Life-threatening fish allergy successfully treated with immunotherapy

Manifestations of fish allergy can include near-fatal anaphylactic reaction. In very sensitive patients, fish odors and cooking vapors may have some al-lergenic activity. We reported a case of life-threatening fish allergy in a girl of 39 months referred for three episodes of Quincke edema with wheezing, cyanosis and severe urticaria after fish consumption or inhalation. Reagins were found against codfish and direct skin prick test with fresh food (cod fish) showed important local reaction. Strict avoidance of fish in the diet is usually the only recommended procedure. However, in this particular case, the life-threatening nature of the allergic reaction was the major considera tion to perform a desensitization. The child was treated by RUSH immuno therapy using codfish extracts from BENCARD company, following the schedule for insect venom allergy described by Pharmacia. Immunotherapy was performed immediately after determination of the threshold of sensi tivity by specific skin prick tests and intra-dermal injections. Desensitiza tion was initiated with a 1/10 dilution of the cut-off solution and 5 subcuta neous injections were administered daily. When important local reactions were observed, additional doses were necessary to obtain tolerance. After the RUSH therapy, the child was submitted to uncooked codfish odors without any reaction. No reaction has been observed even when the child has accidentally eaten a little piece of codfish.     

Insect allergy in children

Allergic reactions to insect bites and stings are common, and the severity of reactions range from local reaction to anaphylaxis. In children, large local reaction to bites and stings is the most common presentation. Stings from insects of the order Hymenoptera (bees, wasps and ants) are the most common cause of insect anaphylaxis; however, the proportion of insect allergic children who develop anaphylaxis to an insect sting is lower than that of insect allergic adults. History is most important in diagnosing anaphylaxis, as laboratory tests can be unreliable. Venom immunotherapy is effective, where suitable allergen extract is available, but is only warranted in children with systemic reactions to insect venom. Large local reactions are at low risk of progression to anaphylaxis on subsequent stings, and hence, venom immunotherapy is not necessary.     

Food allergy therapy: is a cure within reach?

There is an unmet medical need for an effective food allergy therapy; thus, development of therapeutic interventions for food allergy is a top research priority. The food allergen-nonspecific therapies for food-induced anaphylaxis include monoclonal anti-IgE antibodies and Chinese herbs. The food allergen-specific therapies include oral, sublingual, and epicutaneous immunotherapy with native food allergens and mutated recombinant proteins. Diet containing heated milk and egg may represent an alternative approach to oral immunomodulation. Oral food immunotherapy remains an investigational treatment to be further studied before advancing into clinical practice.     

Practice Guidelines for Peanut Allergies

This article reviews the latest recommendations and clinical practice guidelines for peanut allergies among the pediatric population. Recommendations in this paper were compiled using information collected from a variety of publications of accredited professional organizations. Peanut allergies are the body's response to what it sees to be an unwanted substance in the body. This article focuses on the causes, signs and symptoms, prevention, diagnosis, and management of peanut allergies.     

Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence

Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient’s daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness.     

New visions for basic research and primary prevention of pediatric allergy: An iPAC summary and future trends

Hydrolyzed formula feeding, delayed introduction of solid food, indoor allergen avoidance, smoke and pollutants avoidance have been applied for several decades as primary preventive measures for allergic diseases. Unfortunately, some of these strategies have had no or modest success. Therefore, resources need to be focused on better understanding of the early allergic events and on interventional studies to investigate new strategies of primary and secondary prevention. Accordingly, this review summarizes the state-of-the-art of genetic, immunological and clinical aspects of primary prevention of allergic diseases. Studies investigating gene-by-gene and gene-by-environment interactions suggest that prevention of allergic diseases must be tailored to the individual genetic susceptibilities ('gene profiling') and environmental exposures. The expanding knowledge on new T cell populations (Th17, TSLP (thymic stromal derived lymphopoietin)-dependent 'inflammatory Th2 cells') is also inspiring new concepts on the origins of allergic diseases. The old concept of 'blocking immunoglobulin G antibodies' has been re-appraised and it is likely to generate novel preventive and therapeutic strategies. The major task for future clinical research is to clearly define the timing of optimal exposure to potential allergens. In addition, the role of microbial products such as certain bacteria, or their components, and of helminths or their larvae at different times in early life, alone or with potential allergens, definitely need to be further investigated. The benefit of efficient allergy prevention, based on focusing resources on novel and promising research lines, will be of prime importance to both affluent countries and other parts of the world where allergy is only currently emerging.     

