Dietary Avoidance Research Articles

Current and Emerging Therapies for IgE-Mediated Food Allergy.

Food allergies are a growing clinical problem leading to increased health care utilization and decreases in patient quality of life. Current treatment recommendations include strict dietary avoidance of the offending food as well as use of self-injectable epinephrine in case of accidental exposure with allergic reaction. Although many individuals will eventually outgrow their food allergies, a substantial number will not. Significant effort has been made to find novel treatments that protect patients from food-triggered reactions as well as to develop immune-modulating therapies that could lead to tolerance. In this review, three therapies that have shown the most promise for the treatment of food allergies are highlighted: oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy.

Role of Regulatory T-cells in Oral Tolerance and Immunotherapy

Food allergies encompass a range of disorders ranging from being an inconvenience to even causing fatalities, mainly due to anaphylaxis. A large number of individuals are affected and this presents great health and economic implications. However as yet, apart from dietary avoidance, effective treatment strategies are practically non-existent. The immune environment related to allergen-tolerance is highly complex and the role of regulatory T-cells in allergenspecific tolerance, their interaction with other cells in inflamed tissues, and their role in antibody regulation have been demonstrated in several studies. Regulatory T-cells are able to control acquired immunity and achieve oral tolerance to food allergens. Immunotherapy for food allergies focuses on desensitisation by increasing the allergen reactivity threshold. So far, the only long-term curative treatment used effectively is allergen-specific immunotherapy which involves the administration of increasing doses of the causative allergen, such that a state of allergen-specific immune tolerance is induced over the course of the treatment. This review covers various forms of allergen-specific immunotherapy, focusing on the role of regulatory T-cells in such therapies, and includes a number of small studies providing ideas for future work in the area.

Coeliac Disease: Gluten Free Diet and… What Else?

Coeliac Disease (CD) is a permanent gluten intolerance, whose pathogenesis involves multiple factors including genetics and environment. CD has different representations and non-specific symptoms such as diarrhea, bloating, pain, flatulence and constipation may sometimes be misleading. Once diagnosed of CD, patients must adhere to Gluten Free Diet, which consists in the lifelong avoidance of gluten containing foods and of those naturally gluten free but at risk of contamination. This dietary approach is considered the only therapy in order to avoid symptoms exacerbation and to reduce the digestive mucosa inflammation, which has been related to higher risks of lymphoproliferative malignancy and other immunological disorders. However, being on a Gluten Free Diet is not as resolving as it may seem since it has several criticalities. First of all, excluding gluten means limiting food variety so that coeliac patients may have unbalanced intake of several nutrients and develop clinical or subclinical deficiencies. This can be due to scarce attention to qualitative and quantitative composition of diets and poor information about gluten-containing foods, which only patient-tailored dietetic protocol and long-term follow-up can achieve. Secondly, Gluten Free Diet may not result in complete remission of mucosal damage or in resolution of symptoms. Unintentional contamination of gluten or poor adherence to diet are the main culprits of the incomplete mucosal healing but other triggers may be involved. Recent research has focused on the role of FODMAPs in changing gut microbiota and on the improvement of Irritable Bowel Syndrome (IBS) symptoms after their dietary avoidance or reduction. Since CD and IBS may share many clinical presentations, further studies are needed to evaluate if a subgroup of CD patients whose symptoms are not improved by Gluten Free Diet could benefit from a new therapeutic approach consisting in both gluten/wheat and FODMAPs avoidance.

Improving the safety of oral immunotherapy for food allergy.

Food allergy is a major public health problem in children, impacting upon the affected individual, their families and others charged with their care, for example educational establishments, and the food industry. In contrast to most other paediatric diseases, there is no established cure: current management is based upon dietary avoidance and the provision of rescue medication in the event of accidental reactions, which are common. This strategy has significant limitations and impacts adversely on health‐related quality of life. In the last decade, research into disease‐modifying treatments for food allergy has emerged, predominantly for peanut, egg and cow's milk. Most studies have used the oral route (oral immunotherapy, OIT), in which increasing amounts of allergen are given over weeks–months. OIT has proven effective to induce immune modulation and ‘desensitization’ – that is, an increase in the amount of food allergen that can be consumed, so long as regular (typically daily) doses are continued. However, its ability to induce permanent tolerance once ongoing exposure has stopped seems limited. Additionally, the short‐ and long‐term safety of OIT is often poorly reported, raising concerns about its implementation in routine practice. Most patients experience allergic reactions and, although generally mild, severe reactions have occurred. Long‐term adherence is unclear, which rises concerns given the low rates of long‐term tolerance induction. Current research focuses on improving current limitations, especially safety. Strategies include alternative routes (sublingual, epicutaneous), modified hypoallergenic products and adjuvants (anti‐IgE, pre‐/probiotics). Biomarkers of safe/successful OIT are also under investigation.

