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Food allergy: Lessons from the past
THE JOURNAL OF
ALLERGY AND
CLINICAL V O L U M E 69
NUMBER 3
Commentary Food allergy: lessons from the past Charles D. May, M.D. Quechee, Vt.
Because finite studies are customarily published as the observations are completed, general principles and unifying concepts may be difficult to discern. When the contributions to a field of study are viewed in retrospect and in their entirety, the concepts and common understanding that influenced the kind of observations made and the interpretations of the findings may be' more apparent. Periodic attempts to identify obstacles to scientific progress in the past should serve to lessen the clutter in the path of further advancement of knowledge. The need for this exercise in the field of food allergy has been urgent, and this is an effort to that end. (J ALLERGY CL1N IMMUNOL 69:255, 1982.)
To be unaware of the lessons from history is to risk repeating the errors of the past. The life span of one reaching the age of 78 years in 1980 would have encompassed the entire period since the discovery of anaphylaxis by Portier and Riche0 in 1902--likewise the period of accumulation of existing knowledge of food sensitivity, in the modem sense of adverse reactions based on immunologic mechanisms. While there were noteworthy contributions along the way, progress was hampered by a number of obstacles, including confused concepts and lack of objectivity in clinical observations. Indeed, the field of food allergy may be taken as a model of obstruction to the advancement of learning. The current growing enthusiasm for food "allergy" as an explanation for an astonishing array of
Reprint requests to: Charles D. May, M.D., P. O. Box 272, Quechee, VT 05059.
complaints should be viewed historically to avoid further obstacles in the way of scientific comprehension of adverse reactions to foodstuffs. What follows is not a comprehensive review but a consideration of selected articles published in the past that appear to have been most influential in molding common opinion about food sensitivity. The nature of the obstacles encountered and why confusion came., to prevail will be revealed. Unless the lessons to be drawn are heeded by investigators, practitioners, editors, and officials of medical organizations, the errors and confusion of the past will be perpetuated. Some of the earliest clinical and experimental studies of food sensitivity set examples of excellence that, had they been followed faithfully, would have precluded confusion and a sound state of knowledge would have been established sooner. Six years after the original description of anaphylaxis in experimental animals, the earliest clinical diagnoses of sensitivity reactions to food were made by analogy between the manifestations in animals and
0091-6749/82/030255+05500.50/0 9 1982 The C. V. Mosby Co.
Vol. 69, No. 3, pp. 255-259
256
May
the symptoms of patients. For example, in 1908, Hutinel2 reported severe, immediate-type reactions to cow's milk in artificially fed infants, which were recognized as the counterpart of anaphylaxis in animals. Between 1911 and 1914, simultaneous with the first clinical descriptions of anaphylactic reactions to foods, Richet himeself, 3 his son, 4 and one of his students 5 undertook to produce food sensitivity in experimental animals. Animals were sensitized to foods via the gastrointestinal tract, so that subsequent oral challenge produced anaphylactic reactions. Actually, the first experimental demonstration of sensitization via the gastrointestinal tract had been published in 1906 by Rosenau and Anderson. 6 During a search for the cause of reactions to injections of antisera, just being introduced into therapy of diphtheria, they sensitized guinea pigs to horse serum and beef meat by oral feeding. Pioneer studies of food sensitivity by Schloss 7 reported in 1912 have never been surpassed in concept, design, execution, or interpretation. Introduction of allergens into the skin to detect sensitization had been proposed in 18738 and applied in isolated cases of food sensitivity around 1910, but Schloss was the first to evaluate skin tests for diagnosis of food sensitivity in a sophisticated manner. He subjected the materials he used in skin tests (scratch technique) to procedures, with proper controls, that ensured their specificity and reliability; he examined fractions of foodstuffs for the active ingredients, determined the size and characteristics of cutaneous responses associated with clinical reactions to the corresponding foods, demonstrated that the sensitization could be passively transferred to animals, and conducted trials of oral desensitization. He subjected the active antigenic materials to various manipulations to ascertain stability and chemical characteristics. Schloss and associates carried on extensive investigations for more than a decade, unearthing many of the essentials of current knowledge of immunologic sensitivity to foods by 1920. 