumab treatment protocol: a case series and literature review.

Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease characterized by recurrent attacks of fever and serositis. Although colchicine is the first line treatment in FMF, 5-10% of patients do not respond to colchicine. Canakinumab, an anti-IL-1ß monoclonal antibody, has been reported to be effective and safe in colchicine-resistant FMF patients, but the adequate duration and interval of treatment is still a matter of debate. Aim of this study was to evaluate the success of the standardized treatment protocol for canakinumab applied in our Pediatric Rheumatology Department in colchicine-resistant FMF cases with a review of the literature. Nine patients included in this study had indications for canakinumab use as colchicine resistance and recurrent corticosteroid need for pleural/pericardial effusions. Canakinumab was administered monthly for 6 months (initial treatment), bimonthly for 6 months (maintenance treatment), then treatment was discontinued. For the patients who developed a new attack after one-year treatment period, canakinumab was readministered with 3-month intervals (continuation treatment). The mean follow-up time beginning from the first canakinumab injection was 24.3 ± 10.2 (6-33) months. None of the patients had an attack during the first-year treatment. Four of the patients developed an attack 9.0 ± 2.9 (6-12) months after discontinuation of treatment and switched to the continuation treatment period, with no more attacks. We suggest that this standard protocol may be used successfully in colchicine-resistant FMF patients.

Deficiency of Interleukin-1 Receptor Antagonist: A Case with Late Onset Severe Inflammatory Arthritis, Nail Psoriasis with Onychomycosis and Well Responsive to Adalimumab Therapy.

DIRA (deficiency of the IL-1Ra) is a rare condition that usually presents in the neonatal period. Patients with DIRA present with systemic inflammation, respiratory distress, joint swelling, pustular rash, multifocal osteomyelitis, and periostitis. Previously, we reported a patient with a novel mutation in IL1RN with a healthy neonatal period, a late-onset of pustular dermatosis, inflammatory arthritis, and excellent response to canakinumab treatment. Herein, we are presenting a new case of late-onset DIRA syndrome, carrying a different mutation and showing different clinical findings. This patient is the first one in the literature with the inflammatory arthritis, nail psoriasis, and onychomycosis and with her remarkable response to monoclonal antibodies. The case responded well and fully recovered after treatment with adalimumab, but not with canakinumab. The DIRA disease can lead to death from multiple organ failures and if recognized early, the treatment with replacement of the deficient protein with biologic agents induces rapid and complete remission. Therefore, clinical symptoms should be learned exactly by the pediatricians, pediatric rheumatologists, and immunologists; and molecular analysis targeting this defect must be performed as early as possible.

Anti-ß2 Glycoprotein I Antibodies in Children with Rheumatologic Disorders.

Anti-beta-2-glycoprotein I antibodies (anti-ß2GPI) which are the main antiphospholipid antibodies that characterize the autoimmune "antiphospholipid syndrome" are pathogenic and are contributing to thrombosis. We aimed to evaluate the presence and the diagnostic importance of these antibodies in children with different rheumatologic diseases with or without thrombosis risk. A total of 100 children with different rheumatologic diseases evaluated retrospectively. The mean anti-ß2GPI IgG (p = 0.108), IgA (p = 0.547), and IgM (p = 0.807) levels showed no statistically significant difference between different diagnosis groups. But anti-ß2GPI IgA and IgM levels were higher in SLE patient group. The mean anti-ß2GPI IgG (p = 0.375), IgA (p = 0.811), and IgM (p = 0.276) levels were not also showed difference between disease groups with/without predisposition to thrombosis even though concentrations were higher in thrombosis group. In children with rheumatological complaints, anti-ß2GPI antibody measurements should not be the first diagnostic criteria if vasculitis is not thought as the primary defect underlying the clinical symptoms.

Thymic output changes in children with clinical findings signaling a probable primary immunodeficiency.