特异性舌下免疫疗法治疗食物过敏的研究进展

食物过敏患病率呈上升趋势,而目前有效的临床治疗方法是严格回避致敏食物并对症处理.近年来,特异性舌下免疫疗法为食物过敏的治疗提供了新的思路.该文就特异性舌下免疫疗法在治疗食物过敏中安全性及有效性的研究进展进行综述.     

儿童食物过敏的口服免疫治疗

到目前为止,食物过敏治疗尚没有确切的有效治疗方法,主要采用回避过敏原和针对严重过敏反应急诊处理等方法,口服免疫治疗(oral immunotherapy,OIT)作为一种新的食物过敏治疗方法,它能诱导IgE介导的儿童食物过敏的脱敏,但仍不了解诱导耐受的状况能否持续.虽然OIT治疗过程中发生严重过敏反应并不多见,但不良反应是共同存在的.今后需在严格设计的多中心随机、双盲、对照研究基础上,进一步了解OIT治疗后过敏原耐受状况能否维持,并明确耐受的特异性实验室指标.

Abstract：

At present there is no definitive therapy for food allergy and the mainstays of treatment are allergen avoidance and ready access to emergency medications. Significant progress toward an novel oral immunotherapy (OIT)for food allergy has been made. These preliminary data on OIT are encouraging, OIT can be effective in desensitizing at least a subset of children with IgE-mediated food allergy, however, it remains uncertain whether OIT can induce long-term tolerance. During OIT, allergic reactions are common, although severe reactions are less common. Additional studies are needed to realize whether tolerance would be maintained, and to determine the specific laboratory indicators in rigorous multicenter randomized and placebo-controlled trials.     

OPINION: Primary prevention of allergy – Will it soon become a reality?

It is generally accepted that allergic diseases are not curable and not preventable, but mainly controllable using pharmacotherapy (i.e. symptomatic medication). Recent research, however, demonstrated that a number of specific interventions can lead to (partial) primary prevention of allergy, especially of atopic dermatitis (AD) and food allergy (FA). Three types of primary prevention strategies have been successfully studied: early administration of bacterial products (most studies are on probiotics), early moisturizing in infants at risk for AD and early exposure to allergenic foods (peanut and egg). Results of these studies indicate that the stage might have been set. Surely, much more research needs to be carried out before advice can be given in clinical practice. This opinion article discusses the three types of beneficial interventions and gives ideas for future research, which might show the way for better strategies in primary prevention of allergic diseases.     

儿童牛奶蛋白过敏的口服免疫治疗

牛奶蛋白过敏是儿童食物过敏的一种常见类型,90%的牛奶蛋白过敏患儿可在3岁内获得自发耐受,预后良好,但少部分患儿牛奶蛋白过敏持续存在,常可因意外接触牛奶或奶制品而反复发生过敏反应,甚至危及生命,影响儿童的成长及心理健康。除牛奶蛋白回避及替代配方奶喂养之外,口服免疫治疗经临床实验证实可以有效帮助脱敏,但目前还没有规范的治疗方案,其安全性及长期有效性也限制其临床应用。文章就牛奶蛋白口服免疫治疗的过程、机制、优化方案及其相关内容进行综述。     

Safety and efficacy of epicutaneous immunotherapy for food allergy

Food allergy is increasingly common in children, affecting about 4%‐8%. The mainstays of management remain allergen avoidance and emergency preparedness to treat allergic reactions with emergency medications. Unfortunately, these approaches are unsatisfactory for many patients and their families as the restrictions, constant vigilance, and unpredictable severity of allergic reactions negatively impact quality of life. In recent decades, there has been significant interest in developing treatments for food allergy that lead to desensitization to increase thresholds for triggering allergic reactions and decrease the risk of reacting to allergen‐contaminated food products. Epicutaneous immunotherapy (EPIT) is a novel therapy that is currently under investigation, delivering allergen via repeated applications to the skin and targeting antigen‐presenting cells in the superficial skin layers. Murine models have demonstrated that allergen uptake is an active process by skin dendritic cells with subsequent migration to draining lymph nodes. Allergen exposure to the non‐vascularized epidermis limits systemic absorption, contributing to the high‐safety profile. Results from murine experiments showed that EPIT has comparable efficacy as subcutaneous immunotherapy in terms of challenge outcomes, airway hyper‐responsiveness, and immunologic parameters. Several clinical trials of EPIT have recently been completed or are ongoing. Results support the high safety and tolerability of this approach. Efficacy data suggest that the change in threshold eliciting dose following 1 year of therapy is less than that seen compared to high‐dose (2‐4 g peanut protein) oral immunotherapy, but more prolonged treatment with EPIT appears to lead to increasing desensitization. Additional data from larger‐scale studies should provide a more robust assessment of safety and efficacy of EPIT.     