9 They had also encountered problems still vexing to investigators and clinicians. Schloss realized that all immunologic reactions to foods were not accounted for by immediate-type (reaginic) sensitization. He clearly described the nonreaginic enteropathies in children and carried out critical studies of serum antibodies in this group, anticipating recent studies of their diagnostic usefulness. What Schloss and his associates did not do was to apply the concept of concentration-response (a certain degree of sensitivity must exist before a reaction to a given quantity of food will be great enough to be observed clinically). Consequently, they looked upon positive skin tests unassociated with clinical symp-
J. ALLERGY CLIN. IMMUNOL. MARCH 1982
toms as "false positives." This misconception has discolored the clinical management of food sensitivity ever since. Lesson 1." General physiologic principles should not be overlooked in interpretation of clinical and laboratory observations in immunologic disorders. In 1919, a monograph entitledAnaphylaxie Alimentaire 1~ was published by Charles Richet, Jr., and associates, which summarized the earliest European clinical and experimental studies. This publication is rich in clinical observations, trustworthy because they were almost entirely derived from cases of overt, severe reactions to foods. The categories of symptoms described are close to classifications of food sensitivity in use today. Discussions of pathogenesis are limited and neglectful of immunologic aspects, considering that the exemplary studies of Schloss had appeared in 1912 in the United States. A large part of the confusion about food sensitivity came from puzzlement over what were called "false positive" and "false negative" results in skin tests, thereby discrediting a major diagnostic tool. This left the clinician without a handy means for objective substantiation of tentative diagnoses based on histories of reactions to foods. This dilemma was aggravated by a misunderstanding of the proper use and interpretation of the intradermal technique for performing skin tests. This technique was widely used after being adopted by some influential allergists in the 1920s. 11 The intradermal technique detects the lesser degrees of sensitization compared with the scratch technique, and so inevitably more positive intradermal skin tests were found not to be associated with clinical reactions; instead of the proper interpretation that such positive tests were indicative of asymptomatic but true sensitization, they were considered "false positive." This fallacious interpretation, coupled with the use of undefined and unstandardized materials in skin testing, made confusion inevitable. Lesson 2: Tests performed and interpreted improperly are liable to be misleading, and unless the underlying principle is clearly comprehended, confusion in clinical application will be unavoidable. About 1915, enthusiasm began to mount for food allergy as an explanation for an astounding assortment of complaints. Many articles were published containing reports of single cases or small groups of selected patients and claiming that food allergy caused not only the well-established manifestations of allergy but also migraine, epilepsy, nervous complaints, arthritis, intestinal toxemia, cyclic vomiting, fatigue, apathy, dullness, excitement, hyperactivity, scattered spasms and pains, and indigestion.'~-la
VOLUME 69
Food allergy
257
NUMBER 3
There were no restraints on the confidence of physicians in their clinical impressions because it had not yet been shown that double-blind food challenges are necessary to exclude bias and prejudice of observers and to identify psychologic reactions. Nor was the power of the imagination (placebo effect) generally considered in evaluation of the effects of dietary manipulations. Lesson 3: Double-blind food challenge is the best way to avoid deception by clinical impressions. By 1930 the stage was set for overwhelming confusion: the usefulness of skin tests had been discounted, confidence in clinical impressions was high, the distinction between asymptomatic and symptomatic sensitization was not generally made, the placebo effect was not considered in evaluation of therapeutic manipulations, basic immunologic knowledge was limited, and no one resorted to blind challenges to eliminate bias and the power of the imagination as well as the mimicry of neuroses. In 1930, Rowe of the United States and Richet of France combined forces to proclaim their conviction that food "allergy" was undoubtedly responsible for many vague, subjective, chronic manifestations. 2~ The support offered was a collection of case reports from the literature and their clinical experience, without any restraint from objective substantiation. The notion received elaboration in a monograph in 1932. 