Allergy Profile

General information

In recent decades, physicians have witnessed a worldwide increase in the incidence of food and environmental allergies. Epidemiological studies in the past 20 years indicate that there has been an increase in diseases commonly associated with allergies, such as asthma, atopic dermatitis, and allergic rhinitis.^{[1],[2],[3],[4]}  Public awareness has increased, demanding better medical guidance and identification of allergens (such as chemicals, additives and colorings) used in the manufacture of prepared foods.[5] Peer-reviewed medical literature reveals how little is known and how important it is to increase awareness and education of patients regarding the causes, symptoms and prevention of allergic reactions.^[6],[7],[8]

Reactions to food and environmental influences may be due to intolerance or to the specific and non-specific functions of the immune system.  The former involves complex interactions of immune, gastrointestinal, nervous, and endocrine functions.  The role of the immune system includes the production of chemical mediators that influence inflammation and release of antibodies both within the affected tissue and into circulation.  The antibodies most involved are IgE, which is responsible for immediate type hypersensitivity reactions, and IgG, which plays a role in delayed reactions to food allergies.  

The Impact of Allergies

The human body comes into contact with hundreds of different environmental compounds. Defense mechanisms have been created to deal with the potential harm of these foreign materials.  These wind-borne substances can create a problem when they are inhaled and pass through the respiratory tract.  Similarly, allergic symptoms can result from the foods that we eat. 

While keen observers throughout history have no doubt formed that very hypothesis, it has taken a great deal of time for us to recognize the mechanisms by which that might occur.  In the early 20^th century several investigators began to piece together the story behind reactions to our food.  Scientists in the late 1920s and the early 1930s demonstrated that undigested food proteins are able to pass through the mucosal barrier of the gastrointestinal tract and initiate an inflammatory response in tissue elsewhere in the body.[9]  And in 1936, HJ Rinkel, writing in the Journal of the Kansas Medical Society, first described reactions to food that, unlike the well-known anaphylactic reactions, took hours or days to occur.[10] 

Regardless of these findings, and many more which have been described since 1936, the subject of food allergies remains controversial today. There are several reasons why this is so: skin tests used for detection of food allergies have not been reliable; symptoms of some food allergies are commonly delayed in their appearance (e.g. cow’s milk); the offending antigen may have been “hidden” in a food preparation, and some symptoms may be the result of food intolerance rather than food allergies.[11]^,[12]  In addition, foods may initiate complex and individual adverse reactions, varying from minor irritation of the mucosal membranes to severe emotional disturbances.[13]

As a result of these complicating factors, information raising the possibility of food allergies is not conveyed easily from patient to physician in the personal history.  Also, since physicians do not routinely discuss with patients the possibility that food allergies might be causing their symptoms, or that certain lifestyle and nutritional habits may lead to food allergies[14], their treatment may not completely address the underlying problem, and their symptoms may persist.  One case study sampled postpartum women in a hospital setting and concluded that 87 percent were not aware of the need to avoid risk factors that might lead to allergies in their infants[15]. Another study demonstrated that college students who lost time from work and school due to asthma and allergy symptoms did not have patient education or awareness of asthma and allergy management skills.[16] 

Prevalence of Allergies

As stated earlier, the incidence of diseases associated with allergies is on the rise in most parts of the world.  Evidence continues to mount indicating associations of both food and inhalant allergies with common “allergic symptoms,” such as rhinitis, sinusitis, eczema, and asthma.  Food allergies mediated by IgE have been implicated in approximately one third of children with refractory atopic dermatitis presenting to the dermatologist’s office.[17]  Infants are particularly susceptible to some foods and develop intolerance easily.  There is speculation that this is a normal developmental activity of the immune system as it is exposed to new foods.  Approximately 18 percent of infants do develop IgE mediated atopic dermatitis from exposure to cow’s milk, eggs, or peanuts.  Colic is a problem in about 15 to 40 percent of the infant population, and studies indicate that changes in the nursing mother’s diet can alleviate those symptoms.  Colic associated with vomiting has been associated with gastro-esophageal reflux, in some cases due to food intolerance. Even low allergenic protein formulas may induce symptoms in some of these children.[18] In contrast to these early reactions to foods, allergies to inhalants do not usually manifest themselves until after the third birthday.[19]

