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Common Sense in Allergy: Relation to Specific Treatment
COMMON SENSE IN ALLERGY Relation to Specific Treatment WALTER
S.
BURRAGE,
M.D., F.A.C.P. \)
TREATMENT in the allergic diseases is perhaps less standardized than ill any other group of medical conditions. This is not surprising where the fundamental cause of the allergic state is still unknown and where many possible sensitizing substances and a multiplicity of "shock organs" may lead to the appearance of different types of symptoms in various parts of the body. To these factors must be added a wide variation in technic and in interpretation of the typical methods of diagnostic procedure, namely the skin tests. Variation in the stand· ardization of extracts used for both diagnosis and treatment is likewise confusing, for some clinics employ a total protein, others a total nitrogen basis on which to determine the strength of their materials. Such considerations emphasize the desirability of a careful evaluation of the allergic picture as a whole, keeping in mind the relationship of proposed allergic therapy to the general well-being of the patient. Diagnosis in allergy must be both differential and etiologic. The differential diagnosis should be considered first, for all are not necessarily allergic who sneeze, wheeze or itch. In the majority of instances, however, the patient has made his own correct diagnosis when he first comes to his physician and states that he is suffering from asthma, hay fever or hives. It is the etiologic diagnosis that is of paramount importance, for only in the careful search for the underlying trigger mechanism which sets off the patient's symptoms are we able to apply intelligently types of treatment which give the best chance of success. Various weapons are at hand for an attack upon this etiologic or specific diagnosis. The most important of these is the history. It is usually possible to determine whether the patient falls into the hypersensitive group by the use of a modified detective technic coupled with a guided third degree questioning. Are his symptoms characteristic of allergy? Does he admit past or present manifestations of allergy other than his present important symptoms? Has he a positive family history for allergy? One or more leads may thus likewise be obtained as to the possible nature of the offending substance. Are the symptoms seasonal so that they may coincide with the pollination of trees in spring, the
From the Allergy Clinics of the Massachusetts General and Newton-Wellesley Hospitals . .. Assistant Physician, Massachusetts General Hospital; Allergist, Newton-Wel!esley Hospital; Assistant in Medicine, Harvard University. 1131
1132
WALTER S. BUlU\AGE
grasses in summer, or the weeds in fall? Do they run beyond the pollen seasons with Hare-ups between them, suggesting molds as causative agents? Or are they present only with "colds" in winter? Are animals members of the family? What is the bedding made of? Is there evidence that foods have bothered recently or in the past? What is the patient's occupation; what his avocations? Can these be related to his symptoms? How about his medicines; what of nervous tension? These and often many other questions must be answered and recorded before any attempt is made to confirm one's clinical suspicions by skin tests. How many tests should be done; by what methods; how should they be interpreted; what reliance placed upon their results? The reply to these questions could fill many pages. Even allergists would disagree upon the conclusions. As is the case in surgical technic, the answers depend upon the individual experience of the doctor, as well as upon the history which each patient presents, his probable degree of sensitiveness, and the potency of the testing materials. Certain principles based upon common sense are too often overlooked in the enthusiasm of the hunt. Scratch tests are harmless; they will never kill the patient. Intradermal tests are more delicate, of undoubted value, but are potential dynamite and should be used in experienced hands in suitable dilutions in modest numbers at anyone sitting. They should not be done until a careful history has warned the operator of the degree of sensitivity which he is likely to expect. The interpretation of skin tests is a difficult problem. It must be remembered that skin tests may be positive where there is no evidence of clinical sensitivity to the substance tested, and negative in cases of hypersensitiveness. Normal people frequently have skin tests which can be called "positive." Allergic people sometimes have negative skin tests. Moreover, one does not need to use a magnifying glass to detect a positive test. It is important to appreciate that the finding of positive skin tests which coincide with proved clinical sensitivity varies statistically in different types of cases. It is high, for instance, in seasonal hay fever, less so in perennial inhalant allergy, lower still in food allergy, and even lower in urticaria. What may we say then in favor of the value of skin tests as diagnostic weapons in allergy? They are valuable adjuncts with which to try to prove the leads that our allergic history has provided and they occasionally unearth allergens which clinical trial elimination proves to be of importance. The liability of skin tests must be appreciated as well as their assets. The importance of making the specific diagnosis has been mentioned without emphasizing the fact that such a procedure is an integral part of treatment as well; for treatment in allergy must be based upon either elimination of the offending allergen or immunization against it by desensitization-either specific or nonspecific in nature. Trial elimination of suspected offending substances therefore becomes an integral part
