THE REACTION TO TUBERCULOSIS TO TUBERCULIN BY THE CUTANEOUS METHOD, AND THE FREQUENCY OF TUBERCULOSIS IN INFANCY.

BY DR. CLEMENS VON PIRQUET, Vienna.

[Report Expressly for the MEDICAL BRIEF.]

[Address before a combined meeting of the Medical Society of City Hospital Alumni and the St. Louis Medical Society, October 17, 1908.]

If we make an inoculation of small-pox in a person who has never been vaccinated, we see a characteristic reaction, one that appears not after twenty-four hours, but after three or four days. In vaccination we get first a traumatic reaction, but not a specific one; that is, we get the effects of the mechanical scarification. In two or three days we begin to see the specific reaction which gradually increases, day by day. On the eighth or ninth day we see a stage of the reaction at its greatest height, when we see the so-called "areola." If we make a small-pox inoculation in a man who has been vaccinated before, we do not see an absolute reaction, but only a slight one, a reaction which disappears after a week. After twenty-four hours you will find a slight reaction in such a case. This is what I call an “early reaction." As a diagnostic means, we can tell in this way whether a person has been vaccinated before or not.

After having established these facts with vaccinia, I tried to make a similar proof in tuberculosis. In tuberculosis we can not use tubercle bacilli as in vaccinia because we would infect our patients with tuberculosis. But we can use the Old Koch Tuberculin which is the concentrated extract. In a tuberculous subject we get a skin reaction within twenty-four hours, thus distinguishing between a tuberculous and a nontuberculous patient.

I will now demonstrate on my own arm how this vaccination is made. The skin on the upper part of the forearm is rubbed with ether on absorbent cotton for cleansing. It is better to wash the skin with ether for this purpose because it evaporates rapidly and leaves the skin dry, whereas the use of a watery solution of an antiseptic would make the tuberculin run off the spot that you wish to vaccinate.

Then I take a vaccination instrument, which only differs from the ordinary kind in that it has no point; in other words, it is shaped like a chisel. The blade of this instrument which I use is made of platino-iridium. The vaccination is made with this instrument by a rolling motion, making an irregular wound. I advise three wounds to be made on the forearm, one above, with the tuberculin; one in the middle which is a control, and you should put no tuberculin on this one, and one below with tuberculin. With this method you can not go very deep. Drop on two drops of the old tuberculin, then make the rolling motion with the scarifier and then put a little piece of cotton over the tuberculin wound until they dry and then pull off this cotton. This keeps the tuberculin from running.

I will now show you some moulage specimens of the reaction. Some of these specimens show an areola. What does a positive reaction mean? It means that if we get a positive reaction we can say with certainty that the person has had tuberculosis. We have definitely proven this by postmortem examinations of patients, 200 in number, who have undergone. the test. In this 200, there were 109 children with no tuberculosis. In 89 cases, tuberculosis was found post-mortem. Of these 89 cases, 65 gave a positive reaction. I will speak later of the other 24. There were two cases in which there was a positive reaction without an absolute certainty of tuberculosis; in one of these cases there was an adhesion of the pleura and in the other adhesions of the pericardium, so that for practical purposes these two cases can be considered tuberculosis patients. This reaction can be considered as an index of infection with tuberculosis because we look upon it as identical to the "fever reaction" of Koch for which we have many proofs in the adult. It is considered identical because we can get the fever reaction in every case if we resort to enough injection of tuberculin.

I will now speak of all the methods in vogue for obtaining reactions to tuberculosis.

I.

1. Injection Method-Here we have a definite sign of tuberculosis, namely, fever, to which Koch attached the greatest importance.

2. Cutaneous Method-This is the same as the sub-cutaneous method, only differing in that we do not inject under the skin.

3. Eye Reaction-Some time after I described the cutaneous reaction, Calmette and Wolf-Eisner found that the eye was a point where the infection could be detected.

