Chapter XXV: Part II: , Showing Predominance of Malarial Element . . . . 617 (24)

The character of the stools varies much; usually thin and dark, they may be light yellowish or even whitish. Thus, in a severe case with deep jaundice we observed seven liquid and decidedly whitish stools in twenty-four hours. In such instances there is undoubtedly more or less complete closure of the biliary ducts by plugs of mucus or by swelling of the mucous membrane. On the other hand, the stools may be inky black from admixture with altered blood, or, lastly, they may consist of mucus and blood, in which event the complication assumes the form of actual dysentery and is attended with increased abdominal pain and with tenesmus. Dysentery was, as would be expected, quite frequent in the Indian epidemics studied by Carter.[24] It is usually of moderate severity, but occasionally it runs into gangrenous inflammation, is attended with perforation of the bowel, or is followed by hepatic abscess. In one instance we noticed a peculiarly fetid puriform discharge from the anus, which occurred during the relapse and persisted for several weeks, gradually subsiding, as though from some unhealthy ulceration which slowly healed.

[Footnote 24: _Op. cit._, p. 218.]

Jaundice is of frequent occurrence, but has been sufficiently discussed at page 391.

Peritonitis is not rare in its circumscribed form. This statement is based on the comparative frequency with which localized splenic peritonitis, of varying degrees of severity, is found after death in relapsing fever from various causes, and from the great frequency of severe pain and tenderness in the region of the enlarged spleen in favorable cases. In its lesser degrees it may not add materially to the danger of the patient, but in more severe forms, associated with serious splenic lesions, it may run a protracted subacute course and maintain irregular fever.

General peritonitis is, on the other hand, a rare complication, occurring not more than once in several hundred cases. It results from dysenteric perforation of the bowel, from rupture of a splenic abscess, or from rupture of the spleen itself. An example of this latter accident which occurred under our observation has already been given. Speedy death invariably follows, though in the case just referred to the symptoms of peritonitis were totally masked by those of the coexisting double pneumonia, which seemed to be the immediate cause of death.

Suppuration of the mesenteric glands is a rare complication, mentioned especially by Wyss and Bock. As these glands are not usually found enlarged, there being no irritative lesion of the intestines of common occurrence in relapsing fever, it is probable that the collections of pus which have been found were metastatic in origin.

Dyspepsia is not an infrequent sequel, as would necessarily be the case after a disease characterized by so much gastric irritation and by such serious lesions of the liver and spleen. As a consequence, care in diet is often required for a considerable period after the course of the disease has ended; dyspeptic symptoms are frequently complained of, and marked emaciation and anæmia often protract convalescence.

{407} It may be observed that a striking appearance of emaciation is often developed shortly after the crisis of the first paroxysm, or, more particularly, of the relapse. It is partly due to the actual loss of weight during the high pyrexia, but even more to the abrupt transition from a state of extreme febrile turgescence to one of equally extreme relaxation and maceration of the surface.

The amount of urine has been seen (p. 387) to vary greatly in cases distinguished by no special disorder of the kidneys; the extremes in ordinary cases being from twelve or fifteen ounces just before the crisis to from eighty to one hundred and twenty within forty-eight hours after the crisis. Suppression is, however, sometimes noted, and is always a grave symptom, though Parry[25] reports more than one case in which on several successive days there was not more in twenty-four hours than one fluidounce of non-albuminous urine, and in which no symptoms of uræmia occurred, and the sweat had no urinous odor. In one of our fatal cases, with intense jaundice, hematemesis, inky black stools, and oedema of the feet and of the lungs, there was not a drop of urine secreted during the last four days of the initial paroxysm; death occurred on the eighth day, and the kidneys were found intensely engorged, of a deep blackish-blue color, with numerous ecchymoses in the cortex, due to impaction of the convoluted tubules with blood, while the renal epithelium was granular and swollen, and many tubules were filled with epithelial cells and granular matter. At the autopsy the urinary bladder was firmly contracted and contained a very small amount of bloody liquid.

[Footnote 25: _Op. cit._]

More frequently, incontinence of urine, with or without retention, occurs during the febrile stages--according to our observation, most commonly in cases attended with mental disturbance and tending to a typhoid condition. The symptom was not of very grave significance, however, and after the use of the catheter for a few days the bladder regained its tone.

Albumen is quite frequently present in small amounts during the pyrexia of relapsing fever. Thus, in 18 cases of ordinary severity, which all recovered, and in which the urine was carefully examined daily, a trace of albumen was found in 5; in 2 cases it appeared both in the initial paroxysm and in the relapse, but in all instances its presence was of brief duration. In one of these five cases the albumen appeared at both critical periods, when the amounts of urine in twenty-four hours were respectively 150 ccm. and 250 ccm.; but in the other cases the transient albuminuria coincided with free secretion of urine (1250 ccm., 1850 ccm.). It is probable that were the same careful search to be made in all cases the presence of albumen would be detected in fully 20 to 25 per cent. On the other hand, in fatal cases the occurrence of albuminuria is by no means constant, although undoubtedly it is present in a larger proportion of such cases than of those of ordinary severity.

Our experience does not confirm that of Murchison, who states that he never met with typhoid symptoms in relapsing fever without albuminuria or some other evidence of retarded elimination by the kidneys. In several of our cases where the typhoid state was developed in the highest degree repeated examination of the urine failed to discover albumen.

