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Abstract: “Gluten sensitivity” has become commonplace among the public. Wheat allergy (WA) and celiac disease (CD) are well‐defined entities, but are becoming a fraction of individuals following a gluten‐free diet (GFD). Wheat allergy has a prevalence of <0.5%. Wheat, specifically its omega‐5 gliadin fraction, is the most common allergen implicated in food‐dependent, exercise‐induced anaphylaxis. CD is a non‐IgE hypersensitivity to certain cereal proteins: gluten in wheat, secalin in rye, hordein in barley, and to a lesser extent avenin in oat. It is a rare disease, with an estimated prevalence that varied widely geographically, being higher in Northern Europe and the African Saharawi region than in South‐East Asia. In addition to suggestive symptoms, serologic testing has high diagnostic reliability and biopsy is a confirmatory procedure. Patients with CD have extra‐intestinal autoimmune comorbid conditions more frequently than expected. A third entity is nonceliac gluten sensitivity, which has been created because of the increasing number of subjects who claim a better quality of life or improvement of their variety of symptoms on switching to a GFD. The phenomenon is being fueled by the media and exploited by the industry. The lack of a specific objective test has been raising substantial controversy about this entity. Allergists and gastroenterologists need to pay attention to the multitudes of individuals who elect to follow a GFD. Many such subjects might have WA, CD, or another illness. Providing them with appropriate evaluation and specific management would be of great advantages, medically and economically. [ABSTRACT FROM AUTHOR]

Several seeds have been increasingly incorporated in various food items, with consequent risk of hypersensitivity reactions that are often severe. Identification of the specific seed as the culprit is often not explored or is difficult to verify. In this article, we reviewed the English literature from January 1930 to March 2016 using PubMed and Google Scholar searching for publications relevant to hypersensitivity to common edible seeds, namely sesame, sunflower seed, poppy seed, pumpkin seed, flaxseed, and mustard seed. Considering the worldwide consumption of those seeds, the number of published articles on the subject was relatively small and was mainly as case reports rather than large series. Allergy to sesame was more reported than to other seeds, with an estimated prevalence of 0.1-0.2%. In this review, we summarize the information relevant to each of the six seeds and their oils regarding the manifestations, routes of exposure, identified major allergens, and cross-reactivity with other seeds or other foods. We also addressed the important role of a thorough history taking in suspecting seed allergy, the limited reliability of routine diagnostic procedures, and the importance of verification by appropriate challenge tests. At present, management is basically dietary avoidance and the use of symptomatic medications that may include epinephrine auto-injectors. We did not encounter any well-designed studies on immunotherapy for seed allergy, but it is hoped that such a gap be filled by the development of safe effective protocols in the near future. [ABSTRACT FROM AUTHOR]

Serum IgD levels in 83 healthy adults were measured by a radioimmunoassay technique and analysed according to each subject's smoking habit. The IgD geometric mean in cigarette smokers was twice as high as in non-smokers (408.6 vs 202.0 μg/dl). Serum IgD levels of 1,000 μg/dl or greater were noted in 22% of smokers but in none of the rare smokers or non-smokers. In the smokers group, the highest mean IgD level was found in those who did not actively inhale the smoke (7626 μg/dl), followed by that in moderate smokers (5638 μg/dl), and was lowest in heavy smokers who inhaled the smoke (2830 μg/dl). The number of years a person smoked did not appear to have a significant effect on IgD levels. In exsmokers, the mean IgD level (199.8 μg/dl) was similar to that in non-smokers, suggesting reversibility of the IgD changes following cessation of smoking. It seems prudent that the smoking habit should be taken into consideration in the interpretation of serum IgD levels. [ABSTRACT FROM AUTHOR]

