Chapter III: Part 3

In considering the complications of influenza one again comes up squarely against the question: What is influenza and what is the specific micro-organism responsible for it? If the Pfeiffer bacillus is the specific cause, what pathology can be attributed to it? It has been an almost universal observation that the lesions in the lungs and pleura which characterized the group of cases with lung involvement rarely yielded a pure culture of the Pfeiffer bacillus, and that secondly in a large percentage of cases the Pfeiffer bacillus apparently was absent, and that other micro-organisms, such as the pneumococcus, streptococcus, micro-organisms commonly found in the pneumonic processes, were present and predominated. The question arises, therefore, may not all the influenzas with lung involvement be _complications_ of influenza? It is our feeling that Pfeiffer bacillus is present throughout the respiratory tract in all cases, and while it may of itself produce a lesion like a broncho-pneumonia or a lobar pneumonia, it chiefly prepares the soil for other germs which may happen to be present, and which are more commonly found in the pneumonias. We, therefore, look upon the lesion commonly found in the lung as being a part of rather than a complication of influenza, and look upon lesions elsewhere, due to the influenzal or other micro-organisms, as a definite complication.

There is no doubt that the most frequent complication of influenza, especially in the present epidemic, is in connection with the pleural membranes. When one recalls that pneumonia rarely occurs without there being also a pleuritis, and also when one recognizes that in an influenzal infection of the lungs the specific micro-organism, together with any other micro-organism which may happen to be present, seems to run riot, apparently abandoning its usual mode of invasion, it can be readily understood why this complication is so frequent and so varied. The pleurisy was usually of the fibrinous type, and rarely was accompanied with demonstrable fluid. Of the 153 soldiers in only 3 was fluid detected in the chest, and of the 394 civilians only 10 showed fluid. In many more cases fluid was suspected, but X-ray examinations and free needling of the chest showed that we had misinterpreted the physical signs.

After our experience in the epidemic of pneumonia in the spring of 1918, when the disease was also so prevalent in the cantonments, we of course expected to see many cases of empyæma and lung abscess in the present epidemic. In this we were agreeably disappointed. Only one case of empyæma and only one case with abscess of the lung were found up to the time of collecting our data and the compiling of our statistics. Both of these were among the civilians. From our experience since the compiling of our statistics, we are inclined to believe that this low incidence of empyæma may not altogether represent the real state of affairs, as we have since received in the hospital several cases of empyæma, as well as of abscess of the lung, which seemed to have followed an influenzal infection which had occurred three or four months previously. One of these cases was a particularly remarkable one, in that the patient had already been admitted to the hospital twice since his initial attack of influenza in October for suspected pleurisy with effusion. We were unable to find any fluid with the needle, though we felt certain of having demonstrated it a number of times physically and with the X-ray. About eight weeks after the second admission, however, pus was found after several needlings in the left chest, axillary space, apparently along the inter-lobar sulcus. This case was a good example of many we have seen in which a pneumonia, or possibly, as we see it now, a pleurisy, or even a localized empyæma, seemed to confine itself about the sulcus or fissure between the upper and lower lobes of the lung. Frequently the process began posteriorly, apparently at the apex of the lower lobe, and traveled forward and downward across the axillary space until it appeared in the anterior part of the chest. In most cases we interpreted our signs as those of a consolidated lung, and scarcely knew whether the consolidation was in the upper part of the lower lobe or in the lower part of the upper, or in both. In some cases we suspected a localized empyæma or an abscess in the sulcus, but in none did we find pus after exploring with the needle until this recent case occurred. The passage of the needle in this case, which was done several times before pus was found, always gave the impression that it was going through dense fibrous tissue for some distance before the abscess was finally found. From this experience, and from the extensive and irregular invasion of the pleura which we have seen demonstrated at autopsies, there can be no doubt that the clinical history of the complications of influenza in this epidemic is not a closed chapter.

In six patients there was a purulent inflammation of the pharynx, larynx and trachea. It was extensive and produced profound general symptoms, dyspnœa and profuse purulent expectoration. The lungs were clear, but the patient seemed for a time in danger of death. The condition was considered a grave complication. There was only one case of acute sinusitis, one case of antrum disease, and only four cases of middle ear infection were recognized. This is in marked contrast to other epidemics which have occurred to our knowledge in the past fifteen years or more, and which have been spoken of as influenza or “grippe.” Disease of the tonsils, middle ear disease, mastoid disease and sinus disease occurred with great frequency in those sporadic epidemics. This again seems to show that the deep respiratory tract was more generally and more severely affected in this epidemic than the upper respiratory tract.

With the exception of the pleura, the serous membranes were remarkably free from infection. Only one case of acute endocarditis, three cases of meningitis (all pneumococcic), none of pericarditis, peritonitis or arthritis were recognized among the 547 cases of influenza.

The kidneys did not seem to be involved in the infection. Albumen was present in the urine, as might be expected in febrile conditions, but no evidence of acute clinical nephritis, such as suppression of urine, general œdema or uræmia, was recognized. The condition of the urine in this epidemic will be described more in detail in another paper of this series.

A peculiar pathological process in the muscles was brought to our attention by Dr. Klotz, who demonstrated a myositis or hyaline degeneration of the lower end of the recti abdominalis. This lesion is carefully described in the pathological section. After our attention had been called to this lesion we recognized several cases clinically having the same condition. One was in the right sterno-cleido-mastoid muscle and another was in the left ilio-psoas muscle. This last patient while he was convalescing developed a severe pain in the left hip, extending upward into the lumbar region and downward into the thigh. His decubitus was like that of one suffering with psoas abscess. Every test available was made to confirm this diagnosis, but all the findings were negative. The patient rested in the hospital, in bed, for some time, gradually improved, and eventually made a complete recovery.