COMMON SENSE IN ALLERGY
1133
of the specific treatment of many cases of allergy. It is in the control of this often laborious procedure of trial elimination that constant level-headed caution must be exercised to make sure that the general welfare of the patient is not sacrificed. The following two cases illustrate types of difficulty not infrequently encountered in this group. CASE I.-Mrs F. P. B., a slender woman of 61, had had a vague history of indigestion for two months, when a friend advised her to have skin tests done. These were said to be positive to about forty foods. It is of interest that the patient stated that she was unable to see any red areas about the scratch tests on her arms reported as positive by her physician. A test-negative diet was ordered. Her symptoms did not improve and she lost weight. She was retested four months later and was told that her "chemistry had changed" and that some of the previous tests had become negative, others positive. Another diet was prescribed. When first seen in the clinic nine months after the onset of her symptoms she had lost 25 pounds in weight, looked emaciated, and was obviously extremely nervous. Her vague gastrointestillal symptoms had increased. Inquiry as to her diet during her previous treatment showed that she had become suspicious of most foods and was living largely on noodle soup and crackers. Physical examination was negative except for evidence of weight loss. Gastrointestinal and gallbladder x-rays were negative; gastric acidity and blood studies were normal with a 1 per cent blood eosinophilia. A psychiatric evaluation revealed no evidence of neuropsychiatric disease, although it was evident that her dietary problem was very much on her mind. Skin tests by both the scratch and intradermal methods were negative. She gave no history of other manifestations of possible past or present allergy or of clear-cut food idiosyncrasy. There was no positive family history for allergy. The patient was advised that no evidence of food allergy could be found and she was given a well-rounded normal diet to follow. This proved no easy matter, however, as the seed of distrust in her food tolerance had been deeply planted. Months of reassurance and dietary readjustments were required before her confidence was restored. Six months later she had regained her weight and had almost lost her gastrointestinal symptoms upon a normal diet.
Comment.-This woman was 60 years old at the time of the onset of her symptoms-late in life for the beginning of food allergy. Multiple positive skin tests by the scratch method are uncommon in such cases. The inability of the patient to observe any positive reactions and the subsequent negative retesting in this clinic confirms the impression that the skin tests were originally interpreted with a magnifying glass technic. Disregarding the scanty evidence for food allergy here, this case stresses the fact that any type of trial·elimination diet should be checked frequently from the standpoint of sound medical progress. A similar danger is present, not alone in cases of food allergy, but with inhalant allergy as well. CASE H.-B. D. G., a 41 year old male author, entered the clinic complaining of symptoms consistent with the diagnosis of vasomotor rhinitis of twelve months' duration. Six months prior to admission, his case had been reviewed elsewhere. Careful otolaryngological studies then had demonstrated no infectious or faulty
1134
WALTER S. BURRAGE
mechanical factors of importance. His nose showed only a mild moderately pale vasomotor rhinitis. X-rays of the sinuses were negative. His history and clinical picture had indicated the possibility of a mild dust inhalant hypersensitivity as a possible cause for his nasal symptoms. Scratch tests had been negative, but among twenty intracutaneous tests there were muderate sized positive reactions to house dust, silk and wheat. He had been placed upon a wheat-free diet, given detailed printed instructions for control of dust in his home, and advised to avoid exposure to silk at all times. He had likewise been given a prescription for nose drops to relieve his symptoms. Questioned about his interval progress on such a regimen, it developed that both the patient and his wife were scrupulously conscientious in the carrying out of their instructions. Not only was the wheat-free diet followed to the letter, but it was decided that eating away from home would provide undue risk of failure of the experiment. Exposure to silk, as well as to house dust, would be hard to avoid abroad, so the patient and his wife gave up the movies and all outside contacts. His nose steadily became worse; the emotional situation more tense; his publishers were returning his stories unwanted. The nose drops were used six or eight times in each twenty-four hours. Skin tests were repeated in the clinic and found to be essentially unchanged. It was perfectly obvious that the cure in this instance had been far worse than the disease, as was emphasized when both the patient and his wife burst into tears upon being advised to seek out the nearest restaurant, have a big meal of anything they desired, and then go to the movies. Discontinuation of the nose drops was recommended. A month later, the patient's symptoms had almost subsided, his spirits had improved, and he stated that his publishers had accepted a short story.
