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."

• 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..

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.

The Evolving Nature of Hypersensitivity

The following discussion and case histories show that 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.

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.