Allergic (immune-mediated) reactions to cow milk and other dietary proteins encountered during infancy are responsible for some of the adverse symptoms and syndromes observed in infants intolerant to cow milk, infant formulas and occasionally human milk. Iron deficiency anemia associated with gastrointestinal blood loss, protein losing enteropathy, enterocolitis, colitis, and malabsorption syndrome are examples of putative allergic reactions to dietary antigens which occur in infancy. A number of symptoms referable to the gastrointestinal tract such as, vomiting, colic and chronic non-specific diarrhea occur in infants both with and without immune-mediated reactions to dietary antigens. Verification of adverse reactions to dietary antigens, including allergic reactions, should be accomplished through the use of double-blind, placebo-controlled food challenge, with the dietary antigen to be tested presented in a liquid vehicle or, in older children, in capsule form. Approximately 8%-25% of children with immediate hypersensitivity to cow milk have been found to be allergic to soy products. Soy and other intact protein substitutes for cow milk, such as beef and lamb based formulas, have produced anaphylactic reactions both in human infants and in animal models. Hypoallergenic formulas should have a chemically modified protein base which demonstrates significant reduction in antigenicity when tested in the laboratory both in vitro and in vivo. Such formulas should meet rigorous standards for hypoallergenicity in clinical testing in human allergic infants or infants at high risk for developing allergy before being labelled hypoallergenic. [ABSTRACT FROM AUTHOR]

. Information derived from the compulsory national scheme of medical registration of births in Norway has been utilized in a study of the course and outcome of pregnancy in women with epilepsy. The series comprises 371 pregnancies in women with epilepsy and, as controls, 112530 pregnancies in women reporting no disease before or during the pregnancy. Comparisons indicate that women with epilepsy experience an excess of complications during pregnancy and labour, and that their babies are more frequently born prematurely and of low birth weight, and moreover have an excess of congenital malformations and higher perinatal and neonatal mortality rates. Epileptics, undoubtedly, constitute a high risk group in need of special attention during pregnancy and special care during labour. A proper interpretation of the findings in terms of causation, however, will call for additional data obtainable only through especially designed inquiries. [ABSTRACT FROM AUTHOR]

Abstract The popularity of shellfish has been increasing worldwide, with a consequent increase in adverse reactions that can be allergic or toxic. The approximate prevalence of shellfish allergy is estimated at 0.5-2.5% of the general population, depending on degree of consumption by age and geographic regions. The manifestations of shellfish allergy vary widely, but it tends to be more severe than most other food allergens. Tropomyosin is the major allergen and is responsible for cross-reactivity between members of the shellfish family, particularly among the crustacea. Newly described allergens and subtle differences in the structures of tropomyosin between different species of shellfish could account for the discrepancy between in vitro cross-antigenicity and clinical cross-allergenicity. The diagnosis requires a thorough medical history supported by skin testing or measurement of specific IgE level, and confirmed by appropriate oral challenge testing unless the reaction was life-threatening. Management of shellfish allergy is basically strict elimination, which in highly allergic subjects may include avoidance of touching or smelling and the availability of self-administered epinephrine. Specific immunotherapy is not currently available and requires the development of safe and effective protocols.

Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.

The past few decades have witnessed an increasing understanding of the role of food allergy in human disease. Nevertheless, controversies still exist in several aspects of this area. One such controversy concerns the body systems that can be the target of food hypersensitivity reactions. Another is the role of noningestant exposure to food in a nonoccupational setting. Both of these aspects are vividly demonstrated in the case presented here. [ABSTRACT FROM AUTHOR]

Abstract Background Skin testing (ST) is the most common screening method for allergy evaluation. Measurement of serum specific IgE is also commonly used, but less so by allergists than by other practitioners. The sensitivity and specificity of these testing methods may vary by type of causative allergen and type of allergic manifestation. We compared ST reactivity with serum specific IgE antibodies to common indoor allergens in patients with respiratory allergies. Methods 118 patients (3 mo-58 yr, mean 12 yr) with allergic rhinitis and/or bronchial asthma had percutaneous skin testing (PST) supplemented by intradermal testing (ID) with those allergens suspected by history but showed negative PST. The sera were tested blindly for specific IgE antibodies by the radioallergosorbent test (Phadebas RAST). The allergens were D. farinae (118), cockroach (60), cat epithelium (90), and dog epidermal (90). Test results were scored 0–4; ST ≥ 2 + and RAST ≥ 1 + were considered positive. Results The two tests were in agreement (i.e., either both positive or both negative) in 52.2% (dog epidermal) to 62.2% (cat epithelium). When RAST was positive, ST was positive in 80% (dog epidermal) to 100% (cockroach mix). When ST was positive, RAST was positive in 16.3% (dog epidermal) to 50.0% (D. farinae). When RAST was negative, ST was positive in 48.5% (cat epithelium) to 69.6% (D. farinae). When ST was negative, RAST was positive in 0% (cockroach) to 5.6% (cat epithelium). The scores of ST and RAST showed weak to moderate correlation (r = 0.24 to 0.54). Regardless of history of symptoms on exposure, ST was superior to RAST in detecting sensitization to cat epithelium and dog epidermal. Conclusion For all four indoor allergens tested, ST was more sensitive than RAST. When both tests were positive, their scores showed poor correlation. Sensitizations to cat epithelium and dog epidermal are common, even in subjects who claimed no direct exposure.