Comment.-The original allergic studies appear adequate and the program of trial elimination justifiable. Frequent periods of follow-up would have demonstrated that the positive skin tests were not of clinical importance and that the general situation was getting out of control. The subsidence of his symptoms could have been dependent upon the removal of the nose drops to which he may have become sensitive as well as to the relief from his previous emotional tension. Elimination or avoidance is not always possible or feasible in allergy. This is particularly true in hay fever and in certain types of asthma. Specific desensitization is then indicated whenever possible. The tendency here is to rely too implicitly upon positive skin tests, to make an extract consisting of all the test-positive substances, and to treat the patient with it. This is quite proper only to the extent that the patient's clinical history coincides with adequate evidence that he is exposed to the positive reactors, and that his symptoms are caused by them. For example, many patients who have clinical ragweed hay fever, have positive skin tests to grasse's as well as to ragweed, but have no symptoms in the grass season. To include grasses in the treatment of such a case changes the character of the therapy from specific to nonspecific and, in the instances in which pollen mixtures are employed, reduces the concentration of the effective ragweed. Dosage in specific desensitization should vary with the sensitivity of each individual patient rather than be guided by routine instructions covering all patients. Not all diabetics need the same amount of insulin,
COMMON SENSE IN ALLERGY
1135
nor does any given diabetic tolerate changes in dosage prescribed on other than an individual basis. In like manner, not all allergic patients obtain optimum results on standardized doses. The hay fever sufferer of average sensitivity may do well on an average schedule, but the patient with a high degree of sensitivity may have recurrent constitutional or severe local reactions while the one with slight sensitivity may receive no benefit on the same dosage regimen. Some of the unsatisfactory results in hay fever therapy are due not so much to the inadequacy of the many excellent available extracts for treatment as to error in the selection of the proper specific pollens required, and failure to give optimum dosage. The size of the local reaction following treatment is the best guide to the determinatioll of the amount of the next dose. The patient should be instructed to observe all local reactions as well as any generalized symptoms, however mild, such as itching, sneezing or wheezing. Such observations will act as a warning signal advising caution against an immediate increase of dosage. Last year's record is a great aid in this year's treatment. Many doses may be saved or higher concentrations reached as the physician becomes more familiar with the patient's degree of tolerance. CASE Ill.-Mrs. F. B. T., aged 32, gave a history of typical ragweed hay fever of four years' duration, confirmed by large positive skin tests by the scratch method in dilutions as high as 1:5000. An initial high dilution ragweed extract with a chart and conservative dosage schedule was sent to the patient's local doctor with the request that it be returned after six doses had been given, with comments as to the local reactions. In the middle of the ragweed season, the patient appeared with severe hay fever. Inquiries as to her treatment divulged the fact that the first three inoculations gave no local reactions. Her doctor had therefore stated that the material could not be any good and that further treatment was useless.