Immunotherapy – risk/benefit in food allergy

Food allergy is a growing health concern in the westernized world with approx. 6% of children suffering from it. A lack of approved treatment has led to strict avoidance of the culprit food proteins being the only standard of care. Nowadays in‐depth research is conducted to evaluate the possible use of allergen‐specific immunotherapy (SIT) as an active therapeutic option for food allergy. Various routes of administration for the immunotherapy are investigated, including subcutaneous, oral, sublingual, and epicutaneous, and some appear to be successful in inducing a temporary tolerant state. Most research has been conducted with oral immunotherapy due to its efficacious and relatively safe profile. Increasing interest is dedicated to safer and more convenient approaches, such as sublingual and epicutaneous SIT; however, doubts exist about their possible capacity to induce temporary tolerant state and permanent oral tolerance. The high frequency of allergic adverse reactions of the various approaches and the inability to achieve permanent oral tolerance have highlighted the need of refinements in the strategies. A promising strategy for preventing IgE cross‐linking and thus enhancing safety of SIT, while still activating T cells, is the use of tolerogenic peptides. The implementation of such an immunotherapy approach has the potential of not only increasing the chance of achieving a permanent state of tolerance, but also improving the safety and tolerability of the therapy. Immunotherapy for food allergy is still not ready for the clinic, but current and upcoming studies are dedicated to collect enough evidence for the possible implementation of allergen‐SIT as a standard treatment for food allergy.     

Evaluation of the risk of anaphylactic reactions by wasp venom-extract challenges in children

Diagnostic sting challenges have been shown to provide information on the risk of further anaphylactic reactions to bee stings. We present a follow-up study in wasp venom-hypersensitive children after diagnostic venom extract challenges to analyze their risk of further anaphylactic reactions. Responses were obtained from 104 patients with wasp venom hypersensitivity out of 115 former patients. Only one of the 104 patients showed more than a severe local reaction to the sting challenge irrespective of the performance of a single or sequential challenge; therefore, only one patient received venom immunotherapy. The performance of a diagnostic sting challenge with wasp venom extract in children had a high negative predictive value of 94.6% for the risk of further systemic reactions. This was shown by analysis of later field stings, since 37 children experienced further field stings and only two of these children(5.4%) developed a mild systemic reaction (urticaria) equal to or less severe than the index sting. The value of the venom extract challenge can be interpreted in two ways: either it is less sensitive than a native sting challenge since the rate of systemic reactions to the challenge was very low, or the prognosis of wasp venom hypersensitivity in children is extremely favorable. Since the latter hypothesis is supported by the low incidence of systemic field sting reactions, we postulate that venom immunotherapy is necessary only in a minority of children with wasp venom hypersensitivity with an index sting reaction of Mueller grade I or II. However, the value of venom extract challenges as a general diagnostic instrument in children with Mueller I and II reactions due to wasp venom hypersensitivity may be questioned. It may have a place as a safe procedure in demonstrating to parents and physicians the often self-limiting natural course in most of these children.     

Quantitative assessment of the compliance with once-daily sublingual immunotherapy in children (EASY Project: Evaluation of A novel SLIT formulation during a Year)

Compliance is a major determinant for allergy treatment, especially in children. Sublingual immunotherapy (SLIT) is self-managed at home, and no quantitative data on pediatric adherence are available. We studied the compliance in a large real-life setting. A simplified schedule of SLIT was used, consisting of a 10-day updosing phase followed by maintenance treatment in monodose containers to be taken daily (SLITOne). Italian specialists throughout Italy assessed the compliance in children who were newly prescribed SLIT according to guidelines. Parents were contacted with unscheduled telephone interviews at the third and sixth month of therapy and asked to count at that moment the remaining vials. Data from 71 children (38 boys, age range 2-13 yr) were enclosed in the database. Thirty had rhinoconjunctivitis, four asthma and 37 rhinoconjunctivitis + asthma. SLIT was prescribed for: mites in 57 (81%) subjects, grasses in 11 (15%) and 3 (4%) grass + olive mixture. Compliance data were available for all children at 3 months, and for 56 at 6 months. At 3 months, 85% of subjects had a compliance rate >75% (69% of them adhered >90%). At 6 months, 84% had a compliance rate >75% (66% of them adhered >90%). In four cases SLIT was discontinued for economical reasons, and in one case (1.4%) for side effects probably related to therapy. These data obtained in a quite large sample of children and in real-life confirm that the compliance with SLITOne is good, despite the therapy managed at home.