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Delayed, Type III Pattern Food Allergy

A Cause of Chronic Illness

The type III pattern is delayed hypersensitivity presenting as a whole-body systemic response involving several organ systems - a chronic illness with features of a recurrent flu-like syndrome. Gastrointestinal tract dysfunction seems to be central to the pathogenesis of a variety of systemic manifestations. The most common, milder manifestations involve IBS as the center of the type III pattern and other diagnoses cluster around the central gastrointestinal tract dysfunction - migraine, Fibromyalgia, fatigue, depression, chronic rhinitis, sinusitis, asthma, and arthralgias are typical associations.

Knicker stated: "Delayed adverse reactions to foods are exceedingly varied, and may involve virtually any organ system. Some reactions are classically allergic and at times may reflect delayed IgE-mediated mechanisms. Others involve a single organ system, or multiple organ systems (e.g. the central nervous system, respiratory system, skin, musculoskeletal apparatus, gastrointestinal system, cardiovascular system etc.) with puzzling combination of symptoms."

Mechanisms in delayed patterns of food allergy are the:

  • the neuro-immunologic responses of the gastrointestinal tract with local symptoms and broadcast of peptides and cytokines which produce systemic symptoms
  • increased gastrointestinal tract permeability and the abnormal entry of food antigens and/or immune complexes into the circulation
  • the formation of circulating immune complexes
  • complement activation usually by immune complexes
  • the action of chemical mediators released by activated mucosal, circulating, and tissue-bound immune cells
  • the activation of cell-mediated immunity involving mast cells, eosinophils macrophages, lymphocytes and a host of cytokines.

Since this category of disease is based on a complex of pathophysiological mechanisms, it contains a surprisingly large spectrum of disease. Consider three categories of disorders:

  1. Common recognized syndromes
  2. Specific diseases
  3. Nonspecific illness

Syndromes such as irritable bowel syndrome, migraine, panic disorder, depression, chronic fatigue, fibrositis or fibromyalgia can be collected under the title of type III pattern. All the rheumatic diseases, autoimmune diseases, multiple sclerosis, type 1 diabetes, thyroiditis, Crohn's disease, psoriasis are hypersensitivity diseases that can be included along with common specific problems that are related to classical allergy - asthma, atopic dermatitis, urticaria, anaphylaxis, angioedema, allergic gastroenteropathy, and allergic arthritis.

Many of the ever-enlarging pool of patients who are not well but who do not have the markers of specific can be included. Patients with in-between disease have some of the symptoms and signs that suggest the diagnosis of specific disease but not everything fits together. Most chronic diseases take many years to evolve so that many in-between patients are on their way to the final disease product.

The concept of delayed patterns of immune response ("food allergy") to food materials provides both a theoretic and practical basis for interpreting symptoms of patients with both specific diseases and non-specific syndromes. The presence of food allergy (as a pathophysiological mechanism) is concealed in a variety of nosological diagnoses such as migraine headaches, asthma, eczema, irritable bowel syndrome, depression, panic disorder, and arthritis. These syndromes tend to cluster in type III patients.

Serum Sickness Leads to Inflammation in Target Organs

Von Pirquet first described serum sickness, the prototype of Immune Complex disease. Any food protein entering the circulation in sufficient quantity can produce symptom patterns resembling serum sickness. Serum sickness manifests as a systemic illness, typically evolving over a period of 7-10 days. Manifestations include general malaise, fever, flushing, sweating, hives, swelling, bruising, arthralgias and myalgias, progressing in the worst case to inflammatory disease in target organs. Circulating immune complexes may lead to inflammation in target organs. Type III events lead to Type IV hypersensitivity. Flu-like or non-specific symptoms tend to become more specific disease as target organ effects become manifest.

Type IV, cell-mediated immunity produces inflammation with local dysfunction, associated with systemic symptoms from immune mediators released into the bloodstream. If a macrophage-lymphocytic network is activated by food antigens the pathogenic consequences depend on the dose, frequency, and distribution of antigen, and the location of lymphocytes. The idea is that any part of the body can be involved in an immune skirmish. The consequences depend on the importance of the target organ the nature and extent of problems caused by immune activity. Events in the nose will be experienced as discomfort. Events in the eye or other critical areas of the brain may be catastrophic.