Discusses sex differences in urinary tract infections in children. Earlier onset, a shorter delay in diagnosis, and a shorter duration in boys; Higher frequency of malformations, a greater number of rehospitalizations, and a greater need for surgical intervention in boys; Proteus infection; Enterococcus and Staphylococcus were more frequent in girls.

Background: Cow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes. The addition of probiotics to a specialized formula has also been proposed as a potential approach to possibly increase the benefit. We systematically reviewed specialized formulas for infants with CMA to inform the updated World Allergy Organization (WAO) DRACMA guidelines., Objective: To systematically review and synthesize the available evidence about the use of specialized formulas for the management of individuals with CMA., Methods: We searched from inception PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations, for randomized and non-randomized trials of any language investigating specialized formulas with or without probiotics. We included all studies irrespective of the language of the original publication. The last search was conducted in January 2024. We synthesized the identified evidence quantitatively or narratively as appropriate and summarized it in the evidence profiles. We conducted this review following the PRISMA, Cochrane methods, and the GRADE approach., Results: We identified 3558 records including 14 randomized trials and 7 observational studies. Very low certainty evidence suggested that in infants with IgE-mediated CMA, eHF-CM, compared with AAF, might have higher probability of outgrowing CMA (risk ratio (RR) 2.32; risk difference (RD) 25 more per 100), while showing potentially lower probability of severe vomiting (RR 0.12, 95% CI 0.02 to 0.88; RD 23 fewer per 100, 95% CI 3 to 26) and developing food protein-induced enterocolitis syndrome (FPIES) (RR 0.15, 95% CI 0.03 to 0.82; RD 34 fewer per 100, 95% CI 7 to 39). We also found, however, that eHF-CM might be inferior to AAF in supporting a physiological growth, with respect to both weight (-5.5% from baseline, 95%CI -9.5% to -1.5%) and length (-0.7 z-score change, 95%CI -1.15 to -0.25) (very low certainty). We found similar effects for eHF-CM, compared with AAF, also in non-IgE CMA. When compared with SF, eHF-CM might favor weight gain for IgE CMA infants (0.23 z-score change, 95%CI 0.01 to 0.45), and tolerance acquisition (RR 1.86, 95%CI 1.03 to 3.37; RD 27%, 95%CI 1%-74%) for non-IgE CMA (both at very low certainty of the evidence (CoE)). The comparison of eHF-CM vs. HRF, and HRF vs. SF, showed no difference in effect (very low certainty). For IgE CMA patients, low certainty evidence suggested that adding probiotics ( L. rhamnosus GG, L. casei CRL431 and B. lactis Bb-12) might increase the probability of developing CMA tolerance (RR 2.47, 95%CI 1.03 to 5.93; RD 27%, 95%CI 1%-91%), and reduce the risk of severe wheezing (RR 0.12, 95%CI 0.02 to 0.95; RD -23%, 95%CI -8% to -0.4%). However, in non-IgE CMA infants, the addition of probiotics ( L. rhamnosus GG) showed no significant effect, as supported by low to very low CoE., Conclusions: Currently available studies comparing eHF-CM, AAF, HRF, and SF provide very low certainty evidence about their effects in infants with IgE-mediated and non-IgE-mediated CMA. Our review revealed several limitations in the current body of evidence, primarily arising from concerns related to the quality of studies, the limited size of the participant populations and most importantly the lack of diversity and standardization in the compared interventions. It is therefore imperative for future studies to be methodologically rigorous and investigate a broader spectrum of available interventions. We encourage clinicians and researchers to review current World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines for suggestions on how to use milk replacement formulas in clinical practice and what additional research would be the most beneficial., Competing Interests: HJS and JLB, on behalf of McMaster University, received a research grant from the World Allergy Organization to conduct this review that was deposited into the university research account. RS participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Abbott, Else, and Nestlé. HS serves as a board member of the International Scientific Association for Probiotics and Prebiotics (ISAPP), an unpaid and voluntary role. They have participated as a clinical investigator, advisory board member, consultant, and speaker for several companies, including Arla, BioGaia, Biocodex, Danone, Dicofarm, Nestlé, NNI, Nutricia, Mead Johnson, and Novalac. YV has participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Abbott Nutrition, Alba Health, Arla, Ausnutria, Biogaia, By Heart, CHR Hansen, Danone, ELSE Nutrition, Friesland Campina, Nestle Health Science, Nestle Nutrition Institute, Nutricia, Mead Johnson Nutrition, Pileje, Sanulac, United Pharmaceuticals (Novalac), Yakult, Wyeth. SW is the president of the Canadian Allergy Asthma and Immunology Foundation, and participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Pfizer, Kaleo, Bausch Health, GSK, AZ, Sanofi, CSL Behring, Leo, AbbVie, Takeda, Medexus Pharma, MiravoHealth, BioCryst, ALK, Novartis. They also covered the positions of: BOD Asthma Canada, CHAEN. MS works for Allergy & Anaphylaxis Australis, which receives unrestricted educational grants from infant formula companies. AW works for Allergy UK works with corporate partners including those providing foods for special medical purposes, such as Nutricia/Danone, Abbott, Reckitt Benckiser/Mead Johnson. They have been a speakers for 2 Nutricia symposia, with honoraria being paid to the charity. All other authors declare that they have no relevant conflicts of interest to disclose., (© 2024 The Author(s).)

Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity., Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants., Methods: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3., Results: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate., Conclusion: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Allergy to cow's milk is the most common food allergy in infants and it is usually outgrown by 5 years of age. In some individuals it persists beyond early childhood. Oral immunotherapy (OIT, oral desensitization, specific oral tolerance induction) has been proposed as a promising therapeutic strategy for persistent IgE-mediated cow's milk allergy. We previously published the systematic review of OIT for cow's milk allergy (CMA) in 2010 as part of the World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines., Objective: To systematically synthesize the currently available evidence about OIT for IgE-mediated CMA and to inform the updated 2022 WAO guidelines., Methods: We searched the electronic databases including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations. We included all studies irrespective of the language of the original publication. The last search was conducted in February 2021. We registered the protocol on Open Science Framework (10.17605/OSF.IO/AH2DT)., Results: We identified 2147 unique records published between 2010 and 2021, including 13 randomized trials and 109 observational studies addressing cow's milk OIT. We found low-certainty evidence that OIT with unheated cow's milk, compared to elimination diet alone, increased the likelihood of being able to consume ≥150 ml of cow's milk in controlled settings (risk ratio (RR): 12.3, 95% CI: 5.9 to 26.0; risk difference (RD): 25 more per 100, 95% CI 11 to 56) as well as accidently ingest a small amount (≥5 ml) of cow's milk (RR: 8.7, 95% CI: 4.7 to 16.1; RD: 25 more per 100, 95% CI 12 to 50). However, 2-8 weeks after discontinuation of a successful OIT, tolerance of cow's milk persisted in only 36% (range: 20%-91%) of patients. OIT increased the frequency of anaphylaxis (rate ratio: 60.0, 95% CI 15 to 244; rate difference 5 more anaphylactic reactions per 1 person per year, 95% CI: 4 to 6; moderate evidence) and the frequency of epinephrine use (rate ratio: 35.2, 95% CI: 9 to 136.5; rate difference 268 more events per 100 person-years, 95% CI: 203 to 333; high certainty). OIT also increased the risk of gastrointestinal symptoms (RR 6.9, 95% CI 1.6-30.9; RD 28 more per 100, CI 3 to 100) and respiratory symptoms (RR 49.0, 95% CI 3.12-770.6; RD 77 more per 100, CI 62 to 92), compared with avoidance diet alone. Single-arm observational studies showed that on average 6.9% of OIT patients (95% CI: 3.8%-10%) developed eosinophilic esophagitis (very low certainty evidence). We found 1 trial and 2 small case series of OIT with baked milk., Conclusions: Moderate certainty evidence shows that OIT with unheated cow's milk in patients with IgE-mediated CMA is associated with an increased probability of being able to drink milk and, at the same time, an increased risk of serious adverse effects., (© 2022 Published by Elsevier Inc. on behalf of World Allergy Organization.)

