The Diagnosis of Tuberculosis by Tuberculin Injections. / BY / CHARLES DENISON, A. M., M. D., DENVER, COL., Professor of Diseases of the Chest and of Climatology, Medical College, University of Denver; Ex-president of the American Climatological Association ; Author of the Rocky Mountain Health Resorts; Climates of the United States in Colors, etc. REPRINTED FROM STpe Neto ¥orfc fUeDtcal for February 3, 189 f Reprinted from the New York Medical Journal for February 3, 189If. THE DIAGNOSIS OE TUBERCULOSIS BY TUBERCULIN INJECTIONS* By CHARLES DENISON, A. M., M. D., DENVER, COL., PROFESSOR OF DISEASES OF THE CHEST AND OF CLIMATOLOGY, MEDICAL COLLEGE, UNIVERSITY OF DENVER ; EX-PRESIDENT OF THE AMERICAN CLIMATOLOGICAL ASSOCIATION ; AUTHOR OF THE ROCKY MOUNTAIN HEALTH RESORTS ; CLIMATES OF THE UNITED STATES IN COLORS, ETC. In this discussion of phthisis I think I do well to try to present one phase only at this time, because of the great extent of the field to be gone over. Then, having settled upon my portion, it may be of inter- est to you who are present for me to say that by my invi- tation three physicians should be here with us who have taken either the tuberculin (Koch's) or tuberculocidin (Klebs's) treatments under very discouraging conditions, but with positive benefit, of which any fair physical investi- gation would give abundant proof. This is worthy of note, for the virtues of tuberculin have been appreciated by very few physicians, the great majority contenting themselves to go with the strong current against its use, which set-back was the natural result of the first overzealous and too sanguine expectation. * Read before the Denver Medical Association and Arapahoe County Medical Society, November 14, 1893. Copybight, 1894, by D. Appleton and Company. 2 THE DIAGNOSIS OF TUBERCULOSIS In the absence of uniform positive demonstration in tuberculin's favor, hearsay reports are quite sufficient for doubting minds, and careless statements about reinfection, or the alleged discovery of the Bacillus tuberculosis in the tuberculin of Koch by zealous and unreachable opponents in foreign lands are accepted as conclusive evidence of the worthlessness of the new remedy. This conclusion is reached, notwithstanding the an- nounced method of preparation of the lymph, by heating to 400° F. and filtering through porcelain, a process which is then proved, as we understand, by microscopic examina- tion, to free the remedy from any germ life whatever. On several occasions I have verified this freedom of the lymph from the Bacillus tuberculosis. It would probably be better if the mistakes of experi- menters were attributed to causes which are more within our reach, such as, among others : 1. The lack of due discrimination as to which are suit- able cases for this particular treatment. 2. The indiscriminate dosage, regardless of the favor- able conditions and environment necessary to success. 3. The looseness and inadequacy of technique in ad- ministration and the want of method in recording results. 4. The lack of a thorough appreciation of climatic con- ditions and the defective lung ventilation, especially in bed- fast cases and acute phthisis. It is unfortunate for the affirmative side of any such discussion that this question of diagnosis should have to be introduced, but it is really a vital part of the matter. It is not my purpose to throw undue discredit upon our means of diagnosis of phthisis in its incipiency. Theoret- ically, so far as our text-books go, the profession may seem to be well fortified for the work, but practically, whether due to defective means, method, or conception on the part BY TUBERCULIN INJECTIONS. 3 of the physician, there are too often cases of evident tuber- culosis unrecognized till such a time that the most favora- ble season for arresting the process has already passed. Without here going into the details of the early physical signs of phthisis, it is sufficient for our present purpose to show that in these uncertain and doubtful cases Koch's new discovery, tuberculin, has the power to bring to our knowledge their true nature and extent with precision and gratifying certainty. For the proper appreciation of this wonderful power some familiarity with or knowledge of the local reaction of the remedy in tubercular lung tissue is necessary. Tn my report on Tuberculin and the Living Cell to the American Climatological Association in 1892, I reiterated what I believed I had been the first to discover the previous year-that this reactionary effect " consists mainly in a harsh, puerile, or an exaggerated broncho-vesicu- lar breath sound, as heard with the stethoscope over the affected area. This is an exaggeration of what was heard before the tuberculin reaction, or it is heard in localities in which the breath sound was previously inaudible or very different. It is not an evanescent effect, but usually con- tinuous, though in a lessened or lessening degree during the whole course of treatment." Sometimes this local lung reaction is very feeble, while the systemic reaction, as shown by temperature, pulse, etc., is quite marked and characteristic. The following is an excellent illustration of tuberculin diagnosis in a case where neither the physical signs nor a microscopic examination of sputum could satisfy my decided suspicion that the case was of a tubercular nature : Case I.