Food Allergy Abstracts 3


The diagnosis and treatment of food allergy
            (Atkins and Metcalfe, 1984) Download
In discussing a topic as complex as food sensitivity, a precise definition of terms is necessary to avoid confusion. adverse food reactions may be separated into two distinct categories that are distinguished by whether or not the immune system participates in the development of the reaction. By this criterion, the term "food intolerance" is designated to refer to idiosyncratic, pharmacologic, metabolic, or toxic reactions to foods in which the immune system does not participate. The terms "food allergy" and "food hypersensitivity" are synonomous and refer to adverse reactions to foods in which the immune system plays a prominent role.

Food allergy: separating the science from the mythology
            (Brandtzaeg, 2010) Download
Numerous genes are involved in innate and adaptive immunity and these have been modified over millions of years. During this evolution, the mucosal immune system has developed two anti-inflammatory strategies: immune exclusion by the use of secretory antibodies to control epithelial colonization of microorganisms and to inhibit the penetration of potentially harmful agents; and immunosuppression to counteract local and peripheral hypersensitivity against innocuous antigens, such as food proteins. The latter strategy is called oral tolerance when induced via the gut. Homeostatic mechanisms also dampen immune responses to commensal bacteria. The mucosal epithelial barrier and immunoregulatory network are poorly developed in newborns. The perinatal period is, therefore, critical with regard to the induction of food allergy. The development of immune homeostasis depends on windows of opportunity during which innate and adaptive immunity are coordinated by antigen-presenting cells. The function of these cells is not only orchestrated by microbial products but also by dietary constituents, including vitamin A and lipids, such as polyunsaturated omega-3 fatty acids. These factors may in various ways exert beneficial effects on the immunophenotype of the infant. The same is true for breast milk, which provides immune-inducing factors and secretory immunoglobulin A, which reinforces the gut epithelial barrier. It is not easy to dissect the immunoregulatory network and identify variables that lead to food allergy. This Review discusses efforts to this end and outlines the scientific basis for future food allergy prevention.

Diagnosing and managing common food allergies: a systematic review
            (Chafen et al., 2010) Download
CONTEXT: There is heightened interest in food allergies but no clear consensus exists regarding the prevalence or most effective diagnostic and management approaches to food allergies. OBJECTIVE: To perform a systematic review of the available evidence on the prevalence, diagnosis, management, and prevention of food allergies. DATA SOURCES: Electronic searches of PubMed, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials. Searches were limited to English-language articles indexed between January 1988 and September 2009. STUDY SELECTION: Diagnostic tests were included if they had a prospective, defined study population, used food challenge as a criterion standard, and reported sufficient data to calculate sensitivity and specificity. Systematic reviews and randomized controlled trials (RCTs) for management and prevention outcomes were also used. For foods where anaphylaxis is common, cohort studies with a sample size of more than 100 participants were included. DATA EXTRACTION: Two investigators independently reviewed all titles and abstracts to identify potentially relevant articles and resolved discrepancies by repeated review and discussion. Quality of systematic reviews and meta-analyses was assessed using the AMSTAR criteria, the quality of diagnostic studies using the QUADAS criteria most relevant to food allergy, and the quality of RCTs using the Jadad criteria. DATA SYNTHESIS: A total of 12,378 citations were identified and 72 citations were included. Food allergy affects more than 1% to 2% but less than 10% of the population. It is unclear if the prevalence of food allergies is increasing. Summary receiver operating characteristic curves comparing skin prick tests (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.81-0.93) and serum food-specific IgE (AUC, 0.84; 95% CI, 0.78-0.91) to food challenge showed no statistical superiority for either test. Elimination diets are the mainstay of therapy but have been rarely studied. Immunotherapy is promising but data are insufficient to recommend use. In high-risk infants, hydrolyzed formulas may prevent cow's milk allergy but standardized definitions of high risk and hydrolyzed formula do not exist. CONCLUSION: The evidence for the prevalence and management of food allergy is greatly limited by a lack of uniformity for criteria for making a diagnosis.

Allergic rhinitis caused by food allergies
            (Cingi et al., 2010) Download
Food allergies occur in 1-2% of adults and in 8% of children under 6 years of age. Food-induced allergies are immunological reactions that cause a variety of symptoms affecting the skin, gastrointestinal tract, and respiratory tract. The reactions are mediated by both IgE- and non-IgE-dependent (cellular) mechanisms. Isolated food-induced allergic rhinitis is not common as it frequently occurs together with other food allergy symptoms such as asthma, eczema, oral allergic manifestations, urticaria, and gastrointestinal symptoms. The present paper provides an overview of food allergies and food-induced allergic rhinitis.