Patient care in the allergy and respiratory fields is advancing rapidly, offering the possibility of the inclusion of a variety of digital tools that aim to improve outcomes of care. Impaired access to several health care facilities during the COVID-19 pandemic has considerably increased the appetite and need for the inclusion of e-health tools amongst end-users. Consequently, a multitude of different e-health tools have been launched worldwide with various registration and access options, and with a wide range of offered benefits. From the perspective of both patients and healthcare providers (HCPs), as well as from a legal and device-related perspective, several features are important for the acceptance, effectiveness,and long-term use of e-health tools. Patients and physicians have different needs and expectations of how digital tools might be of help in the care pathway. There is a need for standardization by defining quality assurance criteria. Therefore, the Upper Airway Diseases Committee of the World Allergy Organization (WAO) has taken the initiative to define and propose criteria for quality, appeal, and applicability of e-health tools in the allergy and respiratory care fields from a patient, clinician, and academic perspective with the ultimate aim to improve patient health and outcomes of care., (© 2022 The Authors.)

Introduction: As the prevalence of food allergies (FAs) increases worldwide, our understanding of their pathophysiology and risk factors is markedly expanding. In the past few decades, an increasing number of genes have been linked to FA. Identification of such genes may help in predicting the genetic risk for FA development, age of onset, clinical manifestation, causative allergen(s), and possibly the optimal treatment strategies. Furthermore, identification of these genetic factors can help to understand the complex interactions between genes and the environment in predisposition to FA., Areas Covered: We outline the recent important progress in determining genetic variants and disease-associated genes in IgE-mediated FA. We focused on the monogenic inborn errors of immunity (IEI) where FA is one of the clinical manifestations, emphasizing the genes and gene variants, which were linked to FA with some of the most robust evidence., Expert Opinion: Genetics play a significant role, either directly or along with environmental factors, in the development of FA. As a multifactorial disease, it is expected that multiple genes and genetic loci contribute to the risk for FA development. Identification of the involved genes should contribute to the area of FA regarding pathogenesis, prediction, recognition, prognosis, prevention, and possibly therapeutic interventions.

