Food Allergy

Venugopal P.
Assistant Professor, Department of Respiratory Medicine, Medical College, Alappuzha

Introduction

Food allergy is a common situation encountered by allergy specialists worldwide. The term “food allergy” refers to adverse immunological reactions to food. Food allergy occur more among atopic individuals. Incidence of food allergy varies between 5% and 7.5% of children and between 1% and 2% of adults¹. The diagnosis of food allergy rests with the detection of food-specific IgE in the context of a convincing history of type I hypersensitivitymediated symptoms after ingestion of the suspected food or by eliciting IgE-mediated symptoms after controlled administration of the suspected food. Presently, the only available treatment of food allergies is dietary vigilance and administration of self-injectable epinephrine.

Although there has been a great concern in western countries about food allergies, in India the prevalence of food allergy has not been systematically studied. Unfortunately there is not much awareness about food hypersensitivity reaction in India. Indian food is quite complex and it is necessary for a high risk person to know  what kind of food he is allergic to.

Natural History of Food Allergy

Food allergy isoften the first manifestation of allergy in early childhood. The prevalence of food allergy peaks at 1 year (6% to 8%) of age and then falls progressively until late childhood, after which the prevalence remains stable at 4%. Most food allergy is acquiredin the first 1 to 2 years of life². Loss of food allergy is a variable process, depending on both the individual child and the specific food allergy. For example, whereas most milk allergy is outgrown over time, most allergies to peanuts and tree nuts are never lost. In addition, whereas some children may lose their milk allergy in a matter of months, the process may take as long as 8 or 10 years in other children.

Once established in adults, food allergy is rarely cured. The most common food sensitivities in adults include peanut, tree nuts, fish, and shellfish, all of which are most often life-long.

Pathogenesis of food allergy³

Food allergy is typically IgE mediated. Foods enter the gastrointestinal tract and undergo protein digestion and then antigen (Ag) processing. Sensitization begins with transit of relatively intact food antigens across the intestinal barrier. As the antigen-presenting cell presents Ag to the T cell, specific cytokines are produced. In the allergic individual, the T cells will secrete increased amounts of IL-4, IL-5, and IL-13, among other mediators, and reduced amounts of IFN-ã and TNF-á when compared to that in an individual who is not allergic. The T cell in turn regulates eventual specific IgE production by B cells. These specific IgE is attached to mast cells in the gastrointestinal tract, skin, and respiratory tract mucosa. Subsequently, on ingestion of the allergic food, in the allergic individual, the protein is digested and the Ag binds the specific IgE on the mast cell, causing activation of the mast cell with mediator release at the mucosal site. Clinical symptoms follow.

Usual protective mechanisms- gastric pH, digestive enzymes, mucosal glycoprotiens, peristalsis prevent this transmit to a certain extent. But the gut may be unable to effectively exclude intact antigens because of immaturity (infants), injury, malabsorption or infection. Agents causing increased intestinal permeability, such as alcohol, tobacco and aspirin and exercise immediately after food intake may hasten the process.

Common food allergens

Over 90% of IgE-mediated food allergies in childhood are caused by eight foods: cows milk, hens egg, soy, peanuts, tree nuts (and seeds), wheat, fish and shellfish5. In children, milk (casein, lactoglobulins) & egg (ovalbumin, conalbumin) are the common agents causing food allergy. In order of prevalence, the most common food allergens at all age in western countries are citrus fruits, tomato, egg, strawberry, soy, wheat and fish. Common food allergens among Indians are cashew nut, coconut, wheat, fish (especially shellfish), peanut, milk, egg, meat, rice, etc. allergy to spices are rare except for mustard and garlic.

Life-threatening food allergies

Most commonly to nuts, peanuts, or shellfish, fish, eggs, celery, legumes, and cheeses that contain mold. Mostly occur in children. Those who develop lifethreatening food allergies either have asthma or a family history of atopy. Death occurs in two ways- laryngospasm and anaphylaxis.

