Part 6

Assistance from the laboratory was meager, especially in the early days of the epidemic. This was due largely to the inability to get laboratory workers in sufficient numbers to follow the work through, but more largely to the fact that we were unable to interpret the unusual laboratory results which were available. When we were once fully aware of the difficulties in diagnosis which confronted us, we utilized every practical means at our disposal. Among these was an examination of the chest with the X-ray. On account of lack of facilities and of help, it was impossible to make routine X-ray examinations of the chest in all cases. Besides, it was difficult to interpret the X-ray findings, on account of the unusual character of the lesions. Also, many of the patients were so desperately ill one hesitated to disturb them. We hear that other clinics had similar experiences, and that very little substantial help came from the X-ray, except in cases with complications. Several attempts were made to determine the kind of shadow, if any, the “cyanotic, œdematous, wet” lung would make, but no satisfactory observations have been forthcoming. From our own observations and from the discussions of other observers, it would seem to us that the stereoscopic examination of these chests is the only possible way of getting satisfactory plate readings in these cases where the pathology seems so lawless in its extent and peculiar in its distribution. This method of examination, however, demands facilities convenient at the bedside and perfect co-operation of the patient—difficult conditions to meet under the circumstances. In the acute cases, when the desire to make a diagnosis not only of the presence but of the extent of the disease was keen, X-ray examination was largely impractical. In cases of delayed resolution, or in cases with complications with prolonged convalescence, X-ray examinations were extremely helpful.

Diagnosis of Influenzal Pneumonia

In the consideration of any disease the well-trodden path of a painstaking history, a thorough physical examination, and reliable laboratory investigation, together with an intelligent interpretation, will usually lead to a definite diagnosis. In certain diseases, as is well known, the stress must be placed about equally on all of these factors, while in others one or other factor predominates. In influenzal pneumonia, until more is known of the etiology (bacteriology) and of the pathological changes and of the physiological disturbances, the controlling factor in the diagnosis (we feel embarrassed to admit) must be the history. This is true not only of the diagnosis of influenza with or without pulmonary involvement, but is also true of the diagnosis of the various complications, and will be found to be particularly true in the recognition of the bizarre sequelæ, which no doubt in the succeeding months or years will be attributed to or will follow in the train of influenza.

With the knowledge that there is a prevailing epidemic of influenza and that the manifestations are largely in the respiratory tract, any pulmonary disturbance will necessarily make one suspicious of the presence or the oncoming of an influenzal pneumonia in the patient under consideration. The history of the onset, as of simple influenza, is the greatest factor. This with a continued temperature, cough, cyanosis, slow pulse, continued asthenia, or even an unusual leucopenia, may have a greater weight in determining the diagnosis of lung involvement than will the apparently definite or, as it may happen, the confusing chest signs. To differentiate from ordinary bronchitis, broncho-pneumonia and catarrhal pneumonia, one need only refer additionally to the severity and persistency of the disease when it is of the influenzal type, as compared with the mildness of the ordinary type. To differentiate it from croupous pneumonia, one need only compare the confusing symptom picture of the influenzal pneumonia with the definite, clear picture of ordinary pneumonia; or the confusing kaleidoscopic chest signs of the one with the definite, clear-cut signs of the other. The laboratory thus far has been the smallest factor in making the diagnosis, in that sputum examinations, blood examinations, blood cultures and urine examinations are mostly negative in their results, or at least the findings are not specific. We do not, however, mean to indicate that these tests are not of the greatest value. The leucopenia is the one outstanding feature which seems to have separated this infection from other acute lung infections, excepting miliary tuberculosis. The differentiation of influenzal pneumonia from an acute tuberculous process in the lung may be difficult, especially if there is no reliable history available. However, the fact that pulmonary tuberculosis usually begins at the apices of the lungs and influenzal pneumonia at the bases or at the apices of the lower lobes is quite helpful. Of course, the examination of the sputum for tubercle bacilli will be a deciding factor.

The differentiation between influenzal pneumonia and diseases of the pleura is one which practically rarely needs to be made, for there seem to be very few cases of influenzal infection of the lungs in which the pleura is not also involved to a greater or lesser extent.

Complications

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.