4. Dermo-reaction-Legnieres found by rubbing tuberculin into the skin that he could detect tuberculosis in that way.

All these reactions are the same. It is simply a question of telling which reaction to apply in a given case. The eye reaction is easy to perform, but has the disadvantage of being dangerous to the eye when a very strong reaction occurs. The eye reaction is good in cattle.

The most sensible reaction is the injection method, but in many cases. the subcutaneous method is not allowed because of the high fever and constitutional symptoms. The skin reaction is more difficult to apply, but it is absolutely harmless. I have made over 3,000 scarifications and I have seen no harmful effects in any case. In 50% of the cases there is a rise in temperature, but if you are very careful in making the scarification and do not go deep into the tissues, you will not even get a fever afterwards.

It is necessary to rub the skin very hard in doing the reaction. The reaction differs in different individuals because you can not always make them in the same way, but for those who fear this, they can use the dermo

reaction. It is easy to make the cutaneous reaction, yet it is sometimes expedient to make the subcutaneous reaction as well, merely as a control.

The meaning of the reaction is different in adults than it is in children. We know this from the work of Nageli, that tuberculosis is more prevalent in adults than in children. For instance, 90% of the adults who come to autopsy in Vienna show signs of tuberculosis. This is not always a clinical tuberculosis, but may be a tuberculosis of glands. Even a slight tuberculous infection is sufficient to give this cutaneous reaction. We can not tell so much from tuberculin reactions in adults because they react so easily from slight degrees of infection. Only a very strong reaction the first time of application is significant in adults. The mucosa of the eye is sufficient to arouse bodies which make tuberculous activity. Again, repeated inoculations in adults without any reacton is valuable information in adults. If you inoculate three times in an adult one week after the other, you can say with certainty that the patient is free from tuberculosis, when no reaction occurs in these three attempts.

In children it is different. I spoke before of the twenty-four cases in which tuberculosis was found at autopsy without any activity at all during the lifetime of these subjects. These cases were those in which the reaction was made too late. A first negative inoculation does not prove that the person is not infected with tuberculosis, because there are some conditions in which no reactivity exists, and that is in the last stage of the disease. There is no reaction in the terminal stage of the disease-this fact was well known with the older injections method. Secondly, we have no reaction in children in the last stage of meningitis or generalized tuberculosis, also none in miliary tuberculosis. Thirdly, the reaction ceases as the children get older. Fourthly, we have certain diseases in which the tuberculin reaction ceases. This is true of measles. During measles attacks there is absence of the reaction after the first week. The reaction disappears with the appearance of the exanthem, and the reaction comes back on the sixth or eighth day of the skin eruption of measles. We do not know why this is true, but it is probably due to the old clinical phenomenon that tuberculosis spreads during a measles attack. If the bodies in measles belong to the anti-bodies, then we have an explanation for this occurrence. Other diseases of childhood, diphtheria, scarlatina, do not make this phenomenon. Now this explains why I did not get the reaction in the twenty-four cases.

There are other cases in which there was healed tuberculosis in which there is no reaction. If tuberculosis overwhelms the organism, the reactivity to tuberculin is so low that there occurs no visible reaction on the skin. Some of these twenty-four cases were only tried once, and perhaps some of them might have reacted if we had tried it a second time. I call this a state of "secondary reaction." Secondary reactions are sometimes found in apparently healthy adults. We seldom find tuberculosis in

small children confined to one small area, but in them it is generally found scattered over the body. Therefore, the most reliable time for the reaction is in the first years of life, ceasing with increasing age of the child. The cases in which it is of most practical utility are those of small children in our ambulant service where the parents do not object to a slight reaction; besides there is no necessity to take the temperature of the children. You can tell these patients to come back in a day or two.