In several cases we also detected an osteitis, especially of the bodies of the vertebræ. One was of the cervical vertebræ and the other of the dorsal. The first died after intense suffering. An autopsy was not obtained. The other had a plaster cast applied as in Pott’s disease, and improved sufficiently to leave the hospital in comfort. One hesitates under the circumstances to attribute these bone lesions definitely to the same infecting micro-organism which was responsible for the epidemic of influenza, as it might easily have happened that a coincident quiescent tuberculous lesion was present and relighted during the epidemic. However, in one case from the service of Dr. J. O. Wallace the possibility of the bone lesions being due to the Pfeiffer bacillus was demonstrated. This was a child of 16 months with an epiphysitis of the upper end of the tibia. The inflamed area was incised and pus was found. A smear at the time showed the B. influenzæ, which was grown in pure culture.

A most interesting complication noted in a few of our cases was a transient glycosuria. The first case brought to our attention was a middle-aged female, who complained of failure of vision. Upon making an ophthalmoscopic examination a papillitis of a mild type was noticed. This led to a careful study of the urine, and sugar was found in a small amount for a short period of three days, although the glycosuria readily disappeared by cutting down the carbohydrate intake, the vision came back to normal more slowly. In fact, it was almost one month before the symptoms and signs of the retinal change had entirely disappeared. It is interesting in this connection to recall similar cases referred to in Allbutt’s System of Medicine, vol. vi, on influenza, following the epidemic of 1890 in England. Other transient glycosurias showed no visual changes. We do not consider these to be true cases of diabetes mellitus. In all a transient hyperglycæmia was also noted.

_Pregnancy_

A condition which can scarcely be considered as a complication of influenza, but which, however, was a large factor in increasing the mortality among women, was pregnancy. Among the cases included in this study were five pregnant women, who came to the hospital and were referred to the medical service. As soon as a complication relative to the existing pregnancy arose they were referred to the Obstetrical Department. On account of the great amount of work in caring for the influenzal patients, and on account of the scarcity of physicians and nurses, we were unable to follow these cases closely enough to give any such definite data as we wish. Three miscarried or went into premature labor. Happily only one of them died. The two which did not miscarry recovered and left the hospital well.

We very soon recognized in consultation with the obstetricians that the pregnant woman was in a really dangerous condition if she contracted influenza. She was likely to have a termination of her pregnancy in the height of the infection, no matter how recent or how remote pregnancy had taken place. If pregnancy did not terminate, the chances of recovery were less than those of the non-pregnant woman; if it did terminate, the chances for recovery were still less. To the pregnant woman with pneumonia very little hope of recovery could be offered. I am indebted to Dr. Paul Titus, of the Obstetrical Department of the School of Medicine, University of Pittsburgh, for a report which includes the cases seen by himself and his assistant, Dr. J. M. Jamison, during this epidemic. Dr. Titus was kind enough to include in his report certain conclusions which merit consideration. The report is as follows: “A series of 50 cases, at all stages of gestation. Interruption of pregnancy occurred in 21, or 42 per cent., of the cases; 29, or 58 per cent., in which pregnancy was uninterrupted. Mortality of pregnant women developing epidemic influenza is higher than that of ordinary individuals, even though their pregnancy is undisturbed, since 14 of the 29 in whom pregnancy was not interrupted died, an incidence of 48–2/10 per cent. If a pregnant woman miscarries or falls into labor, the mortality increases to 80–9/10 per cent. (17 of the 21 in whom pregnancy was interrupted died). The period of gestation has less influence on the outcome than the interruption itself. Of 10 at term, 3 lived and 7 died after delivery.

“Two main features of this condition as a complication of pregnancy are: First, pregnant women developing epidemic influenza are liable to an interruption of their pregnancy (42 per cent. aborted, miscarried or fell into labor); second, the prognosis, which is already grave on account of the existence of pregnancy, becomes more grave if interruption of pregnancy occurs.

“The cause of the frequency of interruption of pregnancy is probably a combination of factors: (1) The theory of Brown-Sequard that a lowering of the carbon-dioxid content of the blood causes strong uterine contractions sufficient to induce labor. (2) The toxæmia causes the death of the fœtus, particularly if not mature, when it acts as a foreign body and is extruded (10 premature fœtuses were born dead, while 1 was born alive, although 9 out of 10 at full term were born alive and survived).

“The cause of the frequency of death following interruption of pregnancy is also due in all probability to a combination of factors: (1) Shock incident to labor. (2) Increase from muscular labor of carbon-dioxid in blood already overloaded by the deficiency of the diseased respiratory organs. (3) Sudden lowering of intra-abdominal pressure by the delivery. (4) Lowering of blood pressure by the hemorrhage of the delivery. (5) Strain of labor on an already impaired myocardium.”

If one had been told a year ago that an epidemic could occur which would result in the death of 60 per cent. of all pregnant women affected, it would have been thought too unlikely to warrant any consideration. Though the effect upon pregnancy of the acute infectious diseases forms an important chapter in the pathology of pregnancy, it seems that the profession, and in this the obstetrician is no exception, has never realized how pernicious and tragic the results of an influenzal epidemic can be in a community. From the experience in previous epidemics we cannot but feel that the infection in the present epidemic was unusually fatal. Whitridge Williams (“Text-book of Obstetrics”) speaks of the interruption of pregnancy as having occurred in 6 out of 7 cases with one observer, and in 16 out of 21 in another, while a third has found it only twice in 41 cases. However, none of these writers speaks of having had a death.

_Sequelæ_

In referring to some of the associated conditions of influenza one scarcely knows whether to consider them as complications or sequelæ. The pathological process certainly had its origin from the influenzal attack, but at times apparently assumed an inactive stage. The patient is usually free from any specific influenzal symptoms, but retains for a long time other symptoms referable to various organs, or he may have been normal for a shorter or a longer period and then suddenly develop symptoms apparently independent of the previous infection. It may be well to consider all such conditions which followed the febrile attack, whether immediately or more remotely, as sequelæ, and I shall therefore speak of them as such.