Clinical and biochemical effects of a combination botanical product (ClearGuard) for allergy: a pilot randomized double-blind placebo-controlled trial
            (Corren et al., 2008) Download
BACKGROUND: Botanical products are frequently used for treatment of nasal allergy. Three of these substances, Cinnamomum zeylanicum, Malpighia glabra, and Bidens pilosa, have been shown to have a number of anti-allergic properties in-vitro. The current study was conducted to determine the effects of these combined ingredients upon the nasal response to allergen challenge in patients with seasonal allergic rhinitis. METHODS: Twenty subjects were randomized to receive the combination botanical product, (CBP) 2 tablets three times a day, loratadine, 10 mg once a day in the morning, or placebo, using a randomized, double-blinded crossover design. Following 2 days of each treatment and during the third day of treatment, subjects underwent a nasal allergen challenge (NAC), in which nasal symptoms were assessed after each challenge dose and every 2 hours for 8 hours. Nasal lavage fluid was assessed for tryptase, prostaglandin D2, and leukotriene E4 concentrations and inflammatory cells. RESULTS: Loratadine significantly reduced the total nasal symptom score during the NAC compared with placebo (P = 0.04) while the CBP did not. During the 8 hour period following NAC, loratadine and the CBP both reduced NSS compared with placebo (P = 0.034 and P = 0.029, respectively). Analysis of nasal lavage fluid demonstrated that the CBP prevented the increase in prostaglandin D2 release following NAC, while neither loratadine nor placebo had this effect. None of the treatments significantly affected tryptase or leukotriene E4 release or inflammatory cell infiltration. CONCLUSION: The CBP significantly reduced NSS during the 8 hours following NAC and marginally inhibited the release of prostaglandin D2 into nasal lavage fluid, suggesting potential clinical utility in patients with allergic rhinitis.

Sensitivity-related illness: the escalating pandemic of allergy, food intolerance and chemical sensitivity.
            (Genuis, 2010) Download
The prevalence of allergic-related diseases, food intolerance, and chemical sensitivities in both the pediatric and adult population has increased dramatically over the last two decades, with escalating rates of associated morbidity. Conditions of acquired allergy, food intolerance and chemical hypersensitivity are frequently the direct sequelae of a toxicant induced loss of tolerance (TILT) in response to a significant initiating toxic exposure. Following the primary toxicant insult, the individuals become sensitive to low levels of diverse and unrelated triggers in their environment such as commonly encountered chemical, inhalant or food antigens. Among sensitized individuals, exposure to assorted inciting stimuli may precipitate diverse clinical and/or immune sequelae as may be evidenced by clinical symptoms as well as varied lymphocyte, antibody, or cytokine responses in some cases. Recently recognized as a mechanism of disease development, TILT and resultant sensitivity-related illness (SRI) may involve various organ systems and evoke wide-ranging physical or neuropsychological manifestations. With escalating rates of toxicant exposure and bioaccumulation in the population-at-large, an increasing proportion of contemporary illness is the direct result of TILT and ensuing SRI. Avoidance of triggers will preclude symptoms, and desensitization immunotherapy or immune suppression may ameliorate symptomatology in some cases. Resolution of SRI generally occurs on a gradual basis following the elimination of bioaccumulated toxicity and avoidance of further initiating adverse environmental exposures. As has usually been the case throughout medical history whenever new evidence regarding disease mechanisms emerges, resistance to the translation of knowledge abounds.

Differentiating food allergies from food intolerances.
            (Guandalini and Newland, 2011) Download
Adverse reactions to foods are extremely common, and generally they are attributed to allergy. However, clinical manifestations of various degrees of severity related to ingestion of foods can arise as a result of a number of disorders, only some of which can be defined as allergic, implying an immune mechanism. Recent epidemiological data in North America showed that the prevalence of food allergy in children has increased. The most common food allergens in the United States include egg, milk, peanut, tree nuts, wheat, crustacean shellfish, and soy. This review examines the various forms of food intolerances (immunoglobulin E [IgE] and non-IgE mediated), including celiac disease and gluten sensitivity. Immune mediated reactions can be either IgE mediated or non-IgE mediated. Among the first group, Immediate GI hypersensitivity and oral allergy syndrome are the best described. Often, but not always, IgE-mediated food allergies are entities such as eosinophilic esophagitis and eosinophilic gastroenteropathy. Non IgE-mediated immune mediated food reactions include celiac disease and gluten sensitivity, two increasingly recognized disorders. Finally, non-immune mediated reactions encompass different categories such as disorders of digestion and absorption, inborn errors of metabolism, as well as pharmacological and toxic reactions.


Anti-allergic effects of herbal product from Allium cepa (bulb)
            (Kaiser et al., 2009) Download
Allium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.

Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line.
            (Kempuraj et al., 2006) Download
Mast cells are involved in inflammatory processes and in allergic reactions where immunologic stimulation leads to degranulation and generation of numerous cytokines and inflammatory mediators. Mast cells have been proposed as an immune gate to the brain, as well as sensors of environmental and emotional stress, and are likely involved in neuropathologic processes such as multiple sclerosis. Among mast cell products, the protease tryptase could be associated with neurodegenerative processes through the activation of specific receptors (PARs) expressed in the brain, while interleukin (IL)-6 likely causes neurodegeneration and exacerbates dysfunction induced by other cytokines; or it could have a protective effect against demyelinisation. In this report we show that quercetin, a natural compound able to act as an inhibitor of mast cell secretion, causes a decrease in the release of tryptase and IL-6 and the down-regulation of histidine decarboxylase (HDC) mRNA from human mast cell (HMC)-1 cells. As quercetin dramatically inhibits mast cell tryptase and IL-6 release and HDC mRNA transcription by HMC-1 cell line, these results nominate quercetin as a therapeutical compound in association with other therapeutical molecules for neurological diseases mediated by mast cell degranulation.


Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats
            (Kumar et al., 2008) Download
Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml(-1)) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg(-1); p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg(-1) of HK showed significant (P < 0.01) protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg(-1) showed significant (P < 0.01) reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg(-1) it showed significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001) decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors.

Food allergies: detection and management
            (Kurowski and Boxer, 2008) Download
Family physicians play a central role in the suspicion and diagnosis of immunoglobulin E-mediated food allergies, but they are also critical in redirecting the evaluation for symptoms that patients are falsely attributing to allergies. Although any food is a potential allergen, more than 90 percent of acute systemic reactions to food in children are from eggs, milk, soy, wheat, or peanuts, and in adults are from crustaceans, tree nuts, peanuts, or fish. The oral allergy syndrome is more common than anaphylactic reactions to food, but symptoms are transient and limited to the mouth and throat. Skin-prick and radioallergosorbent tests for particular foods have about an 85 percent sensitivity and 30 to 60 percent specificity. Intradermal testing has a higher false-positive rate and greater risk of adverse reactions; therefore, it should not be used for initial evaluations. The double-blind, placebo-controlled food challenge remains the most specific test for confirming diagnosis. Treatment is through recognition and avoidance of the responsible food. Patients with anaphylactic reactions need emergent epinephrine and instruction in self-administration in the event of inadvertent exposure. Antihistamines can be used for more minor reactions.


Immunomodulatory effects of curcumin in allergy
            (Kurup and Barrios, 2008) Download
Recent years have witnessed a global increase in allergy and asthma, particularly in developed countries. Attempts to develop effective control measures for allergy and asthma resulted in the exploration of alternate medicines including herbal remedies traditionally used in old world countries. Turmeric is known for its multiple health restoring properties, and has been used in treating several diseases including several respiratory disorders. Turmeric is a common spice used in the culinary preparations in South and East Asian countries. The active component of turmeric is curcumin, a polyphenolic phytochemical, with anti-inflammatory, antiamyloid, antiseptic, antitumor, and antioxidative properties. Curcumin was reported to have antiallergic properties with inhibitory effect on histamine release from mast cells. The effectiveness of curcumin in allergy and asthma has been further investigated using a murine model of allergy. The results indicate a marked inhibition of allergic response in animals treated with curcumin suggesting a major role for curcumin in reducing the allergic response. The present review focuses on the results of research aimed to understand the immunomodulation induced by curcumin and its associated roles in the amelioration of allergy. These findings needed further evaluation, extrapolation, and confirmation before using curcumin for controlling allergy and asthma in humans.

Management of food allergy: vitamins, fatty acids or probiotics?
            (Laitinen and Isolauri, 2005) Download
The dietary approach to allergic disease in infancy is evolving from passive allergen avoidance to active stimulation of the immature immune system, the aim of which is to support the establishment of tolerance. This may include probiotics providing maturational signals for the gut-associated lymphoid tissue and by balancing the generation of pro and anti-inflammatory cytokines in addition to their capacity to reduce the dietary antigen load by degrading and modifying macromolecules. Probiotics have also been shown to reverse the increased intestinal permeability characteristic of children with food allergy and to enhance specific IgA responses frequently defective in children with food allergy. The promotion of gut barrier functions by probiotics also includes the normalization of the gut microecology, alterations in which have been demonstrated in allergic individuals. Dietary lipids, especially long-chain polyunsaturated fatty acids, regulate immune function and may modify the adherence of microbes in the mucosa thereby contributing to host-microbe interactions. The properties of specific dietary compounds in optimal combinations and the joint effects of nutrients can be exploited in the development of specific prophylactic and therapeutic interventions. To meet these targets, rigorous scientific effort is required to elucidate how the food matrix and the dietary content impacts on the complex cascade of interrelated immunological mechanisms in food allergy.

Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.
            (Osborn and Sinn, 2006) Download
BACKGROUND:  Allergies and food reactions are common and may be associated with foods including adapted cow's milk formula. Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance. However, it is unclear whether hydrolysed formula can be advocated for prevention of allergy and food intolerance in infants without evidence of allergy or food intolerance. OBJECTIVES:  To determine the effect of feeding hydrolysed formulas on allergy and food intolerance in infants and children compared to adapted cow's milk or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas. To determine which infants benefit, including infants at low or high risk of allergy and infants receiving early, short term or prolonged formula feeding. SEARCH STRATEGY:  The standard search strategy of the Cochrane Neonatal Review Group was used. The review was updated with searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966-March 2006), EMBASE (1980-March 2006) and CINAHL (1982-March 2006) and previous reviews including cross references. SELECTION CRITERIA:  Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with >80% follow up of participants were eligible for inclusion. DATA COLLECTION AND ANALYSIS:  Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model. MAIN RESULTS:  Two trials compared early, short term hydrolysed formula to human milk feeding. No significant difference in infant allergy or childhood cow's milk allergy (CMA) were reported. No eligible trial compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to cow's milk formula feeding. No significant benefits were reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00). Ten eligible studies compared prolonged feeding with hydrolysed formula versus cow's milk formula in high risk infants. Meta-analysis found a significant reduction in infant allergy (seven studies, 2514 infants; typical RR 0.79, 95% CI 0.66, 0.94), but not in the incidence of childhood allergy (two studies, 950 infants; typical RR 0.85, 95% CI 0.69, 1.05). There was no significant difference in infant eczema (eight studies, 2558 infants, typical RR 0.84, 95% CI 0.68, 1.04), childhood eczema incidence (two studies, 950 infants, typical RR 0.83, 95% CI 0.63, 1.10), childhood eczema prevalence (one study, 872 infants; RR 0.66, 95% CI 0.43, 1.02), or infant or childhood asthma, rhinitis and food allergy. One study reported a significant reduction in infants with CMA with confirmed atopy (RR 0.36, 95% CI 0.15, 0.89). Subgroup analysis of trials blinded to formula found no significant difference in infant allergy (four studies, 2156 infants; typical RR 0.87, 95% CI 0.69, 1.08) or childhood allergy incidence (one study, 872 infants; RR 0.91, 95% CI 0.73, 1.14). No eligible trial examined the effect of prolonged hydrolysed formula feeding on allergy beyond early childhood. There is evidence that preterm or low birthweight infants fed a hydrolysed preterm formula have significantly reduced weight gain, but not in other growth parameters (head circumference or length). Studies in term infants report no adverse effects on growth. Subgroup analysis of trials of partially hydrolysed versus cow's milk formula found a significant reduction in infant allergy (six studies, 1391 infants; typical RR 0.79, 95% CI 0.65, 0.97) but not childhood allergy, or infant or childhood asthma, eczema or rhinitis. Methodological concerns were the same as for the overall analysis. Analysis of trials of extensively hydrolysed formula versus cow's milk formula found no significant differences in allergy or food intolerance. Infants fed extensively hydrolysed formula compared with partially hydrolysed formula had a significant reduction in food allergy (two studies, 341 infants; typical RR 0.43, 95% CI 0.19, 0.99), but there was no significant difference in all allergy or any other specific allergy incidence. Comparing extensively hydrolysed casein containing formula with cow's milk formula, one study (431 infants) reported a significant reduction in childhood allergy incidence (RR 0.72, 95% CI 0.53, 0.97). Meta-analysis found a significant reduction in infant eczema (three studies, 1237 infants; typical RR 0.71, 95% CI 0.51, 0.97). One study reported a significant reduction in childhood eczema incidence (RR 0.66, 95% CI 0.44, 0.98) and prevalence (RR 0.50, 95% CI 0.27, 0.92). AUTHORS' CONCLUSIONS:  There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy compared to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is limited evidence that prolonged feeding with a hydrolysed formula compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. In view of methodological concerns and inconsistency of findings, further large, well designed trials comparing formulas containing partially hydrolysed whey, or extensively hydrolysed casein to cow's milk formulas are needed.



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Chafen, J. J., et al. (2010), ‘Diagnosing and managing common food allergies: a systematic review’, JAMA, 303 (18), 1848-56. PubMed: 20460624
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