2' Because this tempting explanation for a host of problems that were frustrating practitioners was set forth with impressive authority, a steady stream of disciples have followed with similar anecdotal reports. Among the mass of clinical impressions, some valid observations may well be buried, or truly toxic reactions may be disguised by the misnomer "allergic." The clinical accounts are so ill defined, uncontrolled, and unsubstantial that the views held by Rowe and Richet and their followers have been viewed with skepticism in scientific circles. Lesson 4: Useful knowledge could be lost in a chaos of myths unless pains are taken to subject clinical impressions to scientific evaluation. In scientific circles, serious attention should not be given to impressionistic reports. Recent objective studies 2z-24 employing doubleblind food challenges do not point to frequent occurrence of nervous manifestations and vague chronic disorders as features of immunologic or true food sensitivity, or as a consequence of chemical intoxication by food constituents or contaminants. More objective studies are required to determine whether such manifestations occur uncommonly. One of the most difficult clinical impressions to confirm objectively is the common report that symp-
toms are often delayed in appearance for days after ingestion of a suspected food." If eiToneous associations are frequently made in cases of immediate-type reactions, how much more likely are mistaken associations between foods eaten and symptoms observed days afterwards? Prolonged direct observation under strictly controlled conditions during performance of blind challenges and dietary manipulations will be necessary to learn whether or how often claims of delayed reactions are true. There were several comprehensive textbooks with extensive chapters on food allergy published between 1930 and 1950. 25-28 The authors were prestigious allergists exhibiting impressive critical judgment in general. Although the chapters on food allergy contain considerable information that deserves attention today, the discussions naturally reflect the contemporary literature and therefore exhibit the deficiencies already described. The textbooks did not appear to relieve the frustrations or to dispel the confusion that had engulfed the field of food allergy. The period after 1950 may be characterized as one of growing confusion and discontent about food sensitivity among practitioners and lack of interest by investigators, and publications on the subject were relatively few. In recent years an awakening of interest in scientific research in food sensitivity has emerged, but shades of the past linger on. Comprehensive reviews of current knowledge have appeared elsewhere.2,,, 23 From the foregoing account of highlights of the history of food allergy, it is clear that the obstacles that plagued efforts to advance knowledge of food sensitivity have beset all of medicine, namely: (1) overconfidence in clinical impressions, (2) failure to improve the accuracy of observations by procedures for elimination of bias, (3) faulty performance and interpretation of diagnostic tests, (4) fuzzy concepts based on false assumptions, (5) inadequate appreciation of the power of the imagination--the placebo effect, 29 (6) tendency to believe that whatever relief occurs after a therapeutic maneuver is a result of the therapy, (7) susceptibility to fashion in explanations of vague complaints, and (8) a desire to have knowledge come easily. The probability of encountering these obstacles in the future through repetition of the errors of the past would be lessened by curbing certain tendencies that interfere with learning from the lessons of the past, for example: (1) lack of historical perspective, (2) incompetence in weighing evidence, and (3) the faulty habit of adoption of opinion by feeling rather than reasoning from facts. Some additional protection from error may be af-
258
May
J, ALLERGY CLIN. IMMUNOL. MARCH 1982
forded by a common understanding of the roles of the various categories of healers. The disorders of mankind may be visualized in the following scheme:
Physical Body Science
Mental Psyche Psychology/magic
Spiritual Soul Religion
