the evolution of allergies in childhood
TRANSCRIPT
The Journal of Asthma Research. Vol. 4, No. 4, June, 1967
The Evolution of Allergies in Childhood
M. MURRAY PESHKIN, M.D.
For those who wish to gain an appreciation and understanding of the evolu- tion of allergies in childhood, only a searching study of the various scientific disciplines of the past can lead to productive results and stiniulate thinking. A summary review of the historic development of allergic complexes since 1900 should provide a satisfactory presentation of the subject.
At the dawn of the 20th century came the discovery of the remarkable phenomenon of anaphylaxis. Foreshadowing the current theories of allergic diseases, the concept of anaphylaxis developed during the first quarter of the present century, although several observations which harnionizc with present- day views were recorded earlier.
Experimental anaphylaxis induced in animals was reported by Magendie in 1839 and by Flexner in 1894, but the first serious consideration of the subject in man really began with Blackley in 1873. In each instance these earlier observations were apparently lost sight of and were rediscovered sub- sequently when the term “anaphylaxis7’ and experimental data were analyzed by Richet and Portier in 1902. Local anaphylaxis was investigated by Arthus in 1903, and allergy in man through serum sickness was described by Pirquet and Schick in 1905. The site of the anaphylactic reaction, or “shock organ”, as Doerr (1909) called it, was different in the three animals in which the phe- nomenon mas studied.
Doerr, in 1926, who was the first to attempt classification of hypersensi- tiveness in the hunian being, believed with Zinsser in 1927 that the similari- ties between allergy and anaphylaxis are of more significance than are the differences. Continued research has largely diminished the significance of these differences, which were formerly assumed by Coca and his associates to be of fundamental importance. Coca himself, in 1920, continued to insist on the rigid separation of atopy (a term he coined as apposed to allergy) from anaphylaxis, basing his contention on the establishment of heredity as the sole determining factor (1926-1927). Cooke and his associates in 1917 initi- ally embraced the concept of atopy, only to abandon i t for the term “al- lergy” in the later years of their lives. We may expect some allergists to regard the current conceptualized evolution of allergy and the proposals for a broadened understanding of the various allergic conditions, especially asthma, as traitorous to the pristine purity of their “old time atopic dogma.”
Modern Aspects of Allergy
The modern treatments of eczema, asthma and hay fever are immunologi- cally based. Skin tests for allergy have been solely responsible for the con-
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sidei.able progress made in the management of allergies as they affect man. Allergy is more common in childhood than in adult life.
Since allergy in nian has its roots in childhood, even though syil~ptorlls may remain a t the subclinical level during that period, our responsibility to be- come acquainted with the effccts of scientific advances on the various aspects of childhood allergy is obvious. Our immediate concern may be better under- stood if we realize that of the 60,000,000 children under 15 years of age in this country, a t least 10 per cent, or 6,000,000 children, are afflicted with an allcrgic disease in need of treatment. The United States National Health Survey reported seven years ago that there were a t least 2,000,000 children afflicted with asthma and hay fever. Today with the increasing incidence of allergic disease i t is safe to estimate from available published figures that 3,000,000 children have asthma and/or hay fever. Of these 3,000,000 children, a t least 8 per cent, or 240,000, have chronic intractable asthma. This allergy is a common American ailment, and i t is our responsibility to diagnose i t early and treat i t intelligently. The majority of infants with eceenia develop asthma, or hay fever, or both, between the ages of 1 and 6 years. From 70 to 80 per cent of the specifically untreated children with hay fever develop asthma.
Dcspite a voluminous literature which contains a vast accumulation of val- uable material, there is still much controversy concerning the role that aller- genic sensitization plays, espccially in the direct and contributory etiology of asthma, which is the major allergy syndrome. A discussion of asthma is in essence a discussion of all allergies. More controversy was generated with the definition and classification of allergic asthma. Later, the controversy and con- iusion were compounded when Coca introduced the more confining term, “atopic” asthma. Does this imply that there is only one kind of asthma, presumably atopic asthma? Does this mean that there are other kinds of asthma? And if there are, can they be differentiated from atopic asthma? Is there justification in holding to the concept that atopic asthma is the only true asthma, denoting the pres- a c e of an antigen-antibody complex? Moreover, this school of thought main- tains that atopy is a state of hypersensitization occurring only in man, is based on heredity, and is never acquired. According to this school, other kinds of asthma, including allergic asthma, are not regarded as true asthma. If this con- tention were valid, one could deduce that asthma, other than atopic asthma, is non-immunologically based, meaning that the antigen-antibody complex not only cannot be demonstrated but also docs not exist in non-atopic asthma.
These statements clearly embody the concept that the diagnosis of atopic asthma cannot be finalized until after the patient has been proven beyond question to be skin-test positive to specific atopens. Such a conclusion implies that the atopic asthma can be diagnosed only after the causal atopens have bcen brought to light.
Moreover, if the diagnosis of atopic asthma was based initially on the his- tory and/or physical examination of the patient, then, a t best, this could be regarded only as a presumptive diagnosis of atopic asthma.
