Psychologic and somatic interrelationships in allergy and pseudoallergy

THE JOURNAL

OF

Al.LE#tGY AND

AL VOLUME

1,

81

NUMBER 2

Special notice The Fourth Annual Aspen Allergy Conference (Given Institute, Aspen, Colo., July 1 Psychologic and somatic interrelationships allergy and pseudoallergy* David J. Pearson, PhD, FRCP Manchester,

in

England

A wide range of mental, behavioral, and nonspec$c subjective somatic symptoms can be observed commonly in the course of the classic allergic diseases of the atopic syndrome (asthma. rhinitis. eczema, etc). These symptoms do not necessarily imply the presence of psychiatric disorder, nor do they indicate that allergic processes have a direct effect on cerebral function. These changes are the indirect result of the allergy and are usually secondary to extracerebral physical dysfunctions. The potential importance of the cerebral effects of hypoxemia in asthma. and of the central nervous system side effects of antiallergy medication, has received inadequate attention and requires more research. Failure to recognize the true signtfkance of such valid clinical observations, combined with failure to recognize the importance of the use ttf techniques to overcome the effects of the placebo, suggestion, and observer bias have led to several misconceptions concerning the role of foods and inhalants in psychiatric and somatic syndromes unassociated with atopy. It is apparent that publicity directed to such views, and the use of unorthodox or unproven “allergy” procedures, cun cause significant harm. (J ALLEI;S cLINh4MUNOL 1988;81:351-60.)

In the United Kingdom, during the last 5 or 6 years, there has been a great awakening of public interest in allergy, and food allergy in particular, fostered by considerable press and television attention. This has been associated with the rapid expansion of several

From

the Department

of Medicine,

University

Abbreviations

used

CNS: Central nervous system DB: Double-blind HVS: Hyperventilation syndrome PFA:

Pseudofood allergy

of Manchester,

Manchester, England. Received for publication September 1986. Accepted for publication October 1987. Reprint requests: D. Pearson, PhD, Department of Medicine, University Hospital of South Manchester, Nell Lane, Manchester M20 8LR, United Kingdom. *This article is based on a lecture presented at the Aspen Allergy Conference, Aspen, Cola., July 23-26, 1986.

forms of alternative medicine claiming to diagnose and treat “allergy” by a variety of dubious techniques and in a wide range of conditions, for many of which orthodox medicine has nonallergic explanations. The result has been a virtual epidemic of sufferers from PFA. This has not only harmed the victims directly 351

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Pearson

but may, by association, have led to unwarranted suspicion also being thrown on orthodox allergology. A referenced bibliography of claims made in publicity material and on television chat shows, rather than in communications to professional journals, is impossible. There is also a wide, and often extremely individual, spectrum of theories and practices. Diagnostic techniques vary from intracutaneous, sublingual, or cytotoxicity testing, hair or pulse analysis, and “applied kinesiology” to divination. ’ Sometimes impressive looking electronic devices are used. Treatment is usually by recommending avoidance or by sublingual neutralization therapy; occasionally it is by urine injection. The most identifiable and influential group within this spectrum are the clinical ecologists who have obtained very wide mass media coverage for their views through numerous popular books, press releases, and by organizing pressure groups, public meetings, and promotional tours by eminent domestic and U .S . ecologists. The impression made is that the widespread adoption in Europe of what is generally accepted in the United States as a verified “new science” is only being prevented by willful obstruction by reactionary physicians in the pay of the pharmaceutical multinationals . This impression, based on a belief structure incompatible with scientific principles,’ is relatively immaterial to two practical distinguishing features of clinical ecology: (1) that each practitioner believes that his own subjective impression, or the particular “diagnostic test” used by himself (most commonly intracutaneous provocation), is adequate proof of sensitivity, that placebo effects are irrelevant, and that DB procedures are unnecessary; indeed, failure to confirm their own views by DB procedures is taken as proof of the fallability of DB techniques, and (2) that allergy affects the brain directly and is a common, or indeed the usual, cause of undesirable behavior in children and of neuroses and psychoses in adults. Also, the gamut of somatic symptoms that commonly accompany anxiety or depression are themselves indicative of physical allergic processes. Even when such symptoms follow adverse life events, it is argued that they are actually a result of “unmasking” of food allergy and that allergy treatment is more appropriate than attention to the social or personal circumstances that triggered them. Were these to be valid, orthodox medicine could and should revolutionize its practices overnight. But if the public is being subjected to potentially hazardous misinformation, than it is the duty of a responsible profession to say so, loudly and clearly.