Predicting eczema severity beyond childhood

We evaluated factors associated with eczema severity in adolescence. Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test for common food and aeroallergens, highest serum IgE level and eosinophil count were evaluated. Patients with paired NESSs (childhood-NESS is NESS performed at <10 years of age; adolescence-NESS is NESS performed at age >10 years) were further analyzed. Adolescence-NESS (n=383 patients) was associated with eczema onset in infancy, dust mite and food allergen sensitization, dietary avoidance, use of wet wrap, traditional Chinese medicine, immunomodulant (azathioprine or cyclosporine), high IgE level, eosinophil count, but not with family/personal history of atopy. Eighty-two patients had both childhood-NESS and adolescence-NESS (mean follow-up of 6.8 years) showing that adolescence-NESS was associated with childhood- NESS severity grades (P=0.034). Of these patients, 48% remained in the same severity grades, whereas 39% improved, and 13% deteriorated from childhood to adolescence. It is not possible to assure parents that their child can outgrow eczema. In eczema prognosis research, long-term follow-up is warranted.

MG-107 Congenital sucrase-isomaltase deficiency: Identification of the common inuit founder mutation

Objective Congenital sucrase-isomaltase deficiency (CSID) is a rare hereditary cause of chronic diarrhoea in children. Persons with CSID lack the intestinal brush-border enzyme required for digestion of di- and oligosaccharides, including sucrose and isomaltose. Malabsorption results in abdominal pain, distention, copious diarrhoea, and failure to thrive. If recognised, dietary avoidance of the offending carbohydrates is highly effective. Although CSID is known to be highly prevalent (˜5–10%) in several Inuit populations, the genetic basis for this condition has not been described. Methods We sequenced the sucrase-isomaltase gene, SI, in a single Inuit CSID proband with severe fermentative diarrhoea and failure to thrive. We then genotyped a further 128 anonymized Inuit control individuals from a variety of circumpolar locales to assess for a possible founder effect. Results We identified a novel, homozygous frameshift mutation, c.273_274delAG (p. Gly92Leufs*8) in exon 4 of SI in the proband, that is predicted to result in complete absence of functional protein product. This change is indeed very common among Inuit control specimens, with an observed allele frequency of 0.17 (95% confidence interval 0.13–0.22). The predicted Hardy-Weinberg prevalence of CSID in the Inuit, based on this single founder allele is ˜3% (95% confidence interval 1.6–5.0%), comparable with previous estimates. Interpretation Targeted mutation testing for the c.273_274delAG allele should afford a simple and minimally invasive means of diagnosing CSID in persons of Inuit descent. Because CSID is a readily treatable disorder, such testing should be considered at an early stage in the assessment of Inuit patients with chronic diarrhoea.

Managing nut-induced anaphylaxis: challenges and solutions.

The prevalence of peanut and tree nut allergy in the USA has increased, especially in the pediatric population. Nut allergy remains the leading cause of fatal anaphylactic reactions. Management of anaphylaxis includes not only treatment of symptoms during a reaction, but strict dietary avoidance and education on potential situations, which may place the patient at high risk for accidental exposure. Cross-reactivity between various nuts along with various cross-contamination sources should be discussed with all nut-allergic individuals. Exciting research continues to emerge on other potential treatments for patients allergic to nuts, including allergen immunotherapy. Results of such interventions have been encouraging, though further studies are needed regarding safety and long-term outcomes before these can be applied to clinical practice.

Oral immunotherapy in clinical practice

Food avoidance is still considered the gold-standard treatment for food allergy (FA). However, recently it has been consolidating the theory that, where possible, the food intake might facilitate the induction of desensitization and tolerance, resulting more effective and safer -if we consider the possibility of accidental ingestion- than a strict avoidance diet [1]. Furthermore, specific oral immunotherapy (OIT) is the unique active treatment for IgE-mediated FAs [1].

Food Avoidance Diets for Dermatitis.