The Greeks properly conceived these as aspects of an integrated individual. Separation of these facets into areas of interest and expertise is the doing of m o d e m h e a l e r s - - p h y s i c i a n s , psychiatrists/magicians, clergy. The old conflict between science and religion is settled, but the interface between science and psychiatry/magic is still troublesome. Scientific medicine requires expertise in objective observation, controlled experimentation, and critical evaluation in the management of physical disorders. Illnesses based on psychologic and spiritual disturbances call for different emphasis. Recognizing that the division is not absolute and realizing that few healers have expertise in all areas, each category of healers should face the limitations of their expertise and strive to apply their skills appropriately. Mischief arises when unscientific healers attempt to move in scientific circles, for example, when an unscientific healer seeks credence from scientific physicians for his " b e l i e f s " and " f e e l i n g s " as to which illnesses can be explained by food sensitivity. A plea could be made for greater tolerance among the different categories of healers if they would only practice appropriate application of their different skills. From these considerations and the lessons learned from the past, some recommendations to prevent obstacles to further progress can be offered: 1. Beware of self-confidence in clinical impressions. 2. Except for severe reactions, use some objective means to determine whether a suspected reaction is physical in nature, in contradistinction to psychologic or spiritual. Double-blind food challenge is the definitive procedure. 3. Identify an immunologic basis before applying the term " f o o d sensitivity." 4, Just as rigorously, separate toxic (chemical) reactions from psychologic or spiritual disturbances, preferably by double-blind challenge. Identify the toxic agent before being satisfied with this explanation. 5. Do not attempt to correlate faulty clinical impressions and imprecise laboratory tests, and avoid spurious conclusions about tests being "false posit i v e " or "false n e g a t i v e , " 6. Use test materials that have had the antigen
content verified for reliability in specificity, potency, and stability. 7. Utilize current immunologic and physiologic knowledge in formulation of guiding concepts. 8. Respect the power of the imagination in evaluation of therapy by controlling for the placebo effect. 9. Beware of fashions in medicine, especially in assigning vague complaints to hypothetical causes. 10. In the practice of healing, keep in mind the need to appropriately match expertise with the nature of the illness. 11. Be on the alert for infiltration of scientific organizations and publications by healers cloaked with the language but not the substance of the scientific approach. 12. The ultimate solution of clinical problems depends on sound basic research. REFERENCES
1. Portier PG, Richet C: De l'action anaphylactique de certain venins. CR Soc Biol 54:170, 1902. 2. Hutinel: Intolerance pour de lait et anaphylaxie chez les nourrissons. La Clinique vol. 3, April 10, 1908. 3. Richet C: De l'anaphylaxie alimentaire. CR Soc Biol 70:44, 1911. 4. Laroche CT, Richet C Jr, Saint-Girons F: Anaphylaxie alimentaire lactee. CR Soc Biol 70:169, 191I. 5. Barnathan L: L'anaphylaxie alimentaire. Thesis, Facult6 de Medecine de Pads, Paris, 1911. 6. Rosenau MJ, Anderson JR: A study of the cause of sudden death following the injection of horse serum. Hygienic Laboratory Bull. No. 29, 1906, Public Health and Marine-Hospital Service of the United States. 7. Schloss OM: A case of allergy to common foods. Am J Dis Child 3:341, 1912. 8. Btackley CH: Experimental researches on the causes and nature of catarrhus aestivus. London, 1873, Bailli~re, Tindall, and Cox. 9. SchlossOM: Allergy in infants and children. Am J Dis Child 19:433, 1920. 10. Laroche G, Richet C Jr, Saint-Girons F: Anaphylaxie alimentaire. Pads, 1919 (English translation, Universityof California Press, Berkeley, 1930). 1I. Cooke RA: Cutaneous reactions in human hypersensitiveness. Proc NY Pathol Soc 2118, 1921. 12. Hoobter BR: Some early symptoms suggesting protein sensitization in infancy. Am J Dis Child 12" 129, 1916. 13. Turnbull JA: Food allergies in connection with arthritis. Boston Med Surg J 191:438, 1924. 14. Duke WW: Food allergy as a cause of bladder pain. Arch Intern Med 1:178, 1922. 15. Duke WW: Chronic illness often due to common articles of a diet. Arch Intern Med 32:298, 1923. 16. Ward JF: Protein sensitization as a possible cause of epilepsy and cancer. NY Med J 115:592, 1922. 17. Andresen AFR: Gastrointestinal manifestations of food allergy. Med J Rec 122:271, 1925. 18. Eyerman CH: Allergic headache. J ALLERGY11:106, 1931. 19. Alvarez WC: Food sensitivities and conditions that may be
VOLUME 69 NUMBER 3
confused with it. Med Clin North Am 12:1589, 1929. 20. Rowe AH, Richet C ills: Manifestations nerveuses chroniques de l'anaphylaxie alimentaire. J Med Fr 19:170, 1930. 21. Rowe AH: Food allergy. Philadelphia, 1932, Lea & Febiger. 22. May CD, Bock SA: A modern clinical approach to food hypersensitivity. Allergy 33:166, 1978. 23. Bock SA: Food sensitivity: a critical review and practical approach. Am J Dis Child 134:973, 1980. 24. Bernstein M, Day HD, Welsh A: Double-blind challenge in diagnosis of food hypersensitivity in adults, in Proceedings of the 37th Annual Meeting of the American Academy of AI lergy, San Francisco, 1981.