Comment.-Early dosage may possibly be too conservative-or too excessive-in a new patient, but such a fault is easily remedied without discontinuing treatment if there is mutual cooperation between the physician and patient. In instances where infection plays the leading role, particularly when the onset of symptoms comes in or after middle age, skin tests are frequently noncontributory. Whether or not the mechanism which produces asthma in these cases is due to a true bacterial allergy, the eradication of a focus of infection is frequently followed by remission of !,ymptoms which is sometimes permanent. CASE IV.-M. M. B., a 49 year old leather worker, was well until September, 1945, when he developed a head cold, productive cough and, several weeks later, severe asthma. During the next four months he was treated at home and in two different hospitals with varied therapy including the removal of all teeth, the in-
1136
WALTER S. BURRAGE
halation of oxygen and oxygen-helium mixtures under positive pressure, adrenalin by all routes including aerosols, aminophylline by mouth, vein and rectum, iodides, one course of sulfadiazine and one of intramuscular penicillin. In spite of all these measures his asthma persisted. He was first seen by us in early February, 1946, in severe status asthmaticus and was immediately admitted to the hospital for emergency treatment. This consisted of intravenous fluids including aminophylline, oxygen inhalation, sedation, large doses of potassium iodide, and a bronchoscopy, during which several ounces of mucopurulent tenacious sputum were aspirated. Within seventy-two hours the patient had reverted to a condition of severe asthma necessitating an average of eight hypodermic injections of 0.5 cc. of adrenalin in twenty-four hours. Physical examination was not remarkable except for the presence of typical rather "tight" asthmatic breathing. No history of probable extrinsic sensitivity could be elicited. The family history was negative for allergy. Twenty-five intracutaneous skin tests to common foods, dusts and pollens failed to react. The temperature was normal, the white blood cells 30,000, with 18 per cent of eosinophils in the blood smear. X-rays of the sinuses showed slight thickening of the antra and ethmoids with no retained secretion. Chest x-rays and bronchograms gave no clear-cut evidence of bronchiectasis, but rather of a pulmonary fibrosis. The patient consistently raised about 3 ounces of tenacious mucopurulent sputum daily which at first showed a pure culture of Bacillus pyocyaneus, and the same organism was found in the culture of secretion removed from his bronchi by bronchoscopy. Varied efforts were made to control the patient's pulmonary infection during his three months of hospitalization. Among these was the administration of 2 Gm. of sulfadiazine which was followed in three hours by a series of shaking chills and an elevation of temperature to 105° F. by mouth. This was followed by an increase of purulent sputum and the obtaining of a sputum culture of Type III pneumococcus, but by no changes in his chest signs or in his chest x-ray. Intramuscular penicillin in doses of 20,000 units every three hours was then started. The temperature returned to normal in twenty-four hours and the asthma gradually disappeared. He continued to raise 3 ounces of purulent sputum daily which now gave a positive culture for alpha hemolytic streptococcus and, several days later, one for Bacillus coli. At the end of ten days the asthma recurred with its former intensity in spite of continued penicillin therapy. The white counts during this period had varied between 35,000 and 20,000 with sedimentation rates in the neighborhood of 30 mm. in one hour. At this point, streptomycin therapy was instituted and continued for five days in doses of 1 gm. daily, divided into intramuscular injections at three-hour intervals. At the termination of this treatment no change was observed in the patient's condition, but within the next eight days his cough, sputum and asthma gradually disappeared, his white count and sedimentation rate fell to normal, and his sputum culture became negative for bacteria. He was discharged to his home symptomfree the following week. A follow-up one month later indicated that he was still without trouble.
Comment.-The exacerbation in this patient's asthma following sulfadiazine, to which he had apparently become sensitized in a previous course of treatment, was undoubtedly due to the fever accompanying the drug reaction. It is important that his cough, sputum, white count and sedimentation rate remained elevated during this period of freedom from his wheezing and that his asthma recurred. A prolonged follow-up period is necessary before an optimistic prognosis is war-
COMMON SENSE IN ALLERGY
1137
ranted in such cases for, in spite of evidence that this patient's chronic pulmonary infection is under control, it is evident that a seemingly minor respiratory infection may reactivate his process and project him again into seven;) chronic asthma. CONCLUSIONS
These cases have been presented in an attempt to illustrate a few of the pitfalls encountered in the handling of some types of chronic allergic disease. Variation in interpretation of diagnostic evidence must be expected and encouraged, for it is only by such means that continued progress may be expected in a field that is still young. Yet constant watchfulness in the form of frequent and prolonged supervision must be exercised in order that specialized procedures of investigation and treatment may at all times coincide with the principles of good general medicine and sound common sense.