Gastrointestinal manifestations of Food Allergy⁶

Gastrointestinal food allergies resulting from adverse immune responses to dietary antigens include immediate gastrointestinal hypersensitivity(anaphylaxis), oral allergy syndrome, allergic eosinophilic esophagitis, gastritis, and gastroenterocolitis; dietary proteinenterocolitis, proctitis, and enteropathy; and celiac disease.Additional disorders sometimes attributed to food allergy include colic, gastroesophageal reflux, and constipation.

Skin Manifestations of Food Allergy⁷

The skin is one of the target organs that is most often involved in food hypersensitivity reactions. Clinical manifestations of food hypersensitivity in the skin range from symptoms of atopic dermatitis, to urticaria and angioedema and dermatitis herpetiformis. Dermatitis herpetiformis is a chronic papulovesicular skin disorder frequently associated with asymptomatic gluten-sensitive enteropathy. All present with typical skin manifestations of their food-allergic reactions. For most skin manifestations provoked by food hypersensitivity, pruritis is a hallmark of the disease.

Respiratory Manifestations of Food Allergy⁸

Key Points about the role of Food Allergy in Respiratory Disease:

1. Acute food-induced respiratory tract symptoms are typically accompanied by either cutaneous or  gastrointestinal symptoms.

2. Chronic, isolated food-induced respiratory tract symptoms are uncommon.

3. Egg, milk, peanut, soy, fish, shellfish, and tree nuts are the most common food allergens confirmed  to elicit respiratory reactions.

4. Allergic sensitization (positive tests) or clinical  reactions to foods in infancy predict the later development of respiratory allergies and asthma.

5. Food-induced asthma is more common in young pediatric patients than in older children and adults.

6. Children with atopic dermatitis, especially those with food reactions confirmed during blinded food challenges, are at increased risk for food-induced asthma.

7. Food-induced allergic reactions may increase airway hyperresponsiveness in patients with moderate to severe asthma and may do so without inducing acute asthma symptoms.

8. The role of food allergy in otitis media, particularly in patients without other manifestations of atopy (eg, atopic dermatitis, allergic rhinitis) is controversial and probably is extremely rare.

9. Asthmatic reactions to food additives can occur but are very uncommon.

10. Respiratory symptoms, especially asthmatic reactions, induced by food allergens are considered

risk factors for fatal and near-fatal reactions. Following features indicate the need for evaluation

of food allergy in patients with asthma:

1. Asthma triggered after ingestion of particular foods

2. Recalcitrant or otherwise unexplained acute, severe asthma exacerbations

3. Patients with asthma that is accompanied by other manifestations of food allergy (eg, anaphylaxis, moderate to severe atopic dermatitis)

Diagnosis of food allergy

An evaluation is warranted in patients who have the common clinical manifestations of food allergy. The initial evaluation beginning with a thorough history and physical examination, must rule out other differential diagnosis. Once food allergy is identified as a likely cause of symptoms, confirmation of the diagnosis and identification of the implicated food(s) should be done. In patients with acute reactions such as acute urticaria or anaphylaxis, the history may clearly implicate a particular food. In patients with chronic disorders such as atopic dermatitis or asthma, it is more difficult to pinpoint causal food(s).

Maintenance of Food Diary

An intelligent patient may be able to detect food responsible for allergy by maintaining a food diary with the help of the treating physician.

Prick-puncture Skin Testing

In the evaluation of IgE-mediated food allergy, specific tests can help to identify or exclude responsible foods. One method of determining the presence of specific IgE antibody is prick-puncture skin testing9. A positive skin test in isolation cannot be considered proof of clinically relevant hypersensitivity, whereas a negative test virtually rules out IgE-mediated food allergy to the food in question.

In Vitro Testing (Radio Allegro Sorbent Test RAST)

In vitro tests for specific IgE [RAST] are noninvasive but are generally less sensitive than skin tests.

Elimination diet

When patients have a history suggestive of foodrelated illness and tests for IgE antibody to the food are positive, the first course of action is to eliminate the food from the diet. If the symptoms disappear by elimination, it is highly suggestive that the particular food is responsible for the food allergy. When improvement is noted it may be worthwhile repeating the challenge to justify continued exclusion of the suspected food.