-Mrs. K., of Chicago, aged twenty-four years, mar- ried four years, height five feet four inches. No inheritance to consumption. Seen a week after arrival in Colorado. Weight a hundred and two pounds, usual weight a hundred and thirty 4 THE DIAGNOSIS OF TUBERCULOSIS pounds. Gradual loss of weight since a miscarriage two years previously, after which she had la grippe. While at school, aged sixteen, had dry cough and irritation in the throat there- after. Free from this two years in Europe, and then worse in 1889. Lately a wheezing and stuffed-up cond.tion toward even- ing ; sometimes had to sit up all night and frequently had to go to an open window at night during the past year. This was evidently a case of complicated asthma, for there was con- siderable relief of the hard breathing on arrival in Colorado. Expectoration half an ounce per day, dark yellow ; cough spas- modic, circulation poor, patient pale, but catamenia regular. Pulse 94, respiration 20, temperature normal. 10 a. m. : Spiro- metrical record a hundred and twenty-five cubic inches; man- ometer, forty five millimetres. Chest expansion two inches, evenly proportioned to the two sides. The physical signs were not very marked. The expiration was generally prolonged. There was tympanitic resonance over left main bronchus, and cogwheel respiration and blowing expiration in the left mam- mary region. Feeble voice sound and broncho-vesicular respi- ration left apex rear. On the right there was slight dullness and broncho-vesicular breathing front and rear at apex, and voice somewhat exaggerated rear. There were no bacilli in the sputum. The diagnosis was asthma and probably broncho- tuberculosis, and it was decided to test the case with tuberculin. The accompanying diagrams show the characteristic tuberculosis reaction to tuberculin, so far as the pulse and temperature are concerned, taken four times a day, according to the method I have employed for three years. The local lung reactions were first manifest, after the two- and-a-half-milligramme dose, in the left mammary, where the cogwheel breathing was before, and on the right side, junction of the third rib and costal cartilage. After the four-milli gramme dose these stethoscopic signs were also noted above in both first interspaces. These sounds were accompanied, when the temperature rise was great, with decided general reaction- ary symptoms of slight chill, fever, malaise, and headache. The sounds, hoivever, at first dry, became softer and Itss pronounced, as reactionary signs subsided, till they were about gone at the BY TUBERCULIN INJECTIONS. 5 sixty-milligramme dose, when the patient, much improved in weight, strength, feelings, and freedom from the old spasmodic coughing spells, did not react, though a rise of ten milligrammes every third day was given thereafter till a dose of eighty milli- grammes was reached. Note that the dose can be increased much more rapidly in such a case than in one in whom there are any advanced tubercular lesions in the lungs. In the latter condition, of course, such marked temperature reactions should not be tolerated. Note also that the general reac- tions, as indicated by the temperature rise, reached its maximum on the day following the injections. From this fact alone it is reasonable to conclude that the general dyscrasia exceeds any existing local lung lesion. T conceive that the more rapid capillary circulation in lung tissue-five times more than in the periphery of the body-may account for some of the quick reactions (in three to five hours) in tubercular lung tissue. In my considerable experience with tuberculin (Koch's), and lately with tuberculocidin (Klebs's), this gratifying diagnosis and result has been exceeded, for certainty of effect, by only two cases, which are worthy of more ex- tended mention than we can give them here. Case II.