Food allergy is relatively common in both children and adults, and its prevalence is increasing. Early exposure of food allergens onto skin with an impaired epidermal barrier predisposes to sensitization and prevents the development of oral tolerance. While immediate-type food allergies are well described, less is known about delayed-type food allergies manifesting as dermatitis. This is due, in part, to limitations with current diagnostic testing for delayed-type food allergy, including atopy patch testing. We conducted a systematic review of food avoidance diets in delayed-type food allergies manifesting as dermatitis. While beneficial in some clinical circumstances, avoidance diets should be used with caution in infants and children, as growth impairment and developmental delay may result. Ultimately, dermatitis is highly multifactorial and avoidance diets may not improve symptoms of delayed-type food allergy until combined with other targeted therapies, including restoring balance in the skin microbiome and re-establishing proper skin barrier function.

Dairy and nondairy beverage consumption for childhood atopic eczema: what health advice to give?

Many parents of children with atopic eczema (AE) practise empirical dietary avoidance and supplementation, and seek healthcare advice on whether consumption of dairy and nondairy beverages may be beneficial or detrimental for this condition. We investigated if frequency of consumption of beverages was associated with disease severity and quality of life (QoL). Parent-reported frequency of drinks and beverages were recorded in consecutive children with AE, and disease severity (Nottingham Eczema Severity Score; NESS), QoL (Children's Dermatology Life Quality Index; CDLQI), skin hydration (SH), transepidermal water loss (TEWL), blood pressure (BP), resting heart rate (RHR) and body mass index (BMI) were evaluated. AE was associated with worse QoL than miscellaneous non-AE skin diseases (P < 0.001). Compared with children without AE, there was a trend for children with AE to drink less milk (P = 0.06) and more miscellaneous beverages (such as Chinese herbal tea and soymilk; P = 0.03). In children with AE, NESS correlated with CDLQI (ρ = 0.66, P < 0.001) and reduced SH (ρ = -0.32, P < 0.001), whereas CDLQI correlated with a higher RHR (ρ = 0.25, P < 0.01). Multiple logistic regression showed that male sex (OR = 0.44, 95% CI 0.20-0.97; P = 0.04) and drinking fresh milk (OR = 0.42, 95% CI 0.20-0.93; P = 0.03) were independent factors associated with less severe disease. Moderate to severe impairment of CDLQI was associated with NESS (OR = 1.48, 95% CI 1.28-1.71; P < 0.001) and RHR (OR = 1.05, 95% CI 1.02-1.08; P < 0.01) but not with reported habits of beverage consumption. Concerning cardiovascular health in AE, frequency of formula milk consumption was associated with RHR (ρ = 0.17, P = 0.04), and soft drink consumption was associated with higher systolic blood pressure (SBP) (ρ = 0.18, P = 0.04). This study provides evidence for parental/patient guidance. Children with AE who reported more fresh milk consumption had less severe disease. There was no correlation between consumption of nondairy beverages with disease severity or QoL, but frequency of soft drink consumption correlated with SBP. With these results being supported by a literature review, it is reasonable to advise parents that fresh milk can be consumed by unsensitized children with AE. Soft drinks and other beverages should not be consumed in excess for optimal cardiovascular health and for other health reasons.

Probiotic Lactobacillus rhamnosus GG therapy and microbiological programming in infantile colic: a randomized, controlled trial.

Probiotic Lactobacillus reuteri and reduced allergen load may lessen the daily crying of colic infants, but the role of Lactobacillus rhamnosus GG (LGG) has remained obscure. Infants with colic (n = 30) were enrolled during the first 6 wk of life. All families received behavioral support and allergen avoidance diet: breastfeeding mothers followed cow's milk elimination diet and formula-fed infants received extensively hydrolyzed casein formula. The randomized, double-blind intervention employed of LGG 4.5 × 10(9) cfu/d or placebo for a 4-wk study period. Daily crying was recorded by diaries and parental interviews. Fecal calprotectin and gut microbiota composition by quantitative PCR were evaluated before and after the intervention. Daily crying time was comparable between the probiotic (173 min) and the placebo group (174 min; P = 0.99) at the end of the intervention according to the parental diary. However, parents reported a decrease of 68% (95% confidence interval (CI): 58-78) in daily crying in the probiotic and 49% (95% CI: 32-66) in the placebo group (P = 0.05). LGG in infants treated in tandem with behavioral support and a cow's milk elimination diet did not provide additional treatment effect for diary-verified colic crying although parental report of crying suggested the probiotic intervention effective.

Food for thought: progress in understanding the causes and mechanisms of food allergy.