This study was an examination of the immediate effects of remote learning during the COVID-19 shutdown in New Jersey during Spring 2020. This mixed methods study relied on survey data capturing the experiences, difficulties, and successes of 708 New Jersey public school educators during the first few weeks of the school closures. These educators were teachers, administrators, school librarians, and other school personnel. The disruptions of COVID-19 will leave indelible changes on education in New Jersey and beyond, and this research examines the beginning of these changes. The findings indicate that while educators found support from their administration, they also encountered a spectrum of difficulties relating to the absence of face-to-face contact with students, in addition to success in coping with the situation as well as some success that surpassed their experiences of schooling before the shutdown., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Background: The 2010 Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow's milk allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment., Objectives & Methods: Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on milk allergy literature. We also reviewed their impact on successive food allergy and CMA guidelines at national and international level. We describe some economic consequences of their application., Results: DRACMA are the most cited CMA guidelines, and the second cited guidelines on food allergy. Many subsequent guidelines took stock of DRACMA's metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines., Conclusions: DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician's knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Summary: We describe the case of a 24-year-old male with hyper-IgE syndrome (HIES) which was diagnosed at 4 years of age and died from a very rare cardiac complication. He had typical clinical and laboratory manifestations of HIES, including total serum IgE as high as > 100,000 IU/mL. Stem cell transplantation was not available. During the 20-year follow-up, he suffered numerous various infections of the skin and deep organs, partial lung resection, as well as multiple bone fractures. At age 24, he developed acute decompensated heart failure associated with elevated serum troponin I and brain natriuretic protein. Two-dimensional echocardiogram revealed global hypokinesis of the left ventricle with estimated ejection fraction 20-25%, and catheterization revealed ectasia of multiple coronary arteries. Endomyocardial biopsy showed lymphocytic myocarditis, focal necrosis, mild fibrosis, and myxoid degeneration, but cultures were negative. The patient improved on corticosteroid therapy and was discharged on heart failure therapy and external defibrillator. Six weeks later, he developed supraventricular tachycardia and persistent global hypokinesis and was treated with amiodarone. A trial of intravenous immunoglobulin was initiated and was repeated as outpatient every four weeks for four times. However, his cardiac function did not improve and he developed severe hypotension and pulseless electrical activity arrest. Resuscitation was unsuccessful. To the best of our knowledge, this is the first reported case of HIES complicated with lymphocytic myocarditis. Both immunologists and cardiologists need to be aware of such a complication and practice caution in using immunosuppressants when the patient's immune status is markedly compromised.

Food protein-induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To identify patients' characteristics associated with double balloon endoscopy (DBE) outcomes in investigation of obscure gastrointestinal bleeding (OGIB)., Methods: Retrospective study performed at an academic tertiary referral center. Evaluated endpoints were clinical factors associated with no diagnostic yield or non-therapeutic intervention of DBE performed for OGIB evaluation., Results: We included fifty-five DBE between August 2010 and April 2012. The mean age of the sample was 67 with 32 males (58.2%). Twenty-four DBE had no diagnostic yield and 30 DBE did not require therapy. Non-diagnostic yield was associated with performing two or more DBE studies in one day [odds ratio (OR): 13.72, P = 0.008], absence of blood transfusions within a year of the DBE (OR: 7.16, P = 0.03) and absence of ulcers or arteriovenous malformations (AVMs) on prior esophagogastroduodenoscopy (EGD) or colonoscopy (OR: 19.30, P = 0.033). Non-therapeutic DBE was associated with performing two or more DBE per day (OR: 18.579, P = 0.007), gastrointestinal bleeding episode within a week of the DBE (OR: 11.48, P = 0.003), fewer blood transfusion requirements prior to DBE (OR: 4.55, P = 0.036) and absence of ulcers or AVMs on prior EGD or colonoscopy (OR: 8.47, P = 0.027)., Conclusion: Predictors of DBE yield and therapeutic intervention on DBE include blood transfusion requirements, previous endoscopic findings and possibly endoscopist fatigue.

Background: Food allergy has been gaining increasing attention, mostly as causing gastrointestinal and cutaneous reactions. Its role in asthma seems to be under-recognised., Objectives: This study's aim is to explore the frequency of involvement of a common food, namely cow's milk, in childhood asthma., Methods: 32 children (5 months to 11 years; median 24 months; mean 34 months) with asthma and a suspected history of cow's milk allergy were studied. They underwent skin prick testing (SPT) and specific IgE (sIgE) testing to whole cow's milk (WCM), casein, α-lactalbumin, and β-lactoglobulin, followed by single-blind oral milk challenge., Results: Reactions to milk challenge occurred in 12 (37.5%) including wheezing in 5 (41.7%, or 15.6% of the whole group). Children who developed wheezing at the time of challenge were younger than those who had negative challenge (23.0 months vs. 34.8 months). Challenge was positive in 33.3% of subjects who had a positive SPT, and SPT was positive in 50% of challenge-positive subjects. Regarding sIgE, challenge was positive in 26.7% of sIgE-positive subjects, and sIgE was positive in 33.3% of challenge positive subjects. Skin or serum testing with individual protein fractions did not seem to add significant advantage over testing with WCM alone., Conclusion: This study shows that cow's milk can cause wheezing in children with asthma. Although SPT seemed to be more reliable than sIgE testing, both had suboptimal reliability. It is worth considering possible milk allergy in children with asthma, particularly when poorly controlled in spite of proper routine management., (Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.)