S.
BURRAGE,
M.D., F.A.C.P. \)
TREATMENT in the allergic diseases is perhaps less standardized than ill any other group of medical conditions. This is not surprising where the fundamental cause of the allergic state is still unknown and where many possible sensitizing substances and a multiplicity of "shock organs" may lead to the appearance of different types of symptoms in various parts of the body. To these factors must be added a wide variation in technic and in interpretation of the typical methods of diagnostic procedure, namely the skin tests. Variation in the stand· ardization of extracts used for both diagnosis and treatment is likewise confusing, for some clinics employ a total protein, others a total nitrogen basis on which to determine the strength of their materials. Such considerations emphasize the desirability of a careful evaluation of the allergic picture as a whole, keeping in mind the relationship of proposed allergic therapy to the general well-being of the patient. Diagnosis in allergy must be both differential and etiologic. The differential diagnosis should be considered first, for all are not necessarily allergic who sneeze, wheeze or itch. In the majority of instances, however, the patient has made his own correct diagnosis when he first comes to his physician and states that he is suffering from asthma, hay fever or hives. It is the etiologic diagnosis that is of paramount importance, for only in the careful search for the underlying trigger mechanism which sets off the patient's symptoms are we able to apply intelligently types of treatment which give the best chance of success. Various weapons are at hand for an attack upon this etiologic or specific diagnosis. The most important of these is the history. It is usually possible to determine whether the patient falls into the hypersensitive group by the use of a modified detective technic coupled with a guided third degree questioning. Are his symptoms characteristic of allergy? Does he admit past or present manifestations of allergy other than his present important symptoms? Has he a positive family history for allergy? One or more leads may thus likewise be obtained as to the possible nature of the offending substance. Are the symptoms seasonal so that they may coincide with the pollination of trees in spring, the
From the Allergy Clinics of the Massachusetts General and Newton-Wellesley Hospitals . .. Assistant Physician, Massachusetts General Hospital; Allergist, Newton-Wel!esley Hospital; Assistant in Medicine, Harvard University. 1131
1132
WALTER S. BUlU\AGE
grasses in summer, or the weeds in fall? Do they run beyond the pollen seasons with Hare-ups between them, suggesting molds as causative agents? Or are they present only with "colds" in winter? Are animals members of the family? What is the bedding made of? Is there evidence that foods have bothered recently or in the past? What is the patient's occupation; what his avocations? Can these be related to his symptoms? How about his medicines; what of nervous tension? These and often many other questions must be answered and recorded before any attempt is made to confirm one's clinical suspicions by skin tests. How many tests should be done; by what methods; how should they be interpreted; what reliance placed upon their results? The reply to these questions could fill many pages. Even allergists would disagree upon the conclusions. As is the case in surgical technic, the answers depend upon the individual experience of the doctor, as well as upon the history which each patient presents, his probable degree of sensitiveness, and the potency of the testing materials. Certain principles based upon common sense are too often overlooked in the enthusiasm of the hunt. Scratch tests are harmless; they will never kill the patient. Intradermal tests are more delicate, of undoubted value, but are potential dynamite and should be used in experienced hands in suitable dilutions in modest numbers at anyone sitting. They should not be done until a careful history has warned the operator of the degree of sensitivity which he is likely to expect. The interpretation of skin tests is a difficult problem. It must be remembered that skin tests may be positive where there is no evidence of clinical sensitivity to the substance tested, and negative in cases of hypersensitiveness. Normal people frequently have skin tests which can be called "positive." Allergic people sometimes have negative skin tests. Moreover, one does not need to use a magnifying glass to detect a positive test. It is important to appreciate that the finding of positive skin tests which coincide with proved clinical sensitivity varies statistically in different types of cases. It is high, for instance, in seasonal hay fever, less so in perennial inhalant allergy, lower still in food allergy, and even lower in urticaria. What may we say then in favor of the value of skin tests as diagnostic weapons in allergy? They are valuable adjuncts with which to try to prove the leads that our allergic history has provided and they occasionally unearth allergens which clinical trial elimination proves to be of importance. The liability of skin tests must be appreciated as well as their assets. The importance of making the specific diagnosis has been mentioned without emphasizing the fact that such a procedure is an integral part of treatment as well; for treatment in allergy must be based upon either elimination of the offending allergen or immunization against it by desensitization-either specific or nonspecific in nature. Trial elimination of suspected offending substances therefore becomes an integral part