Karaca N, Azarsiz E, Akarcan SE, Aksu G, Kütükçüler N. Thymic output changes in children with clinical findings signaling a probable primary immunodeficiency. Turk J Pediatr 2019; 61: 885-894. Thymic maturation evaluation is inevitable for patients with clinical and laboratory findings for a primary immunodeficiency, as the T cellimmunodeficiencies are the most severe type. In this study, we aimed to show the usage of T cell surface molecule `CD31` for the evaluation of thymic output in patients (n: 66) with a large spectrum of findings signing a probable primary immunodeficiency. Besides the classical clinical and laboratory approach for these patients, T cell subpopulations as naive, memory, recent thymic emigrant cells were also investigated. The humoral immunodeficiency (34.8%), combined immunodeficiency (34.8%) and cardiopathy (7.6%) were the most frequent diagnosis groups. CD4+CD45RA+ naive T-cells percentages (p: 0.011) and absolute counts (p: 0.004) and absolute CD4+CD45RA+CD31+ RTE (recent thymic emigrant) cell counts (p: 0.007) were significantly lower in combined immunodeficiency group. Naive T-cells (p: 0.037) and RTE cells (p: 0.032) were also lower in patients who had cardiac surgery in the past. In conclusion, flow cytometric CD31+thymic naive RTE cell evaluation may provide rapid clinical information especially on T-cell immune dysfunction and CD4+CD45RA+CD31+ RTE cells may be used as an alternative to TRECs in the diagnosis of combined immunodeficiencies.

Two male siblings with a novel LRBA mutation presenting with different findings of IPEX syndrome.

INTRODUCTION: LPS-responsive beige-like anchor (LRBA) protein deficiency is a disease of immune dysregulation with autoimmunity affecting various systems. CASE PRESENTATION: Two male siblings with a novel LRBA mutation had different primary findings at admission: the younger sibling had chronic early-onset diarrhoea and the elder one had autoimmune haemolytic anaemia. During long-term follow-up for IPEX phenotype, both developed hypogammaglobulinaemia, enteropathy and lung involvement. The patients partially responded to immunosuppressive therapies. A homozygous c.2496C>A, p.Cys832Ter (p.C832*) mutation in the LRBA gene causing a premature stop codon was detected. After molecular diagnosis, abatacept, as a target-specific molecule, was used with promising results. CONCLUSION: LRBA deficiency is a recently defined defect, with variable presentations in different patients; a single, definitive treatment option is thus not yet available.

Familial inheritance and screening of first-degree relatives in common variable immunodeficiency and immunoglobulin A deficiency patients.

Common variable immunodeficiency (CVID) and immunoglobulin A deficiency (IgAD) are the most prevalent primary immunodeficiency disorders. High rates of familial inheritance have been described in CVID and IgAD, but it is unknown in different ethnic populations. We aimed to determine the prevalence of familial cases and whether they showed more severe clinical characteristics than sporadic ones in Turkish patients. A total of 40 CVID and 70 IgAD patients and their 251 first-degree relatives (FDRs) were evaluated. Demographic, clinical, and laboratory data were reviewed. A familial case was defined as a patient with at least one affected FDR (A-FDR). The rate of parental consanguinity was 19.1%. There were 37 familial cases (37/110) (33.6%) with at least one A-FDR. There were 48 A-FDRs who had immunoglobulins lower than age-related normals (48/251) (19.1%). Pulmonary infections were significantly higher in familial cases. To our knowledge, this study includes the highest number of CVID/IgAD patients and their FDRs in literature. Familial cases are at least 30% of the IgAD and CVID patients, and they have more frequent lower respiratory tract infections than sporadic ones, so these patients have to be evaluated depending on their being familial or sporadic for better management. The risk of carrying any immunologic alterations in relatives of patients with IgAD and CVID is approximately 20%. Although most A-FDRs are asymptomatic, considering the risk of progression to CVID by age, we highly recommend routine screening for FDRs.

Gain-of-Function Mutations in STAT1: A Recently Defined Cause for Chronic Mucocutaneous Candidiasis Disease Mimicking Combined Immunodeficiencies.

Chronic Mucocutaneous Candidiasis (CMC) is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF) (c.1154 C>T, p.Thr385Met) in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT) was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.

Necrotizing Liver Granuloma/Abscess and Constrictive Aspergillosis Pericarditis with Central Nervous System Involvement: Different Remarkable Phenotypes in Different Chronic Granulomatous Disease Genotypes.