-Dr. G , of Vermont, aged thirty-eight years. Positive inheritance, his mother and five sisters, out of seven |n family, having died of consumption. His wife had died of tubercular meningitis three years previously, from whom he may have been infected, as the disease was general in her. He had had-a seton put in the back of bis own neck twelve years ago for meningitis, which it seemed to relieve, and eight years ago had suffered fracture of the ribs, with septicaemia re- sulting. Three years ago had la grippe and double pneumonia, chiefly right side. Sick six months. Came then to Colorado, and gained seventeen pounds in as many days. 6 THE DIAGNOSIS OF TUBERCULOSIS November 20, 1892. -After a cough in Vermont, had what was termed basilar meningitis ; sick since. Headache continu- ous, and lately very severe up to April 20, 1893, when (in Colo- rado) the following-described relief came: There was no ex- pectoration to examine, and only slight dullness, lessened move- ment, fremitus, exaggerated voice, and broncho vesicular breath sounds on the right side. The temperature, pulse, and respiration were found to be about regular for two days-98-5° F., 60, and 20, respectively-when one milligramme of tuberculin was injected. The genuine diagnostic reaction did not start till twenty-two hour? afterward, and then was chiefly general and not local in the 1-ng. It was manifest by temperature 100'5° F. and pulse 82 to 90, and continued more or less for about fifteen hours, dur- ing which at one time he vomited. The day following its cessation a slight increase in dose of tuberculin was given, which was fallowed, in four to six hours, bv a slighter reaction than before. By that time the headache had entirely ceased, and the patient, who had been confined in bed for four weeks, was enabled thereafter to be daily out of doors with comfort. The constriction about the base of the brain, which was marked with the first reaction, gradually disappeared. In less than four weeks, after reaching a dose of thirteen milligrammes and feeling well able to do so, the doctor returned to his Vermont home, where he has been engaged in practice since, enjoying, so he writes, good health. This remarkable case is given as possibly the first diagnos:s on record of tubercular meningitis by tuberculin. Case III.-A case of tubercular arthritis in both knee joints in a young lady of twenty-eight years, who was taken thus while nursing a sister in an Eastern sanitarium, who died of tuberculosis of the bones of the pelvis and spine Three years afterward, after having tried several kinds of surgical treatment in hospital, the patient referred to submitted to a test with tuberculin at my suggestion. She bad lost the use of her limbs and was compelled to use a wheel-chair for locomotion. The reaction at the third, sixth, seventh, and ninth milligramme doses of tuberculin were both general-i. e., headache, malaise, some fever and general distress, and somewhat local in the BY TUBERCULIN INJECTIONS. 7 left lung, where at the age of sixteen she had suffered some slight disease. Seven months after this diagnosis an attack of la grippe seemed to center the tubercular poison in the glands on the left side of the neck, which, being removed, showed tubercle bacilli in giant cells in the center. This confirmation of the previous diagnosis led to a continuance of the tuberculin treatment in Colorado from October, 1892, to May, 1893. The result has been successful, for the young lady, now in Vermont, enjoys excellent health, and walks considerable distances without her crutches. Other instances of decided diagnosis of tuberculosis if cited would include two cases of tubercular ulceration of colon ; lymphadenoma, with general glandular involve- ment ; scrofular cases (glandular); and supposed pulmonary fibroses. An important consideration to be drawn from some of the above and other of my cases is that there is an active tubercular stage-pretubercular, if you wish to call it so- before the bacillus of tubercle makes its appearance as a factor in the case, so far as we are able to judge. I do not refer to such manifestly tubercular cases as where the full picture of an acute phthisis is given, ex- cepting the bacillus of tubercle microscopically demon- strated in the sputum, perhaps as with a young lady pa- tient T have in mind, whose expectoration was loaded with sporesone week, and the next gave fifty bacilli " to the field," the first found in her case. Nor is reference in- tended to be made to other cases where active tuberculosis can be inferred as going on away from the bronchial tract, and the more acute and septic on that account-i. e., be- cause the bacilli are not thrown off. But reference is in- tended to those intricate slowly acting blood changes which come under the classification of dyscrasite, which may be, for all we know, the sine qua non of the bacillus of 8 THE DIAGNOSIS OF TUBERCULOSIS tubercle's existence, that state which may indicate the more or less complete annihilation of the body's natural antago- nism to this particular foe. If our judgment and means of knowing the first ap- pearance of the bacillus are not wholly at fault, then there is certainly enough in this idea of a definite pretubercular state to bring great credit upon him who will elucidate this interesting and important problem. Among the phases