To obtain an objective evaluation, we need to recognize that most of the reliable data concern atopic allergic disease. Clearly, there are genuine associations between atopic manifestations, psychologic phenomena, and subjective symptoms, such as feelings of tiredness etc. We therefore need to address two questions: (1) Are associations due to causal relationships? (2) If psychologic changes can be the result of allergy, are they primary manifestations or purely secondary to extracerebral bodily functions? The second answer will determine the validity of the arguments, extrapolating data from established allergic diseases to psychiatric states without obvious physical disorder. INDIRECT MENTAL

EFFECTS OF ALLERGY

(Table I)

Hypoxia The prime physiologic consequence of asthma is hypoxemia.3 The predominant clinical features of hypoxemia are mental changes and were well established early this century. Haldane et al4 observed, “A knowledge of them is of great importance in practical medicine.” Surprisingly, the symptoms of oxygen deficiency go unacknowledged in many contemporary texts on asthma and allergy. In both experimental oxygen deprivation and asthma, marked mental changes can occur caused by cerebral hypoxia in the absence of significant distress from dyspnea. The victim is characteristically unaware of progressive disturbance; therefore, “if the anoxemia is suddenly relieved by oxygen or air, the corresponding sudden increase in powers is an intense surprise.“4 By combining findings from mountain and aerospace medicine4-’ with data on the effects of airway obstruction,3 it may be predicted that the arterial oxygen desaturation associated with falls in FEV, of 25% are likely to produce measurable mental effects in adults and that significant higher function impairment would be usual with FEV, levels of 50% of predicted values or less. Cerebral effects may occur even earlier in children in whom brain metabolism demands a much higher percentage of total body oxygen uptake. Cerebral anoxic symptoms occur with smaller degrees of arterial oxygen desaturation in asthma than in other chronic lung diseases. The differences between a subject with asthma and a subject with chronic bronchitis can be likened to differences between a flier in an unpressurized aircraft and an aclimatized mountain dweller. The subject with asthma suffering intermittent attacks does not undergo the several physiologic adaptions that minimize tissue anoxia in chronic persistent hypoxemia. Indeed, the hypocarbia char-

WLUME El NUMBER 2

acteristic of asthma will actually increase tissue anoxia, both by cerebral vasoconstriction’ and by reducing the dissociation of oxyhemoglobin.4 Classic descriptions of the mental effects of hypoxia are to be found in the works of Haldane et a1.4 and have since been amply confirmed.5‘9 Marginal acute hypoxia produces subtle degrees of impairment of consciousness with poor judgment, diminished alertness. reduced attention span, difficulty in performing intellectual tasks, in judging time, and with memory, particularly in the area of new learning. Emotional symptoms can include emotional lability, irritability, or depression. Anxiety may be a notable feature of increasing hypoxia. There may be more obvious mental slowing. irrational fixed ideas, and uncontrollable outbursts. “Without reason he may begin to laugh. sing, burst into tears, or become dangerously violent, ‘-“ A sense of fatigue is notable with more severe degrees of hypoxia, which would normally be associated with evident cyanosis. Apathy, emotional indifference, incoherence of speech, disorientation for place, person. and time, muscular twitching, tremor, or fits may develop. Perceptual distortions include illusions and hallucinations. Drowsiness progresses through to coma. The special senses are lost in a specific sequence with worsening hypoxia. Pain sensation is lost early. Hearing is maintained until a later time.4 The main symptom of chronic mild hypoxia is lethargy. The picture resembles severe fatigue with tiredness, apathy, inattentiveness, poor concentration, and delayed responding. Sleep may be reduced in quantity and quality. The clinical picture has several similarities with both depressive states and the organic brain syndrome of chronic sleep deprivation. These symptoms are actually the presenting complaint in a small number of subjects with asthma who are usually curiously unaware of the marked variations in their airways that are revealed by sequential peak flow monitoring. These patients often fail to wake despite dramatic nocturnal falls in peak expiratory flow rate. The secondary nature of the mental symptoms may be confirmed by their response to regular inhaled corticosteroid or bronchodilator therapy. Apart from understandable anxiety, the observations in objective studies of psychologic changes in the course of acute asthmatic attacks are entirely compatible with being the result of hypoxia.” Stagnant anoxic cerebral injury also appears to be the most probable explanation in old case reports”s’4 of mental symptoms, usually with focal neurologic signs, occurring in the course of severe generalized reactions to foods. Although these are still sometimes quoted

Interrelationships

TABLE

in allergy

I. Indirect Secondary

mental

anti

effects

organic brain

nseu~~ralkrgv

353

of ailergy :~yndroni~.-~

Cerebral hypoxia CNS side effects of medieatiur Corticosteroids

Antihistamines Theophylline Decongestants

/3-Adrenergic agonists Sleep deprivation

Psychologicreactions to II! health Anxiety Depression Irritability Personalily/social -l_l~

development ..-.I___

.-.-_-

as evidence for a direct brain effect of allergy, identical changes can follow any form of circulatory collapse. Side effects of antiellergy

mediition

It is now evident that most drugs used in asthma and allergic diseases can have significant CNS side effects. In addition, toxicity of large caffeine intakesI is probably the true explanation of some nonatopic physical and mental symptoms reported as being caused by tea or coffee “allergy”‘” and can also account for “hyperactive” and other disturbed behaviors in children taking cola drinks.” ” Mild caffeinelike CNS stimulation is common after initiation of theophylline therapy, appears to have little direct relationship to serum concentration” and rapidly becomes tolerated by most adults. More severe and persistent effects are associated with serum concentrations 320 mg/L” and are sometimes related to high coincident tea or coffee ingestion. A very small number of adults appear unable to tolerate normal therapeutic concentrations because of continuing agitation? headache, insomnia, or terrifying nightmares, and acute paradoxic depressive states are also recorded.“” However, about 5% of children treated may have behavioral or school problems caused by long-term theophylline therapy.” An improvement in intelligence test scores, sleeping, irritability, distracribihty, and memory, without appreciable change in controi of asthma, can follow substitution of cromolyn therapy for theophylline in these cases.” Minor degrees of elevation of mood are very common with quite moderate systemic doses of corticosteroids. This is often only noted in retrospect because the patient complains of relative anergy on returning to normality with drug withdrawal. Overt euphoria is also common in previously normal individuals on high