The prevalence of cow’s milk allergy is currently between 2 and 5 percent.[20] Peanut allergy is increasing dramatically and represents a more serious threat to health than other food allergies.  The number of food allergens continues to grow, and the clinical indications are evolving into more complex symptom pictures.[21]  Adverse reactions to foods and food additives represent a common problem in the United States.  About 10 percent of the US population are affected by immune-modulated food sensitivities.[22]  One reason for the increased prevalence of food allergies may be the early introduction of highly allergenic foods, such as peanuts and other nuts. [23] 

Exposure to chemical toxins may also correlate with food allergies.  Studies illustrate that a number of individuals who report feeling ill when repeatedly exposed to low levels of environmental chemical odors may also be experiencing food sensitivities.[24]  Foods that are consumed excessively may trigger an immune response in time.  On the other hand, some patients who experience an adverse reaction or find that they are IgG positive for a particular food may indicate in their diet history that they rarely eat the food.  Careful questioning, however, about meals may reveal that this food is included in many prepared foods the patient consumes.[25] 

Unusual situations may also increase the individual’s risk for development of food allergies.  An interesting study from Bangladesh reported that acute, watery diarrhea in children correlated with an increase in IgG antibodies to lactoglobulin.  IgE antibodies to lactoglobulin developed after the diarrheal episode in approximately 12 percent of these children.[26]

Family Patterns

There is considerable evidence supporting the position that genetic predisposition plays a role in allergies, especially to foods.  An examination of the family history of the allergic patient will often disclose parents and siblings who also experience allergic reactions.  Studies indicate that as many as 69 percent of children presenting with allergy symptoms have a positive family history.[27]  Another study found that 67 percent of children whose parents were both allergic and 33 percent of those with one allergic parent are likely to experience allergic reactions.[28]  A more recent study found that 70.5 percent of the allergic children and adolescents participating had a family history of atopic disease. [29]

Common Allergens

The US BioTek Standard and Vegetarian Food Allergy Panels each include 88 of the most commonly eaten foods.  Numerous studies indicate that most of these foods have been associated with allergic reactions in children and adults. Many of these foods are staples in the American diet and are often found in prepared foods. BioTek’s Food Allergy Panels can play an important role in diagnosing allergies and helping the patient to avoid the insulting foods. 

In a recent report, over 50 percent of patients with rhinoconjunctivitis had food hypersensitivity.  The foods most commonly identified in this study were shellfish, tomato, rice, and peanuts. There was also a high incidence of inhaled allergens in this group of individuals.[30] Other foods that have been identified as common allergens include mustard and codfish.[31] The most common food allergens in patients diagnosed with immediate food reactions in a Zurich hospital from 1983 to 1987 were celery, carrots, and spices.[32]

An early serological marker that appears in infancy occurs in response to an IgE-mediated egg allergy.  The presence of this egg marker may be followed by the development of antibodies to milk, another very common food allergen.  Inhalant allergies, however, generally develop after infancy.[33] Another study examining age-dependent allergic reactions found that peanut allergy was quite common and represented a very serious health problem. Peanut allergy is likely to be the first allergy to occur after the age of three. While peanuts are the most common nut allergen, other nuts that initiated allergic reactions included Brazil nut, almond, and hazelnut.[34]

Evidence that food allergens can pass from breast milk to the nursing infant can be found in a case report from the University of California.  In this instance, the mother had been drinking four to five glasses of cow’s milk each day since the birth of the child. The infant, who had developed rectal bleeding, had IgE  antibodies to cow’s milk (1.5 I/ml as determined by radioallergosorbent (RAST) test).  In this particular case, symptoms resolved when the infant was given a casein hydrolysate formula.[35]  In adults, milk allergy may be more common than  thought, owing to the fact that symptoms in the adult are often vague and nonspecific.[36]

Airborne substances commonly causing allergic reactions include Aspergillus, Cladosporium, and Penicillium molds.  Such inhalants have been reported to contribute to respiratory reactions in children.[37]  Other risk factors for respiratory symptoms associated with increased allergic reactions are animal dander, dust, and cigarette smoke.[38] 

Symptoms and Diseases Associated with Allergies

 

Allergies are associated with a broad range of symptoms and a variety of disease states, in addition to the classic “anaphylaxis” of immediate hypersensitivity.  A number of well-documented case reports indicate that some individuals with rheumatoid arthritis may have exacerbation of symptoms when they ingest certain foods to which they are allergic, in particular milk, corn, and cereals.[39]  Additional evidence was found in a 1992 study of six rheumatoid arthritis patients in Amsterdam, four of whom showed reactions to specific foods and increased levels of serum IgE.[40]  In a few patients with juvenile arthritis, food allergens may also play a role in exacerbation of joint pain.[41]