{408} Most observers have been struck with the comparative immunity of the kidneys from serious disturbance in a disease presenting such complicated morbid processes and widespread lesions as relapsing fever. To show, however, that these organs suffer specially in certain epidemics, it may be mentioned that Obermeier[26] reports having found albumen with tube-casts of various kinds in 32 out of 40 cases of relapsing fever, thus showing that, in the particular epidemic he was studying, catarrhal nephritis was of almost uniform occurrence. It is true that serious interference with the elimination of urea and other nitrogenous matters may occur without the coexistence of albuminuria, so that it is impossible to deny that severe nervous symptoms may result from impaired renal activity even when the urine contains no albumen.

[Footnote 26: "U. d. wiederkehrende Fieber," _Arch. f. path. Anat. u. klin. Med._, Bd. xlvii. p. 170.]

Attention has already been called to the variations presented in the amounts of urea, but more extended observations are required to show the precise relations of these variations to the graver nervous phenomena. It will be found, we venture to opine, that, while in one group of relapsing-fever cases of grave type, cerebral symptoms are dependent upon the retention and accumulation in the system of urea and other effete nitrogenous products, owing to interference with renal activity from pre-existing organic disease of the kidneys or from an exceptional degree of congestion of those organs, there are other groups where similar typhoid cerebral symptoms are more directly dependent upon the specific toxæmia, upon the hyperpyrexia, upon exhaustion of the nerve-centres by intense peripheral irritation, or upon congestion or other morbid conditions of the nerve-centres themselves.

In all cases where cerebral symptoms manifest themselves in relapsing fever the daily examination of the urine--which here, as in other zymotic diseases, is a duty in all cases--becomes of extreme importance. Three conditions should be borne in mind in such examinations. In the first place, the attack of fever may have occurred in one already the subject of organic kidney disease, and, considering the classes from which the majority of the cases of relapsing fever are drawn, this possibility cannot be of rare occurrence. Out of eighteen post-mortem examinations in which the kidneys were studied with especial care we found positive evidence of pre-existing organic disease four times. In these cases the albuminuria was marked and persistent, though tube-casts were rarely found, and severe cerebral symptoms of typhoid type were prominently present. In another highly interesting case the patient, who had amyloid disease of the liver, spleen, and kidneys, contracted severe relapsing fever; he had increased albuminuria during both febrile stages, suppurative parotitis, but no grave cerebral symptoms, and apparently recovered. After an apyretic period of six weeks, during which the symptoms of the amyloid visceral disease persisted, a sudden and rapidly fatal pyrexia occurred. Unfortunately, the existence of spirillar infection of the blood was not known at the time.

In the second place, the attack of fever may become complicated with acute nephritis from special localization of the poison, as in Obermeier's cases, or from vulnerability of the kidneys. In such cases careful study of the urine should indicate the event, and the prognosis, though grave, is not so hopeless as in the first instance. An interesting example of {409} this occurred under our observation, where the patient, who had apparently an ordinary attack, was seized with acute catarrhal nephritis, with temporary uræmia, during the relapse, but after a dangerous illness recovered without any organic renal disease as a sequel.

In the third place, may be found the more usual and more readily-determined condition of slight and transient albuminuria (with variations in urea excretion) which has already been discussed, and which has no serious prognostic significance.

The following very interesting case deserves special mention: The patient, a man aged thirty-six, was admitted on the fifteenth day of an attack of acute catarrhal nephritis, with slight ascites, marked oedema of the feet and legs, and highly albuminous urine. In the course of ten days the oedema and albuminuria were much diminished, when on the thirteenth day after admission he was attacked with relapsing fever, the ward in which he lay containing a number of persons ill with that disease. The initial paroxysm was severe, but without any grave cerebral symptoms; the urine grew scanty, dark, and bloody, and the oedema increased and invaded the pelvis. Crisis occurred on the fifth day, temperature falling 9°, sweating copious, urine 473 ccm. in twenty-four hours, color of porter, highly albuminous, and depositing blood, renal epithelium, hyaline, granular and epithelial casts, all stained reddish. Two days later, urine 1600 ccm., light colored, with only a small amount of albumen.

A slight and brief relapse (101° for two days) occurred after an interval of four days; a second imperfect relapse (100.5° for three days) after a further interval of six days; and finally, after a further interval of only two days, a violent relapse (temperature rising rapidly to 106°) with crisis (fall of 8° in twelve hours) at close of fifth day. The oedema gradually diminished from the time of the first crisis, did not increase in the relapses, and disappeared completely and finally about ten days after the last relapse. The urine was very free after the first paroxysm, averaging from 2000 to 2300 ccm. During the subsequent febrile periods it did not decrease, and indeed on the second day of the last relapse, with the temperature at 105°, the amount in twenty-four hours was 3200 ccm. Four days subsequently, during crisis, the amount was only 350 ccm.

The albumen disappeared entirely from the urine in two weeks from the close of the last relapse; there had then been no tube-casts for some days, and the patient was discharged entirely well a short time afterward. The treatment consisted of hot vapor-baths, repeated dry cupping over the kidneys, infusion of digitalis with acetate of potash during pyrexia, and Basham's iron mixture in the intermissions. It seemed that the occurrence of the relapsing fever interfered wonderfully little with the recovery from nephritis.

Hematuria is a comparatively rare and very grave complication. It may occur as an additional evidence of the dyscrasia of the blood in connection with hemorrhages from other surfaces, or as in the case we have before referred to or in that reported by Murchison,[27] it results from intense engorgement of the kidneys. In Murchison's case hematuria, with much albumen and tube-casts, occurred in both paroxysms {410} without any uræmic or typhoid symptoms, and was followed by satisfactory recovery.

[Footnote 27: _Op. cit._, p. 370.]

Sugar is sometimes present in small quantity as a transient symptom; and diabetes has been observed as a sequel.[28]

[Footnote 28: Tyson, _Phila. Med. Times_, 1871, i. 418.]