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doses. Comparatively low doses can produce hypomania, severe depression, or a sudden switch from one phase of manic-depressive illness to another in predisposed individuals. Sympathomimetics have amphetamine-like stimulant effects. The more severe side effects of ephedrine include euphoria, toxic confusional states, and psychoses.23,24 Although ephedrine is now rarely prescribed for asthma, it and other sympathomimetits, such as oxymetazoline, pseudoephedrine, phenlyephrine, and phenylpropanolamine are used widely in nose drops and proprietary oral cough and decongestant preparations. Acute euphoric, psychotic, and chronic hallucinatory and delusional states have been linked to abuse of both oral and topical preparations in adults.25-29Severe nightmares and daytime behavioral problems may be quite common in children taking supposedly normal doses.30 Even selective B-agonists have some central antidepressant and euphoriant effects that occasionally have led to abuse and toxic psychoses.31-33 All antihistamines, with the exception of the newly introduced terfenadine and astemizole, have marked sedative effects. These are long established, are frequently volunteered by patients or their relatives, and must have very significant effects on work, school, and examination performance at all ages, as well as on general behavior in young children. Psychologic

reactions

to physical

illness

In addition to being a feature of the organic brain syndrome of hypoxia, anxiety is also a perfectly natural human response to any potentially lethal illness. Both severe acute asthma and anaphylaxis can be terrifying experiences at any age. Depression is also an understandable reaction in any persistent illness that chronically interferes with normal day-to-day personal, family, and social life. Many of the earlier studies concerning psychologic aspects of allergy were based on now largely discredited psychoanalytic theories of psychosomatic causation, were mainly anecdotal, and usually concerned only severely affected hospitalized patients, many of whom would have been referred for psychiatric treatments, even if they had not suffered from coincident atopy.34 The studies disagreed considerably concerning the typical personality or abnormality of parent-child relationship presumed to be of etiologic significance.35 However, there was a trend to record the allergic child as insecure, with a tendency to cling to an either rejecting or overprotective mother. The older sufferer was observed as emotionally immature, lacking in self-confidence, and with feelings of inadequacy, sometimes with compensatory aggression

or repressed hostility. If such traits are accurate, they are probably more the result of predictable influences of severe atopic disease on family relationships and personality development. Exaggeration of a parent’s proper concern can lead to overprotectiveness with increased isolation and emotional dependency of the child on its parents. Parental guilt or doubts about their ability to cope may lead to rejection of the child. Exercise-induced asthma can affect a child’s ability to play with peers, cause difficulties in socialization, and generally restrict physical activity, affecting the development of self-esteem, or influence the adoption of more passive interests. The revulsion with which others often greet eczema is also likely to decrease self-esteem, impede social integration, and even be the origin of sexual difficulties which themselves can lead to further adjustment problems. Despite all the preceding statements, the most striking finding of studies of adequately sized groups of school-age and adult atopic subjects is their psychologic normality compared with control subjects.36-38 That is not to say that the former cannot be neurotic, but the frequency and range of severity of psychologic disorder is virtually identical to that in the nonallergic population.38 Small increases in psychiatric morbidity found in some studies are restricted to the subgroup with the most severe somatic disease and is entirely compatible with its being secondary to the physical disability.36s37Similar rates of maladjustment and neuroticism are found in children with severe asthma compared to children similarly limited by congenital heart disease3’ or other nonallergic physical handicaps. 36In adults, neuroticism and anxiety increase with increasing respiratory disability but are actually rather less in adults with asthma than in adults with chronic bronchitis. The situation concerning preschool children is confused both by the difficulty of delineating psychiatric syndromes in this age group and by misuse of terms, such as hyperactivity, virtually rendering them meaningless. Disordered behavior in childhood is often the result of social factors or parental psychopathology, and depressed parents who have difficulty in coping with natural exuberance may describe a normal child as pathologically overactive. Children of this age become difficult when they are ill for any reason. Clearly, crying, fidgeting, or other behavioral change may be the only outward manifestations of allergyinduced nose or skin itching, colic, or sleep disturbance in a child who cannot describe his symptoms. In some series linking “hyperactivity” to food sensitivity, the population studied has been highly atopic4’; other investigators have not recorded whether or not