Chronic granulomatous disease (CGD) is a primary immune deficiency causing predisposition to infections with specific microorganisms, Aspergillus species and Staphylococcus aureus being the most common ones. A 16-year-old boy with a mutation in CYBB gene coding gp91phox protein (X-linked disease) developed a liver abscess due to Staphylococcus aureus. In addition to medical therapy, surgical treatment was necessary for the management of the disease. A 30-month-old girl with an autosomal recessive form of chronic granulomatous disease (CYBA gene mutation affecting p22phox protein) had invasive aspergillosis causing pericarditis, pulmonary abscess, and central nervous system involvement. The devastating course of disease regardless of the mutation emphasizes the importance of early diagnosis and intervention of hematopoietic stem cell transplantation as soon as possible in children with CGD.

Early Diagnosis and Hematopoietic Stem Cell Transplantation for IL10R Deficiency Leading to Very Early-Onset Inflammatory Bowel Disease Are Essential in Familial Cases.

Alterations of immune homeostasis in the gut may result in development of inflammatory bowel disease. A five-month-old girl was referred for recurrent respiratory and genitourinary tract infections, sepsis in neonatal period, chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin lesions. She was born to second-degree consanguineous, healthy parents. Her elder siblings were lost at 4 months of age due to sepsis and 1 year of age due to inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out severe congenital neutropenia and classic severe combined immunodeficiencies. Quantitative determination of oxidative burst was normal, excluding chronic granulomatous disease. Colonoscopy revealed granulation, ulceration, and pseudopolyps, compatible with colitis. Very early-onset colitis and perianal disease leading to fistula formation suggested probability of inherited deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon of the IL10RB gene, resulting in a stop codon at position p.W159X, was identified. The patient underwent myeloablative hematopoietic stem cell transplantation from full matched father at 11 months of age. Perianal lesions, chronic diarrhea, and recurrent infections resolved after transplantation. IL-10/IL-10R deficiencies must be considered in patients with early-onset enterocolitis.

Guillain-Barre syndrome in a 7-month-old boy successfully applied plasma exchange.

Despite being the most common cause of acute flaccid paralysis in children Guillain-Barré syndrome has a low incidence under 18 years old, and is even rarer under the age of 2. Established treatment regimens include intravenous immunoglobulin and plasma exchange in older children and adults. However very limited data are available for the efficacy and safety of plasma exchange in infants younger than 12 month-old. This article presents the experience of plasma exchange in the case of 7-month-old boy diagnosed with Guillain-Barré syndrome. A 7-month-old boy was referred to the pediatric intensive care unit with a 10-day history of progressive weakness, feeding difficulty and constipation. He was diagnosed with axonal Guillain-Barré syndrome on the basis of clinical and electromyographical findings. The patient recovered fully with intravenous immunoglobulin and plasma exchange. Plasma exchange may be a safe option in the treatment in infants with Guillain-Barré syndrome as young as 7-month-age.

Efficacy and safety of IV levetiracetam in children with acute repetitive seizures.

BACKGROUND: Levetiracetam has been proven to be effective in both partial and generalized seizures in children. However, few studies have reported its efficacy in the treatment of acute repetitive seizures. We aimed to investigate the efficacy and safety of levetiracetam in children with acute repetitive seizures. METHODS: The medical records of children from the age of 1 month-18 years who received levetiracetam because of acute repetitive seizures in the pediatric intensive care unit between 2010 and 2013 were reviewed retrospectively. RESULTS: Of the 133 patients, levetiracetam terminated seizures in 104 (78.2%). Side effects such as agitation and aggression were observed in three patients (2.2%). The likelihood of treatment failure was increased by four times by younger age at seizure onset; by six times in the individuals with neurological abnormalities; and by 22 times in the patients with West syndrome. The patients who used levetiracetam as the first treatment option for acute repetitive seizures had a longer duration of epilepsy, a higher rate of neurological abnormality, and a higher proportion of medically resistant epilepsy compared with the individuals who used levetiracetam as an add-on treatment to the other intravenous antiepileptic drugs. However, no differences were detected between these two groups in terms of treatment response. CONCLUSIONS: Intravenous levetiracetam appears to be effective and safe in the treatment of acute repetitive seizures. Randomized clinical trials are needed to determine whether intravenous levetiracetam may replace other antiepileptic drugs as the first-line therapy in the management of acute repetitive seizures.