The community burden of food allergy appears to be rising, yet the causes and mechanisms are not completely understood. The purpose of this review is to provide a snapshot of the state of play of IgE food allergies, with a focus on recent advances. There are still wide discrepancies regarding measures and definitions of food allergy. Even recent studies still rely on food sensitization, self-reporting, or parent-reporting rather than more robust measures. Population-based sampling strategies using objective measures are underway in some countries. Emerging data suggest substantial geographical and ethnic differences in food sensitization and allergy. Trans-cutaneous sensitization, particularly in those with eczema or filaggrin mutations, has been posited as a potential mechanism, as well as gut microbiota and genetics/epigenetics. Treatments for food allergy are still lacking, yet progress is being made, and immunotherapy appears more effective than dietary avoidance. Non-IgE food allergy remains drastically under-explored. Food allergy is a complex immune-mediated disease consisting of numerous environmental/genetic/epigenetic risk factors; yet interventions are likely to be simple and cost-effective.

Progress in sublingual immunotherapy for food allergy

The incidence of food allergy has increased in recent years.The current management of food allergy includes strict dietary avoidance and rapid medical treatment in case of accidental exposure.As a new immunotherapy method, sublingual immunotherapy has shown promising as alternative treatment for food allergy.This review discusses the clinical effectiveness and safety of sublingual immunotherapy for food allergy that are recently being investigated. Key words: Food allergy; Sublingual immunotherapy; Safety; Effectiveness

Dietary management of peanut and tree nut allergy: what exactly should patients avoid?

Peanut and tree nut allergies are the commonest cause of life-threatening food-allergic reactions and significantly affect quality of life in children and their families. Dietary nut avoidance and provision of emergency medication is currently the mainstay of treatment. Nut avoidance has consequences on both quality of life and nutrition. We review the terminology that may cause confusion and lead to unnecessary dietary restrictions. In peanut or tree nut-allergic children, introduction of specific nuts to which the child is not allergic may improve quality of life and should be considered in patients with multiple foods allergies, vegan or ethnic-specific diets, in whom nuts are an important source of protein. Nut-allergic consumers do not just need to avoid foods containing nuts as an ingredient, but also contend with pre-packed foods which frequently have precautionary allergen labelling (PAL) referring to possible nut contamination. Although the published rate of peanut contamination in 'snack' foods with PAL (see Box) ranges from 0.9-32.4%, peanut contamination in non-snack items with PAL is far less common. We propose that in some peanut-allergic patients (depending on history of reactivity to trace levels of peanut, reaction severity, other medical conditions, willingness to always carry adrenaline, etc.), consideration may be given to allow the consumption of non-snack foods containing PAL following discussion with the patient's (and their family's) specialist. More work is needed to provide consumers with clearer information on the risk of potential nut contamination in pre-packed food. We also draw attention to the change in legislation in December 2014 that require mandatory disclosure of allergens in non-pre-packed foods.

Impact of elimination diets on growth and nutritional status in children with multiple food allergies.

Impairment of growth has been reported in food-allergic children. It is not known whether this is related to the extent of food allergies. We sought to compare growth, nutritional status, and nutrient intake in children with food allergy either avoiding cow's milk or avoiding cow's milk and wheat, which are staples of the diet in young children. Infants and young children with challenge-proven allergy were recruited to this prospective study. They were strictly avoiding their allergic food triggers, either cow's milk, or cow's milk and wheat. They were counseled by a dietitian specialized in food allergies on food avoidance diets and nutritionally adequate supplementation at regular intervals. A 3-day food diary was kept. Children's height, weight, and laboratory data for nutritional parameters were monitored at 8-month intervals. A total of 18 patients avoiding milk and 28 patients avoiding milk and wheat were evaluated at an average of 12, 21, and 28months of age. During the follow-up, the markers of nutritional status, nutrient intake or height for age, and weight for height were comparable between the two groups, although the means for anthropometric measures were below the average for age in both groups. The extent of food elimination diet has no impact on growth or nutritional status of food-allergic children, when diet is adequately supplemented. Close physician and dietitian follow-up are essential for food-allergic children when avoiding one or more foods, which are staples of the diet.

Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review.

Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary.

Traveler's diarrhea: a clinical review.