The first and probably the most interesting and confusing are the conditions found in the lungs following influenza. A chronic bronchitis, an old bronchiectasis, or a previous tuberculous lesion in whatsoever stage, may present acute symptoms and signs which are difficult to interpret. The question always arises in the individual case—is this a process due to the recent influenzal attack, or was it there before the attack? Is it of streptococcic, pneumococcic, or tuberculous origin? The history of previous diseases of the lungs may help to arrive at a diagnosis. The history of the severity of the influenzal attack is of very little help, because the apparently mildest attack may be followed by the most profound changes in the lungs, and the gravest attack with a history of definite lung infection may leave the lungs without a trace of the previous pathology. The physical examination is helpful, of course, in determining whether the lesion is at the apices or at the bases, and from this a reasonably safe inference may be drawn as to whether it is from a previous tuberculous lesion or a recent influenzal infection. The Roentgenologist depends almost entirely upon this localization. If the linear striæ are only at the apex, it is probably tuberculous; but if they are only at the base, or also at the base, it is likely to be an influenzal lung. In fact, the Roentgenologist with his present information is ready to admit that it is most difficult to speak definitely of the lungs in these cases. The possibility of confusing the post-influenzal lung with a tuberculous lesion is not peculiar to this epidemic. After the epidemic of 1889 and 1890 the same condition was observed by clinicians. Dr. Roland G. Curtin, of Philadelphia, in 1892 and 1893 conducted a series of clinics at the Philadelphia Hospital, in which he spoke of the “non-bacillary form of phthisis,” and showed case after case which he said might be diagnosed as pulmonary tuberculosis, but because of the recent epidemic and the absence of the tubercle bacillus he diagnosed them as post-influenzal lung.

In the present stage of our knowledge, many of these post-influenzal lungs will not be diagnosed properly until sufficient time is given for either the lung to clear up or the tubercle bacillus to appear in the sputum. We would emphasize the importance at the present time of finding the tubercle bacillus in all suspicious lung lesions before giving a positive opinion as to the tuberculous nature, even though the physical signs are very definite.

Another group of sequelæ is that due to thyroid disturbance, or disturbance of the endocrin system in general. Since the epidemic a number of patients have been seen who noticed an enlargement of a previously normal thyroid gland or greater enlargement of a previously hypertrophied gland. In the same way the symptoms of hyperthyroidism appeared, new in some or a recrudescence in others.

In some of these there was a disturbance of carbohydrate metabolism, as shown by an occasional glycosuria and an increase in the blood sugar, or by a possible disturbance of the suprarenals, as brought out by the administration of adrenalin hypodermatically (Goetsch test). In the application of this test in post-influenzal patients it appeared that the whole endocrin system was in a state of imbalance.

It appears to us not at all improbable that the so-called psychoneuroses of which fatigue, nervousness, irritability and tachycardia play such an important part might also be explained in the same way. These constitute a group of sequelæ which were frequently recognized after previous epidemics, and which are again coming to the foreground.

We are of the opinion, on account of the apparent absence of any specific pathology of the gastro-intestinal tract and its appendages during the attack of influenza, that the sequelæ referred to the digestive system are largely due to exacerbations of previous physiological disturbances or pathological processes. The patient with a previous peptic ulcer has a recurrence of his ulcer. The patient with an infection of the biliary tract has an acute exacerbation, or may have an attack of biliary colic. In fact, there seem to have been many more cases of this kind since the epidemic than before, and most of the patients date the time of the onset from a period soon after recovering from influenza.

Very few, if any, patients in our experience have exhibited sequelæ due to disease of the cardio-vascular or genito-urinary systems. It may be that these will appear later when the more remote effects of an acute infection are recorded.

A very commonplace sequel, but of more or less interest, is the tendency to furunculosis. Our attention was particularly called to the associated hyperglycæmia. The blood sugar readings varied from 0.2 to 0.41. There was no glycosuria, acetone or diacetic acid. We have no explanation to offer for this, although one might dilate readily on many attractive theories. The hyperglycæmia, one may add, was readily reduced by a lowered carbohydrate intake, which also had a curative action on the furunculosis.

Finally we would mention the peculiar epidemic which has been observed apparently over the world, encephalitis lethargica. We do not for a moment put ourselves on record as regarding this disease as a post-influenzal affair, but no one will deny that it has a peculiar time relation to the epidemic; and further, that its distribution is apparently identical. Its bacteriology seems to be unknown. Its local pathology in the mid-brain is not peculiar or at variance with encephalitis produced by known organisms. We have seen five cases; three of whom had had undoubted influenza, while the other two were entirely free from even the slightest suggestion of any type of illness previous to the attack. All of these cases recovered. It has been stated that following the 1890 epidemic a clinical condition was observed in Europe which bears a close resemblance to what has been termed at the present time encephalitis lethargica.

_Prognosis and Mortality of Influenza_

In giving a prognosis of influenza one has to take into consideration the peculiar manifestations of the disease, especially the possible and sudden changes which are liable to take place in the lungs. The points which lead one to feel that the outlook is grave occur in about the following order, which is also about the order of the severity of the symptoms. First, _cyanosis_. This usually appeared quite early and was considered a forerunner of definite lung infection. It may have been a symptom only of the “wet lung,” to which reference has been made, but it was usually followed with definitely recognized pathology in the chest, and it immediately made the outlook unfavorable. Second, _continuation of elevated temperature_. If the temperature fell to normal in three or four days, the outlook was, of course, good; but if it went up again, or if the temperature did not fall in that time, the chances were that there was a lung involvement, even though the chest signs were negative or only those of an acute bronchitis. Strange to say, however, when definite chest signs were once recognized, the height of the temperature or the continuation of fever was not so important a prognostic factor. Third, _increase in pulse rate_. The pulse, as was noted before, was unusually slow, even though the patient seemed desperately ill; when, however, it began to increase in rate the condition was usually very grave. Fourth, _the extent of lung involvement_. This was of very little prognostic value. Both lower lobes might be solid, and yet if there was no cyanosis and the pulse and respirations were satisfactory, the outlook was rather good. On the other hand, there might be the slightest involvement of the lung, and if the pulse were rapid and cyanosis present the outlook was grave. Fifth, _depression and stupor_, or loss of so-called “morale.” If the patient remained clear in his mind, bright and hopeful, no difference how extensive the involvement or how grave the symptoms, the prospect of recovery was better. This is, of course, not peculiar to influenza, but it seemed particularly striking during the epidemic. Sixth, _a gradually rising rate in respiration_, which often was not more than two per minute per day, if progressive, even in the absence of other untoward signs, conveyed a serious prognosis.