Metastatic inflammation of the kidneys, with centres of suppuration, was observed by Wyss and Bock.

When menstruation occurs during relapsing fever, as it may do at any time, it is apt to be excessive, and may amount to severe hemorrhage. Crisis has been known to occur in this manner.

The numerous cases reported by various observers of relapsing fever occurring in pregnant women establish the rule that abortion almost invariably occurs, whatever may be the stage of the pregnancy. In a large majority of cases the mother recovers, but the child, if viable, is stillborn or dies in a few hours. Only two of our patients were pregnant women, and the result in each was unusual. In one, the patient, already the mother of several children, was in the fifth month of gestation; the initial paroxysm was severe, with delirium, but no symptoms of abortion occurred; the intermission lasted six days, during which she felt very well; the relapse was also severe, and crisis occurred on the fifth day, the temperature falling below normal, and the case promising to do well; but on the following day there was a sudden rebound of temperature, pulse 140, severe præcordial pain, and death occurred in twenty-four hours, the contents of the uterus being partially expelled during the act of dying. In the other case, a girl of eighteen years, who had aborted at the third month of gestation eight months previously, and who was again three months advanced in pregnancy when attacked with relapsing fever, went safely through a bad attack and carried her baby successfully to full term.

MORBID ANATOMY.--The surface of the body often presents patches of livid discoloration, and jaundice persists in cases where it has been present during life. There is but little appearance of emaciation, except in cases where it has been present before the attack.

When death occurs while the temperature is high the body remains warm an unusual length of time. Thus, in one case where death occurred at 11.30 P.M., the temperature at 12 was 103°, and at 1 A.M. it was 101-3/5°, that of the room being 73°; at 6 A.M. it remained at 93°, the room being at 73°; between 9 A.M. and 2 P.M. the room was kept at 55°, but the body was still at 82° at the latter hour.

The voluntary muscles are often jaundiced, and in prolonged cases they may be found flabby and having undergone marked granular degeneration. In many cases, however, they remain quite dark and firm. Ecchymoses of the muscular substance are met with occasionally.

In one case, where during life there had been painful swelling of the left parotid region, with fistulous openings on the cheek, and where death occurred on the twelfth day of the disease, the masseter muscle was swollen, with patches of dark, almost black, discoloration from ecchymosis, and was studded throughout with small collections in its substance. The fluid from these contained very numerous cells indistinguishable from leucocytes. The muscular fibrils were friable and granular, and there was multiplication of the nuclei of the sarcolemma. {411} These unusual lesions seemed to have originated in interstitial disintegrating thrombi, with consequent inflammation of the muscle.

The muscle of the heart is more frequently affected, and in the fatal cases our attention was particularly drawn to those lesions. Ponfick[29] has also described them minutely. The degree of change varies from a partial loss of transverse striation, with slight granular appearance, up to a very high degree of granulo-fatty degeneration. The organ is then flabby, its substance pale gray or brownish, either wholly or in streaks, and microscopic examination shows an extreme degree of fatty granular change. It must not be forgotten, however, that many of the subjects of relapsing fever have been leading irregular and dissipated lives, and that in some instances the lesions of fatty degeneration detected in their organs may have been the result of their previous habits.

[Footnote 29: _Virchow's Archiv. f. path. Anat._, Bd. lx. Hft. 2, p. 162.]

Lesions of the cardiac muscle were most marked in those of our patients who had been intemperate, and in whom fatty degeneration of the viscera (chiefly liver and kidneys) was also found. They were most fully developed in cases where death occurred at a comparatively late period, while in some very severe cases, in which death occurred as early as the fifth day, the cardiac fibre presented merely faintness of striation without actual granular degeneration.

Ponfick in particular notes that the great majority of the bodies he examined were of persons who had been habitual drunkards.

Pericarditis is occasionally present, and is marked by the usual lesions. In a very severe case in which it contributed largely to the production of the fatal result it was associated with pneumonia. In addition to this, effusions of blood beneath the endocardium and pericardium are not rare; and we have seen them quite large and numerous in cases where the muscular fibre was firmly contracted and the cavities contained quite firm decolorized clots.

Thus in our case No. 62, Series C., "the heart was normal in size, with no appearances of previous disease. There were numerous ecchymoses of both layers of the pericardium. The right cavities contained large, firm, yellowish, fibrous clots, forming a cast of the upper part of the ventricle and of the auricle, and extending both into the pulmonary artery and back into the veins, and so firm that by gentle traction a complete cast of these vessels was drawn out. The clot in the pulmonary artery was throughout firm, fibrous, and yellowish. There were numerous ecchymoses of the pleura and of the mucous membranes of the stomach and urinary bladder, hemorrhagic infarctions in the kidneys and lungs, and granulo-fatty degeneration of the cardiac muscle." Death had occurred in this case about the close of the third week, and was preceded by hematemesis and suppression of urine. We must note in this connection the tendency to embolism that exists in this disease.

Especial interest attaches to the condition of the blood in relapsing fever. Usually it presents no abnormal appearance if drawn during life, though in grave cases it may coagulate imperfectly. We have no knowledge of its minute chemical characters, save that in several cases where there was great diminution in the amount of urine, with uræmic symptoms, urea has been found in considerable amount in the blood (Murchison, p. 368). The red globules present no definite or {412} characteristic changes. In some of our examinations they appeared of light color and became crenated very quickly on exposure. On the other hand, the white corpuscles have repeatedly been observed to be increased in number, at times considerably so (Cormack, Thompson, Zuelzer, Carter, Boeckmann, and ourselves), though this change is not regarded as constant or essential. It has, however, a very great interest in connection with the characteristic lesions of the spleen which will be described hereafter. In several cases we observed that many white corpuscles were small and apparently imperfectly developed. Boeckmann[30] concludes that they increase in number during the febrile paroxysm, reaching their highest number at the crisis, and then diminishing gradually to the normal. The red globules are much decreased during the fever, and return to the normal slowly during convalescence.

