Allergic diseases are characterized by focal inflammation in certain target organs. These include the bronchi in asthma; the nasal mucosa and conjunctivae in allergic rhinitis; the gastrointestinal mucosa in allergic gastroenteropathy; the skin in atopic dermatitis, urticaria, and allergic contact dermatitis; and alveolae and lung interstitium in hypersensitivity pneumonitis. Multiple target organs are involved in systemic anaphylaxis and in serum sickness. During the course of illness of any of these localized diseases, the allergic patient may experience systemic symptoms such as fatigue or other focal symptoms in parts of the body not directly involved in the allergic inflammation. These collateral symptoms are sometimes explainable pathophysiologically, for example, as secondary effects of hypoxemia and hyperventilation in asthma or from cranial and neck muscle tension from excessive sneezing in rhinitis. Locally released inflammatory mediators and cytokines may produce systemic effects, although direct proof is lacking.

On the other hand, certain practitioners have proposed that a variety of systemic complaints, especially fatigue, drowsiness, weakness, body aching, nervousness, irritability, mental confusion, sluggishness, and poor memory—in the absence of any clinical sign of allergic inflammation–are caused by exposure to environmental allergens. The allergens most often implicated are foods, food additives, environmental chemicals, and drugs. This has been referred to as allergic toxemia, allergic tension fatigue syndrome (3), or cerebral allergy (4). The literature on this subject is largely anecdotal. No definitive controlled studies have yet shown the existence of such a syndrome (5). Patients often claim dramatic improvement from eliminating certain foods or chemicals, but this is not supported by scientific evidence.

The allergic toxemia concept is also used to explain allergy as the cause of certain psychiatric conditions. Attention deficit disorder and attention deficit hyperactivity disorder (ADD, ADHD) in children are attributed to food coloring and preservatives (6). Several controlled studies, however, do not support this concept (7). The claim that ingestion of wheat and certain other foods cause or contribute to adult schizophrenia (8,9) has not been confirmed.

For years a small group of physicians have accepted a concept that environmental chemicals cause a variety of physical and psychological illnesses. This concept was applied to patients with a host of nonspecific complaints without objective physical signs of disease. These patients also attribute their symptoms to multiple food sensitivities.

This practice is known as clinical ecology (10–12), which postulates disease from failure of the human species to adapt to synthetic chemicals (13). One theory proposes that symptoms represent an exhaustion of normal homeostasis from ingestion of foods and inhalation of chemicals. An alternative theory is that common environmental substances are toxic to the human immune system (14). These and other clinical ecology theories rely on certain unique and unscientific concepts, such as a maximum total body load of antigen, masked food hypersensitivity, and a “spreading phenomenon” whereby the presence of one specific allergy induces others of different specificities.

Clinical ecology practitioners diagnose “environmental illness,” also called multiple chemical sensitivities, ecologic illness, chemical hypersensitivity syndrome, total allergy syndrome, and 20th century disease. The term idiopathic environmental intolerances (IEI) is the most appropriate one, because it avoids unproved mechanisms (15). Patients with this diagnosis generally have a wide range of symptoms that are often compatible with conversion reactions, anxiety and depression, or psychosomatic illness. The diagnosis is subjective with no requirement for any specific physical findings or abnormal laboratory test results.

Lacking a characteristic history or pathognomonic physical signs or laboratory abnormalities (16–18), the diagnosis usually depends on the provocation-neutralization procedure described below. Some clinical
ecologists also measure serum immunoglobulins, complement components, blood level of lymphocyte subsets, and blood or tissue level of environmental chemicals to supplement provocation-neutralization testing. It is not clear, however, how these test results indicate the presence of environmental illness. The few published reports show variable and often conflicting abnormalities of dubious clinical significance, because they lack proper controls or evidence of reproducibility (5).

The primary treatments advocated by clinical ecologists are avoidance and neutralization therapy. Avoidance of foods believed to cause or aggravate illness is accomplished by a rotary diversified diet, because multiple food “sensitivities” are believed to occur in this illness. Avoidance of all food additives, environmental synthetic chemicals, and even some natural chemicals is recommended, but the extent of avoidance varies with the enthusiasm of the patient and physician and not on scientific evidence of efficacy. Patients often avoid scented household products, synthetic fabrics and plastics, and pesticides. They generally try to limit exposure to air pollutants, gasoline fumes, and vehicle exhaust fumes. Several isolated rural communities have been established for these patients.

Neutralization therapy with food and chemical extracts, megadose vitamin therapy, mineral or amino acid supplements, and antioxidants are commonly recommended. Drug therapy is generally condemned as a form of chemical exposure, although oxygen, mineral salts, and antifungal drugs are frequently prescribed. None of these forms of treatment—either singly or in combination—have been evaluated in properly controlled trials to determine efficacy or potential adverse effects.

Environmental illness is also alleged to be caused by Candida albicans normally resident in the microflora of the gastrointestinal and female genitourinary mucous membranes. Many persons with no clinical evidence of Candida infection and no evidence of defective local or systemic immunity, pregnancy, diabetes mellitus, endocrine diseases, or medications known to cause opportunistic candidiasis are said to suffer an illness known as Candida hypersensitivity syndrome (19,20). Clinically, the syndrome is indistinguishable from environmental illness. C. albicans also has been claimed to cause behavioral and emotional diseases and a variety of physical illnesses and symptomatic states. Individuals who have ever received antibiotics, corticosteroids, birth control pills, or have ever been pregnant, even in the remote past, are said to be susceptible to this syndrome. Diagnosis is made by history and not by diagnostic testing. The recommended treatment is avoidance of sugar, yeast, and mold in the diet, and the use of a rotary diversified diet. Nystatin, ketoconazole, caprylic acid, and vitamin–mineral supplements are recommended. This syndrome is reminiscent of the concept of autointoxication that was popular in the early 20th century. In the opinion of some practitioners of that era, the bacterial component of the normal intestinal flora was considered to cause numerous physical and psychologic disabilities (21).

Atmospheric mold sensitivity has recently replaced environmental chemical sensitivity as causing a variety of subjective complaints or illnesses in persons living in homes or working in buildings that have sustained water damage from flooding or excessive humidity, promoting indoor mold growth (22). Fungi are a major component of the environment, and fungal spores are almost always present in the atmosphere. In contrast to well-recognized infectious and allergic diseases caused by molds, a combined toxicity/hypersensitivity theory is often invoked (23) as in the case of environmental illness.

One particular fungus, Stachybotrys atra (chartarum), has created considerable publicity because of the suspicion that Stachybotrys mycotoxin was the causative agent in cases of pulmonary hemorrhage/hemosiderosis in young infants living in water-damaged homes (24). The role of the mycotoxin in these cases has been called into question (25), but there remains unsubstantiated fear of the presence of any indoor mold spores as pathogenic. This unproved theory should not be confused with allergic diseases caused by fungal allergy, especially asthma, some cases of hypersensitivity pneumonitis, allergic bronchopulmonary aspergillosis, and allergic fungal sinusitis. These can be identified by localized symptomatology, objective physical findings, functional and imaging studies that confirm pathology, and the presence of the relevant immune response by the patient.

Acupuncture, Chinese herbal therapy, homeopathy, naturopathy, and similar alternative practices have all been used for allergy treatment. None of these are based on accepted scientific principles of physiology, immunology, or pharmacology. Reasonably acceptable clinical trials have failed to show benefit (26–28).

The procedures included in this category are not based on sound scientific principles, and they have not been shown by proper controlled clinical trials to be capable of assisting in the diagnosis of any condition.