Food allergy 259 25. Rackemann FM: Clinical allergy. New York, 1931, Macmillan Book Co., Inc. 26. Coca AF, Walzer M, Thommen AA: Asthma and hay fever. Springfield, II1., 1931, Charles C Thomas, Publisher. 27. Vaughan WT: Practice of allergy. St. Louis, 1939, The C. V. Mosby Co. 28. Cooke RA, editor: Allergy in theory and practice. Philadelphia, 1947, W. B. Saunders Co. 29. Wolf S: Placebos. Proc Assoc Res Nerv Ment Dis 37:147, 1959.
ALLERGY AND
CLINICAL V O L U M E 69
NUMBER 3
Commentary Food allergy: lessons from the past Charles D. May, M.D. Quechee, Vt.
Because finite studies are customarily published as the observations are completed, general principles and unifying concepts may be difficult to discern. When the contributions to a field of study are viewed in retrospect and in their entirety, the concepts and common understanding that influenced the kind of observations made and the interpretations of the findings may be' more apparent. Periodic attempts to identify obstacles to scientific progress in the past should serve to lessen the clutter in the path of further advancement of knowledge. The need for this exercise in the field of food allergy has been urgent, and this is an effort to that end. (J ALLERGY CL1N IMMUNOL 69:255, 1982.)
To be unaware of the lessons from history is to risk repeating the errors of the past. The life span of one reaching the age of 78 years in 1980 would have encompassed the entire period since the discovery of anaphylaxis by Portier and Riche0 in 1902--likewise the period of accumulation of existing knowledge of food sensitivity, in the modem sense of adverse reactions based on immunologic mechanisms. While there were noteworthy contributions along the way, progress was hampered by a number of obstacles, including confused concepts and lack of objectivity in clinical observations. Indeed, the field of food allergy may be taken as a model of obstruction to the advancement of learning. The current growing enthusiasm for food "allergy" as an explanation for an astonishing array of
Reprint requests to: Charles D. May, M.D., P. O. Box 272, Quechee, VT 05059.
complaints should be viewed historically to avoid further obstacles in the way of scientific comprehension of adverse reactions to foodstuffs. What follows is not a comprehensive review but a consideration of selected articles published in the past that appear to have been most influential in molding common opinion about food sensitivity. The nature of the obstacles encountered and why confusion came., to prevail will be revealed. Unless the lessons to be drawn are heeded by investigators, practitioners, editors, and officials of medical organizations, the errors and confusion of the past will be perpetuated. Some of the earliest clinical and experimental studies of food sensitivity set examples of excellence that, had they been followed faithfully, would have precluded confusion and a sound state of knowledge would have been established sooner. Six years after the original description of anaphylaxis in experimental animals, the earliest clinical diagnoses of sensitivity reactions to food were made by analogy between the manifestations in animals and
0091-6749/82/030255+05500.50/0 9 1982 The C. V. Mosby Co.
Vol. 69, No. 3, pp. 255-259
256
May
the symptoms of patients. For example, in 1908, Hutinel2 reported severe, immediate-type reactions to cow's milk in artificially fed infants, which were recognized as the counterpart of anaphylaxis in animals. Between 1911 and 1914, simultaneous with the first clinical descriptions of anaphylactic reactions to foods, Richet himeself, 3 his son, 4 and one of his students 5 undertook to produce food sensitivity in experimental animals. Animals were sensitized to foods via the gastrointestinal tract, so that subsequent oral challenge produced anaphylactic reactions. Actually, the first experimental demonstration of sensitization via the gastrointestinal tract had been published in 1906 by Rosenau and Anderson. 6 During a search for the cause of reactions to injections of antisera, just being introduced into therapy of diphtheria, they sensitized guinea pigs to horse serum and beef meat by oral feeding. Pioneer studies of food sensitivity by Schloss 7 reported in 1912 have never been surpassed in concept, design, execution, or interpretation. Introduction of allergens into the skin to detect sensitization had been proposed in 18738 and applied in isolated cases of food sensitivity around 1910, but Schloss was the first to evaluate skin tests for diagnosis of food sensitivity in a sophisticated manner. He subjected the materials he used in skin tests (scratch technique) to procedures, with proper controls, that ensured their specificity and reliability; he examined fractions of foodstuffs for the active ingredients, determined the size and characteristics of cutaneous responses associated with clinical reactions to the corresponding foods, demonstrated that the sensitization could be passively transferred to animals, and conducted trials of oral desensitization. He subjected the active antigenic materials to various manipulations to ascertain stability and chemical characteristics. Schloss and associates carried on extensive investigations for more than a decade, unearthing many of the essentials of current knowledge of immunologic sensitivity to foods by 1920. 