As discussed earlier, food allergies are found in one third of children presenting with atopic dermatitis, and are associated with gastro-esophageal reflux in infants.  In 70 patients presenting with allergic reactions to peaches, the most common symptoms were oral allergy syndrome and contact urticaria.[42]  It is worth noting that a positive correlation was made between high Helicobacter pylori titers and food allergies in children, although the H. pylori antigen involved has not been identified.[43]   Researchers in France report their clinical experience with food allergies in children and note that allergies in children often manifest in atopic dermatitis, urticaria, edema, asthma, anaphylaxis, gastrointestinal symptoms, oral syndrome, and rhinoconjunctivitis.[44] 

The physician examining patients with recurrent aphthous ulceration should consider food and other allergies in the diagnostic work up of these patients.[45]  Circulating antibodies to wheat, soy and milk proteins were identified in children with juvenile diabetes mellitus.[46]^,[47] Food and food additives have played a role in the development of neurogenic vascular headaches.[48]  Twenty-one children who complained of migraines and/or hyperkinetic behavior were successfully treated with a low allergy diet.  These children also experienced enuresis, and 12 of them had improvement of this comorbidity while on the oligoantigenic diet.[49] 

Types of Reactions Initiated by the Immune System

Type I immune responses (also known as Immediate Hypersensitivity Reactions) occur within seconds to minutes following exposure to t-he offending antigens. IgE antibodies, bound non-specifically on the surface of mast cells and basophils (via their Fc receptors), come into contact with the offending antigen.  Attachment of antigen results in the release of the contents of cytoplasmic granules (e.g., histamine), as well as in synthesis and secretion of biologically active products of arachidonic acid (e.g., leukotrienes) and other chemotactic and proinflammatory agents.  Mast cell products increase vascular permeability and constrict bronchial smooth muscle.  Type I responses are responsible for such allergic phenomena as urticaria, seasonal rhinitis, asthma, and in settings where large amounts of allergens enter the host circulation, systemic anaphylaxis.

Type II immune responses (also known as Acute Inflammation Mediated by Cytotoxic Antibodies) occur in hours to one day, and result in severe tissue destruction following the binding of complement-fixing antibodies (IgG or IgM) to erythrocytes, platelets or leukocytes.  Once bound with the antigens, the complement cascade is initiated resulting in the deposition of complement fragments (e.g., the opsonin C3b) on the surface of  these cells.  Fixed or free phagocytes (containing receptors for the complement fragments or immunoglobulins) then eliminate the cells from circulation. Type II responses are associated with autoimmune hemolytic anemia, thrombocytopenia and systemic lupus erythematosus.

Type III immune responses (also known as Immune Complex-mediated Reactions) occur within hours to 1 day following exposure to antigen.  Type III responses involve the formation of both IgG and IgM mediated antibody-antigen complexes.  Once complexes are formed, they circulate throughout the body.  This often leads to the accumulation of neutrophils, eosinophils and macrophages in local tissues with resultant inflammation.  Type III responses are responsible for such conditions as Rheumatoid arthritis, glomerulitis and systemic lupus erythematosus.

Type IV immune responses (also known as Chronic Inflammatory Reactions or Delayed-Type Hypersensitivity Reactions) involve the interaction of antigen with T lymphocytes on mucosal surfaces and in the skin. Type IV responses do not involve antibodies.  Whereas allergic reactions occur within seconds and minutes, and immune complex reactions occur within several hours to one day, delayed-type reactions peak at 2 to 3 days.  Delayed-type hypersensitivity reactions are probably important for host defense against intracellular parasites such as Mycobacterium tuberculosis and against certain viruses, and are prevalent in certain diseases such as sarcoidosis and polymyositis.

IgE and IgG Antibodies and Their Roles

IgE antibodies act by forming cross links on the surface of mast cells within the gastrointestinal system.  The chemical mediators that are released as a result of this binding initiate physiological changes that result in inflammation and allows the passage of food antigens into systemic circulation.  In contrast, IgG antibodies are most likely responsible for delayed reactions from food allergens, as they generally circulae longer in the blood. 

Because most food allergies, identified in the past, have been immediate food reactions, most testing has been done on IgE, both total circulating serum levels and specific antiantigen IgE.  Testing with the RAST test can identifies only IgE antibodies.  Likewise skin testing can only measure those immediate reactions that occur as a result of IgE activity. 