[Footnote 30: _Deutsch. Arch. f. klin. Med._, Sept. 1881, p. 513.]

In addition to these changes, various abnormal elements have been observed more or less constantly. By far the most important of these is the spirillum or spirochete of Obermeier, which has been already carefully described. In proportion as this organism has been carefully looked for it has been found constantly, so that the evidence has become very strong in favor of its uniform presence in the blood of relapsing-fever patients during the febrile stage of the disease.

Ponfick in 1874[31] called attention to the occurrence of large granule-cells in the blood in this disease. They are found during life as well as after death, when they exist in largest proportion in the blood of the splenic, hepatic, and portal veins. Their shape is spherical, ovoid, or elongated; the basis of the cells is a delicate, translucent, albuminous substance; and the granules are of a fatty nature, as shown by the action of reagents. These cells have been found by other observers, and the view is generally received that they are derived from the lymphoid elements of the spleen, and perhaps of other portions of the lymphatic system; and Carter, who has studied them carefully, is inclined to think there is some connection between them and the development of the spirillum.

[Footnote 31: _Centralbl. f. d. med. Wissensch._, 1874, p. 25.]

Ponfick also first described[32] certain other large, irregularly-shaped, pale, granular, nucleated cells, which occur in smaller number in the blood in relapsing fever, and which he regarded as altered endothelium, derived from the lining of the blood-vessels, of the lymphatics, or of the lacunar spaces of the spleen. Occasionally these cells are found with such highly granular contents as to make them closely simulate the large granule-cells described above. These results of Ponfick have been confirmed by other observers.

[Footnote 32: _Loc. cit._]

In several of our reports of examinations of blood there is mention made of quite abundant, free granular matter--an appearance also observed by Carter. Finally, the latter describes the occurrence of thread-like filaments and of short, rod-like bodies.

There are no characteristic lesions connected with the gastro-intestinal canal. The mucous membrane of the stomach may be normal or merely injected, though where there has been much vomiting, and especially bloody vomiting, there is marked injection, and not rarely ecchymosis and submucous extravasations of blood, with softening of the membrane. {413} These extravasations are usually small, but Cormack reports a case where one-third of the mucous membrane of the stomach was the seat of ecchymosis and extravasation. In one of our own cases the extravasations occupied an area of four inches square.

The small intestines exhibit patches of congestion or ecchymosis less frequently than the stomach, though it is usual to find injection of the mucous membrane, especially of the lower portion, in cases where there has been diarrhoea. Carter, observing the disease in India, found in one-half of all autopsies some amount of congestion, hemorrhage, or inflammation of the ileum. In two instances he found a layer of diphtheritic deposit over the mucous membrane of the lower part of the ileum.

There are no special alterations of the solitary or agminated glands, and ulceration never occurs. Even in cases where the constitutional infection is severe, whether diarrhoea has been present or not, it is noteworthy that there is rarely any swelling of the solitary glands or Peyer's patches, such as is met with in many other acute specific diseases. It was not present in any of our autopsies.

The large intestine in like manner exhibits no characteristic lesions. Patches of congestion and occasionally submucous ecchymoses may be observed, and croupous exudation occurs here somewhat more frequently than in the small intestine.

Wyss and Bock[33] speak of enlargement of the mesenteric and retroperitoneal glands as of frequent occurrence, but we did not observe it, and Murchison states that these glands present no abnormal appearance.

[Footnote 33: _Op. cit._, p. 223.]

Alterations of vascularity of the brain or its membranes are met with, but they are variable and bear no definite relation to the precedent symptoms. Ecchymoses of the membranes are occasionally observed, and in one of our cases extensive meningeal hemorrhage was found. Murchison reported a case in which embolism of the left femoral artery occurred, and subsequently of the left middle cerebral artery, inducing death. The suggestion may be hazarded that in some of the cases where there is severe delirium ending in stupor and death there has been multiple capillary embolism of the cerebral vessels.

There is occasionally the evidence of catarrhal inflammation of the upper air-passages, and in some epidemics diphtheritic exudation in the pharynx and larynx has been noted (Wyss and Bock); and Ponfick found acute oedema of the glottis in a considerable proportion of the fatal cases at Berlin. The lesions of pleurisy are met with in a small proportion of cases; in our own autopsies this complication was more frequent than in most epidemics.

The lungs may be normal, and Murchison concludes that they are more frequently so than in typhus. Still, they often present congestion or oedema, and subpleural ecchymoses, hemorrhagic infarctions, and pneumonic consolidation are not rare. Lobar pneumonia was present in 33 per cent. of our own autopsies, in 28 per cent. of Carter's, and in 20 per cent. of those conducted by Ponfick. The inflammation usually presents the regular stages, and is associated with a moderate degree of plastic pleurisy; but occasionally, as in one of our cases, it terminates in gangrene. In the instance referred to there was an area of gangrene about three inches square and one inch in depth, involving the pleura and a {414} superficial layer of lung on the antero-lateral aspect of the left lower lobe. In another remarkable instance, already referred to on account of the suppurative inflammation of one masseter muscle, the lungs, which were stained yellow throughout, presented numerous deep purplish patches, which on section altogether resembled the secondary metastatic deposits of pyæmia, with yellowish softening or even puriform centres surrounded by a rim of purplish livid discoloration. Very numerous similar patches, varying from the size of a pea to that of a hazel-nut, and presenting every stage of development, were found throughout both lungs. In a few instances we found the lesions of chronic phthisis, which had, of course, existed before the attack of relapsing fever. The bronchial glands were found swollen and infiltrated in cases where inflammatory processes in the lungs have existed.