Our mortality among the civilians in comparison with the soldiers was exceedingly high. The first cases seen by us were among the soldier patients sent to the hospital. These were as fine a lot of healthy young men as one can well imagine. They came to the hospital comparatively early in the infection. After the first week it appeared as though our experience would be entirely different from those in other localities, for we had very few deaths. In another week our mortality began to rise, but never as high as among the civilians, as will be seen by the following figures.

Of the 153 soldiers 87 were without lung involvement, and of these none died; 66 had lung involvement, and of these 16 died. Mortality among the 153 was 10 per cent. Of the 394 civilians 157 were without lung involvement, and of these 1 died; 237 had lung involvement, or some other complication, and of these 93 died. Mortality among the 394 was 23.6 per cent.

It will be seen that the mortality in the civilians was more than twice as high as in the soldiers. It has already been mentioned that the soldiers were ordered to the hospital promptly. The civilian patients, on the other hand, were later in coming to the hospital, some of them appearing when they had already developed serious complications. Another factor in determining the mortality were the ages of the patients. The soldiers ranged from 18 to 34 years, with an average of 20 years. The civilians ranged from 6 months to 73 years, with an average of 30 years. Generally speaking, the greater the age the higher was the mortality.

A third factor which should be considered in determining the actual mortality is the result of later complications and sequelæ. The figures as given are those of 547 patients, 110 of whom had died in the Mercy Hospital and 437 of whom had been discharged therefrom between September 22 and November 30, 1918, the length of the quarantine. Those who were discharged had been up and about for a week or 10 days before leaving the hospital. From our experience with post-influenzal patients admitted to the Mercy Hospital since November 30, we are of the opinion that some of the patients discharged before November 30 as recovered may have later developed sequelæ which might have proved fatal. No follow-up system has been pursued as yet which enables us to speak definitely and statistically of the present condition of those discharged.

This compilation does not readily lend itself to drawing any more specific conclusions, but we cannot desist from expressing our opinion that in the clinical study of this recent epidemic we find very little that may not have been observed by clinicians in previous epidemics.

THE URINE AND BLOOD IN EPIDEMIC INFLUENZA

By PETER I. ZEEDICK, M. D.

Epidemic influenza, unlike other acute infectious processes as diphtheria and scarlet fever, seemingly attacks the kidney in a rather mild manner. This statement refers only to the uncomplicated cases, as other bacterial or toxic agents do play a part in the nephritides occurring so often with the pneumonias or other complications following influenza. It is, however, true that in many simple epidemic cases there is evidence of a transient mild nephritis, or possibly, more correctly stated, a nephrosis. Some writers observed albuminuria in 80 per cent. of the cases, while the incidence in other reports varies from 4 to 66 per cent. It is not always stated with reference to these figures that the patients clinically were free from the common complication—pneumonia. The findings of various observers differ greatly, but they all agree that acute nephritis as a serious sequel is somewhat rare.

In the literature of the past epidemics general acknowledgment has been accorded to the presence of albumin in the urine during the acute stage of the disease. Many times this has received no further notice or comment than “febrile albuminuria.” The association of occasional hyaline and granular casts has also been mentioned. One is impressed with the fact that the older observers laid but little emphasis on the urinary findings. It also seems to be true that nephritis as a clinical entity is not prone to follow the epidemics. In general, our conclusions from the last epidemic are about the same.

The data for this paper was obtained from examination of 994 specimens of urine from 750 patients; of this number 517 specimens were examined at the Magee Hospital, where members of the S. A. T. C., all young men, were treated, and 447 specimens from the Mercy Hospital, where, in addition to the S. A. T. C., we had men, women and children. On account of the large amount of material and work on hand, as a rule only one specimen of urine was examined from each patient, but where complications were suspected repeated daily examinations were made. We have grouped our results in tables, so that the various points may be more readily followed.

Table I shows the urinary findings of uncomplicated influenza cases admitted to the wards of the Mercy Hospital. None of these cases developed pneumonia and, after running the usual course, recovered. We would call attention to the fact that 25 per cent. showed albuminuria. The amount of albumin was never excessive, and very often was little more than a faint trace. On the other hand, we have had a few patients where a previous kidney lesion was known to be present, and naturally in these cases a heavy cloud of albumin was met with. The albuminuria was almost always a transient affair, lasting only during the acute part of the illness, and would rightly come under the class of febrile albuminuria. We regard it as being more the evidence of nephrosis than a nephritis. As a rule, the time for the appearance of albumin was after the fever had been present for at least two or three days. One rarely met with it in the short attacks of influenza where the temperature came to normal in less than 72 hours. A certain time factor appeared to be necessary in order for the nephrosis to develop. Another point of interest is the presence of red and white blood cells seen relatively frequently during the early days of the illness. One wonders if this finding is analogous to the bleeding from the nose and lung so often met with at the onset of the disease. The red blood cells were seen microscopically, and only very rarely did we encounter a smoky urine.