Research has identified that many allergic responses to foods do not occur until hours or days after the exposure to the offending allergen.  IgG, once exposed to antigens, initiates the release of chemical mediators which activate the physiological changes associated with food allergies. Frequency of exposure to the antigens influences a delayed immune response as a result of IgG activity.[50] 

Inflammation of the intestinal tract as a result of the release of the chemical mediators in IgE and IgG reactions, causes damage to the mucosal barrier and allows for the passage of more allergenic food molecules.[51]  Intestinal inflammation has been measured using markers such as fecal eosinophil cationic protein, tumor necrosis factor-alpha, and alpha-1 antitrypsin in patients with atopic eczema.  The patients were challenged with cow’s milk, and these indicators of inflammation all rose.  In those patients who exhibited delayed type reactions to the milk, the rise in TNF-alpha concentration was particularly noteworthy.[52] 

Increased levels of IgG to various foods, including egg white, orange, and wheat, may indicate an increased risk to the development of IgE reactions to those food allergens, as well as to animals and mites.[53]  It is therefore helpful to identify both the IgE and the IgG antibodies to the suspected foods.

Testing for Allergies

Elimination of all potential food allergens followed by an oral challenge of those foods one by one is still considered by some to be the most reliable test to identify food allergies.  There are some major problems associated with conducting these tests, however, including compliance of the patient with the rigorous dietary schedule.  Not only is the test difficult to do from the standpoint of avoidance and the slow challenge, but it is also very difficult to identify delayed food reactions through this method.  Symptoms often appear in parts of the body in which the patients have no suspicion of problems and no direct exposure to the antigens. Thus it is difficult for them to see the cause and effect relationships.  

In addition, skin testing, which has been used for a number of years to detect airborne allergens, has been found to be unreliable for detecting food allergies.  Skin tests have only been shown to be useful only for measuring immediate reactions to allergens.  Differences in interpretation (which has also been a problem with RAST in the past) has limited the usefulness of the skin test for studying food allergies.[54]

US Biotek Allergy Profile

US Biotek offers testing for both IgE and IgG antibodies to 88 foods on the Standard or Vegetarian Food Allergy Panels, and over 135 foods and spices on the Extended Food Allergy Panel.  In addition, an inhalant panel identifies IgE antibodies to common airborne substances and pet allergens.

US BioTek's ELISA is considered “state-of-the art” for the following reasons: US BioTek currently has two distinguished scientists on staff (with over 29 combined years of ELISA experience including the development of over 60 unique immunoassays). To start with, close attention is paid to working with quality materials.  The use of robotics avoids day-to-day variability and technical (human) pipetting error.  In the assay itself, all samples are run in duplicate (this alone validates both the assay and the test results).  The ELISA  is highly sensitive (it can detect less than 1 ng/ml of IgE in serum, and less than 500 picogram/ml of IgG).  The ELISA, as we have developed it, is accurate, consistent and reproducible.  It provides physicians with reliable test results that can enhance the diagnosis of allergies and improve the clinical outcomes (by allowing the physician and patient to review changes as they occur during the treatment protocol).

The results are returned to the physician in a very timely manner (within 3-5 days after the blood sample is drawn) and are presented in a very user-friendly report.  Foods are identified within their food group for ease of finding specific results.  Color bar graphing offers an immediate visual representation of the findings.  Total serum IgG and IgE levels are furnished in the report as well as the specific amount of antibody produced against each food.  In addition, the data are provided in such a way that absolute measurements of each individual test sample (against a panel of antigens) are evaluated based on a standard bell curve of normal individuals.  This allows the physician to see how their individual patient’s values relate to a large known population.

[1] Hill DJ, Hosking CS, Heine RG. Clinical spectrum of food allergy in children in Australia and South-East Asia: identification and targets for treatment. Ann Med. 1999;31(4):272-281.

[2] Eseverri JL, Cozzo M, Marin AM, Botey J. Epidemiology and chronology of allergic diseases and their risk factors. Allergol Immunopathol (Madr). 1998;26(3):90-97.

[3] Hofer MF. The child, his mother, and allergies. Rev Med Suisse Romande. 1999;119(8):623-627.

[4] King WP. Food hypersensitivity in otolaryngology. Manifestations, diagnosis, and treatment. Otolaryngol Clin North Am. 1992;25(1):163-179.

[5] Hourihane JO. Prevalence and severity of food allergy—need for control.  Allergy. 1998;53(46 Suppl):84-88.