An obscure question that has been frequently solved by this reaction is one like this: If there is atrophy in a child, due either to simple bowel trouble or tuberculosis, you can make the differential diagnosis in this way. Then, if there is an eczema or a scrofulosis, you can make the diagnosis satisfactorily. Then, if there is a difficulty in breathing, which is the first indication of glandular tuberculosis, you can get full light with this test. As a hygienic measure, and we may within a few years make this test in young children, in that way we can take out of school those who are tuberculous. There is no doubt but that this would prevent much of the infection from the sick to the healthy of tuberculosis in kindergartens. As a scientific measure we can make an early diagnosis of tuberculosis in children, in the very early stages of the disease. We now are making diagnoses of tuberculosis, which we think are early diagnoses, but they are really diagnoses of advanced stages. If we make a reaction every year in children we can control the fact whether they are infected or not; then in looking through the history of a child, we can recognize possibly a simple coryza as the first clinical manifestation of an infection with tuberculosis.

PAIN IN INFANTS.

BY W. B. DRUMMOND, M. B., C. M., F. R. C. P.

Assistant Physician to the Royal Hospital for Sick Children, Edinburgh.

[Written for the MEDICAL BRIEF.]

A doctor may be in practice for many years without seeing a single example of many of the diseases which are treated of most fully in the text-books. On the other hand, he is quite sure to be called not infrequently to attend to such cases as are dealt with in this article, and his text-books may fail to give him the precise assistance he needs.

A doctor is called, let us say, to see an infant a few months old which has suddenly begun to cry loudly as if in severe pain. Every effort has been made to soothe it, but in vain. Hour after hour, perhaps, the screams of distress have continued. Now and again, for a few moments, they may have subsided and the child, exhausted, may have appeared to be going off to sleep. But, no! Almost directly the pitiful cries have been resumed until in desperation the doctor is summoned to find out what is the matter and to give relief.

Now, it is a recognized rule in medicine that treatment should be based upon a correct diagnosis, and in such cases as these every effort should be made to find out the cause of the infant's pain. But it does not follow that one should make no attempt at treatment until one has completed one's diagnosis. On the contrary, pain itself is a symptom which demands speedy relief. If it is not relieved there is a danger of the child becoming exhausted and even suffering from convulsions. Moreover there can be no doubt that pain alone may cause death, and although the danger of such an event is doubtless remote, the fact that it has occurred is an indication of the magnitude of the nervous depression which pain may bring about. If, therefore, severe pain is allowed to continue unrelieved the infant's health vitality may suffer for a long time afterwards.

Nevertheless one should always try to ascertain the probable origin of the pain without delay, and for this purpose the history of the case is most important. One should ascertain, especially, whether the infant has ever appeared to be in pain before, and minute inquiries should be made as to the feeding of the child and the occurrence of dyspeptic symptoms-vomiting, constipation, diarrhea, flatulence, abnormal appearance of the stools, etc. It very seldom happens that pain is the only symptom present. It may be the master symptom, beside which all others seem of such trivial importance that they are never mentioned unless expressly inquired for. But for the purpose of arriving at a diagnosis no symptoms are trivial, and it is no waste of time to procure a history of the case as full and accurate as possible. This involves finding out not only what symptoms have been present, but the order in which they have occurred. On this last point I would lay special stress. It is often of the greatest value in diagnosis. If an infant is suffering from pain and vomiting, for example, one should make out quite clearly whether the pain preceded the vomiting or the vomiting the pain. A definite history of the order in which the various symptoms have appeared will often be of the greatest assistance in forming an opinion as to the nature of the illness.

Pain in infancy, in the great majority of cases, is of abdominal origin. The pain is most frequently due to intestinal colic, associated with flatulence. There is seldom much difficulty in making a diagnosis. The expression of the child's face, the character of its cry, the attitude of the body, the movements of the limbs, all combine to form a clinical picture with which the practitioner soon becomes familiar. Moreover the child is usually being fed on cow's milk, which has not appeared to agree quite perfectly. Previous, but less severe, attacks of pain have occurred. Possibly the strength of the milk mixture has been increased recently. Constipation has probably been present. If the number of stools is normal, their character may be unsatisfactory. For example, they may be too scanty or too dry, and they may contain undigested curd.