TABLE I

URINE ANALYSIS IN CASES OF UNCOMPLICATED INFLUENZA AT THE MERCY HOSPITAL

───────┬─────────┬───────────────────────────────┬──────┬──────┬──────
Day of │Total No.│ │ │ │
Disease│ of │ SPECIFIC GRAVITY │ Alb. │R.B.C.│Casts
│Specimens│ │ │ │
───────┼─────────┼───────┬───────┬───────┬───────┼──────┼──────┼──────
│ │1001–10│1011–20│1021–30│1031–40│ │ │
───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼──────
2│ 118│ 8│ 31│ 61│ 18│ 29│ 17│ 8
3│ 97│ 8│ 15│ 62│ 12│ 23│ 10│ 11
4│ 51│ 9│ 22│ 17│ 3│ 11│ 7│
5│ 24│ 4│ 2│ 14│ 4│ 5│ 3│ 4
6│ 11│ │ │ 8│ 3│ 4│ │
7│ 25│ │ 10│ 14│ 1│ 8│ │
8│ 12│ │ 2│ 8│ 2│ 6│ │ 3
9│ 4│ │ 2│ 1│ 1│ 2│ │
18│ 2│ │ 1│ 1│ │ │ │
───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼──────
Totals │ 344│ 29│ 95│ 186│ 44│ 88│ 37│ 26
───────┴─────────┴───────┴───────┴───────┴───────┴──────┴──────┴──────

TABLE II

URINE ANALYSIS IN CASES OF UNCOMPLICATED INFLUENZA AT THE MAGEE HOSPITAL

───────┬─────────┬───────────────────────────────┬──────┬──────┬──────
Day of │Total No.│ │ │ │
Disease│ of │ SPECIFIC GRAVITY │ Alb. │R.B.C.│Casts
│Specimens│ │ │ │
───────┼─────────┼───────┬───────┬───────┬───────┼──────┼──────┼──────
│ │1001–10│1011–20│1021–30│1031–40│ │ │
───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼──────
1│ 101│ 6│ 22│ 49│ 24│ 5│ │ 3
2│ 127│ 1│ 17│ 75│ 34│ 13│ │ 3
3│ 82│ 3│ 13│ 55│ 11│ 13│ 1│ 4
4│ 36│ 1│ 14│ 18│ 3│ 4│ │ 2
5│ 40│ 2│ 9│ 24│ 5│ 6│ 1│ 2
6│ 23│ 1│ 5│ 15│ 2│ 7│ 1│ 3
7│ 5│ │ 1│ 4│ │ 3│ │ 2
8│ 5│ 1│ │ 4│ │ │ │
9│ 2│ 1│ │ 1│ │ │ │
10│ 10│ 1│ 3│ 5│ 1│ 2│ │ 1
11│ 3│ │ │ 3│ │ 2│ │ 1
12│ 3│ │ 1│ 2│ │ 2│ 1│
13│ 1│ │ 1│ 3│ │ │ │
14│ 1│ │ │ 1│ │ │ │
15│ 5│ │ 1│ 4│ │ │ │
───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼──────
Totals │ 447│ 17│ 87│ 263│ 80│ 57│ 4│ 21
───────┴─────────┴───────┴───────┴───────┴───────┴──────┴──────┴──────

The results shown in Table II illustrate the urinary findings at the Magee Hospital, and, as in the previous table, include cases of influenza which did not develop pneumonia. The specimens examined were obtained from young, healthy men, between the ages of 20 and 32, and showed albumin in 13 per cent. of the cases. This age factor probably accounts for the lower incidence of albuminuria for this group.

TABLE III

URINE ANALYSIS IN CASES OF PNEUMONIA (INFLUENZAL) AT THE MERCY HOSPITAL

───────┬─────────┬───────────────────────────────┬──────┬──────┬──────
Day of │Total No.│ │ │ │
Disease│ of │ SPECIFIC GRAVITY │ Alb. │R.B.C.│Casts
│Specimens│ │ │ │
───────┼─────────┼───────┬───────┬───────┬───────┼──────┼──────┼──────
│ │1001–10│1011–20│1021–30│1031–40│ │ │
───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼──────
1│ 47│ 4│ 14│ 25│ 2│ 36│ 7│ 6
2│ 22│ 1│ 8│ 9│ 4│ 19│ 1│ 4
3│ 9│ 2│ 3│ 3│ 1│ 7│ 1│
4│ 6│ 1│ 3│ 2│ │ 4│ 1│
5│ 6│ 1│ │ 5│ │ 5│ │ 1
6│ 16│ 2│ 7│ 7│ │ 13│ 2│ 7
7│ 9│ │ 5│ 3│ 1│ 8│ │
8│ 3│ │ 1│ 2│ │ 3│ │
9│ 3│ │ 2│ │ │ 2│ │
10│ 1│ │ │ │ │ 1│ │
11│ │ │ │ │ │ │ │
12│ 3│ │ 2│ 1│ │ 2│ │
13│ 4│ │ 1│ 3│ │ 3│ │ 1
14│ 2│ │ │ 2│ │ 2│ │
15│ │ │ │ │ │ │ │
16│ │ │ │ │ │ │ │
17│ │ │ │ │ │ │ │
18│ 1│ │ │ 1│ │ 1│ │
19│ │ │ │ │ │ │ │
20│ 1│ │ 1│ │ │ │ │
───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼──────
Totals │ 133│ 11│ 47│ 63│ 8│ 106│ 13│ 19
───────┴─────────┴───────┴───────┴───────┴───────┴──────┴──────┴──────

Table III includes the urinary findings of patients diagnosed as influenzal pneumonia. In this table the term “Day of Disease” indicates the day on which the physical signs of pneumonia could be demonstrated, and not the day on which the patient was taken ill with influenza. The incidence of albuminuria—79 per cent.—is very high, while the presence of casts and red blood cells is low. These results are really what one would expect. As we have noticed in the late stages of uncomplicated influenza a greater tendency for urinary changes to become apparent, one would, therefore, most likely find considerable urinary disturbance in the pneumonia immediately following the epidemic disease. Pneumococcic pneumonia is prone to be accompanied by an albuminuria. So when we have both influenzal and pneumococcic etiological factors involved, it is but natural to have most of the patients showing signs of kidney disturbance. The amount of albumin present, although generally greater than in uncomplicated influenza, was not excessive. At times there was little more than a trace. We noted the relative scarcity of casts—a condition which differs greatly from our past experience in the ordinary lobar pneumococcic pneumonia. On the transient nature of this kidney involvement we have considerable positive evidence, but there is no question that the time required for the urine to return to normal is longer after pneumonia than uncomplicated influenza. We have observed but one or two cases which afterward returned to us presenting clinical signs of acute nephritis. In fact, in going over our hospital records of the winter and spring we noted that an unusually small number of acute nephritics have been admitted. This would seem to be evidence that, as has been noted in the past, the kidney is not a vulnerable organ in this epidemic disease.