[6] Royal College of Physicians and Royal College of Pathologists. Good allergy practice—standards of care for providers and purchasers of allergy services within the National Health Service. Clin Exp Allergy. 1995;25(7):586-595.

[7] Joyce DP, Chapman KR, Balter M, Kesten S. Asthma and allergy avoidance knowledge and behavior in postpartum women. Ann Allergy Asthma Immunol. 1997;79(1):35-42.

[8] Rachelefsky GS. National guidelines needed to manage rhinitis and prevent complications. Ann Allergy Asthma Immunol. 1999;82(3):296-305.

[9] Wilson SJ, Walzer M. Absorption of undigested proteins in human beings. IV. Absorption of unaltered egg protein in infants. Am J Dis Child. 1935;50:49-54.

[10] Rinkel HJ. Food Allergy. J Kansas Med Soc. 1936;37:177.

[11] Deamer WC, Gerrard JW, Speer F. Cow’s milk: a critical review. J Fam Pract. 1979;9(2):223-232.

[12] Schnyder B, Pichler WJ. Food intolerance and food allergy. Scweiz Med Wochenschr. 1999;129(24):9280933.

[13] Kitts D, Yuan Y. Joneja J, et al. Adverse reactions to food constituents: allergy, intolerance , and autoimmunity. Can J Physiol Pharmacol. 1997;75(4):241-254.

[14] Eseverri JL, Cozzo M, Marin AM, Botey J.  Epidemiology and chronology of allergic diseases and their risk factors.  Allergol Immunopathol (Madr). 1998;26(3):90-97

[15] Joyce DP, Chapman KR, Balter M, Kesten S. Asthma and allergy avoidance knowledge and behavior in postpartum women. Ann Allergy Asthma Immunol. 1997;79(1):35-42.

[16] Jolicoeur LM, Boyer JG, Reeder CE, Turner J. Influence of asthma or allergies on the utilization of health care resources and quality of life of college students. J Asthma. 1994;31(4):251-267.

[17] Eigenmann PA, Sicherer SH, Borkowski TA, et al.  Prevalence of IgE-mediated food allergy among children with atopic dermatitis.  Pediatrics. 1998;101(3):E8.

[18] Hill DJ, Hosking CS, Heine RG. Clinical spectrum of food allergy in children in Australia and South-East Asia: identification and targets for treatment. Ann Med. 1999;31(4):272-281.

[19] Kulig M, Bergmann R, Klettke U, et al.  Natural course of sensitization to food and inhalant allergens during the first 6 years of life. J Allergy Clin Immunol. 1999;103(6):1173-1179.

[20] Moneret Vautrin DA. Cow’s milk allergy. Allerg Immunol (Paris). 1999;31(6):201-210.

[21] Rance R, Kanny G, Dutau G, Moneret Vautrin DA. Food allergens in children. Arch Pediatr. 1999;6(Suppl1):61S-66S.

[22] Opper FH, Burakoff R. Food allergy and intolerance. Gastroenterologist. 1993;1(3):211-220.

[23] Sampson HA. Food allergy. JAMA. 1997;278(22):1888-1894.

[24] Bell IR, Schwartz GE, Peterson JM, et al. Possible time-dependent sensitization to xenobiotics: self-reported illness from chemical odors, foods, and opiate drugs in an older adult population. Arch Environ Health. 1993;48(5):315-327.

[25] Hourihane JO. Prevalence and severity of food allergy—need for control.  Allergy. 1998;53(46 Suppl):84-88.

[26] Ahmed T, Sumazaki R, Shin K, et al. Humoral immune and clinical responses to food antigens following acute diarrhoea in children. J Paediatr Child Health. 1998;34(3):229-232.

[27] Eseverri JL, Cozzo M, Marin AM, Botey J. Epidemiology and chronology of allergic diseases and their risk factors. Allergol Immunopathol (Madr). 1998;26(3):90-97.

[28] Taub EL. Food allergy and the allergic patient. Springfield: Thomas. 1978.

[29] Rance R, Kanny G, Dutau G, Moneret Vautrin DA. Food allergens in children. Arch Pediatr. 1999;6(Suppl1):61S-66S.

[30] Ortega Cisneros M, Vidales Diaz MA, del Rio Navarro BE, Sienra Monge JJ. Cutaneous reactivity to foods among patients with allergic rhinoconjunctivitis.  Rev Alerg Mex. 1997;44(6):153-157.

[31] Rance R, Kanny G, Dutau G, Moneret Vautrin DA. Food allergens in children. Arch Pediatr. 1999;6(Suppl1):61S-66S.

