Chapter XXVI: Part II: , Showing Predominance of Malarial Element . . . . 617 (25)

Acute yellow atrophy of the liver occurs chiefly in pregnant women, though it is also met with in men and children; but it is so rare that should a case of it come under observation during the prevalence of relapsing fever there is considerable danger that its nature would be overlooked. It resembles relapsing fever in the occurrence of jaundice and other signs of hepatic disorder, of delirium, and of a tendency to hemorrhage from various surfaces. The temperature, however, is more moderate, and does not exhibit the sudden remission of relapsing fever; the liver is usually demonstrably diminished in size; severe nervous disturbances, such as convulsions followed by stupor and then by coma, are more constant; while the occurrence of spirilla in the blood of relapsing fever and of leucin and tyrosin in the urine of acute yellow atrophy serves to distinguish completely the two diseases. Acute yellow atrophy is, moreover, invariably fatal.

With ordinary care there is but little danger that any of the local complications of relapsing fever will so absorb attention as to lead to a neglect of the specific general disease, so that the cerebral symptoms should be readily distinguished from the onset of any acute intracranial affection; the parotitis which occasionally appears early in the disease should not be confounded with idiopathic mumps; and so for other complications. There is far more danger, indeed, lest some of the complications may be overlooked; and this is especially true of pneumonia, one of the most frequent and most important of them all. Its occurrence is the cause of the supervention of grave typhoid symptoms or of the modification of the normal course of the pyrexia in so many cases that nothing but a systematic daily examination of the lungs will avert serious oversights.

MORTALITY AND PROGNOSIS.--The rate of mortality has varied in different epidemics from 2 or 3 to 24 per cent. Murchison shows that out of 2115 cases admitted to the London Fever Hospital during a period of twenty-two years, and embracing two distinct outbreaks, only 39 proved fatal, making 1.84 per cent. mortality. Adding to these the results of Scotch and Irish epidemics, a total of 18,859 cases, with 761 deaths, is reached, giving the rate of mortality for Great Britain as 4.03 per cent. The great Indian epidemics studied by Carter gave 111 deaths out of 616 cases, equal to 18.02 per cent. Recent German epidemics have given from 5 to 10 per cent. The above rates are obtained where all the cases observed during an epidemic are included. If, however, the mortality of the ordinary form of relapsing fever is computed separately from that of the bilious typhoid form, it does not exceed 2 to 5 per cent., whilst the mortality of the latter form rises to from 33 to 50 per cent., or even higher.

In the Philadelphia epidemic, out of a total of 1174 cases there were, as nearly as can be ascertained, 169 deaths, giving a rate of mortality of 14.4 per cent. Taking all the cases admitted to the hospital under our observation, many of which entered at a late period of the disease and not a few when moribund, the mortality was not less than 13 per cent. {423} The mortality among the negroes who were attacked with the disease was considerably greater than among the whites. Finally, if the mortality of the bilious typhus form be considered separately--although from the frequency of jaundice in this epidemic and the numerous gradations of severity presented it is difficult to form a sharply defined group of this character--it was certainly not less than 50 per cent.

The date of death varies with the epidemic, the form of the disease, and the previous condition of vitality of those attacked. Ordinarily, by far the larger proportion of deaths occur during the first relapse or the second interval, but in bilious typhoid cases, presenting grave complications, especially pneumonia or severe hemorrhages at an early date, or in cases occurring in intemperate subjects, or in those previously in impaired health, the mortality is much heavier in the initial paroxysm or the first interval than at later periods.

Youth exerts the same favorable influences upon the result of relapsing fever as it does in the case of typhus and typhoid. Murchison states that of 717 male patients under twenty-five years of age admitted into the London Fever Hospital, not one died, and in most epidemics similar, though not equally marked, results have been noted. In some epidemics the mortality among young children has been considerable. As a rule, the percentage of deaths increases with each decade after thirty years.

Sex does not exert any definite or constant influence upon the mortality. The number of males affected is far greater; they are liable to be exposed to the contagion in its most concentrated form; a larger proportion of them are probably the subjects of intemperance than in the case of females; and thus most statistics agree in making the mortality somewhat greater in the male sex; but, all things being equal, there is no good reason for holding that sex itself has any value in determining the result.

As in other zymotic diseases, the mortality from relapsing fever is highest during the early period of an epidemic, and the type of the disease grows milder as the epidemic declines. Cases of the bilious typhoid form have become notably less frequent during the later stages of some epidemics than at an earlier period.

Marked difference has been observed also as to the action of remedies at different stages of epidemics, the early cases exhibiting an extraordinary resistance to remedies, and especially to anodynes, which passes away later. When typhus and relapsing fevers have prevailed together, and a clear discrimination between the two sets of cases has not been made, it has appeared that the mortality increased as the epidemic advanced, but this apparent exception has been due to the fact that at first the cases of relapsing fever were in the majority, while later those of typhus, the much more fatal disease, preponderated.