COMMON SENSE IN ALLERGY
1133
of the specific treatment of many cases of allergy. It is in the control of this often laborious procedure of trial elimination that constant level-headed caution must be exercised to make sure that the general welfare of the patient is not sacrificed. The following two cases illustrate types of difficulty not infrequently encountered in this group. CASE I.-Mrs F. P. B., a slender woman of 61, had had a vague history of indigestion for two months, when a friend advised her to have skin tests done. These were said to be positive to about forty foods. It is of interest that the patient stated that she was unable to see any red areas about the scratch tests on her arms reported as positive by her physician. A test-negative diet was ordered. Her symptoms did not improve and she lost weight. She was retested four months later and was told that her "chemistry had changed" and that some of the previous tests had become negative, others positive. Another diet was prescribed. When first seen in the clinic nine months after the onset of her symptoms she had lost 25 pounds in weight, looked emaciated, and was obviously extremely nervous. Her vague gastrointestillal symptoms had increased. Inquiry as to her diet during her previous treatment showed that she had become suspicious of most foods and was living largely on noodle soup and crackers. Physical examination was negative except for evidence of weight loss. Gastrointestinal and gallbladder x-rays were negative; gastric acidity and blood studies were normal with a 1 per cent blood eosinophilia. A psychiatric evaluation revealed no evidence of neuropsychiatric disease, although it was evident that her dietary problem was very much on her mind. Skin tests by both the scratch and intradermal methods were negative. She gave no history of other manifestations of possible past or present allergy or of clear-cut food idiosyncrasy. There was no positive family history for allergy. The patient was advised that no evidence of food allergy could be found and she was given a well-rounded normal diet to follow. This proved no easy matter, however, as the seed of distrust in her food tolerance had been deeply planted. Months of reassurance and dietary readjustments were required before her confidence was restored. Six months later she had regained her weight and had almost lost her gastrointestinal symptoms upon a normal diet.
Comment.-This woman was 60 years old at the time of the onset of her symptoms-late in life for the beginning of food allergy. Multiple positive skin tests by the scratch method are uncommon in such cases. The inability of the patient to observe any positive reactions and the subsequent negative retesting in this clinic confirms the impression that the skin tests were originally interpreted with a magnifying glass technic. Disregarding the scanty evidence for food allergy here, this case stresses the fact that any type of trial·elimination diet should be checked frequently from the standpoint of sound medical progress. A similar danger is present, not alone in cases of food allergy, but with inhalant allergy as well. CASE H.-B. D. G., a 41 year old male author, entered the clinic complaining of symptoms consistent with the diagnosis of vasomotor rhinitis of twelve months' duration. Six months prior to admission, his case had been reviewed elsewhere. Careful otolaryngological studies then had demonstrated no infectious or faulty
1134
WALTER S. BURRAGE
mechanical factors of importance. His nose showed only a mild moderately pale vasomotor rhinitis. X-rays of the sinuses were negative. His history and clinical picture had indicated the possibility of a mild dust inhalant hypersensitivity as a possible cause for his nasal symptoms. Scratch tests had been negative, but among twenty intracutaneous tests there were muderate sized positive reactions to house dust, silk and wheat. He had been placed upon a wheat-free diet, given detailed printed instructions for control of dust in his home, and advised to avoid exposure to silk at all times. He had likewise been given a prescription for nose drops to relieve his symptoms. Questioned about his interval progress on such a regimen, it developed that both the patient and his wife were scrupulously conscientious in the carrying out of their instructions. Not only was the wheat-free diet followed to the letter, but it was decided that eating away from home would provide undue risk of failure of the experiment. Exposure to silk, as well as to house dust, would be hard to avoid abroad, so the patient and his wife gave up the movies and all outside contacts. His nose steadily became worse; the emotional situation more tense; his publishers were returning his stories unwanted. The nose drops were used six or eight times in each twenty-four hours. Skin tests were repeated in the clinic and found to be essentially unchanged. It was perfectly obvious that the cure in this instance had been far worse than the disease, as was emphasized when both the patient and his wife burst into tears upon being advised to seek out the nearest restaurant, have a big meal of anything they desired, and then go to the movies. Discontinuation of the nose drops was recommended. A month later, the patient's symptoms had almost subsided, his spirits had improved, and he stated that his publishers had accepted a short story.