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EVOLUTIOX O F ALLERGIES IN CHILDHOOD 255
It may be eniphasized a t this time that the basic criteria for diagnosing asthma in children, a t any age, rests on clinical and not laboratory tests. Al- lergy te,its are done to determine what causes the asthma, not to find out whether a child has asthma.
Today, we know much more about the disease and its treatment, but can we say with certainty that we have a clear grasp of the asthmatic syiidrorne with special reference to the recognition of its earliest symptoms? At what stage of the total symptom complex commonly accepted as the asthmatie state can one begin to define asthma? Does the degree of asthmatic symptoms, no matter how mild or how transient, have any bearing on arriving a t a realistic defini- tion? What are the pathognomic signs of asthma? Has the practical application of allergic principles in the treatment of asthma brought about a change in the concept and definition of asthma?
However, in the light of our present knowledge, every effort should be made to determine the exciting causes of asthma. The younger the patient and the sooner appropriate treatment is begun, the better are the prospects for con- trolling the condition and enabling the child to lead a normal, useful aiid happy life. Thus one of our major problems is the deciphering of the various words which imply different kinds of asthma or deny the presence of asthma when it truly exists. We are confronted with such terms as bronchial asthma, true al- lergic bronchial asthma, atopic asthma, asthmatic bronchitis, extrinsic and intrinsic asthma, bacterial asthma, infectious asthma, obstructive asthma, and para-asthma. This imposing list would be incomplete without the timeworn clichk, “All is not asthma that wheezes.”
It is well known that during the early years of childhood acute respiratory infections occur more frequently in children genetically predisposed to asthma than in those not allergenetically disposed. The initial wheezes following an acute respiratory infection are commonly diagnosed as asthmatic bronchitis. The monotonous repetition of this episode is finally labeled “infectious or bacterial asthma”. Here, infections in infants are the primary irritants that trigger the asthmatic symptoms, but i t is erroneous to conclude that the infant has a primary bacterial asthma.
It must be conceded that no child is immune from acute respiratory infec- tions. Moreover, less than 5 per cent of the total childhood population ini- tially reveals symptoms of “asthmatic bronchitis” after acute respiratory in- fections. The incidence of positive skin test reactions to allergens in the total childhood population is 10 per cent. These two groups of children show a com- parable incidence of 90 per cent of positive skin test reactions to noii-viable allergens. Over 80 per cent of the children in the two groups show a positive antecedent family history of allergy. Moreover, i t is significant that after spe- cific hyposensitization treatment, the majority of children with asthmatic bron- chitis either become less susceptible to respiratory infections or are not ad- versely affected with asthmatic symptoms during the course of the infection. Most children who are tagged with asthmatic bronchitis and are denied hyposensitization treatment struggle along with their breathing difficulties for
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several years before “true” allergic asthma or atopic asthma supervenes. Then typical asthma attacks appear independently of acute respiratory infections.
Definition of Asthma Based on Symptoms and Physical Signs To know what asthma is, we must trace i t from its inception and follow its
evolutionary course to its severest stage. Bronchial asthma may be defined on the basis of many scientific disciplines.
The syndrome of asthma cannot be confined to only one stage of the symptom coniplex. I t is simpler, more realistic and more advantageous to speak of an asthmatic syndrome and to consider the attack of asthma as one phase of the syndrome. Asthma may be broadly defined as a recurring dyspnea, usually more marked in expiration and associated with wheezing. This definition read- ily lends itsclf to the earlier stages of the disease. Asthma can he divided into three distinct stages:
1. Respiratory or retrosternal oppression is a subjective symptom com- plained of only by older children. It consists of a sense of tightness in the chest and difficulty in drawing a deep breath. No wheezing is present during this stage.
2. The wheezing or pre-attack stage is frequently wrongly diagnosed as bronchitis or asthmatic bronchitis. The attack of asthma is absent during this stage. The type of asthma, with insidious onset, is characterized by wheez- ing and dyspnea, after repeated attacks of allergic rhinitis and/or acute res- piratory infection.
3. The attack stage represents the peak of the asthmatic syndrome. This stage of asthma is too typical to require description.
I n children up to two years of age, the prominent symptoms of acute asthma may be an alarming increase in the rate of respiration, with coughing spasms or troublesome croup and fever. This condition is often wrongly diagnosed as acute pneumonia.
When an attack of asthma persists for more than 48 hours, in spite of re- peated injections of bronchodilators and other drugs, it is then called status asthmaticus.
When asthma is protracted over a long period of time, despite specific al- lcrgic treatment, and symptoms are continual or are only partially or briefly relieved with the aid of various drugs, it is called chronic intractable asthma. The continual need for corticosteroids to maintain a state of less severe asthma in these patients corroborates the diagnosis. No matter what may be the rea- bon for the control state of severe asthma in a child who has been denied ade- quate formal treatment for a t least one year, the diagnosis of intractable asthma in this instance is unjustified.