Much interest attaches to the state of the genito-urinary organs in relapsing fever, but caution is required to distinguish lesions that have existed prior to the attack from those properly referable to it.

Owing to the intemperate and exposed lives of many of the patients, renal lesions might reasonably be expected in no small proportion. The comparative rarity of albuminuria (see p. 407), even in severe cases, is suggestive of the view that when it is present it may at least sometimes be due to pre-existing lesions aggravated by the acute infectious process, and further that the extreme gravity generally presented by such cases may be in part due to the impaired condition of the kidneys.

The morbid changes most frequently referable to the fever are moderate enlargement and congestion, occasionally very intense so that we find it described in our notes as deep blackish-purple or blue; ecchymoses of the capsule or of the mucous membrane of the pelvis; small hemorrhagic infarctions, usually in the cortex; and cloudy swelling of the glandular cells. Less commonly are found hemorrhagic infarctions, or small embolic patches advanced to various stages of disintegration, even to the formation of small puriform collections. In quite rare cases the lesions of acute nephritis are present, while caution must be used in interpreting other changes occasionally met with, such as pallor with granulo-fatty degeneration or other advanced alterations of the glandular cells, or hyperplasia of the intertubular connective tissue, with or without contraction of the kidneys.

The mucous membrane of the bladder, as already mentioned, may present ecchymoses, or, more rarely, croupous exudation (Wyss and Bock). The urine contained may be bloody, or, as in one of our cases where there had been total suppression of urine for over seventy-two hours before death, there may be but a small amount of almost pure blood, containing a few phosphate crystals, but no tube-casts. In this case there were also ecchymoses of the bladder and of the pelvis of the kidneys, with intense congestion and numerous small hemorrhagic infarctions of the kidneys.

The liver is constantly though variously affected. It is found enlarged in the great majority of cases, especially if death has occurred during the febrile stage. The ordinary degree of enlargement in our cases was from four to four and a half pounds, but in a few instances the liver weighed one hundred or one hundred and two ounces, though in most of these extreme cases the patients had been drunkards, and there was such advanced fatty alteration of the liver as to make it probable that the {415} organ had been diseased previously. These figures correspond with the results of other observers.

In many cases, especially when death occurs early and during the febrile stage, the capsule and substance of the liver are congested, at times intensely so; and when ecchymoses are found elsewhere they are apt to be present here also, appearing as purplish patches dotted over the capsule and extending into the superficial layer of hepatic tissue. Not rarely, however, the liver substance is paler than normal, and presents a yellowish tinge, apart from the decided yellowish staining present in cases attended with jaundice. Carter describes a partial mottled paleness of the liver as having been frequently observed in his cases, the circumscribed pale areas presenting a corresponding localized degeneration of the cells, as though from some local interruption of circulation.

Cloudy swelling and fatty degeneration of the liver-cells are indeed very often present, and in some epidemics with preponderance of bilious symptoms are constantly found (Ponfick). The degree of the cell-alteration varies from a slight granulo-fatty change to an advanced fatty degeneration, even with a marked tendency, in rare cases, to disintegration of the cells, so as to produce lesions analogous to those of acute yellow atrophy (St. Petersburg epidemic).

The whitish deposits described by Küttner as due to albuminous or fibrinous infiltration are probably referable to transformed hemorrhagic infarctions, and the minute puriform collections that have been observed at the centre of the acini (Wyss and Bock) may have been metastatic in origin, or attributable to the disintegration of minute thrombi associated with irritative hyperplasia of the adjacent lymphoid elements. The consistence of the liver varies: when death occurs early and bilious symptoms have not been marked, it may be even firmer than normal, but more frequently it is softer, and it may be relaxed, flabby, and friable.

The condition of the bile-ducts is of great interest in view of the frequency of jaundice as a symptom in relapsing fever, and most authorities unite in saying that they present no lesions capable of explaining it.

The gall-bladder is usually found full of dark bile, but there is no such degree of inspissation, except in rare instances, as could interfere with its passage through the ducts. Murchison quotes the statement of Peacock that in some instances the bile was thick and viscid, so as apparently to cause obstruction, but all observations agree in showing that this is exceptional. The mucous membranes of the larger ducts may present evidences of slight catarrhal inflammation, but in nearly all cases where they have been carefully examined, even when jaundice had been marked, they have been found patulous and free, so that the jaundice cannot be regarded as due to obstruction of the larger ducts save in rare instances (Pastau). In further confirmation of this may be stated the fact that there is no want of bile in the duodenum and feces.

On the other hand, a careful consideration of the lesions of the substance of the liver will show that it would be most improbable that the minute biliary ducts in the areas most affected should escape implication. Münch, who investigated this subject carefully, found that there was a catarrhal state of the fine bile-ducts in every case of relapsing fever with jaundice; and Litten found the smallest ducts plugged with bile-stained pellets of mucus. It would appear, therefore, that in many cases at least {416} the jaundice is really obstructive in its origin, the seat of the obstruction being in the too-rarely examined minute bile-ducts, though further investigation of this interesting question is required.

The clinical bearing of these conditions has been fully discussed in the appropriate section.