Comment.-The original allergic studies appear adequate and the program of trial elimination justifiable. Frequent periods of follow-up would have demonstrated that the positive skin tests were not of clinical importance and that the general situation was getting out of control. The subsidence of his symptoms could have been dependent upon the removal of the nose drops to which he may have become sensitive as well as to the relief from his previous emotional tension. Elimination or avoidance is not always possible or feasible in allergy. This is particularly true in hay fever and in certain types of asthma. Specific desensitization is then indicated whenever possible. The tendency here is to rely too implicitly upon positive skin tests, to make an extract consisting of all the test-positive substances, and to treat the patient with it. This is quite proper only to the extent that the patient's clinical history coincides with adequate evidence that he is exposed to the positive reactors, and that his symptoms are caused by them. For example, many patients who have clinical ragweed hay fever, have positive skin tests to grasse's as well as to ragweed, but have no symptoms in the grass season. To include grasses in the treatment of such a case changes the character of the therapy from specific to nonspecific and, in the instances in which pollen mixtures are employed, reduces the concentration of the effective ragweed. Dosage in specific desensitization should vary with the sensitivity of each individual patient rather than be guided by routine instructions covering all patients. Not all diabetics need the same amount of insulin,
COMMON SENSE IN ALLERGY
1135
nor does any given diabetic tolerate changes in dosage prescribed on other than an individual basis. In like manner, not all allergic patients obtain optimum results on standardized doses. The hay fever sufferer of average sensitivity may do well on an average schedule, but the patient with a high degree of sensitivity may have recurrent constitutional or severe local reactions while the one with slight sensitivity may receive no benefit on the same dosage regimen. Some of the unsatisfactory results in hay fever therapy are due not so much to the inadequacy of the many excellent available extracts for treatment as to error in the selection of the proper specific pollens required, and failure to give optimum dosage. The size of the local reaction following treatment is the best guide to the determinatioll of the amount of the next dose. The patient should be instructed to observe all local reactions as well as any generalized symptoms, however mild, such as itching, sneezing or wheezing. Such observations will act as a warning signal advising caution against an immediate increase of dosage. Last year's record is a great aid in this year's treatment. Many doses may be saved or higher concentrations reached as the physician becomes more familiar with the patient's degree of tolerance. CASE Ill.-Mrs. F. B. T., aged 32, gave a history of typical ragweed hay fever of four years' duration, confirmed by large positive skin tests by the scratch method in dilutions as high as 1:5000. An initial high dilution ragweed extract with a chart and conservative dosage schedule was sent to the patient's local doctor with the request that it be returned after six doses had been given, with comments as to the local reactions. In the middle of the ragweed season, the patient appeared with severe hay fever. Inquiries as to her treatment divulged the fact that the first three inoculations gave no local reactions. Her doctor had therefore stated that the material could not be any good and that further treatment was useless.