9 They had also encountered problems still vexing to investigators and clinicians. Schloss realized that all immunologic reactions to foods were not accounted for by immediate-type (reaginic) sensitization. He clearly described the nonreaginic enteropathies in children and carried out critical studies of serum antibodies in this group, anticipating recent studies of their diagnostic usefulness. What Schloss and his associates did not do was to apply the concept of concentration-response (a certain degree of sensitivity must exist before a reaction to a given quantity of food will be great enough to be observed clinically). Consequently, they looked upon positive skin tests unassociated with clinical symp-
J. ALLERGY CLIN. IMMUNOL. MARCH 1982
toms as "false positives." This misconception has discolored the clinical management of food sensitivity ever since. Lesson 1." General physiologic principles should not be overlooked in interpretation of clinical and laboratory observations in immunologic disorders. In 1919, a monograph entitledAnaphylaxie Alimentaire 1~ was published by Charles Richet, Jr., and associates, which summarized the earliest European clinical and experimental studies. This publication is rich in clinical observations, trustworthy because they were almost entirely derived from cases of overt, severe reactions to foods. The categories of symptoms described are close to classifications of food sensitivity in use today. Discussions of pathogenesis are limited and neglectful of immunologic aspects, considering that the exemplary studies of Schloss had appeared in 1912 in the United States. A large part of the confusion about food sensitivity came from puzzlement over what were called "false positive" and "false negative" results in skin tests, thereby discrediting a major diagnostic tool. This left the clinician without a handy means for objective substantiation of tentative diagnoses based on histories of reactions to foods. This dilemma was aggravated by a misunderstanding of the proper use and interpretation of the intradermal technique for performing skin tests. This technique was widely used after being adopted by some influential allergists in the 1920s. 11 The intradermal technique detects the lesser degrees of sensitization compared with the scratch technique, and so inevitably more positive intradermal skin tests were found not to be associated with clinical reactions; instead of the proper interpretation that such positive tests were indicative of asymptomatic but true sensitization, they were considered "false positive." This fallacious interpretation, coupled with the use of undefined and unstandardized materials in skin testing, made confusion inevitable. Lesson 2: Tests performed and interpreted improperly are liable to be misleading, and unless the underlying principle is clearly comprehended, confusion in clinical application will be unavoidable. About 1915, enthusiasm began to mount for food allergy as an explanation for an astounding assortment of complaints. Many articles were published containing reports of single cases or small groups of selected patients and claiming that food allergy caused not only the well-established manifestations of allergy but also migraine, epilepsy, nervous complaints, arthritis, intestinal toxemia, cyclic vomiting, fatigue, apathy, dullness, excitement, hyperactivity, scattered spasms and pains, and indigestion.'~-la
VOLUME 69
Food allergy
257
NUMBER 3
There were no restraints on the confidence of physicians in their clinical impressions because it had not yet been shown that double-blind food challenges are necessary to exclude bias and prejudice of observers and to identify psychologic reactions. Nor was the power of the imagination (placebo effect) generally considered in evaluation of the effects of dietary manipulations. Lesson 3: Double-blind food challenge is the best way to avoid deception by clinical impressions. By 1930 the stage was set for overwhelming confusion: the usefulness of skin tests had been discounted, confidence in clinical impressions was high, the distinction between asymptomatic and symptomatic sensitization was not generally made, the placebo effect was not considered in evaluation of therapeutic manipulations, basic immunologic knowledge was limited, and no one resorted to blind challenges to eliminate bias and the power of the imagination as well as the mimicry of neuroses. In 1930, Rowe of the United States and Richet of France combined forces to proclaim their conviction that food "allergy" was undoubtedly responsible for many vague, subjective, chronic manifestations. 