The changes in the spleen are constant, and even more remarkable than those in the liver. It is enlarged with rare exceptions, and especially so if death has occurred during the febrile stage. Upon the subsidence of the fever the spleen probably returns to its normal size more rapidly than the liver. The more common extent of the enlargement in our own cases was from ten to eighteen ounces, though we found the spleen in one case weighing twenty-nine and a half ounces and in another forty-four and a half ounces. In neither of the latter instances was there any reason to suspect malarial complication. The most extensive enlargement we have found recorded is sixty-eight ounces in a case reported by Küttner.[34]

[Footnote 34: _Schmidt's Jahrb._, 1865, vol. cxxvi.]

There is usually a correspondence between the stage and extent of the splenic and hepatic lesions, but this is not invariable, and one or the other organ may present a far higher degree of enlargement or much more intense interstitial changes. It may be mentioned, moreover, that in some unusual cases the lesions of the lungs, such as ecchymoses and hemorrhagic infarctions, may be disproportionately marked as compared with those of either the liver or spleen.

The capsule of the spleen often presents a mottled look, with at times large purplish ecchymoses; it is apt to be more or less opaque, and local peritonitis, with thin layers of plastic exudation often forming friable adhesions with the abdominal wall, may exist.

In one of our cases the capsule presented a small perforation or rupture, with an exudation of plastic lymph over an area of four by six inches, and diffuse peritonitis, with effusion of bloody liquid with shreds of lymph throughout the abdominal cavity. This fatal termination is fortunately rare, but there are several other instances on record. The splenic pulp may retain its consistency and firmness, even in cases that have run a long course; but more frequently it is softened, and may be almost diffluent. The pulp is often swollen, so that when cut it projects above the section. The color is darker than normal, and often is of a deep maroon color. This swelling is due to enlargement of the blood-vessels, associated with great increase of the cellular elements of the pulp and with enlargement of the Malpighian corpuscles.

When death occurred early in the disease we found these bodies grayish or grayish-yellow in color and of the size of hempseed, so that the section very thickly studded with them closely resembled shad-roe, and this stage of the lesion is frequently described in our notes as the shad-roe spleen. Subsequently, the Malpighian bodies enlarge still more, and stand out above the section a line or more in diameter, and of a lighter color; not rarely, several of them come in contact, and thus form a considerable mass of irregular shape, resembling the infarctions described below.[35] It is probable that central softening may occur later in the {417} Malpighian bodies, though we are inclined to regard the puriform collections frequently found as chiefly due to the disintegration of hemorrhagic infarctions or of embolic patches. Of these, hemorrhagic infarctions are by far the most common and present the familiar appearances. They may be quite numerous, superficial, or deep-seated, and of variable shape and size. At first dark reddish, firm, and sharply separated from the surrounding pulp, they grew reddish-yellow or yellowish later, softened in the centre, and eventually were transformed into puriform collections. Doubtless, in a large proportion of cases that recover such infarctions exist and are slowly absorbed. Ponfick has shown that these are venous infarctions, the arterioles leading to them being patulous. True arterial embolism does, however, occur, though much more rarely (Ponfick, Murchison), giving rise to firm, wedge-shaped infarctions at the periphery of the spleen, which may undergo degenerative changes similar to those above described. The resulting abscesses may burst into the peritoneum, pleura, lung, or bowel. The microscopic appearances have been most fully described by Ponfick, our own comparatively meagre observations having accorded entirely with his subsequent accurate description. The cells of the swollen pulp contain red blood-discs and pigment, and some present collections of bright granules. The lymphoid cells of the Malpighian corpuscles are at first in a state of cloudy swelling with multiplication of their nuclei, and later show marked granular fatty degeneration.

[Footnote 35: Thus, Wyss and Bock describe "multitudes of minute abscesses as large as poppy or hempseed, and containing a single drop of pus."]

The lymphatic glands present no lesions, and the pancreas is normal.

The peritoneum is not affected as frequently as other serous membranes in this disease. Superficial ecchymoses are, however, quite common, especially so over the solid viscera; and more rarely effusions of blood have been found in the subperitoneal connective tissue, involving the muscular or glandular tissues beneath. We have already mentioned (p. 406) the occasional occurrence of local peritonitis, most frequently of the splenic capsule, and also the rare accident of diffuse inflammation from rupture of the spleen.

The marrow of the bones was carefully examined by Ponfick, who first called attention to the presence of important changes in relapsing fever, which have since been confirmed by other observers. These changes consist in proliferation and subsequent degeneration of the lymphoid cells of the marrow, with multiplication of the nuclei in the walls of the minute vessels and fatty degeneration of their coats. As a result of these changes, spots of puriform softening may form, chiefly in the cancellous tissue of the extremities of the long bones, with the production of localized necrosis, and possibly with extension of inflammation to the neighboring articular cavity.

Considerable space has been devoted to the detailed consideration of the pathological changes in relapsing fever, partly because we believe the fact has not been sufficiently recognized that the disease is constantly attended with important and characteristic lesions. These consist, in brief, of remarkable changes in the blood; of widespread ecchymoses and infarctions, which not rarely undergo puriform disintegration; of hyperplasia and subsequent degeneration of the Malpighian corpuscles of the spleen, with changes in the cellular elements of the splenic pulp; of cloudy swelling of the gland-cells of the liver and kidneys, with a {418} marked tendency to fatty degeneration; of changes in the marrow of the long bones; and, finally, of granulo-fatty degeneration of the muscles, and especially of the heart.

DIAGNOSIS AND RELATION TO OTHER DISEASES.--The entire question of the diagnosis of relapsing fever is dominated by that of spirillar infection. Before Obermeier's discovery the differential diagnosis of the initial paroxysm, and to a less extent that of the subsequent events of a case of relapsing fever, was attended with considerable difficulty. But if, as now seems established, immediately before and throughout the initial paroxysm and subsequent relapses a characteristic spirillum is to be detected in the blood upon proper examination, while it rapidly disappears after the crisis, it is evident that as soon as a suspicion is aroused as to the possible presence of relapsing fever the question may be settled conclusively by the microscope.