Oral Food Challenges

Double blind, placebo-controlled food challenges are considered the gold standard for diagnosing food allergy10. After intravenous access is obtained, graded doses of either a challenge food or a placebo food are administered. The food is hidden either in another food or in opaque capsules. Medical supervision and immediate access to emergency medications, including epinephrine, antihistamines, steroids and inhaled beta agonists, and equipment for cardiopulmonary resuscitation are required because reactions can be severe. During the challenge, patients are assessed frequently for changes in the skin, gastrointestinal tract and respiratory system. Applying DNA technology, up to 40 food allergens have been produced in recombinant form, which implies standardized quality and unlimited quantity of the respective proteins. Hence such molecules may be useful in improving diagnosis in future.

   Difficulties in diagnosis

   Improper history

   May be allergic to multiple foods

   Pseudoallergens- colors, preservatives, etc

   Artificial food- hidden allergens

   rovocation tests and skin tests itself can precipitate reactions.

Differential diagnosis:

Many food related reactions are not true allergies. Food allergy needs to be distinguished from other types of adverse reactions to food, including food intolerance (eg,lactose malabsorption), pharmacological reactions to food components (eg, vasoactive amines), food poisoning (eg, food-borne bacterial gastroenteritis), toxic reactions (eg, to staphylococcal enterotoxin), food intolerance- due to digestive enzyme deficiency, reactions to chemicals in food (e.g. Tyramine, caffeine, nitrites, etc) and psychosomatic problems.

Oral Allergy Syndrome

The oral allergy syndrome is characterized by pruritis and edema of the oral mucosa occurring after the ingestion of certain fresh fruits and vegetables¹¹. The symptoms rarely progress beyond the mouth. The reaction occurs primarily in patients with allergic sensitivity to pollens and is caused by IgE antibodies directed toward cross-reacting proteins found in pollens, fruits and vegetables. Patients with birch-pollen hay fever may have symptoms of oral allergy syndrome after ingesting hazelnut, apple, carrot and celery, whereas patients with IgE sensitivity to ragweed pollen may react to melons and banana. Interestingly, patients are usually able to ingest cooked forms of the foods without symptoms because the responsible allergens are destroyed in the heating process. It is crucial to differentiate the symptoms of oral allergy syndrome from the early symptoms of a systemic reaction to food.

Chinese Restaurant Syndrome

Sensation of warmth & burning over head and shoulders, headache, stiffness, weakness of limbs, etc following ingestion of Chinese food. This is due to the Mono Sodium Glutamate (Ajinomoto), which is a common ingredient of Chinese food. May precipitate asthma.

Sulphite sensitivity

Sodium metabisulphate is used as a preservative in wines, canned & tinned food, frozen food, biscuits, cookies, vinegar, dried fruits, beverages & medicines. It is also an ingredient in eye drops, nebulising solutions, solutions for TPN & dialysis, etc. Can precipitate asthma, anaphylaxis & cutaneous reactions. Cross sensitivity exists with MSG & Aspirin

Migraine & food allergy

Migraine like headaches can be a manifestation of food allergy (cerebral allergy)

Eg. Hot dog headache (nitrites)

Chinese restaurant syndrome

Cocktail headache (alcohol)

Auriculotemporal syndrome (Frey syndrome) may be misdiagnosed as a food allergy. This is manifested as immediate unilateral or rarely bilateral facial flushing, sweating, or both, localized to the distribution of the auriculotemporal nerve, in response to gustatory and occasionally tactile stimuli¹². It can occur in adults as a result of surgical injury or trauma to the parotid gland. The flushing typically begins in children a few seconds after eating and resolves approximately 30 to 60 minutes later.

An example of a non -IgE-mediated adverse pulmonary response to food is Heiner syndrome¹³. This uncommon syndrome of infancy is characterized by an immune reaction to cow’s-milk proteins with precipitating antibody (IgG) to cow’s-milk protein resulting in pulmonary infiltrates, pulmonary hemosiderosis, anemia, recurrent pneumonia and failure to thrive.