2~ The support offered was a collection of case reports from the literature and their clinical experience, without any restraint from objective substantiation. The notion received elaboration in a monograph in 1932. 2' Because this tempting explanation for a host of problems that were frustrating practitioners was set forth with impressive authority, a steady stream of disciples have followed with similar anecdotal reports. Among the mass of clinical impressions, some valid observations may well be buried, or truly toxic reactions may be disguised by the misnomer "allergic." The clinical accounts are so ill defined, uncontrolled, and unsubstantial that the views held by Rowe and Richet and their followers have been viewed with skepticism in scientific circles. Lesson 4: Useful knowledge could be lost in a chaos of myths unless pains are taken to subject clinical impressions to scientific evaluation. In scientific circles, serious attention should not be given to impressionistic reports. Recent objective studies 2z-24 employing doubleblind food challenges do not point to frequent occurrence of nervous manifestations and vague chronic disorders as features of immunologic or true food sensitivity, or as a consequence of chemical intoxication by food constituents or contaminants. More objective studies are required to determine whether such manifestations occur uncommonly. One of the most difficult clinical impressions to confirm objectively is the common report that symp-
toms are often delayed in appearance for days after ingestion of a suspected food." If eiToneous associations are frequently made in cases of immediate-type reactions, how much more likely are mistaken associations between foods eaten and symptoms observed days afterwards? Prolonged direct observation under strictly controlled conditions during performance of blind challenges and dietary manipulations will be necessary to learn whether or how often claims of delayed reactions are true. There were several comprehensive textbooks with extensive chapters on food allergy published between 1930 and 1950. 25-28 The authors were prestigious allergists exhibiting impressive critical judgment in general. Although the chapters on food allergy contain considerable information that deserves attention today, the discussions naturally reflect the contemporary literature and therefore exhibit the deficiencies already described. The textbooks did not appear to relieve the frustrations or to dispel the confusion that had engulfed the field of food allergy. The period after 1950 may be characterized as one of growing confusion and discontent about food sensitivity among practitioners and lack of interest by investigators, and publications on the subject were relatively few. In recent years an awakening of interest in scientific research in food sensitivity has emerged, but shades of the past linger on. Comprehensive reviews of current knowledge have appeared elsewhere.2,,, 23 From the foregoing account of highlights of the history of food allergy, it is clear that the obstacles that plagued efforts to advance knowledge of food sensitivity have beset all of medicine, namely: (1) overconfidence in clinical impressions, (2) failure to improve the accuracy of observations by procedures for elimination of bias, (3) faulty performance and interpretation of diagnostic tests, (4) fuzzy concepts based on false assumptions, (5) inadequate appreciation of the power of the imagination--the placebo effect, 29 (6) tendency to believe that whatever relief occurs after a therapeutic maneuver is a result of the therapy, (7) susceptibility to fashion in explanations of vague complaints, and (8) a desire to have knowledge come easily. The probability of encountering these obstacles in the future through repetition of the errors of the past would be lessened by curbing certain tendencies that interfere with learning from the lessons of the past, for example: (1) lack of historical perspective, (2) incompetence in weighing evidence, and (3) the faulty habit of adoption of opinion by feeling rather than reasoning from facts. Some additional protection from error may be af-
258
May
J, ALLERGY CLIN. IMMUNOL. MARCH 1982
forded by a common understanding of the roles of the various categories of healers. The disorders of mankind may be visualized in the following scheme:
Physical Body Science
Mental Psyche Psychology/magic
Spiritual Soul Religion