None the less is it important to consider carefully, but briefly, the symptoms by which relapsing fever is to be distinguished from various affections which may simulate it, because even the most experienced observers admit that the spirillum cannot be invariably detected; because it is not yet known that a similar organism may not be found in some other affections; and, finally, because on the outbreak of an epidemic of relapsing fever, especially in America, where its occurrence has hitherto been so rare, there is strong probability that the nature of the early cases will not be even suspected until the relapse occurs.

Typhus fever often prevails in an epidemic form simultaneously with relapsing fever, so that it was inevitable they should have been for a time confused. Their essential non-identity is, however, now too well recognized to require any lengthy demonstration. The following statement of the heads of the argument may therefore suffice.

In typhus there is no characteristic spirillum, and the lesions which are truly characteristic of relapsing fever are totally wanting. There are convincing differences in the symptoms, course, and results of the two diseases. There is no evidence to show that when fever has been imported into a locality by a single case, typhus fever has ever produced other than typhus, or relapsing other than relapsing fever. The two diseases often prevail together, and may coexist in the same house, each preserving its own distinct characteristics; and persons exposed to the double contagion may contract one or the other, or first one and then the other at a shorter or longer interval, so that an attack of either exerts no protective power against the other. It must be noted, however, that in a large majority of such cases of successive contagion it is relapsing fever which has been followed by typhus, while the reverse has been observed much more rarely.

In 1869-70 the two diseases were prevalent in Philadelphia, and the wards of the municipal hospitals constantly contained a considerable number of cases of both. Three instances came under our care in which after recovery from relapsing fever the patient contracted typhus. All of these patients were employed as assistant nurses, and were continuously under observation from the early part of their attack of relapsing fever to the end of the attack of typhus. In one case the interval of health between the close of the relapse and the onset of typhus was forty-four days; in the second it was thirteen days. In both cases the original disease was {419} thoroughly characteristic and the subsequent attack of typhus was typical. In both death followed, and the post-mortem examination verified the above statement. The third patient had severe relapsing fever, from which he recovered and returned to work, though with pains in the legs, shoulders, and forehead. After an interval of apparent health of eleven days he developed a well-marked attack of typhus, which terminated on the twelfth day in recovery. It may be added that although typhus is not of frequent occurrence in any portion of North America, there have been a number of epidemics unattended with a single case presenting the features of relapsing fever.

Between well-marked cases of the two diseases there should be no difficulty in making a prompt diagnosis. Relapsing fever is distinguished from typhus clinically by the severity of the initial chill; the rapid elevation of the pulse and temperature; the comparative infrequency and mildness of cerebral symptoms, despite the intense fever; the severity of the gastric symptoms, nausea and vomiting; the enlargement of the liver and spleen, with marked abdominal pain and soreness; the frequency of jaundice, of epistaxis, and of other hemorrhages, and of anæmic murmurs over the heart and large vessels; obstinate insomnia; vertigo; peculiar rheumatoid pains and perversions of sensation; the frequency of sweating during the high pyrexia; by the occurrence of crisis, subnormal temperature, apyretic interval, and relapse; the rarity of measly eruption and of bed-sores; the frequency of pneumonia, diarrhoea, ophthalmia, oedema, and desquamation as complications and sequelæ; the usual occurrence of abortion in pregnant females; the protracted course of the disease, and its remarkably low mortality despite the severity of the symptoms, except in cases of complicated or typhoid type; and, finally, by the modes in which death occurs. Of course to this must be added the specific result of examination of the blood in relapsing fever.

Doubt will arise only in very rare cases where a measly eruption appears on or before the fifth day of relapsing fever, with headache and mild delirium, but without severe gastric symptoms, epistaxis, or jaundice. If no relapsing fever were prevalent at the time, such a case might well be regarded as one of mild typhus until the crisis and the relapse disclosed its real nature. But if the two diseases were known to be prevalent in the community, examination of the blood would properly be made at once and the diagnosis be established.

The diagnosis between ordinary cases of relapsing fever and typhoid is readily made by the gradual onset and peculiar course of the pyrexia in the latter disease, as well as by the frequency of delirium, of abdominal distension, and of diarrhoea, and by the characteristic eruption. The occurrence of epistaxis, bronchial irritation, and splenic enlargement is common to both, and an eruption of small rose-pink spots has been noted by some observers (Carter, pp. 194, 317). But jaundice, enlargement of the liver, hypochondriac pain and soreness, excessive nausea and vomiting, severe rheumatoid pains, and numbness and tingling of the extremities, are very significant symptoms of relapsing fever. Attention has already been called to the grave type of relapsing fever in which the typhoid state is fully developed, and to the fact that in such cases the pyrexia is often modified, the onset less abrupt, the crisis imperfect, and the interval occupied by an irregular post-critical {420} symptomatic fever. It is altogether probable that such cases have not rarely been regarded as of true typhoid character; and indeed the attempt has been made by Griesinger to establish as a separate and independent affection, under the name of bilious typhoid fever, a group of cases which close examination seems to show to be chiefly composed of grave complicated relapsing fever with a certain proportion of true typhoid fever, complicated with jaundice.