Management of food allergy

The core of treatment is identification absolute and complete lifelong avoidance of the offending food in any form, especially if the patient has had life threatening allergies. Artificial food should be avoided as far as possible and eating out discouraged. Scrutinisation of labels on packages is advised. Medical management of the manifestations of food allergy using antihistamines and steroids are the next step of management. (e.g., topical therapy for atopic dermatitis, inhaled medication for asthma, management of anaphylaxis, etc). There is no evidence to support role of immunotherapy or oral desensitization in treatment of food allergy. However, for peanut allergy, immunotherapy has been tried and found to provide partial benefit¹⁴.

Management of Life-threatening food allergies

Treatment of life-threatening food allergies need a kit with easily injectable epinephrine (EpiPen) or adrenaline inhaler (sublingually or into the cheek, not inhaled). Caregivers must be taught the indications for the use and administration of epinephrine and antihistamine medications. The subcutaneous route is no longer recommended in the management of anaphylaxis, because of the variable systemic levels of adrenaline that result from this mode of administration. If the patient does not respond to the initial dose of adrenaline, it may be repeated at five-minute intervals according to cardiorespiratory function. Continuing deterioration requires volume expansion, intravenous aminophylline, or nebulised bronchodilators. In addition to oxygen, ventilatory support and tracheostomy maybe required in life threatening airway compromise.

Indications of prescribing adrenaline autoinjectors?

There are no clear-cut guidelines. However it may be recommended in the following situations¹⁵:

• In the event of a previous life threatening reaction or airway compromise

• An allergic child with severe or poorly controlled asthma

• Reactions induced by traces or small amounts of allergen, a strongly positive skin test, and difficult access to emergency care—that is, families living in isolated rural areas.

Prevention

Early identification of food allergy is important, especially in children due to 2 reasons:

• For initiating an appropriate avoidance diet for their existing allergies

• Also to institute preventive measures against developing additional food allergies, as well as asthma and allergic rhinitis in future

Breastfeeding: Exclusive breastfeeding for 4– 6 months by favoring the development of gut flora populations of bifidobacteria and lactobacilli. Perinatal administration of Lactobacillus casei GG has been reported to reduce the incidence of atopic dermatitis, but not food allergy, in at-risk children during the first 4 years of life.

Delay solid food: Introduction of all solids should be delayed until after the age of 6 months, and the more highly allergenic foods — egg, peanuts, tree nuts, and fish — can be delayed for 2–3 years. Currently there is no evidence for the protective role of maternal elimination diets during pregnancy¹⁶.

Avoid Smoking: Parents should refrain from smoking, as smoking increases the risk of recurrent wheeze and asthma, which may lead to life threatening food allergy.

Future therapeutic options

Several novel treatments for food allergy are currently under evaluation.
Sublingual immunotherapy The role of injectable immunotherapy for treating food allergy is limited because of the high risk of inducing anaphylaxis. By contrast, sublingual immunotherapy to food allergens may be better tolerated in children, although its clinical efficacy has not yet been clearly shown.
Recombinant anti-IgE antibody (omalizumab) has been used with limited success to treat food allergy. A recent study of patients with severe peanut allergy showed an increased threshold of tolerance (on average, from onehalf to nine peanuts) on oral food challenge after being given a course of omalizumab¹⁷.

The major safety concern regarding food allergen immunotherapy has been addressed by engineering “hypoallergenic” forms of major allergenic food proteins. These mutated (“engineered”) major food proteins have lost their ability to bind to IgE but retained the ability to interact with T cells¹⁸.

The effect of eliminating IgE binding can also be achieved with vaccines that consist of overlapping peptides (10–20 amino acids long) that represent the entire sequence of a specific protein¹⁹. The antigen-presenting cells are provided with all possible T-cell epitopes, but mast cells are not activated because the short peptides are of insufficient length to cross-link 2 IgE molecules.