TABLE IV

URINE ANALYSIS IN CASES OF PNEUMONIA (INFLUENZAL) AT THE MAGEE HOSPITAL

───────┬─────────┬───────────────────────────────┬──────┬──────┬──────
Day of │Total No.│ │ │ │
Disease│ of │ SPECIFIC GRAVITY │ Alb. │R.B.C.│Casts
│Specimens│ │ │ │
───────┼─────────┼───────┬───────┬───────┬───────┼──────┼──────┼──────
│ │1001–10│1011–20│1021–30│1031–40│ │ │
───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼──────
1│ 3│ │ │ 2│ 1│ 1│ │ 1
2│ 12│ │ 1│ 10│ 1│ 8│ │ 6
3│ 4│ │ │ 4│ │ 1│ 1│ 1
4│ 9│ 1│ 2│ 4│ 2│ 6│ │ 6
5│ 8│ │ 4│ 4│ │ 6│ │ 5
6│ 8│ │ 5│ 3│ │ 7│ 2│ 6
7│ 4│ │ 2│ 2│ │ 3│ │ 2
8│ 10│ │ 2│ 8│ │ 5│ 2│ 5
9│ 4│ │ 2│ 2│ │ 4│ 3│ 4
10│ 6│ │ 1│ 5│ │ 6│ 3│ 5
11│ 1│ │ 1│ │ │ 1│ │ 1
12│ 1│ │ 1│ │ │ 1│ │
13│ │ │ │ │ │ │ │
14│ │ │ │ │ │ │ │
15│ 2│ │ 2│ │ │ 1│ │ 1
───────┼─────────┼───────┼───────┼───────┼───────┼──────┼──────┼──────
Totals │ 70│ 1│ 20│ 45│ 4│ 49│ 11│ 40
───────┴─────────┴───────┴───────┴───────┴───────┴──────┴──────┴──────

Table IV includes specimens obtained at the Magee Hospital from patients diagnosed as pneumonia. The results among these young students were very similar to those of the previous chart, where all ages were included. However, casts and red blood cells were more regularly noted.

From the four tables, we are able to note one or two common facts. In acute uncomplicated influenza albuminuria occurred 57 times in 447 specimens, or 13 per cent., at the Magee Hospital. Here we dealt entirely with the young adult. At the Mercy Hospital 88 positive results of albumin in 344 specimens, or 26 per cent., from patients of all types were recorded. The common total would be 781 specimens examined, and 141, or 17 per cent., showing albumin.

With the advent of pneumonia the incidence of albuminuria was increased. At the Magee Hospital it was seen 49 times in 70 examinations, or 70 per cent.; while at the Mercy Hospital 106 positive results were found in 133 specimens examined, a percentage of 79. The combined figures, therefore, would show 155 out of 203, or 76 per cent.

The incidence of albuminuria for the epidemic in all its phases would be, from our figures, 400 in 994 specimens, or 40 per cent.

Red blood cells were present in 5 per cent. of the influenza cases, and in 11 per cent. of the pneumonias. This was always a microscopic observation, save in the case of a slightly smoky urine. Even microscopically the red cells were not numerous. We noted them at times quite early in the disease in some of the severe cases which presented epistaxis and hematemesis. Possibly one might consider the early presence of red blood cells in the urine as a condition analogous to those just mentioned, although we never saw anything suggesting free hemorrhage from the kidney. It is probably better to regard the red cells as a manifestation of an acute nephrosis of toxic origin.

Casts were found in 35 per cent. of the cases showing albuminuria. We are inclined to feel that this observation is somewhat low, but at the same time we have noted that in uncomplicated influenza one frequently sees albumin without casts. We were also impressed with the fact that casts were not as prominent a feature in the influenzal pneumonias as they are in frank lobar pneumonia of essentially pneumococcic origin.

During the course of routine examinations several transient glycosurias were seen. Their transient character was the outstanding feature. The quantity of sugar was very moderate—our figures were never above 1 per cent.—and the daily amount of urine was always within normal limits. Acetone and diacetic acid were absent. A few observations on the blood sugar showed a rise (.2 to .25), which readily came to normal with treatment. Clinically these cases were not classed as diabetes mellitus, but rather as a nervous complication of influenza, involving in some way the carbohydrate metabolism, probably through the central nervous system. One case of special interest, which is mentioned elsewhere, was the association of glycosuria with almost total blindness from a very intense optic œdema. Sugar (1 per cent.) was present on the day of admission, while only a trace was noted on the two following days, and from then on the urine was free from sugar. How many days the sugar had been present before admission to the hospital we cannot say, but we could trace the failure of vision back to almost the day of its onset, which was three weeks previous to our first examination. The eye symptoms were the only complaints. The patient had had a moderately sharp attack of influenza a little over two weeks before the first sign of failure of vision had appeared. We may add that the vision returned slowly to normal several weeks after admission. The urine and blood sugar were normal, on a general diet, over a period of one month while in the hospital. Unfortunately, we have had no further record of this patient regarding the urine, but her vision still remains normal. Cases of this type were observed in England after the 1890 epidemic, and are referred to in Allbutt’s “System of Medicine,” vol. i, on influenza. Our other glycosuria cases did not present changes in the fundus of the eye. The glycosuria and glycæmia were transient, and we feel that they do not represent diabetes mellitus. Most of the patients of this class had long since recovered from an attack of influenza, and came to the hospital usually for treatment of various nervous conditions, which at times simulated neuritis, or otherwise one saw manifestations of general nervousness, not unlike hyperthyroidism. In all probability, we were dealing with a hyperglycæmia associated with a hyperactive thyroid gland. So, after all, the glycosuria, even though rare, is not bewildering. Symptoms and signs of toxic goitre in direct relation to the epidemic we claim to have seen, and one is justified, temporarily at least, in having the thyroid gland father our transient glycosuria.