VOLUME 8: YUMEER 2

the behavioral change was linked to somatic symptomatology.J2. 43 Overall, the evidence is that when significant psychiatric disorder and allergy coexist, the association is usually coincidental rather than causative. However, when the two are associated, interactions are common. The physical disease can be the source of psychologically destabilizing stress, can be the focus of disturbed ideation or behavior, or can be used as a manipulative lever. The physical disorder can also be exacerbated by the emotional state, just as it can be in psychologically normal atopic individuals. We can therefore conclude that food and inhalent allergies can indeed affect mentation, emotion, and behavior, but we can also conclude that all such reliable observations can be adequately explained by well-established processes without incriminating a direct effect of allergy on brain function, for which there is no other objective evidence. It is therefore not valid to extrapolate observations of patients with atopic diseases to patients with other disorders, and most particularly, not to psychiatric states occurring in the absence of classic allergic diseases such as asthma, eczema, and rhinitis. PSYCHOGENIC

PHYSICAL CHANGES

In contrast to evidence that psychiatric disorder is not common in allergic disease, we do have considerable evidence that the physical manifestations of atopic disease are frequently influenced by the mental state. Although most objective work has been related to asthma, it is almost certainly equally relevant to skin, nose, and gut disease. Not only may physiologic changes be initiated but also the response to physical stimuli may be modified by mental events. For example. the size of the wheal-and-flare reaction to skin tests can be altered under hypnosis,44 and exerciseinduced asthma may be prevented by suggestion.45 Psychologically induced atopic changes can be considered to fall into two main groups: purely nonspecific reactions to emotional arousal and the results of suggestion or conditioned reflexes to specific stimuli. Asthmatic, nasal, and gut reactions to emotion have been recognized since Hippocrates warned the subject with asthma to “guard against anger.” Before the beginning of this century, writers such as Salter, Trousseau, and Osler could agree that fright or violent emotion of any kind would produce a paroxysm in most, if not in all subjects with asthma. We can now provide a relatively simple explanation: It is a result of the autonomic nervous system arousal that occurs in emotional states, combined with the altered end organ responsiveness to chemical mediators that characterize atopic diseases,46.47 that is, because of their bron-

chial hyperreactivity, all subjects with asthma will bronchoconstrict with adequate emotional vagai and sympathetic outflow just as they will with inhaled so 2.4%4’1 Under these circumstances, it is easy ro understand how the fear that a supposed allergen might induce an attack can actually produce the reality and then reinforce the possibility that a subsequent exposure will also produce symptoms and lead on to a conditioned relfex. However, it is evident trom animal experiments that conditioned neurogenic bronchoconstriction can be produced without any of the characteristic biochemical abnormalities of the atopic disorder. 50. 5’ Psychogenic asthma can usually be inhibited by atropine in both humans and animals, suggesting that it is predominantly Lagally mediated 51-s1 The literature contains many studies of subjects who have reacted to paintings or photographs of plants or animals, or to artificial flowers, with nasal and eye symptoms, as well as asthma. Experimentally, about half of all subjects with asthma will consistently react with measurable bronchoconstriction to being told that they have been administered an antigen to which they are sensitive.52‘s9In their classic studies on placebo effects in allergic diseases, Graham et aI.@’ demonstrated that measurable changes in gastrointestinal motility and skin blood flow, and even nasal secretion and eosinophilia, could be induced experimentally by similar suggestions. This finding, and considerable experience with placebos in all branches of medicine during the last 30 years, have very much demonstrated the fallibility of both patients’ and physicians’ subjective impressions concerning causation. Together with emerging evidence concerning interactions between nerves and proinflammatory cells, it also implies that not even evidence of cytologic change or chemical-mediator release necessarily proves that the initiating event is physical sensitivity rather than psychologic. We are therefore left with DB provocation as the only acceptable proof of etiology in putative allergy. Statistical method is important in the design of provocation studies. First, we need to recognize that many subjects, and virtually all subjects attributing psychiatric syndromes to allergy, assume that 58% of blind provocations will be “active” and report subjective reactions to this number. Second, in studying groups of patients, we need to be cautious that group data are not corrupted by one or more atypical individual. Therefore, in studying the possible role of food allergy in, for example, angina, a statistically significant positive result for the group as a whole could be provided by a single individual who recognized a

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TABLE II. Syndromes to allergy: Symptoms chronic hyperventilation

misattributed of

General Fatigue Weakness Excessivesweating Poor exercise tolerance Neurologic Central Dizziness Giddiness Poor concentration Blurring or tunneling of vision Hyperacusis Syncope Peripheral Numbness Paraesthesia Other sensory disturbances,including itching, buming, “swollen” hands or feet Cardiovascular Palpitations Tachycardia Chest pains PseudoischemicECG changes Raynaud’s phenomenon Respiratory Dyspnea, paroxysmal or exertional “Asthma” Gastrointestinal Dry mouth Aerophagia Bloating Flatus Heartburn Musculoskeletal Muscle pains Tremors Cramps Tetany Psychiatric Depersonalization Hallucinations Anxiety Panic attacks Phobias, including agoraphobia

food because it gave him urticaria. We therefore need to examine very homogeneous groups from which other proven hypersensitivity diseases have been excluded or, preferably, establish the statistical probability of genuine organic sensitivity for each food separately, for each individual. In practice, this requires six to eight provocations for each food.