Certain portions of bacterial DNA designated as oligodeoxynucleotide immunostimulatory sequences (ISSODN) are potent stimulators of Th1 responses. These bacterial DNA components activate antigen-presenting cells, natural killer cells, and B cells and upregulate Th1 cytokine production (eg, IFN􀀐􀁊). ISS-ODNs have been shown to prevent airway allergic inflammation in the murine models of asthma²⁰.

Probiotics

Probiotics are live bacteria or their components that are reported to have beneficial effect on the health of the host by improving its intestinal microbial balance. The major sources of probiotics are dairy products that contain Lactobacillus and Bifidobacterium species²¹.

References

1. Yocum MW, et al. Epidemiology of anaphylaxis in Olmsted County: a population-based study. J. Allergy Clin. Immunol. 1999; 104:452–456.

2. Robert A. Wood, MD. The Natural History of Food Allergy. Pediatrics. 2003; 111(6): 1631-1637.

3. Wesley Burks J. Peanut allergy: a growing phenomenon. Clin Invest. 2003; 111(7): 950–952.

4. Scott h. Sicherer. Manifestations of Food Allergy: Evaluation and Management. American Family Phycician, 1999: 59(2).

5. Katrina J Allen, David J Hill and Ralf G Heine. Food allergy in childhood. MJA 2006; 185 (7): 394-400.

6. Scott H. Sicherer, MD. Clinical Aspects of Gastrointestinal Food Allergy in Childhood. Pediatrics 2003; 111 (6): 1617-1624.

7. Wesley Burks, MD. Skin Manifestations of Food Allergy. Pediatrics 2003; 111(6): 1625-1630.

8. John M. James, MD. Respiratory Manifestations of Food Allergy. Pediatrics, 2003; 111 (6): 1625-1630.

9. Sampson HA, Albergo R. Comparison of results of skin tests, RAST, and double-blind, placebo-controlled food challenges in children with atopicdermatitis. J Allergy Clin Immunol 1984; 74:26-33.

10. Bock SA, Sampson HA, Atkins FM, Zeiger RS, Lehrer S, Sachs M, et al. Double-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual. J Allergy Clin Immunol 1988; 82:986-97.

11. Ortolani C, Ispano M, Pastorello E, Bigi A, Ansaloni R. The oral allergy syndrome. Ann Allergy.1988; 61: 47 –52

12. Beck SA, Burks AW, Woody RC. Auriculotemporal syndrome seen clinically as food allergy. Pediatrics.1989; 83: 601 –603.

13. Scott h. Sicherer, M.D, Manifestations of Food Allergy: Evaluation and Management. American Academy of Family Physicians, 1999

14. Oppenheimer JJ, Nelson HS, Bock SA, Christensen F, Leung DY. Treatment of peanut allergy with rushimmunotherapy. J. Allergy Clin. Immunol. 1992;90:256–262.

15. Kemp AS. EpiPen epidemic: suggestions for rational prescribing in childhood food allergy. J Paediatr Child Health 2003; 39: 372-375.

16. Prescott SL, Tang ML. The Australasian Society of Clinical Immunology and Allergy positionstatement: summary of allergy prevention in children. Med J Aust 2005; 182: 464-467

17. Leung DY, Sampson HA, Yunginger JW, et al. Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med 2003; 348: 986-993.

18. Ferreira F, Ebner C, Kramer B, et al. Modulation of IgE reactivity ofallergens by site-directed mutagenesis: potential use of hypoallergenicvariants for immunotherapy. FASEB J.1998; 12: 231 –242

19. Li S, Li XM, Burks AW, Sampson HA. Modulation of peanut allergy by peptide-based immunotherapy. J Allergy Clin Immunol.2001; 107: S233

20. Kline JN, Waldschmidt TJ, Businga TR, et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J Immunol.1998; 160: 2555 –2559

21. Majamaa H, Isolauri E. Probiotics: a novel approach in the management of food allergy. J Allergy Clin Immunol.1997; 99: 179 –185.

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