Comment.-Early dosage may possibly be too conservative-or too excessive-in a new patient, but such a fault is easily remedied without discontinuing treatment if there is mutual cooperation between the physician and patient. In instances where infection plays the leading role, particularly when the onset of symptoms comes in or after middle age, skin tests are frequently noncontributory. Whether or not the mechanism which produces asthma in these cases is due to a true bacterial allergy, the eradication of a focus of infection is frequently followed by remission of !,ymptoms which is sometimes permanent. CASE IV.-M. M. B., a 49 year old leather worker, was well until September, 1945, when he developed a head cold, productive cough and, several weeks later, severe asthma. During the next four months he was treated at home and in two different hospitals with varied therapy including the removal of all teeth, the in-
1136
WALTER S. BURRAGE
halation of oxygen and oxygen-helium mixtures under positive pressure, adrenalin by all routes including aerosols, aminophylline by mouth, vein and rectum, iodides, one course of sulfadiazine and one of intramuscular penicillin. In spite of all these measures his asthma persisted. He was first seen by us in early February, 1946, in severe status asthmaticus and was immediately admitted to the hospital for emergency treatment. This consisted of intravenous fluids including aminophylline, oxygen inhalation, sedation, large doses of potassium iodide, and a bronchoscopy, during which several ounces of mucopurulent tenacious sputum were aspirated. Within seventy-two hours the patient had reverted to a condition of severe asthma necessitating an average of eight hypodermic injections of 0.5 cc. of adrenalin in twenty-four hours. Physical examination was not remarkable except for the presence of typical rather "tight" asthmatic breathing. No history of probable extrinsic sensitivity could be elicited. The family history was negative for allergy. Twenty-five intracutaneous skin tests to common foods, dusts and pollens failed to react. The temperature was normal, the white blood cells 30,000, with 18 per cent of eosinophils in the blood smear. X-rays of the sinuses showed slight thickening of the antra and ethmoids with no retained secretion. Chest x-rays and bronchograms gave no clear-cut evidence of bronchiectasis, but rather of a pulmonary fibrosis. The patient consistently raised about 3 ounces of tenacious mucopurulent sputum daily which at first showed a pure culture of Bacillus pyocyaneus, and the same organism was found in the culture of secretion removed from his bronchi by bronchoscopy. Varied efforts were made to control the patient's pulmonary infection during his three months of hospitalization. Among these was the administration of 2 Gm. of sulfadiazine which was followed in three hours by a series of shaking chills and an elevation of temperature to 105° F. by mouth. This was followed by an increase of purulent sputum and the obtaining of a sputum culture of Type III pneumococcus, but by no changes in his chest signs or in his chest x-ray. Intramuscular penicillin in doses of 20,000 units every three hours was then started. The temperature returned to normal in twenty-four hours and the asthma gradually disappeared. He continued to raise 3 ounces of purulent sputum daily which now gave a positive culture for alpha hemolytic streptococcus and, several days later, one for Bacillus coli. At the end of ten days the asthma recurred with its former intensity in spite of continued penicillin therapy. The white counts during this period had varied between 35,000 and 20,000 with sedimentation rates in the neighborhood of 30 mm. in one hour. At this point, streptomycin therapy was instituted and continued for five days in doses of 1 gm. daily, divided into intramuscular injections at three-hour intervals. At the termination of this treatment no change was observed in the patient's condition, but within the next eight days his cough, sputum and asthma gradually disappeared, his white count and sedimentation rate fell to normal, and his sputum culture became negative for bacteria. He was discharged to his home symptomfree the following week. A follow-up one month later indicated that he was still without trouble.
Comment.-The exacerbation in this patient's asthma following sulfadiazine, to which he had apparently become sensitized in a previous course of treatment, was undoubtedly due to the fever accompanying the drug reaction. It is important that his cough, sputum, white count and sedimentation rate remained elevated during this period of freedom from his wheezing and that his asthma recurred. A prolonged follow-up period is necessary before an optimistic prognosis is war-
COMMON SENSE IN ALLERGY
1137
ranted in such cases for, in spite of evidence that this patient's chronic pulmonary infection is under control, it is evident that a seemingly minor respiratory infection may reactivate his process and project him again into seven;) chronic asthma. CONCLUSIONS
These cases have been presented in an attempt to illustrate a few of the pitfalls encountered in the handling of some types of chronic allergic disease. Variation in interpretation of diagnostic evidence must be expected and encouraged, for it is only by such means that continued progress may be expected in a field that is still young. Yet constant watchfulness in the form of frequent and prolonged supervision must be exercised in order that specialized procedures of investigation and treatment may at all times coincide with the principles of good general medicine and sound common sense.