Reactions, such as anaphylactoid events following ingestion of scromboid fish protein, are described under Mechanisms. Urticaria may occasionally occur following ingestion of certain foods containing histamine or as histamine reactors as listed in Table 3. Examples include cheese, alcohol, red wine, or strawberries.
One of the most common gastrointestinal problems that is confused with milk allergy is primary (and secondary) lactose intolerance. The pathogenesis of this reaction is described under Mechanisms. As pointed out, the problem with milk usually begins around age 7, but may start earlier in childhood if the child has had significant gastroenteritis. Then, for the rest of his or her life, ingestion of cow's milk is a problem. This sequence of events is different from that of the individual who is milk protein allergic in that the milk-allergic individual has trouble during early childhood and later is usually able to tolerate milk clinically.
In the lactose-intolerant patient, the degree of exposure to milk sugar is important. Certain foods are better tolerated than others: cheese is better tolerated than whole milk, and naturally fermented yogurt is better tolerated than cheese. Since the problem is common in certain ethnic groups, older family members may report the same problem with milk ingestion, and lactose intolerance is usually simple to diagnose. If it is important to document this syndrome, this can be done by a gastroenterologist using a breath hydrogen test after lactose ingestion.
The triggering of headaches by vasoactive amines naturally or by food additives may occur with the foods listed in Table 3 and described under Mechanisms. Although the issue of allergy being involved in migraine headache pathogenesis has been long debated, it is rarely proven. In a few cases of patients with migraine headaches, chemical mediator release while eating a specific food may be involved in the headache. Migraines are very common in the general population (e.g., 25% of all adult women and 15% of all adult men). In addition, allergies are also common; therefore, it would be easy to find both conditions (migraine headache and atopic disease) present in the same individual.
Adverse reactions to food additives are not nearly as common as is generally believed. Reactions to BHA, BHT, benzonates, and nitrates are very rarely substantiated by objective measurements. The most common FDA-reported food additive reactions are those to aspartame, and the usual type of symptom is headache. Fifteen percent of reports of adverse effects from aspartame, however, are "allergic-like," usually urticaria. Although there are two documented cases of aspartame-induced urticaria/angioedema reported in the world literature, a recent large nationwide, multicenter study using DBPCFC was unable to confirm a significant association between aspartame and urticaria. The types of adverse reactions to food additives that have been confirmed over the years include the Chinese restaurant syndrome resulting from MSG, asthma resulting from SO2 or sulfites in food, and occasional episodes of urticaria/angioedema resulting from food coloring (see Table 3).
The first report of the Chinese restaurant syndrome was a 1968 self-report of a Chinese physician who ate at a Chinese restaurant and experienced symptoms of nausea, headache, sweating, thirst, facial flushing, tightness and burning of the face and chest, abdominal pain, tearing of the eyes, and a sensation of "crawling" in the skin. Typically, the symptoms begin 15-30 min after eating a meal containing a large amount of MSG, which is a salt of a glutamic acid. These symptoms usually subside without specific medical treatment once the individual discontinues ingestion of the MSG-containing food.
The second most likely food additives (after aspartame) to be reported to FDA as being responsible for an adverse reaction are sulfites and SO2. Although a few cases of anaphy-lactoid-type reactions, usually involving urticaria/angioedema, have been reported, most reactions are the result of asthma exacerbation in a known asthmatic. Some of the early cases were serious, and a few led to death. Although SO2 and sulfites have been used for many years as food and beverage preservatives, it was not until the 1970s and 1980s that reports emerged about serious asthma attacks being precipitated directly upon opening a package containing SO2-preserved foods or eating (and inhaling SO2 indirectly) sulfite-containing foods (see Mechanisms). Of particular importance were fresh vegetables and fruits in salad bars in restaurants (especially lettuce) to which a sulfite solution had been applied to preserve that food. FDA has estimated that approx 5% of all asthmatics are at risk for a reaction to SO2 or sulfite, and studies have shown that the more serious asthmatic is at greater risk of an exacerbation of the asthma than a mild asthmatic.
In the late 1980s, FDA made significant changes in the regulations concerning the maximum level of sulfites that could be in foods in the United States, as well as restrictions on the use of sulfites in restaurants, especially in salad bars. Since that time, the number of reports of sulfite-induced asthma has dropped dramatically. Although there have been reports of MSG-induced asthma exacerbations in Chinese restaurants in Australia that were confirmed by challenge studies in the 1980s, there has not been a similar problem with MSG in the United States.
Although in Europe food additives of all types have been implicated as primary causes of chronic urticaria in about 15% of the cases, most studies in the United States have failed to confirm a significant relationship with any additive except for a few isolated cases of color (particularly yellow)-induced urticaria and angioedema (Table 3).
Tartrazine (FD&C yellow #5) was originally felt to "cross-react" in some way with aspirin and to be a factor in asthma exacerbation in aspirin-sensitive asthmatics. Careful DBPCFC with tartrazine in proven aspirin-sensitive asthmatics has failed to confirm this association with yellow #5. Independent of aspirin sensitivity, there are a few isolated asthmatic patients who are sensitive to yellow #5.
Food additives (particularly colors, especially yellows) have been implicated in causing or exacerbating behavioral problems in children. Probably the most widely known theory regarding this relationship was the Feingold theory about colors (and other food additives) causing hyperactivity in patients with ADD (see Tables 2 and 3). Most subsequent studies have shown that colors do have a drug-like effect, but that this effect occurs in no more that 5% of children with ADD, and the effect has to do with learning abilities. There are no studies that show that colors in the market today are not safe for the general population.
In the mid- to late 1980s, diets high in sugar were believed to cause abnormal behavior, especially hyperactivity in normal children, those with ADD, and juvenile delinquents. The misnomer sugar allergy was coined. DBPCFC studies have documented the fact that sugar in the diet does not have an adverse effect on behavior and, in some cases, may have a calming effect. In the 1960s, Pearson coined the term pseudo-food allergy to describe a syndrome that usually occurs in adults who believe that they have food allergy and restrict their diet to such a degree that they develop signs of malnutrition (see Table 2). Almost all the patients who have been reported with this condition have been found to have psychological problems, especially depression. The symptoms they complain about include fatigue, headaches, "mental fuzziness," malaise, arthralgia, and myalgias. When DBPCFC studies were done, none of the patients studied reacted to the foods to which they were supposedly sensitive; with psychological counseling all resumed a normal diet without adverse effect.
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