[32] Muhlemann RJ, Wuthrich B. Food allergies 1983-1987. Scheiz Med Wochenschr. 1991;121(46)”1696-1200.

[33] Kulig M, Bergmann R, Klettke U, et al.  Natural course of sensitization to food and inhalant allergens during the first 6 years of life. J Allergy Clin Immunol. 1999;103(6):1173-1179

[34] Ewan PW. Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations. BMJ. 1996;312(7038):1074-1078.

[35] Wilson NW, Self TW, Hamburger RN. Severe cow’s milk induced colitis in an exclusively breast-fed neonate. Case report and clinical review of cow’s milk allergy.  Clin Pediatr (Phila). 1990;29(2):77-80.

[36] Pelto L, Salminen S, Lilius EM, et al. Milk hypersensitivity – key to poorly defined gastrointestinal symptoms in adults. Allergy. 1998;53(3):307-310.

[37] Garrett MH, Rayment PR, Hooper MA, et al.  Indoor airborne fungal spores, house dampness and associations with environmental factors and respiratory health in children.  Clin Exp Allergy. 1998;28(4):459-467.

[38] Joyce DP, Chapman KR, Balter M, Kesten S. Asthma and allergy avoidance knowledge and behavior in postpartum women. Ann Allergy Asthma Immunol. 1997;79(1):35-42.

[39] Buchanan HM, Preston SJ, Brooks PM, Buchanan WW. Is diet important in rheumatoid arthritis? Br J Rheumatol. 1991;30(2):125-134.

[40] Van d Laar MA, Aalbers M, Bruins FG, et al. Food intolerance in rheumatoid arthritis. II. Clinical and histological aspects.  Am Rheum Dis. 1992;51(3):303-306.

[41] Schrander JJ, Marcelis C, deVried MP, van Santen Hoeufft HM. Does food intolerance play a role in juvenile chronic arthritis? Br J Rheumatol. 1997;36(8):905-908.

[42] Cuesta Herranz J, Lazaro M, de las Heras M.  Peach allergy pattern: experience in 70 patients. Allergy. 1998;53(1):78-82. 

[43] Corrado G, Luzzi I, Lucarelli S, et al. Positive association between Helicobacter pylori infection and food allergy in children. Scand J Gastroenterol. 1998;33(11):1135-1139.

[44] Rance R, Kanny G, Dutau G, Moneret Vautrin DA. Food allergens in children. Arch Pediatr. 1999;6(Suppl1):61S-66S.

[45] Nolan A, Lamey PJ, Milligan KA, Forsyth A. Recurrent aphthous ulceration and food sensitivity. J Oral Pathol Med. 1991;20(10):473-475. 

[46] Kitts D, Yuan Y. Joneja J, et al. Adverse reactions to food constituents: allergy, intolerance , and autoimmunity. Can J Physiol Pharmacol. 1997;75(4):241-254.

[47] Ahmed I, Kamota I, Sumazaki R, et al. Circulating antibodies to common food antigens in Japanese children with IDDM. Diabetes Care. 1997;20(1):74-76.

[48] Trotsky MB. Neurogenic vascular headaches, food and chemical triggers.  Ear Nose Throat J. 1994;73(4):228-230, 225-236.

[49] Egger J, Carter CH, Soothill JF, Wilson J. Effect of diet treatment on enuresis in children with migraine or hyperkinetic behavior. Clin Pediatr (Phila). 1992;31(5):302-307.

[50] King WP. Food hypersensitivity in otolaryngology. Manifestations, diagnosis, and treatment. Otolaryngol Clin North Am. 1992;25(1):163-179.

[51] King WP. Food hypersensitivity in otolaryngology. Manifestations, diagnosis, and treatment. Otolaryngol Clin North Am. 1992;25(1):163-179.

[52] Majamaa H, Miettinen A, Laine S, Isolauri E. Intestinal inflammation in children with atopic eczema: a faecal eosinophil cationic protein and tumour necrosis factor-alpha as non-invasive indicators of food allergy.  Clin Exp Allergy. 1998;26(2):181-187.

[53] Eysink PE, De Jong MH, Bindels PJ, et al. Relation between IgG antibodies to foods and IgE antibodies to milk, egg, car, dog, and/or mite in a cross-sectional study.  Clin Exp Allergy.   1999;29(5):604-610.

[54] Dreborg S. Skin testing in the diagnosis of food allergy. Allergy Proc. 1991;12(4):251-254.