Status asthmaticus and intractable asthma are merely exaggerated third stages of asthma.
The etiology, degree, duration and kind of asthmatic symptoms a patient reveals do not alter my concepts in support of the definition of bronchial asthma as aforementioned.
Roentgenoscopy of the lungs does not reveal any characteristic findings.
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EVOLUTION O F ALLERGIES I N CHILDHOOD 257
Psychogenic Aspects of Asthma
The role of profound psychologic disturbance cannot be ignored in any dis- cussion of bronchial asthma or for that matter any allergic syndrome. Such a role especially concerns those of us who focus our attention on the kind of asthmatic child admitted to a convalescent asthma home.
Many psychiatrists and psychologists continue to maintain that a,sthina 1s
initially a psychosomatic illness, and most of them also contend that the asth- matic child possesses a special type of structured asthmatic personality. Time does not permit a detailed discussion of these concepts, which I consider not to be founded on factual evidence and therefore to be unrealistic. n’ere these con- cepts accepted as valid, then asthma would have to be classified as non- immunologic. A clearer understanding and more meaningful approach to the role of the psyche in asthma may result if i t is recalled that asthma initially (priruarily) in almost all instances is immunologically based (even when skin tests to allergens are negative and antigen-antibody reactions fail to he demon- strated). I have yet to observe a single case of asthma caused primarily by a psychophysiologic disorder. Moreover, asthma has not been experinlentally induced in any person who is not asthmatogenetically predisposed.
It is important to make an early diagnosis of intractable asthnia, because environmental tension, which is a product of the reaction of the child to his parents, seems to be the secondary contributory factor in most cases. Separa- tion of the child from his own home environment (“parentectomy”) is of prime consideration in the operation of an institution especially designed for the treatment of such children.
The failure of modern conventional treatment leaves the intrnctahly asth- matic children pulmonary cripples and candidates for sudden and unex- pected death. The incidence of death during attacks of asthma in this group of children varies from 0.9 per cent to 1.7 per cent.
It can be concluded that the physician who is expected to treat allergies appropriately must be alerted to the recent and not so recent studies of immune response to antigens of every conceivable origin. The physician must recall that the allergic reaction consists largely of increased capillary permeability with resultant edema, and i t would follow tha t allergic reaction can occur wherever there is vascular tissue. This means that all areas of the body, all organs and all tissues can be involved.
This means too that the symptoms may vary widely, depending upon the location of the reaction. The reaction may mimic many organic conditions. Our responsibility to become acquainted with the effects of advances in science on the various aspects of allergy in children is obvious. At this juncture, I am obliged to ask: is the fundamental definition of allergy and its antigen-anti- body theory, given to the world 60 years ago by Pirquet and Schick, in need of modification? This is a moot question. Nevertheless, the allergist must learn and understand the language of the various scientific disciplines, since they have opened up new and wider avenues of approach to the study of various diseases not heretofore associated with specific antigen-antibody seiisitizatioli
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phenomena. In this milieu of scientific achievemcnt, antibodies are literally seen to dance in the blood plasma, and, with fluorescence, can be observed af - fectionately hugging the antigen of tissue cells with the kiss of death. IS i t any wonder then that we today in retrospect regard the basic concept of allergy of Pirquet and Schick as evidence of much more than research minds a t work? Can we not say that the fundamental definition and theory of allergy of Pir- quet and Schick still hold?
Ahout a ciecade ago, Schick again reviewed the physiologic and pathologic hasis of allergy with the idea of especially clarifying the role of allergy in immunity. Hc emphasized the need to note the differences between the defen- sive response in the allergic individual to living bacterial antigens or their derivations and to inert non-viable, non-reproducing allergens.
\Ye may well be on the threshold of important fundamental discoveries of the “how” and “why” of allergic response. The missing links in the chain are being vigorously searched for by workers in various scientific disciplines, as well as by workers concerned with the effects of feeling and emotions on the rnetabolic processes governing function of the body cells.
Various rcsearch workers have stepped up their scientific pace with unabated enthusiasm. The terms “antigen” and “antibody” have taken on a new look. We allergists are living in exciting times. How else can we describe the present scene?
Now to reconsider the diagnosis and treatment of the various allergies, there are, to be sure, many questions which remain unanswered. I n the meantime, theories are necessary and arc helpful in providing the ground from which to advance. We work with what we have, and progress is sometimes painful and slow. We are still in the complicated stages of the study of allergy because we have not yet discovered the basic mechanism of the allergic state. It is quite possible that when the fundamental mechanism of allergy is learned, we may be able to treat patients on a unitarian basis alone and not concern ourselves with the precise details of history-taking, sensitization tests, and specific treatment. But until that fundamental mechanism is discovered, we must continue to use our special detailed knowledge and diagnose and treat our patients as we are doing now.
You may differ in whole or in part with my address this afternoon, but you may get a factual picture of conditions as they are, and i t is hoped that you may be able to utilize these divergent views as a basis of thinking which may add to your usefulness and progress in this field.
450 West End Avenue New York City
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