We have reported that clinically relevant concentrations of valproic acid (VPA) up-regulate the G-protein-coupled melatonin MT1 receptor in rat C6 glioma cells. To determine whether this effect occurs in vivo, the effects of chronic VPA treatment on the expression of both melatonin receptor subtypes, MT1 and MT2, were examined in the rat brain. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR analyses revealed significant increases in MT1 and MT2 mRNA expression in the hippocampus, following VPA (4 mg/ml drinking water) treatment for 17 d. Increases in the mRNA and protein expression of the novel neurotrophic factors, conserved dopamine neurotrophic factor and mesencephalic astrocyte-derived neurotrophic factor, were detected in the hippocampus and/or striatum. In addition, significant changes in persephin, glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor mRNA expression were observed. The robust multi-fold induction of MT1 and MT2 receptors in the hippocampus suggests a role for the melatonergic system in the psychotropic effects of VPA.

Histone deacetylase (HDAC) inhibitors represent a novel class of drugs that selectively induce cell cycle arrest and apoptosis in transformed cells. This study examined, for the first time, the effects of the relatively new HDAC inhibitor, M344 [4-dimethylamino-N-(6-hydroxycarbamoylhexyl)-benzamide], on the proliferation of MCF-7 breast cancer cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays revealed significant concentration- and time-dependent decreases in MCF-7 cell proliferation following treatment with M344 (1-100μM). In contrast to the significant induction of p21(waf1/cip1) mRNA expression following treatment with M344 (10μM) for 1 or 3 days, there was a significant decrease in p53 mRNA expression, although p53 protein levels were unchanged. Similar treatment with M344 also induced expression of the pro-apoptotic genes, Puma and Bax, together with the morphological features of apoptosis, in MCF-7 cells. The results of this study reinforce previous findings indicating that HDAC inhibitors are an important group of oncostatic drugs, and show that M344 is a potent suppressor of breast cancer cell proliferation., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Allergist/clinical immunologist maintenance of certification and training program reaccreditation are mandatory in some countries. The World Allergy Organization conducted surveys in 2009 and 2011 to assess where such programs were available and to promote the establishment of such programs on a global level. This was done with the presumption that after such an "inventory," World Allergy Organization could offer guidance to its Member Societies on the promotion of such programs to assure the highest standards of practice in the field of allergy and clinical immunology. This review draws on the experience of countries where successful programs are in place and makes recommendations for those wishing to implement such programs for the specialty.

Background: Studies on serum IgE levels during pregnancy are limited., Objective: To investigate the course of serum total IgE levels during pregnancy and postpartum., Methods: 159 pregnant subjects provided 218 serum samples during various stages of pregnancy and the postpartum period. Serum total IgE geometric means were compared at various trimesters and postpartum. In addition, the postpartum IgE data were analysed according to the method of delivery. Analysis was also done according to history of allergy., Results: The geometric mean serum total IgE was 20.5 IU/ml in the first trimester, 20.8 IU/ml in the second and 22.2 IU/ml in the third. Postpartum serum IgE level showed a lower mean, 14.9 IU/ml during the early postpartum period (less than 30 days) compared to 30.3 IU/ml during the late postpartum period (30 days-25 weeks). However this was not statistically significant. Serum IgE in the postpartum period also did not differ according to method of delivery. A history of allergy was positive in 98 samples, negative in 61 and unclear in 59. Using analysis of variance, none of these three groups showed significant change in serum total IgE level during pregnancy or postpartum., Conclusion: In this cross-sectional study, serum total IgE levels showed no statistically significant changes during pregnancy or postpartum. This finding would be of greater weight if reproduced in a larger number of subjects with multiple serial samples at fixed regular time intervals during pregnancy and postpartum., (Copyright © 2010 SEICAP. Published by Elsevier Espana. All rights reserved.)