PSEUDOFOOD ALLERGY In 1980, we embarked on a project that was specifically designed to find positive evidence to confirm that psychologic symptoms are commonly the result of food sensitivity. This we singularly failed to do, but instead we have had to conclude that such claims are positively damaging to a group of psychologically vulnerable patients. In our initial study,6’ we examined 23 consecutive

adult patients who, at the time of their presentation to an allergy clinic in the United Kingdom, considered themselves to have food allergy. They were put through a food-exclusion reintroduction protocol similar to that used by workers reporting high frequencies of food sensitivity, but in addition, each incriminated food was subsequently tested in a series of six DB provocations. At the same time, the patients were subjected to an independent psychiatric examination, and psychologic symptoms were followed during the course of provocations with a standardized rating scale. We found that the sort of techniques used could

indeed confirm food hypersensitivity in patients presenting with various combinations of asthma, eczema, urticaria, rhinitis, and gastrointestinal changes but that organic food sensitivity could not be confirmed in 19 other patients. None of the former, but all but one of the latter, were independently classified as “psychiatric cases.” Although a few of the patients in whom food hypersensitivity could not be confirmed were classifiable as atopic on the basis of previous medical history and skin tests, they, like the nonatopic members of the group, were polysymptomatic with multiple subjective somatic symptoms. Rix et a1.62then demonstrated that these patients were virtually identical in terms of both the range and severity of their psychiatric illness to nonselected new outpatient referrals to the psychiatric department of the same hospital. Our findings are probably applicable to those of

the United States. King63 found only two of 26 patients attending a bioecologic disease center to be within the normal range on all pathology scales of the Minnesota Multiphasic Personality Inventory. We have since suggested the term PFA for the false conviction that one suffers from food allergy.64 This may cause confusion with nonimmunologic allergomimetic organic reactions, sometimes described as pseudoallergic reactions. However, it is very difficult to know what else to call this syndrome, or indeed what to call the activities of the more obviously bogus practitioners. In children, the infliction of supposed allergies on the offspring may be a feature of parental psychiatric problems, that is, the allergic form of Meadow’s (Munchausen’s) syndrome by proxy,65 or

VOLLJME 81 NUMBER 2

the healthy parents of a child with a genuine atopic or nonatopic disease may receive improper advice that it is due to allergy.’ The situation evokes serious cause for conem. The risks of new physical diseases as a direct result of dietary restriction are very significant in adults as well as children. h6,67No patient with supposed food allergy observed at our clinic who has been subjected to dietary assessment has had a diet conforming to U.K. minimum recommended daily intakes (which are considerably less than those in the United States for several minerals and vitamins). There are theoretical risks to some of the more bizarre forms of therapy, such as urine injection,6x and the risks of fatal anaphylaxis with unproven investigatory techniques, such as intracutaneous provocation, are more immediate. In addition, false diagnosis of allergy can prevent or fatally delay investigation of other physical conditions (in our experience, from scabes to cancer). We also have some evidence that the persistent belief in allergy has a negative effect on the prognosis of the underlying psychiatric disorder.62 From a personal series of 55 cases, it is possible to offer some observations on PFA. Although, often because of the nature of the problem, not all cases have been subjected to formal assessment by a psychiatrist, the results of longer experience agrees with the conclusion that there is a wide general range of underlying psychiatric diagnosis.62 A small number of cases can be classified as hysteric, somatization disorder, or Munchausen’s syndrome. PFA appears relatively rare in young male subjects, but when it does occur, features suggestive of schizophrenia are common. Older male subjects are virtually always moderately to severely depressed. However, most of our patients are female, most commonly 35 to 50 years of age, and most have mild to moderate depression. About half are suffering from a relatively short-term illness, sometimes with an obvious precipitating cause; the rest provide evidence of lifelong neurotic personality problems. Apart from occasionally very bizarre symptoms in schizoid male subjects, the presenting picture is often very similar. The patients are usually grossly polysymptomatic with somatic symptoms referable to multiple organ systems. Lethargy, tiredness, weakness, or “just not well” are almost universal. Many patients volunteer overtly psychologic symptoms as features of their allergy; other patients strenuously deny the mood change or anxiety, of which they exhibit every external sign. Four physical symptom complexes predominate and can coexist. These are (1) the myriad symptoms of chronic hyperventilation (HVS),69 (2) irritable bowel syndrome, usually distinguishable

Interrelationships

in allergy and pseufloaitergy

TABLE III. Syndromes misattributed allergy: Symptoms of irritable bowel syndrome

357

fc’;

Gastrointestinal General Abdominal pain Distension Audible bowel sounds Lower Diarrhea

Constipation Alternating constipation and diarrhea Excessive flatus Exaggerated gastrocolic reflex Upper