Systemic Lupus Erythematosis (SLE serves as a model of type III - IV patterns of hypersensitivity disease. The typical type III syndrome is the systemic flu-like illness with minimal evidence of target organ involvement. This syndrome may include a malar or butterfly rash, flushing, lymphadenopathy, arthralgias, headaches, fever, sweating, fatigue, dyspepsia, bloating, diarrhea. Arthralgias are associated with generalized aching and stiffness (often diagnosed as fibromyalgia) and infrequently joint swelling occurs. Mild localized inflammation may be associated such as rhinitis, pharyngitis or episodes of localized abdominal tenderness, especially in the right lower quadrant. If the disease advances, increased evidence of target organ inflammation and dysfunction becomes more apparent.

The Evolving Nature of Hypersensitivity

The delayed or type III pattern of food allergy is an evolving process over time. Often there is a "background noise" of milder but chronic symptoms, punctuated episodically by more acute events. This may be a life-long process that begins with colic, rhinitis, recurrent otitis media and/or eczema in infancy and progresses through different symptom patterns as the years go by. A typical presentation of type III pattern food allergy involves symptoms emerging in waves of dysfunction. A typical adult patient will present with recurrent rhinopharyngitis, abdominal pain and bloating, generalized muscle-tension, aching and stiffness with fatigue, weakness, and often cognitive dysfunction. In any given patient, the mechanism of disease may not be demonstrable by objective means especially when the disease is at an early stage of development and dysfunction is relatively mild. Physical signs include flushing, allergic shiners with suborbital edema, butterfly rash, rhinitis, enlarged cervical nodes, increased skin telangiectasias, edema of hands and feet, muscle and connective tissue tenderness with "trigger nodes", skin rashes, tender costochondral junctions, and spot tenderness in the abdomen, most often RLQ and LLQ.

None of this phenomenology would make sense without a standard method of diet revision to reveal the food origin of the disease. Both patient and physician must have the opportunity to demonstrate clearing of symptoms on an elemental nutrient formula (Alpha ENF)and/or an oligoantigenic diet. Both must also have the opportunity to study the patterns of returning symptoms when a reactive food is again eaten.

The most important initial experiment is to require that a sick patient stop eating the food that is making him ill long enough that the pathological processes subside and symptoms clear. An elemental nutrient formula, free of protein and peptide antigens can supply complete nutrition and allows a patient to continue long enough to experience remission - 10 to 20 days is the expected time of symptom clearing.

The Continuous Activity of Immune Networks

To develop a useful clinical understanding of hypersensitivity disease, it is necessary to think of immune networks as continuously active in the human body. A dynamic model of immune networks reveals that mobile cell populations produce evanescent events that are continuously evolving. Immune cell populations moving through boundaries that open and close and as immune networks become more active, the migrations become more hectic and the boundaries become less secure; events tend become turbulent or chaotic. Patients report the kind of events that occur and can tell us about progression of symptoms and diseases over time.

Immune responses to food antigens depend on the dose of antigen, distribution, timing, and frequency of antigen exposure and many other variables related to the state of the host. Outside challenge (antigens) are disturbances which ripple through immune networks, triggering a host of responses. Some of these responses may be useful and others may disrupt normal function without any benefit. Repeated challenges with the same stimulus will produce an array of related responses; never just the same response.

If the basic assumption is that each challenge from the outside renders immune networks temporarily hyperactive and unstable, it is possible understand the experiences of patients who report a fascinating array of events with different timing, duration, topology and consequences.

It is unlikely that one hypersensitivity mechanism cannot operate in isolation from other mechanisms. Each challenge from the outside renders immune networks unstable and may induce chaos if the challenge is sufficiently intense. Some antigens may go beyond activating antigen-specific clones; these super antigens may excite polyclonal cell populations, inducing general hypersensitivity. Staphylococcal enterototoxins, for example, responsible for food poisoning and toxic shock syndrome, act as super antigens and generally activate immune networks.

The histories of patients presenting to my office illustrate the complexity of these immune events over time. For example, one patient described 60 years of immune-mediated disease beginning with childhood illnesses typical of delayed pattern food allergy. Her sequence of major hypersensitivity diseases over 60 years was eczema, asthma, migraines, thyroid ( Grave's disease), fibromyalgia, recurrent "pneumonias", and finally rheumatoid arthritis. Consider the possibility that the whole sequence of hypersensitivity manifestations is linked by a common, underlying pathophysiological process - this connected sequence suggests the possibility that food antigens triggered a variety of immune responses over-time.

The Food Allergy Center is devoted to explaining a complicated and controversial subject. We offer  rich resource online and encourage our readers to further pursue their interest by reading our books.  Hypoallergenic Nutrient Formulas Alpha Nutrient Formulas are gluten free and do not contain cows milk, soya, or egg ingredients. They do not contain food dyes or other additives. They are suitable for vegetarians.

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