DEFINITIONS AND PREVALENCE OF HYPERSENSITIVITY REACTIONS

I. DEFINITIONS AND PREVALENCE OF HYPERSENSITIVITY REACTIONS

Many people have uncomfortable reactions to various foods, and this is often considered to be due to food additives and other artificial chemicals, such as pesticide residues, rather than to the food itself. This discomfort is usually called allergy by nonmedical persons, but there are also nurses and doctors who use the term allergy when they mean various kinds of untoward reactions to foods without knowing the mechanisms of such reactions.

Strictly, an allergy is a harmful physiological reaction caused by an immunologic mechanism . If the mechanism is not an allergic one but the reaction resembles allergic reaction, the term intolerance is often used. The symptoms mimic those seen in allergic reactions, but the amount of agent producing the reaction is small enough not to cause a toxic reaction . When the mechanism is not known, it is better to talk about hypersensitivity,

which can mean both allergic reaction and intolerance ( Tables 1 – 3 ). There are several foods and food additives that can cause both immunologic and nonimmunologic reactions indistinguishable from each other. For example, fish can act both as nonspecific histamine liberators and as true allergens. Tuna, mackerel, and certain cheeses contain histidine and tyrosine to such an extent that histamine and tyramine pro- duced by decarboxylation from them can cause allergic-type symptoms in atopic people (Royal College of Physicians and the British Nutrition Foundation, 1984). Among food additives, cinnamon and nitrogen mustard are the most well-known causes of both allergic

Table 1 Terminology of Hypersensitivity Reactions Hypersensitivity

A small amount of a substance produces symptoms that can be objectively verified and repeated. Allergy

Immunologic mechanisms are involved in the pathogenesis of symptoms. Atopic allergy

The reaction is mediated by immunoglobulin E. Intolerance

A small amount of a substance produces a reaction similar to or closely resembling a true allergic reaction, but immunologic mechanisms are not involved.

Table 2 Allergic Reactions Allergic reaction

(mechanism) Clinical and immunological features 1. Anaphylactic (atopic)

Symptoms (urticaria, allergic rhinitis, conjunctivitis, and asthma; abdominal pain and aches, diarrhea; severe itch and acute worsening of atopic dermatitis) appear usually within minutes and subside within hours.

2. Cytotoxic Very rarely caused by food additives. Purpura due to destruction of platelets is the most common clinical symptom. 3. Immunocomplex disease

Immunoglobulin G and M form complexes with the allergen (an- tigen) resulting in purpura, urticaria, arthritis, and other symp- toms of immunocomplex disease (serum sickness).

3. Delayed allergy Expressed usually as delayed-type contact dermatitis. A rash re- sembling virus exanthema may be produced by ingested aller- gens. Granulomatosis.

Table 3 Intolerance and Other Nonallergic Reactions Nonspecific histamine liberation—Cocoa, citrus fruits, strawberry, etc.

Intestinal diseases—Glutein intolerance produces abdominal and skin symptoms. Primary or acquired enzyme deficiency—Diarrhea and colic in lactase deficiency. Microbes and their toxins—Bacteria, viruses, yeasts, molds, and fungi cause a diversity of

gastrointestinal symptoms. Psychological causes may underlie various kinds of skin, gastrointestinal, and other reactions.

The prevalence of hypersensitivity reactions to food additives has been investigated in certain diseases, such as chronic urticaria and asthma, suspected to be caused by these chemicals. Juhlin (1981) estimated that 30–50% of patients with chronic urticaria react to one or more food additives. In his studies, however, Juhlin used single-blind challenges. This fact makes his results more or less unreliable.

Farr et al. (1979) reached the conclusion that 4–6% of acetylsalicylic acid (ASA, aspirin) sensitive asthmatics, or about 5000 persons in the United States, react to tartrazine. Stevenson et al. (1986) reviewed the studies on the provocative effect of tartrazine in urticaria; they consider tartrazine to be responsible for worsening of urticaria in occasional

Weber et al. (1979) estimated that bronchoconstriction provoked by food dyes and preservatives occurs in about 2% of all asthmatics. Sulfite-induced asthma is thought to affect 5–10% of all asthmatics (450,000 people in the United States) (Stevenson and Simon, 1981). Bush et al. (1986) stated that the figure (5–10%) concerns only severe asthmatics (90,000 people). In their double-blind study on the significance of sulfites in steroid-dependent and non-steroid-dependent asthmatic patients, Bush et al. (1986) showed that the prevalence of sulfite sensitivity in the asthmatic population as a whole would be less than 3.9%, and that these patients are more common among steroid-depen- dent asthmatic patients.

Juhlin (1981) calculated that 0.5% of all people will show intolerance to aspirin, 0.06% to tartrazine, and 0.05% to benzoates. In Denmark, Poulson (1980) estimated that 0.01–0.1% of the population are sensitive to both tartrazine and benzoates. In France, Moneret-Vautrin et al. (1980b) concluded that 0.03–0.15% of the population experience sensitivity to tartrazine. The Commission of the European Communities (1981) estimated the prevalence of food additive intolerance to be 0.03–0.15% in the whole population. Bronchoconstriction to salicylate, sulfite, and tartrazine has been shown to be dose depen-

dent. The median dose eliciting 15% fall in FEV 1 varied between 0.1 and 0.2 mM, and the most sensitive (5%) asthmatics responded to 4.6 mg metabisulfite, 3.4 mg tartrazine, and 2.6 mg salicylate (Corder and Buckley, 1995).

Of adult patients with hay fever and asthma, 1–2% have experienced harmful symp- toms from spices (Eriksson, 1978). Immediate skin test reactions to spices are seen in 20% of atopic patients, especially in those with birch pollen allergy (Niinima¨ki and Hannuksela, 1981). In oral challenge tests, positive reactions were seen in only 14 of 35 patients with positive skin tests with spices. Most skin prick test reactions to cinnamon and mustard are, in fact, nonallergic, but the proportion of allergic and nonallergic skin test reactions to other spices is much higher than those for cinnamon and mustard.

Madsen (1994) reviewed three papers estimating the frequency of food additive intolerance. In an EEC report (Commission of the European Communities, 1982), based on the results of clinical patient studies of chronic urticaria and asthma, the frequency of additive intolerance was estimated to be 0.13%. In a Danish study (National Food Agency of Denmark, 1980) the estimate for additive intolerance in children was 1%. The third study was a large epidemiological study in England (Young et al., 1987) in which 7.4% of 18,582 responders reported problems with food additives. The results of subse- quent interviews and a clinical study including double blind peroral challenges suggested the total prevalence of intolerance to any food additive to be 0.23% in the whole popula- tion.

Thus, adverse reactions to ingested food additives seem to be rare and true allergy to them very rare. Nevertheless, there are a small minority of the population who suffer from these reactions. These individuals are often atopic.