In relation to the positive sugar findings, we have had numerous negative examples of almost equal interest. Furunculosis is a very common sequel of the epidemic. It is well known that in furunculosis there is a hyperglycæmia, but no glycosuria and no acetone or diacetic acid in the urine. All our blood sugar readings were above the normal, and at times unusually high. They varied from .2 to .41. This last unusually high amount was in a young physician with recurrent furunculosis following influenza. There was no glycosuria at any time. Elimination of carbohydrates not only brought the blood sugar to normal limits in the course of a week, but also assisted in the cure of the furunculosis, but in a longer time. In all of this group we saw no incidence of polyuria or glycosuria.

_Hematology_

There is very little evidence, as shown in the literature, that special study on the blood during past influenzal epidemics has been made. A few references to alterations in the count of cells have been reported for the last epidemic (1890), but they are, as a rule, very brief statements. Cabot notes a normal leucocyte count in two-thirds of the cases, and a moderate increase in the rest. Several observers call attention to the leucopenia during the height of the disease, with a subsequent rise after the temperature has fallen to normal. According to Rieder and Herman (American Journal of Medical Science, 1893, cv. 696), the leucocytes were not increased in simple influenza, and only very slightly in the pneumonia following this disease. Herman also noticed a decline in the leucocytes in pneumonia as a fatal ending ensued. This finding was one of the few recorded for the 1890 epidemic. Emerson (Emerson Clinic Diagnosis, 1911, 558) found in influenza almost one-half of the cases showing more than 10,000 leucocytes, some even reaching 25,000. He further notes that early in the disease the count may be low, 3,000 to 5,000, but it usually rose sharply, to fall again when the temperature comes to normal. He lays stress on obtaining a leucocyte curve for each case in order to get a true picture of what changes occur. The past epidemic has brought out many observations on this subject. They vary somewhat, as is to be expected, but a common factor seems to be more or less basic—namely, a leucopenia or a normal count is the most significant single blood picture we have of uncomplicated influenza. Further, a leucocytosis is fairly generally, and we believe correctly, interpreted as evidence of a secondary bacterial invasion in this particular epidemic, and usually of the respiratory system. The leucopenia is as much a part of the clinical picture of influenza as it is of typhoid fever. Leucocytosis always means secondary invasion by other organisms.

During the recent epidemic the clinical laboratory department of the School of Medicine, University of Pittsburgh, has made 747 blood counts on influenza cases. In most of the cases blood counts were made as a routine, while repeated counts were done only on selected patients.

The following table indicates the leucocyte count for our series, comprising the epidemic in all of its phases. There are a few general points which appear striking that we may refer to at this time, and leave until later the discussion of the minor details. One-third of the counts, including, as they do, many cases of pneumonia, showed a leucopenia, while 70 per cent. of the total number fell under 10,000. This last group contains more pneumonias and other complications than simple influenza. But 5 per cent. of the cases counted showed more than 20,000. All of these undoubtedly had pneumonia or some other complication. Comparing this finding with our experience in the past before the epidemic with the pneumococcic lobar pneumonia, one sees at once that, as far as this type of clinical observation is concerned, the two pneumonias are totally different. The writer remembers but one case of lobar pneumonia which showed a persistent white count falling below 10,000. Certainly in this community lobar pneumonia and low leucocyte counts were unusual combinations until the present epidemic. Further, the evident depression of leucocytosis even where there was an actual increase is indicated by 95 per cent. of our counts being below 20,000. This leads us to state that the pneumococcus, although present in practically all of our pneumonias, produced in only a small percentage of the bloods we examined its characteristic increase. The toxic factor of this influenzal epidemic certainly causes a marked change in the white cells of the blood.