Background: The role of genetics in allergy development is well accepted. However, studies could not delineate the mode of inheritance or what is specifically being inherited. The purpose of this study was to determine the effect of genetics on the development of allergy manifestation, serum IgE level, and sensitization to specific allergens., Methods: Fifty-eight twin sets (age 7 months to 11 years) were evaluated for allergy by medical history, family history, physical examination, serum total IgE level, and percutaneous testing to selected common allergens., Results: In 25 monozygotic (MZ) sets, concordance of atopy was significantly higher than in 33 dizygotic (DZ) sets (84.6% vs 62.5%). The age at onset tended to be earlier when the mother was allergic than when the father was (23.5 months vs 30.5 months). When both twins were allergic, the intra-pair difference in age at onset was within <6 months in 50% of MZ sets versus 31.8% in DZ sets. Total IgE level in twins showed a very strong correlation in MZ sets (r 0.92), but only a moderate correlation among DZ sets (r 0.57). Skin test positivity to specific allergens did not show a significant concordance between twins in either group., Conclusion: Our study indicates that the genetic influence was strongest on the inheritance of IgE phenotype, the development of the atopic tendency, the age of onset, and to some extent on the specific allergy manifestation. The effect seemed less on determining the specific offending allergen(s), suggesting possible roles of epigenetic and environmental factors., (Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.)

Objective: To make recommendations based on a critical review of the evidence for the timing of the introduction of solid foods and its possible role in the development of food allergy., Data Sources: MEDLINE searches using the following search algorithm: [weaning AND infant AND allergy]/[food allergy AND sensitization]/[dietary prevention AND food allergy OR allergens]/[Jan 1980-Feb 2006]., Study Selection: Using the authors' clinical experience and research expertise, 52 studies were retrieved that satisfied the following conditions: English language, journal impact factor above 1 or scientific society, expert, or institutional publication, and appraisable using the World Health Organization categories of evidence., Results: Available information suggests that early introduction can increase the risk of food allergy, that avoidance of solids can prevent the development of specific food allergies, that some foods are more allergenic than others, and that some food allergies are more persistent than others., Conclusions: Pediatricians and allergists should cautiously individualize the introduction of solids into the infants' diet. With assessed risk of allergy, the optimal age for the introduction of selected supplemental foods should be 6 months, dairy products 12 months, hen's egg 24 months, and peanut, tree nuts, fish, and seafood at least 36 months. For all infants, complementary feeding can be introduced from the sixth month, and egg, peanut, tree nuts, fish, and seafood introduction require caution. Foods should be introduced one at a time in small amounts. Mixed foods containing various food allergens should not be given unless tolerance to every ingredient has been assessed.

Objective: This review is intended to provide an outline for the evaluation of patients suspected of having immunodeficiency, a problem that is frequently encountered in clinical practice., Data Sources: Information was obtained through a MEDLINE literature search as well as from standard textbooks in immunology. Also included is information that reflects the authors' clinical experience in the field., Results: In general clinical practice, many physicians feel inadequate to evaluate patients with suspected immune deficiencies. They also think that the process of evaluation is time-consuming, which results in misdiagnosis of a substantial percentage of such disorders. Hence, the prevalence of immunodeficiency disorders is much higher than generally thought. At present, there are >80 unique primary immunodeficiency conditions and >50 syndromes that are associated with various immunologic defects. The prevalence of secondary immunodeficiency has also been increasing because of the tragic epidemic of HIV infection, more usage of immunosuppressive medications and bone marrow stem cell transplantation, and the severe degree of malnutrition in underdeveloped countries. It is necessary for clinicians, particularly the specialists in allergy and immunology, to be able to evaluate the status of the immune system., Conclusions: Very valuable information can be gathered from the medical history and physical examination that may exclude or increase the suspicion of immunologic defect. Laboratory tests can then be appropriately selected to define the specific defect. Once the diagnosis has been settled, proper medical management can be instituted with subsequent improvement in morbidity and mortality of such disorders.