Books to Read
Diagnosis of Allergy
The desire for simple, office or laboratory test for allergy is easy to understand, but difficult to fulfill. No single test will ever reveal the complex and variable nature of allergic reactivity. The lack of specific tests for different kinds of allergy have hindered progress in this field.
Skin tests are best used to diagnose airborne allergens which cause hay fever. There is a convenient correlation between nose-reactive IgE and skin-reactive IgE . By introducing tiny amounts of suspected antigens into the skin, a local wheal and flare reaction, similar to a mosquito bite, is produced if reactive IgE is present on skin mast cells. The association of hay fever and some asthma, and skin tests with allergy practice was further confirmed by the relative success of "allergy shots". These shots came to characterize the allergist's office; other aspects of allergy practice often were neglected. Allergy shots are immunological treatments. The immune response to any reactive substance can be modified by giving repeated challenges of the reactive substances. Serum assays of IgE antibodies are useful in diagnosing type 1 food allergy. In a study of patients with asthma, and atopic dermatitis, plasma histamine and tryptase levels rose in the group with immediate reactions to food challenges. An elevated plasma tryptase level is thought to indicate mast cell activation. The authors noted subjects who had delayed symptoms - diarrhea at 4 hours, erythema and urticaria and 8 hours, and exacerbation of atopic dermatitis at 24 hours had slow or low histamine responses with no tryptase elevation.
The idea that standardize protein extracts of foods would be the most reliable and "scientific" tests for food allergy have been thwarted by observations that skin tests with fresh-extracts from food correlated better with symptoms on challenge testing. Food antigens can be complex, multiple, and may not survive processing into standardized extracts. In a review of studies of type 1 reactions to vegetables and fruit, mouth and tongue symptoms dominated. Systemic reactions included urticaria, angioedema, asthma, rhinitis, headaches, and itchy hands. Testing with commercial food-protein extracts was found less reliable than using the fresh food. Skin tests do not reveal the more complex forms of food allergy. Some labs offer other tests for food allergy, including IgG RAST, and immune complex assays. While these tests produce interesting results, they are expensive and do not answer the main question - what should the patient eat?
The reality that I confronted for many years was that very sick patients would get better with diet revision that excluded gluten and other food ingredients regardless of their laboratory tests or biopsy results. My attitude is that positive antibody tests are interesting findings in research, but may not be helpful in the management of sick patients. You have to know that are four major classes of antibodies and many subtypes. It is estimated that one person can make a large number of antibodies that interact with a million or more targets. Every person has circulating serum antibodies to some food proteins, but there is no easy cause and effect connection between the amount of antibody and the activity of a disease. I concluded that antibody test results were not helpful in directing treatment. The prevalent attitude of physicians is that proper diet revision is too difficult to undertake and they would not consider diet revision to be a suitable experiment to undertake when a patient was chronically ill and not benefiting from treatments offered. I believe that the primary duty of the physician is to find an effective treatment for disease.
The IgE model of allergy inspired development of antibody-measuring laboratory tests. The idea was to show the affinity of circulating antibodies to different antigens. RAST has been used instead of, or in addition to, skin prick and scratch tests to assess food allergy. Variations of the RAST bear the acronyms ELIZA, FAST, and MAST. These are all tests for antibodies directed at selected antigens. The principles of RAST testing for IgE are applied to the measurement of other antibody types. Some studies suggest frequent IgG responses to food antigens. Tests measuring food-antigen specific IgG have been offered with an impressive computer-report of "food sensitivities". The levels of food-specific IgG are listed, and avoidance of foods that cause increased antibody levels is advised. Helpful food lists and food rotation instructions accompany some of the lab reports. It would appear that the problem of food allergy diagnosis is solved. Again, this simplistic approach to food allergy diagnosis is bound to mislead. While it is possible that avoidance of IgG-positive foods will be helpful, we do not know whether that avoidance will really resolve the illness problem. IgG is known to play a protective role and high levels may mean less disease. In my experience with the IgG RAST, the predictive value for food reactions is limited.
Kumar et al found IgG4 antibodies to wheat, beef, pork, lamb, soya beans and egg in irritable bowel patients. Levels of IgE antibodies were similar to controls.
Dermatitis Herpetiformis is characterized by the presence of IgA deposits in the upper dermis of skin Karpati suggested that DH develops in people with celiac disease who also produce IgA antibodies to epidermal transglutaminase an enzyme found in found in skin and other tissues.
Tests, such as anti-gliadin, anti-endomysium, and anti-transglutaminase antibody estimation can be used as screening tests in groups considered to be at risk of celiac disease. These include first-degree relatives of celiac patients and patients with irritable bowel syndrome, arthritis, diabetes mellitus, iron-deficiency anemia, epilepsy, cerebellar ataxia, autoimmune diseases, depression, weight loss and malnutrition. While these antibody tests are useful in identifying potential celiacs, they should not be used to “rule out’ gluten-related diseases.
Ciclitiria al demonstrated that jejunal mucosal biopsy specimens cultured in vitro secreted anti-gliadin antibodies of the IgG and IgM types. Circulating anti-gliadin antibodies (IgG) were demonstrated by the ELIZA technique in the serum of 36 of 44 patients with celiac disease. They also found that half the patients with other gastrointestinal disorders had raised titers to alpha-gliadin. The measurement of antigliadin, anti-reticulin R1 and antiendomysium antibodies can be used as screening tests. Anti-reticulin R1 (ARA-R1) and anti-endomysium (AEA) antibodies may be more reliable markers than anti-gliadin (AGA) antibodies. Transglutaminase antibodies (TGA) are now popular markers of CD. Transglutaminase is a normal enzyme and it appears to be the antigen target for AEA.
Patients are Frustrated
The difficulty in diagnosing food allergy and other food-related problems in clinical medicine and disputes within the allergy community have left many patients suffering, frustrated and confused. At the same time as physicians default in the diagnosis and treatment of food-related illnesses, many non-medical practitioners have launched careers in the food and chemical "sensitivity" business, using diverse, sometimes curious and bizarre methods, dubious tests and questionable treatments. Even well-intentioned efforts to diagnose and treat food allergy are often based on faulty premises and fail to deliver proper results.
Food allergy is diagnosed by physicians who understand the multisystem, polysymptomatic patterns of illness involved. These patterns are revealed by a careful history, and the diagnosis made on clinical grounds. The pattern of food-related illness, the sequence of symptom production, and the distribution of disturbances in the body can be explained if complex causation is assumed. Without a well-equipped research laboratory it will not be possible to actually measure the pathophysiological events.