The Greeks properly conceived these as aspects of an integrated individual. Separation of these facets into areas of interest and expertise is the doing of m o d e m h e a l e r s - - p h y s i c i a n s , psychiatrists/magicians, clergy. The old conflict between science and religion is settled, but the interface between science and psychiatry/magic is still troublesome. Scientific medicine requires expertise in objective observation, controlled experimentation, and critical evaluation in the management of physical disorders. Illnesses based on psychologic and spiritual disturbances call for different emphasis. Recognizing that the division is not absolute and realizing that few healers have expertise in all areas, each category of healers should face the limitations of their expertise and strive to apply their skills appropriately. Mischief arises when unscientific healers attempt to move in scientific circles, for example, when an unscientific healer seeks credence from scientific physicians for his " b e l i e f s " and " f e e l i n g s " as to which illnesses can be explained by food sensitivity. A plea could be made for greater tolerance among the different categories of healers if they would only practice appropriate application of their different skills. From these considerations and the lessons learned from the past, some recommendations to prevent obstacles to further progress can be offered: 1. Beware of self-confidence in clinical impressions. 2. Except for severe reactions, use some objective means to determine whether a suspected reaction is physical in nature, in contradistinction to psychologic or spiritual. Double-blind food challenge is the definitive procedure. 3. Identify an immunologic basis before applying the term " f o o d sensitivity." 4, Just as rigorously, separate toxic (chemical) reactions from psychologic or spiritual disturbances, preferably by double-blind challenge. Identify the toxic agent before being satisfied with this explanation. 5. Do not attempt to correlate faulty clinical impressions and imprecise laboratory tests, and avoid spurious conclusions about tests being "false posit i v e " or "false n e g a t i v e , " 6. Use test materials that have had the antigen
content verified for reliability in specificity, potency, and stability. 7. Utilize current immunologic and physiologic knowledge in formulation of guiding concepts. 8. Respect the power of the imagination in evaluation of therapy by controlling for the placebo effect. 9. Beware of fashions in medicine, especially in assigning vague complaints to hypothetical causes. 10. In the practice of healing, keep in mind the need to appropriately match expertise with the nature of the illness. 11. Be on the alert for infiltration of scientific organizations and publications by healers cloaked with the language but not the substance of the scientific approach. 12. The ultimate solution of clinical problems depends on sound basic research. REFERENCES
1. Portier PG, Richet C: De l'action anaphylactique de certain venins. CR Soc Biol 54:170, 1902. 2. Hutinel: Intolerance pour de lait et anaphylaxie chez les nourrissons. La Clinique vol. 3, April 10, 1908. 3. Richet C: De l'anaphylaxie alimentaire. CR Soc Biol 70:44, 1911. 4. Laroche CT, Richet C Jr, Saint-Girons F: Anaphylaxie alimentaire lactee. CR Soc Biol 70:169, 191I. 5. Barnathan L: L'anaphylaxie alimentaire. Thesis, Facult6 de Medecine de Pads, Paris, 1911. 6. Rosenau MJ, Anderson JR: A study of the cause of sudden death following the injection of horse serum. Hygienic Laboratory Bull. No. 29, 1906, Public Health and Marine-Hospital Service of the United States. 7. Schloss OM: A case of allergy to common foods. Am J Dis Child 3:341, 1912. 8. Btackley CH: Experimental researches on the causes and nature of catarrhus aestivus. London, 1873, Bailli~re, Tindall, and Cox. 9. SchlossOM: Allergy in infants and children. Am J Dis Child 19:433, 1920. 10. Laroche G, Richet C Jr, Saint-Girons F: Anaphylaxie alimentaire. Pads, 1919 (English translation, Universityof California Press, Berkeley, 1930). 1I. Cooke RA: Cutaneous reactions in human hypersensitiveness. Proc NY Pathol Soc 2118, 1921. 12. Hoobter BR: Some early symptoms suggesting protein sensitization in infancy. Am J Dis Child 12" 129, 1916. 13. Turnbull JA: Food allergies in connection with arthritis. Boston Med Surg J 191:438, 1924. 14. Duke WW: Food allergy as a cause of bladder pain. Arch Intern Med 1:178, 1922. 15. Duke WW: Chronic illness often due to common articles of a diet. Arch Intern Med 32:298, 1923. 16. Ward JF: Protein sensitization as a possible cause of epilepsy and cancer. NY Med J 115:592, 1922. 17. Andresen AFR: Gastrointestinal manifestations of food allergy. Med J Rec 122:271, 1925. 18. Eyerman CH: Allergic headache. J ALLERGY11:106, 1931. 19. Alvarez WC: Food sensitivities and conditions that may be
VOLUME 69 NUMBER 3
confused with it. Med Clin North Am 12:1589, 1929. 20. Rowe AH, Richet C ills: Manifestations nerveuses chroniques de l'anaphylaxie alimentaire. J Med Fr 19:170, 1930. 21. Rowe AH: Food allergy. Philadelphia, 1932, Lea & Febiger. 22. May CD, Bock SA: A modern clinical approach to food hypersensitivity. Allergy 33:166, 1978. 23. Bock SA: Food sensitivity: a critical review and practical approach. Am J Dis Child 134:973, 1980. 24. Bernstein M, Day HD, Welsh A: Double-blind challenge in diagnosis of food hypersensitivity in adults, in Proceedings of the 37th Annual Meeting of the American Academy of AI lergy, San Francisco, 1981.
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