TABLE V

MERCY HOSPITAL │ MAGEE HOSPITAL
───────────┬──────┬──────┬──────┬─────┬─────┼──────┬─────┬─────┬─────
│ │ │ │ │ │Influ.│ │ │
Leucocyte │ │Influ.│Influ.│ │ │Influ.│ │ │
Count. │Influ.│ Pn. │Compl.│Total│ % │ Pn. │ % │Total│ %
│ │ │ │ │ │Influ.│ │ │
│ │ │ │ │ │Compl.│ │ │
───────────┼──────┼──────┼──────┼─────┼─────┼──────┼─────┼─────┼─────
2000 or│ │ 2│ │ 2│ 38│ 1│ 28│ 3│ 32
less│ │ │ │ │ │ │ │ │
2000–3000│ 3│ 3│ 1│ 7│ │ 13│ │ 20│
3000–4000│ 7│ 12│ 4│ 23│ │ 34│ │ 57│
4000–5000│ 14│ 13│ 9│ 36│ │ 41│ │ 77│
5000–6000│ 17│ 16│ 6│ 39│ │ 42│ │ 81│
│ │ │ │ │ │ │ │ │
6000–7000│ 15│ 13│ 6│ 34│ 40│ 59│ 37│ 93│ 38
7000–8000│ 7│ 8│ 5│ 20│ │ 36│ │ 56│
8000–9000│ 8│ 14│ 8│ 30│ │ 37│ │ 67│
9000–10000│ 15│ 9│ 8│ 32│ │ 39│ │ 71│
│ │ │ │ │ │ │ │ │
10000–12000│ 4│ 12│ 9│ 25│ 20│ 44│ 27│ 69│ 25
12000–14000│ 1│ 1│ 8│ 10│ │ 28│ │ 38│
14000–16000│ 5│ 3│ 2│ 10│ │ 22│ │ 33│
16000–18000│ 3│ 2│ 2│ 7│ │ 16│ │ 23│
18000–20000│ 2│ 2│ 2│ 6│ │ 15│ │ 21│
│ │ │ │ │ │ │ │ │
20000–22000│ │ 1│ 1│ 2│ 2│ 4│ 5│ 6│ 3
22000–24000│ │ │ 1│ 1│ │ 8│ │ 9│
24000–26000│ │ │ 1│ 1│ │ 4│ │ 5│
26000–28000│ │ │ │ │ │ 2│ │ 2│
28000–30000│ │ │ 1│ 1│ │ 3│ │ 4│
│ │ │ │ │ │ │ │ │
30000–32000│ │ │ │ │ │ 3│ 3│ 3│ 2
32000–34000│ │ │ │ │ │ 3│ │ 3│
34000–36000│ │ │ │ │ │ 3│ │ 3│
36000–38000│ │ │ │ │ │ │ │ │
38000–40000│ │ │ │ │ │ 1│ │ 1│
40000–42000│ │ │ │ │ │ 2│ │ 2│
│ │ │ │ ———│ │ ———│ │ ———│
│ │ │ │ 287│ │ 460│ │ 747│
───────────┴──────┴──────┴──────┴─────┴─────┴──────┴─────┴─────┴─────

The blood picture in uncomplicated influenza is a normal one for the red cells and the hæmoglobin, but the white cells are characteristically altered. We have made many observations on the red blood cells, and from all aspects the picture appears to be normal. Similarly, there is nothing significant about the hæmoglobin estimations. Where we have slight alteration in the red count and in the hæmoglobin it is probably safer not to attribute the change to the epidemic. We have no records showing a secondary anæmia due to the initial epistaxis.

A leucopenia or a normal count is what one should see in most of the uncomplicated influenzal cases. We are almost ready to say that any estimation above normal limits means secondary bacterial invasion. The count may remain low throughout the illness, rising to the normal rapidly as the temperature falls. We do not regard a leucocytosis at the end of an epidemic case as part of the blood picture. Our experience is that with convalescence the normal count returns and remains within normal bounds. Very often hidden sinus infection is responsible for some of the post-influenzal leucocytoses. The leucopenia may vary from a slightly subnormal count to a point well below 2,000. Most of the simple epidemic cases showed some degree of leucopenia. As far as we have been able to estimate, we are led to believe that one should not lay any special stress on the grade of leucopenia as being of prognostic significance in uncomplicated influenza. Many of the mildest clinical types showed very low counts, and _vice versa_. There is, however, a prognostic relation to be noted with reference to a falling white count in the pneumonia, but this we shall mention again later. The onset of the leucopenia corresponds to the onset of the disease. It was present with the earliest cases we examined, and remained fairly stationary, although we have records of its fluctuating slightly one way or the other. But one must remember in this regard the personal error in blood counting, and also particularly the error of the apparatus. For careful work only those counting chambers and pipettes should be used that have a Bureau of Standards certificate. The duration of the leucopenia was fairly close to the duration of the disease.

How many cases of influenza of several days’ illness having about 12,000 leucocytes, a few sticky râles in the chest, but no signs of definite consolidation, have been observed by the clinicians? These cases recover without further change, and the diagnosis is handed in as influenza without a complication being mentioned. In collecting the blood reports from this group the 12,000 cells accordingly must be considered as having occurred in a simple influenza. We hold that this is not a case of uncomplicated epidemic disease. There is undoubted evidence, as is acknowledged by the clinician, of a bronchiolitis; and how many lungs showing a bronchiolitis at autopsy fail to have a broncho-pneumonia? True it may not be demonstrable by our physical examination. This is often the origin of many high counts in what apparently is considered uncomplicated influenza.

The blood picture of the pneumonia following the epidemic was more or less constant, although at the same time the features of the count may be quite different. One could roughly divide the results into three groups: (1) leucocytosis, (2) leucopenia, (3) intermediate or normal. Some pneumonias could be followed during their course through all of these classes. Before discussing the white count we can briefly dismiss the other phases of the blood examination by stating that the red blood cells and hæmoglobin presented nothing by the usual examinations which was of special significance, or in any way characteristic.

As an example of the group showing a leucocytosis let us follow a patient through an acute influenzal attack, followed by a pneumonia with a subsequent recovery. An initial leucopenia, gradually or suddenly changing into a very moderate leucocytosis (10,000–15,000), was noted at the onset of the pneumonia. During the course of the complication the number of cells in the majority of cases increased, but rarely advanced beyond 20,000. With lysis or crisis the count dropped toward normal, and by the time the lung signs had disappeared the white cells were at the usual number, or very slightly increased. The point which seemed to us to be of importance was that, even although we had a leucocytosis, it was nothing like the count that one would expect for a lobar pneumonia. Of course, there were a few high counts, but looking at the group as a whole they were relatively low. There are a number of variations to this form of blood picture which we might briefly consider. We have observed secondary rises in the leucocyte count concurrent with a new lung involvement. This type was the one so prone to develop into a condition of non-resolution, fibrosis and ultimate death, with a continuous moderately high leucocytosis to the end. Another variation which we learned to fear was the fall of leucocytes to normal or subnormal after a primary rise, when the clinical course of the case in no way indicated a crisis or lysis pending. Seemingly, the longer the primary leucocytosis had been present the more serious was the subsequent leucopenia. We regard this form of secondary leucopenia, if one may use such a term, as a prognostic sign of some value. As in lobar pneumonia, a high leucocyte count has been, as a rule, a favorable feature.