The recognition of the bilious typhoid type of relapsing fever is based upon the history of the case; the mode of onset; the greater severity of the pains, arthritic and abdominal; the early appearance and intensity of the jaundice; the more marked enlargement of the liver and spleen; the marked tendency to hemorrhages from various surfaces; the peculiarities which careful study of the temperature curve will show, especially about the time of crisis; the rarity of eruption; the characteristic spirillum;[36] and the totally different anatomical lesions, which are, unfortunately, often demonstrable, as this form of relapsing fever is fatal in from 33 to 50 per cent. of cases.

[Footnote 36: As first demonstrated by Motschutkoffsky.]

Since the discovery of the spirillar test for relapsing fever it may be said that Griesinger's bilious typhoid must be stricken from medical nosology as an independent affection.

The case of Charles Hood, on page 396, is a good example of the bilious typhoid form which occurred not rarely in the Philadelphia epidemic.

Murchison points out that, owing to the frequent occurrence of jaundice in relapsing fever, this disease has been mistaken for yellow fever by such good observers as Graves, Stokes, and Cormack. Difficulty in diagnosis would be likely to arise only in regard to the bilious typhoid type of relapsing fever, and since its clinical history has become so well known, a mistake is not likely to occur. The geographical distribution of the diseases is widely different. Yellow fever is influenced powerfully by season and temperature, while relapsing fever is independent of both. Negroes are but slightly liable to yellow fever, while relapsing fever attacks them with special violence. Yellow fever is not contagious, but infectious, and second attacks are extremely rare; relapsing fever is one of the most contagious of the zymotic diseases, but one attack does not protect against a subsequent one. The mortality, the anatomical lesions, the course of the pyrexia, the leading clinical symptoms, are all widely distinct in the two affections; and, finally, no spirillum has been found in the blood in yellow fever. Yellow fever is an extremely fatal disease; the ordinary form of relapsing fever has a mortality of 2 to 10 per cent.; the bilious typhoid form, one of 33 to 50 per cent. In yellow fever the spleen is but slightly enlarged, and the liver is pale and softened; in relapsing fever the liver and spleen are greatly enlarged, and there is great tenderness over the hypochondriac region. In yellow fever albuminuria is much more common, and the urine more frequently suppressed, than in relapsing fever.

The sudden onset, the severe headache and pains in the limbs, the vomiting, jaundice, epigastric tenderness, enlargement of the liver and spleen, occasional epistaxis, hematemesis, or hematuria, absence of characteristic eruption, liability to herpes facialis, pneumonia, and diarrhoea; the occasional occurrence of remissions in the pyrexia, and even of more or less fully-developed chills for several successive days during the initial paroxysm or {421} the relapse, suffice to explain the difficulty which may arise in distinguishing the bilious form of relapsing fever from bilious remittent fever. But the latter disease arises exclusively from malaria, and is therefore powerfully influenced by season and locality; is not contagious; does not present anything approaching to the crisis, the apyretic interval, or the abrupt relapse of relapsing fever; presents pigmentary changes in the blood, instead of the spirillum; and lesions of the spleen and liver totally unlike those characteristic of relapsing fever; can be promptly controlled by antiperiodic doses of quinine, and therefore should have a mortality far less than that of the grave form of relapsing fever. It is not necessary to pursue this subject further, but a reference to the temperature charts of Carter[37] or of Litten[38] will show that in some epidemics single paroxysms resembling those of quotidian ague might occur during the interval between the initial paroxysm and the relapse, or a series of two, three, or more such paroxysms of quotidian or tertian type might represent an entire relapse. Such phenomena are wholly uncontrollable by quinia, and are presumably dependent upon irregularities in the specific infection, instead of upon a blending of malaria with the poison of relapsing fever. There is some ground for believing, however, that those who have recently passed through an attack of the latter are highly, perhaps unusually, susceptible to malarial infection, as we have already seen they are liable to contract typhus.

[Footnote 37: _Op. cit._]

[Footnote 38: _Deut. Arch. f. klin. Med._, xlii. 1874.]

The chill, the sudden and high fever, the acid sweat, the high-colored urine, the intense pains and soreness, and the occasional murmur over the heart, will in some cases of relapsing fever suggest the idea of severe rheumatic fever, with illy-developed articular inflammation and with a tendency to hyperpyrexia. The urgent danger presented by the latter condition and the necessity for immediate recourse to cold baths and large doses of quinine or of the salicylates, render it highly important that no such error of diagnosis should be made. It will usually be avoided readily by observing that in relapsing fever there are great nausea, repeated vomiting, insomnia, peculiar formication of the extremities, jaundice, early enlargement of the liver and spleen, with abdominal pain and soreness, and a tendency to epistaxis; and, further, that despite the high temperature, cerebral symptoms such as result from rheumatic hyperpyrexia are not threatened, except in grave typhoid cases or just preceding the crisis.

The onset of relapsing fever may suggest forcibly the invasion period of small-pox, with its marked rigors, high fever, lumbar pain, aching in the head and limbs, nausea and vomiting, and if the patient is known to have been exposed to the contagion of both diseases a diagnosis would be impossible until the third day. But such a dilemma can rarely occur, and under ordinary circumstances the patient's antecedents will enable a correct opinion to be formed.

Severe cases of simple febricula with marked gastric disturbance may, as remarked by Jenner, closely simulate relapsing fever; and the same is true of attacks of acute gastro-hepatic catarrh, with severe headache, sharp fever, cholæmic eye, epigastric tenderness, and frequent vomiting. Of course there is no danger under ordinary circumstances of these simple conditions being regarded as relapsing fever, but when the latter is prevalent in epidemic form it is probable that the mistake is frequently made. {422} Although an immediate diagnosis might be possible only by microscopic examination of the blood, the peculiar clinical symptoms of relapsing fever would soon be found wanting, and suitable treatment would bring the simpler affection under control.