Aerophagia, belching Dysphagia Early satiety Nausea

Vomiting Genitourinary Pelvic pain Dyspareunia

Frequency Hesitancy Nocturia Extra abdominal Tiredness Unpleasant taste Referred pain (eg, to back)

from food-intolerance syndromes by the characteristic episodic constipation, and often by an associated urethral syndrome,” (3) the somatic concomitants of depression, including disturbances in appetite.“. 72and (4) symptoms directly attributable to starvation, which can include unpleasant experiences on sudden reintroduction of calorie (particularly carbohydrate) loads (Tables II, III, and IV). There are also four main patterns of association (or lack of it) between symptoms and food. (1) The patients remain convinced that they have an unidentified food allergy despite a total failure to identify any precipitating agent by even the most vigomus investigation. One of our patients maintained such a conviction after multiple exclusion diets and even after two separate self-imposed 1Cday periods of taking only bottled mineral water had failed to produce any change in his symptoms. (2) All symptoms are attributed to one or more specific foods, but there is actually no change in symptom frequency. These patients will often say they are fine as long as they avoid the food(s) in question. The lack of actual change may

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TABLE IV. Common

symptoms

in depression

Mood Depression Lack of emotiona response Loss of “feeling” Pessimisticjudgment General loss of interest Unhappiness Weeping Lack of confidence Lowered self-esteem Anxiety Apprehension Tension Irritability Inability to concentrate Outbursts of temper Palpitations Sweating Dry mouth Sleep disturbance Inability to fall asleep Waking unrefreshed Unpleasant dreams Nocturnal waking Early morning waking Daytime drowsiness Anergy Lack of energy Fatigability Tired all the time “Completely exhausted” “Drained of energy” Appetite disturbance Increased appetite, comfort in eating Decreasedappetite, loss of interest in food Reduced enjoyment of food Food tastes bad

Refusal to eat Secondaryto delusions Weight loss Libido disturbance Loss of sexual interest Impotence Frigidity Other somatic symptoms Constipation “Heaviness” or emptiness in abdomen Dizziness Tim&us Dyspnea Pain, generalized Chest Abdomen Hypochondriasis Preoccupation with bodily functions Specific hypochondriacal delusions Belief in “something physical” to account for illness

only be revealed by analysis of symptom diaries, or the patient may presume inadvertent dietary indiscretion, or blame adulteration of his food by others (usually the food and chemical industries). (3) Short-term placebo-induced remissions after each new “allergy” is diagnosed. The most recent food eaten is blamed for each inevitable recurrence, but no prior diagnosis is ever reviewed. Dietary restriction is progressive until finally the patient takes only water, and then even this will be incriminated. (4) Psychogenic physical reactions are developed to specific foods. Apart from psychologically mediated asthma, virtually all psychogenic food reactions are hyperventilatory. Half of our patients with PFA have the chronic HVS and are therefore at risk of developing acute exacerbations after food. The evidence that attacks are psychogenic is that responses to open administration are not repeatable when the same food is given in an identical manner apart from its identity being obscured, and attacks are produced by misleading the subject into believing that they have been given the food when they have not. Evidence that typical symptoms are indeed hyperventilatory is that responses to open provocation are associated with hypocarbia and alkalosis, that they can be prevented by the patient breathing CO,-enriched air, and that they can be reproduced by voluntary hyperventilation. There are four important factors in the genesis of the problem. First, in nearly every case, there has been a deficiency in orthodox medical management, either a failure to diagnose or treat a recognizable syndrome or a failure to communicate adequately with the patient. Second, the provision of misleading information, either directly from supposed “allergists” or indirectly via publicity and books. Third, a tendency to prefer a physical to a psychiatric diagnosis associated with an exaggeration of the view that the latter in some way implies blame or lack of personal worth. Finally, the emotional connotations that almost anything to do with food appears to have in so many different cultures. In these patients, food allergy achieves the psychiatric status of an overvalued idea.62 But the literature from the 1920s to the present day very much suggests that the concept also has an unusual capacity to produce the same distortion of judgment in many physicians who start to investigate it. CONCLUSION

The relationship between psyche and soma is particularly complex in the case of atopic allergic conditions. Evaluation of the evidence according to preconceived views and failure to recognize the possibility of both psychosomatic and somatopsychic processes in the same conditions have historically been the source of several misconceptions.

VOLUME 81 NUMBER 2

In evaluating both the role of organic hypersensitivity and of new diagnostic and therapeutic techniques, it is crucial that we recognize the mechanisms by which psychologic processes can both produce physical changes and the misattribution of causation generally. Adequate DB study designs are the only means of overcoming such effects. The several mechanisms by which allergic diseases can lead to psychologic changes have generally been poorly acknowledged. We need to be more aware of the frequency of higher mental function impairment in moderate to severe asthma and of the nervous system side effects of many of the drugs that we prescribe. It appears very likely that misinterpretation of the significance of observations of such changes have been the origin of several erroneous conclusions. Whatever the results of future research, it is presently evident that the wide publicity alloted to unproven claims about the influence of food on childhood behavior and adult nonatopic physical and psycholgic disease, and the use of dubious diagnostic techniques, have caused significant harm to some individuals. Given the very real dangers, the ethics of continuing to use routinely diagnostic and therapeutic procedures whose efficacy is generally considered disproven, or at best unproven, must be questioned. The opinions in this article are the author’s own, but they have been formed by considerable collaboration and many long discussions with Dr. Keith Rix, to whom there are apologies for any unintentional plagiarisms.