of this subject to be solved, the fol- lowing appear to me to be urgent: * 1. Minute explanations, on pathological grounds, of the adenoid growths in the region of the third tonsil, such as have been known to be removed ad infinitum by specialists, and no microscopic evidence of bacilli found either in the flesh removed or the patient's expectoration. Yet the pa- tient goes on to die of laryngeal tuberculosis, as the gradu- ally increasing peribronchial and apical infiltration and con- solidation (immediately following the surgical interference in the throat) indicated what the result would be. Such a case is just now very distinct in my memory, and will recur to the mind of the distinguished physician who kindly recom- mended the case to me, but very unkindly and, I think, un- wisely prevented my afterward using tuberculin in the case, the only means I know of which would have compassed a cure, however incomplete that would have been. The preju- dice in the minds of some of our best physicians against even the advanced and enlightened use of tuberculin is as unreasonable as it is alarming. 2. An understanding of the absence of tubercle bacilli, or their tardy and very infrequent appearance, compared * These considerations and some other parts of this essay are taken from my paper on The Early Diagnosis of Phthisis, etc., lately read be- fore the Section of Hygiene, Climatology, and Demography of the First Pan-American Medical Congress held in Washington, D. C. BY TUBERCULIN INJECTIONS. 9 with the amount of glandular growth in so-called scrofular glands, with or without a coincident active tubercular pro- cess in some other part of the body. 3. An understanding of the growth of tubercles-the " nodules " which have come down to us (previous to the discovery of the bacillus)-as the essential feature of phthisis. As elsewhere explained in the essay on tuberculin, etc., previously referred to, I have myself a strong belief that these tubercles are the natural prison vaults built for the in- capsulation of the tubercle bacilli, in which condition the germs, if not strangulated, are held so much in quiescence that they are incapable of propagation or further harm. This is a condition of arrest while it lasts, while the natural resist- ance of the system is maintained, which is, perhaps, about all Nature can do in the direction of a cure. But the nat- uial effort to maintain the integrity of the living cell is all the time active, and its mention here is made solely with the hope that some more worthy investigator will by its means-i. e., on natural gounds-elucidate for the medical profession the intricate problems here sug- gested. The late distinguished president of the Royal College of Physicians, London, Sir Andrew Clark, with his usual diagnostic acumen and literary ability, formulated an elabo- rate argument opposed to the ideas of Professor Koch and his followers, but in favor of a bacillary and a non-bacillary classification of phthisis. How large a proportion of Sir Andrew's " non bacillary " class, including his purely fibroid variety, would have had to be transferred to the bacillary division is of course conjectural, but I suspect they would have constituted the total or a very large percentage had those cases been tested thoroughly with tuberculin injec- tions. In my own experience it has been very largely the 10 TUBERCULIN IN THE DIAGNOSIS OF TUBERCULOSIS. chronic bronchorrhoeas and bronchiectatic cavities, of all the chronically affected lung patients daily expectorating yellow matter, which have shown neither bacilli in the sputum nor reaction to tuberculin injections. The failure to find tuber- cle bacilli in the sputum is certainly no adequate proof that tuberculosis does not exist. This statement will be accept- ed as true by every reflective mind, but upon me its validity has been impressed by eight or ten diagnoses by the aid of tuberculin injections similar to the first case given in this paper. In some of these, during the first part of the treatment, bacilli were found in the expectora- tion, which evidence again wholly disappeared as treat- ment progressed. But for such a diagnostic means the extent of latent tuberculosis among the people who walk our streets remains, as it always has been, a mys- tery. Very likely an impression may be given that climatic influence may not be duly accredited in the foregoing effects, and it is extremely probable that neither the com- position of tuberculin nor of the Klebs or Hunter modifi- cation of it are the best and safest possible. Like others, I look for something better, but, until that is found, I am glad that we have in tuberculin so good a referee to decide, in doubtful cases, if tuberculosis exists. The New York Medical Journal. A WEEKLY REVIEW OF MEDICINE. EDITED BY FRANK P. 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