Acute diarrhea is the most common illness that affects travelers to low-income regions of the world. Although improved hygiene has reduced the risk of traveler's diarrhea in many destinations, the risk remains high in others. To review the current state of knowledge on the etiology, risk factors, prevention, and management of traveler's diarrhea. A search of the PubMed, Google Scholar, and Cochrane Library databases for the period 2012-April 2014 was performed for articles on traveler's diarrhea. The database search yielded 2976 articles, of which 37 were included in this review. These were added to 85 articles previously identified by the authors. Improved hygiene has reduced the risk of traveler's diarrhea from 20% or more (for a 2-week stay) to between 8% and 20% in some parts of the world. Acquiring traveler's diarrhea causes 12% to 46% of travelers to change their travel plans. Returning travelers seeking medical care have a diagnosis of gastrointestinal disturbance in approximately one-third of all cases. Postinfectious irritable bowel syndrome may occur in 3% to 17% of patients who have had traveler's diarrhea. Prevention of traveler's diarrhea by dietary avoidance measures is often not successful. Chemoprophylaxis should be restricted to travelers who are at risk of severe complications of diarrhea. Ciprofloxacin is the standard treatment in self-therapy of traveler's diarrhea except when patients are in South or Southeast Asia, where azithromycin is preferred. Diarrhea remains a common problem for international travelers. Persons intending to travel to at-risk countries should be counseled regarding prevention measures and may be given a travel pack that includes medications for self-treatment should they become ill.

Update on egg allergy in children

Egg allergy is one of the most common food allergies in children and has a wide spectrum of clinical presentation including anaphylaxis. Many studies suggested egg-specific IgE cutoff values (diagnostic decision point) and skin prick test size that predict a clinical allergic reaction without oral food challenges. Some patients may react to all forms of egg including raw egg, but many egg-allergic patients tolerate baked egg products. A few studies reported that a high concentration of ovomucoid-specific IgE antibody indicates a high risk of reacting to heated egg white. Recently it has been suggested that regular ingestion of baked egg products may hasten tolerance development. Egg allergy may be more persistent than previously thought. The treatment of egg allergy still relies on dietary avoidance of egg-containing foods until tolerance has developed. In recent years there has been increasing success in clinical trials of egg oral immunotherapy, and oral immunotherapy can be a promising treatment modality for providing protection from reactions caused by accidental egg exposure. However, concerns regarding the safety and long-term efficacy still preclude the general use of oral immunotherapy in clinical practice. In this article, the recent literature regarding egg allergens, clinical presentation, diagnosis, management and natural history of egg allergy will be reviewed.

Food allergies affect growth in children

Growth impairment and nutritional deficiencies, including rickets, iron deficiency, and kwashiorkor, have been reported in children with elimination diets based on real or perceived food allergy (RPFA).1-5 These cases demonstrate that the allergen avoidance diets required in FA management place children at risk for growth and nutritional problems. However, few studies have systematically investigated this concern.

Oral and sublingual immunotherapy for egg allergy.

Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy (OIT) might be an optional treatment, through desensitization to egg allergen. We aimed to assess the successful desensitization and development of tolerance to egg protein and the safety of egg oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy. We searched 13 databases for journal articles, conference proceedings, theses and unpublished trials using a combination of subject headings and text words (the last search was on 5 December 2013). Randomized controlled trials (RCTs) were included. All age groups with clinical egg allergy were to be included. We retrieved 83 studies from the electronic searches. We selected studies, extracted data and assessed the methodological quality. We attempted to contact the study investigators to obtain the unpublished data, wherever possible. We used the I² statistic to assess statistical heterogeneity. We estimated a pooled risk ratio (RR) with 95% confidence interval (CI) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low (I² value less than 50%). We included four RCTs with a total of 167 recruited individuals (OIT 100; control 67 participants), all of whom were children (aged four to 15 years). One study used a placebo and three studies used an avoidance diet as the control. Each study used a different OIT protocol. Thirty nine per cent of OIT participants were able to tolerate a full serving of egg compared to 11.9% of the controls (RR 3.39, 95% CI 1.74 to 6.62). Forty per cent of OIT participants could ingest a partial serving of egg (1 g to 7.5 g; RR 5.73, 95% CI 3.13 to 10.50). Sixty nine per cent of the participants presented with mild-to-severe adverse effects (AEs) during OIT (RR 6.06, 95% CI 3.11 to 11.83). Five of the 100 participants receiving OIT required epinephrine. We cannot comment on whether over- or under-reporting of AEs was a concern based on the available data. Overall there was inconsistent methodological rigour in the trials. The studies were small and the quality of evidence was low. Current evidence suggests that OIT can desensitize a large number of egg-allergic patients, although it remains unknown whether long-term tolerance develops. A major difficulty of OIT is the frequency of AEs, though these are usually mild and self-limiting. The use of epinephrine while on OIT seems infrequent. There are no standardized protocols for OIT and guidelines would be required prior to incorporating desensitization into clinical practice.