REFERENCES 1. David TJ. The overworked or fraudulent diagnosis of food allergy and food intolerance in children. J R Sot Med 1985:78(suppl 5):21-31. 2. Randolph TG. Historical development of clinical ecology. In: Dickey LD. Clinical ecology. Springfield, Ill.: Charles C Thomas, 1976:9- 17. 3. McFadden ER, Lyons HA. Arterial-blood gas tension in asthma. N Engl J Med 1968;278:1027-32. 4. Haldane JS, Priestley JG. Respiration. Oxford: University Press, 1935. 5. Tune GS Psychological effects of hypoxia: Review of certain literature for the period 1950-1963. Percept Mot Skills 1964;19:551-62. 6. Denison DM, Ledwith F, Poulton EC. Complex reaction times at simulated cabin altitudes of 5,000 feet and 8,000 feet. Aerospace Med 1966:37:1010-13. 7. Cahoon RL. Simple decision making at high altitude. Ergonomics 1972;15:157-63. 8. Emsting I. Prevention of hypoxia-acceptable compromises. Aviat Space Environ Med 1978;49:495-502. 9. Harper AM, Glass HI. Effect of alterations in the arterial carbon dioxide tension on the blood flow through the cerebral cortex at normal and low arterial pressure. J Neurol Neurosurg Psychiatry 1965;28:449-52. 10. Weiss JH. Mood states associated with asthma in children. J Psychosam Res 1966;10:267-73.

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11. Kennedy F. Cerebral symptoms induced I>\ angmneurotrc oedema. Arch Neural Psychiatry lY26:i5:28 G? 12. Vaughan WT, Hawke IK. Angioneurotrc e&ma wlrh some unusual manifestiation. J ALLERG) I93 I :2- I Cd 13. Pardee I. Two cases demonstrating allergic i-caci~on\ in the nervous system. J Nerv Ment Dis 1938:X8:Xr-91. 14. Staffiere D, Bentolila L. Levist I.. Hemiplegia and allergic symptoms following ingestion of certam t’on,!i :ann X!lcrpy 1952:10:38-9. 15. Greden JF. Anxiety or caffeinism: a diagno+i!~ dilemma. Am J Psychiatry 1974;131:1089-92. 16. Finn R, Cohen NH. Food allergy hit ?)I ?ICWJ~‘~l:ancet 1978;1:426-8. 17. Silver W. Insomnia. tachycardia. and cola &mbi Pediatrics 1971;47:635. 18. Elkins RN, Rapaport JL, Zahn TP Buchsbaum MS, Weingastner H, Kopin IJ, Langer D, Johnson C 4cute effects of caffeine in normal prepubertal boy\ Am f i’kychiaty 1981; 138:178-83. 19. Ellis EF. Theophylline toxicity. I z%r’, F.KIi\ c’: I\ lnhwnot~ 1985;76:297-301. 20. Murphy MB, Dillon A, Fitzgerald MY Theopbylline and depression. Br Med J 1980;281:1322. 21. Fumkawa CT. Shapiro GG, DuHamei T. Wrlmer L. Pierson WE, Bierman CW. Learning and behaviour problems assoclated with theophylline therapy. Lancet 1984.1:62 1. 22. Furukawa CT, DuHamel T, Weimer L, Shapiro GG. PIerson WE, Bierman CW. Cognitive and behavioral findings in children taking theophylline [in print! 1 AI I.EK<;+- CI.I?J

IMMUNOL. 23. Roxanas MG. Spalding J. Ephedrine abuse p,ychosis Med J Aust 1977;2:639-40. 24. Henidge CF. A’Brook MF. Ephedrine psyclro
360

38. 39. 40.

41.

42. 43.

44.

45.

46.

47.

48.

49.

50. 5 1.

52.

53.

54. 5.5.

Pearson

asthma in children. III. Psychological and social components. Br Med J 1973;4: 16-20. Zealley AK, Aitken RCB, Rosenthal SV. Asthma: a psychological investigation. Proc Roy Sot Med 197 1;64:825-9. Neuhaus EC. A personality study of asthmatic and cardiac children. Psychosom Med 1958;20:181-6. Oswald NC, Waller RE, Drinkwater J. Relationship between breathlessness and anxiety in asthma and bronchitis: a comparative study. Br Med J 1970;2:14-7. Egger J, Carter CM, Graham PJ, Gumley D, Soothill JF. Controlled trial of oligoantigenic treatment in the hyperkinetic syndrome. Lancet 1985;1:540-4. Weiss B, Williams JH, Margen S, et al. Behavioural responses to artificial food colors. Science 1980;207: 1487-8. Swanson JM, Kinsbourne M. Food dyes impair performance of hyperactive children on a laboratory learning test. Science 1980;207:1485-7. Fry L, Mason AA, Pearson RS. Effect of hypnosis on allergic skin responses in asthma and hay fever. Br Med J 1964; 51:1145-g. Godfrey S, Silverman M. Demonstration of placebo response in asthma by means of exercise testing. J Psychosom Res 1973;17:293-7. Lobitz WC, Campbell CJ. Physiologic studies in atopic dermatitis (disseminated neurodermatitis): local cutaneous response to intradermally injected acetylcholine and epinephrine. Arch Dermatol Syph 1953;67:575-89. Kaliner M, Shelhamer JH, David PB, Smith Ll, Ventner JC. Autonomic nervous system abnormalities and allergy. Ann Intern Med 1982;96:349-57. Sheppard D, Wong WS, Uehara CF, Nadel JA, Boushey HA. Lower threshold and greater bronchomotor responsiveness of asthmatic subjects to sulfur dioxide. Am Rev Respir Dis 1980;122:873-8. Koenig JQ, Pierson WE, Horike M, Frank R. Bronchoconstrictor responses to sulfur dioxide or sulfur dioxide plus sodium chloride droplets in allergic, nonasthmatic adolescents. J ALLERGY CLIN IMMUNOL 1982;69:339-44. Ottenberg P, Stein M, Lewis J, Hamilton C. Learned asthma in the guinea pig. Psychosom Med 1958;20:395-400. Justesen DR, Braun EW, Farrison RG, Pendleton RB. Pharmacological differentiation of allergic and classically conditioned asthma in the guinea pig. Science 1970;170:864-6. McFadden ER, Luparello T, Lyons HA, Blecker E. Psychological factors and bronchial asthma. NY State J Med 1971;71:2161-5. Spector S, Luparello TJ, Kopetzky MT. Response of asthmatics to metacholine and suggestion. Am Rev Respir Dis 1976;113:43-50. Dekker E, Groen J. Reproducible psychogenic attacks of asthma. J Psychosom Res 1956;1:58-67. Dekker E, Pelser HE, Groen J. Conditioning as a cause of asthmatic attacks. J Psychosom Res 1957;2:97-108.

J. ALLERGY CLIN. IMMUNOL. FEBRUARY 1988

56. Luparcllo T, Lyons HA, Bleecker ER, McFadden ER. Intluences of suggestion on airway reactivity in asthmatic subjects. Psychosom Med 1%8;30:819-25. 57. McFadden ER, Luparello TJ, Lyons HA, Bleecker E. The mechanism of action of suggestion in the induction of acute asthmatic attacks. Psychosom Med 1969;31:134-43. 58. Luparello TJ, Leist N, Lourie CH, Sweat P. The interaction of psychologic stimuli and pharmacologic agents on airway reactivity in asthmatic subjects. Psychosom Med 1970;32: 509-13. 59. Horton DJ, Suda WL, Kinsman RA, Souhdrada J, Spector SL. Bronchoconstrictive suggestion in asthma: a role for airways hyperreactivity and emotions. Am Rev Respir Dis 1978;117: 1029-38. 60. Graham DT, Wolf S, Wolff HG. Changes in tissue sensitivity associated with varying life situations and emotions: their relevance to allergy. J ALLERGY 1950;21:478-86. 61. Pearson DJ, Rix KJB, Bentley SJ. Food allergy: how much in the mind? Lancet 1983;1:1259-61. 62. Rix KJB, Pearson DJ, Bentley SJ. A psychiatric study of patients with supposed food allergy. Br J Psychiatry 1984; 145:121-6. 63. King DS Can allergic exposure provoke psychological symptom? A double-blind test. Biol Psychiatry 1981;16:3-19. 64. Pearson DJ, Rix KJB. Allergomimetic reactions to food and pseudo food allergy. In: Dukos P, Kallos P, Schlumberger HD, West GB, eds. PAR: pseudoallergic reactions, vol 4. Basel: S Karger AG, 1985:59-105. 65. Warner JO, Hathaway MK. Allergic form of Meadow’s syndrome (Munchausen by proxy). Arch Dis Child 1984;59: 151-6. 66. Tripp JH, Francis DEM, Knight JA, Harries JT. Infant feeding practices: a cause for concern. Br Med J 1979;2:707-9. 67. Tarnow-Mordi WO, Moss C, Ross K. Failure to thrive owing to inappropriate diet free of gluten and cow’s milk. Br Med J 1984;289:1113-4. 68. Executive Committee of the American Academy of Allergy. American Academy of Allergy: position statementscontroversial techniques. J ALLERGY CLIN IMM~JNOL 1981; 67:333-g. 69. Magarian GJ. Hyperventilatory syndromes: infrequently recognised common expressions of anxiety and stress. Medicine (Baltimore) 1982;61:219-36. 70. Whorwell PJ, McCallum M, Creed FH, Roberts CT. Noncoionic features of irritable bowel syndrome. Gut 198627: 37-40. 71. Bums BH, Nichols MA. Factors related to the localisation of symptoms to the chest in depression. Br J Psychiatry 1972;121:405-9. 72. Brenner B. Depressed affect as a cause of associated somatic problems. Psycho1 Med 19799737-46.