Epidemics of relapsing fever prevail at all seasons, but more commonly they are at their height during the colder months of the year. The total mortality will of course correspond, but the actual percentage is not constantly greater during any one season, although it is probable that the greater liability to chest complications during the colder months will render the disease more fatal then.

The gravity of relapsing fever has varied so greatly in different epidemics that it is very difficult to determine what influence upon the mortality {424} has been exerted by mere difference of race. A further source of difficulty is found in estimating the differences in the physical conditions of the poorer classes in the various communities affected. The mortality has been exceptionally high in the Russian and Indian epidemics and in some of the German ones, while in the British epidemics it has uniformly been light. It is interesting to note that in the Philadelphia epidemic, where the great majority of patients were Irish or negroes, the mortality was high, over 14 per cent. The previous condition of the Irish patients must certainly have contrasted favorably with that of the individuals attacked in the Dublin and Belfast epidemics, so that the difference in result seems attributable only to a greater virulence of the disease. As an ample opportunity was here afforded to judge of the relative severity of relapsing fever in the negro and white races when the cases occurred at the same season, at the same stage of the epidemic, and in individuals living under nearly similar conditions, it may be stated that the conclusion of all who studied the question closely was that the disease was much more severe among negroes, and in particular that they displayed a greater tendency to serious complications and to the bilious typhoid form.

Although the degree and virulence of the infection undoubtedly constitute the most important elements in determining the mortality, the previous health and habits of those attacked with relapsing fever exert an influence upon the result. This is especially true of habitual intemperance, which, by disposing to disease of the liver and kidneys, greatly increases the liability to a fatal result. It has been seen (page 409), however, that even when acute catarrhal nephritis existed at the time of the attack severe relapsing fever might terminate favorably. Another observation which we made frequently, and which coincides with what is well known in regard to typhoid and typhus, is that improper exertion and exposure during the stage of incubation and immediately after the invasion produced a highly unfavorable effect on the subsequent course of the disease, and seemed in particular to dispose to dangerous or fatal collapse at the critical periods.

Apart from these general considerations, there are many special points to be considered in regard to the prognosis of relapsing fever:

If after the crisis of the invasion there is not rapid and decided improvement, complications should be suspected.

A sharp rebound of temperature quickly following crisis may be followed by speedy death.

Mere elevation of temperature during the invasion and the relapse, even though to an extreme height, is not attended with the danger which even a somewhat lower degree would indicate in other zymotic diseases.

Increased elevation toward the expected time of crisis should arouse anxiety, as sudden and dangerous cerebral symptoms may occur.

Prolonged duration of the pyrexia, or the substitution of irregular gradual defervescence (lysis) for the characteristic crisis often associated with typhoid symptoms as are these conditions, is significant of complications and of danger.

Wild delirium during the pyrexia, or transient active delirium about the time of crisis, is not necessarily unfavorable, but continuous low delirium, with disposition to stupor, is associated with a typhoid tendency and is frequently followed by death. Excessive muscular {425} tremor or convulsions are highly unfavorable, but not necessarily fatal, symptoms.

Cardiac murmurs are not of serious import. The pulse is not usually as rapid in proportion to the temperature as in typhus or typhoid, and an excessively rapid pulse toward the expected time of crisis, especially if associated with feebleness of the heart's action, points to the danger of sudden collapse at or soon after that time. Previous cardiac disease, especially fatty degeneration in habitually intemperate persons, increases this danger. Continued frequency of pulse after the crisis indicates some complication or the danger of some accident.

Cough of a bronchial origin is not a specially unfavorable symptom, but if associated with the physical signs of pneumonia and with marked disturbance of respiration it indicates extreme danger.

Epistaxis, even when copious, often occurs in favorable cases, but hemorrhage from the stomach or the kidneys is usually, though not invariably, followed by death.

An eruption, measly or of pink spots, with or without minute petechiæ, is rare, and usually occurs in severe cases, but is not of specially unfavorable significance unless associated with the typhoid state or with patches of purpura.

Hiccough is a much less unfavorable symptom in relapsing fever than in typhoid or typhus, and vomiting, even frequent and persistent, may occur in cases of ordinary severity.

Enlargement of the liver and spleen indicates special risk only when persistent for some time after the relapse, in connection with persistent irregular fever. Jaundice has no necessarily unfavorable signification, is frequent in ordinary cases in some epidemics, but when it is associated with the other features of the bilious typhoid form the danger is extreme, at least 33 per cent. of such cases proving fatal.

Slight transient albuminuria may exist without special danger, but if associated with evidences of catarrhal nephritis, or if extreme diminution of urine, with or without albuminuria, exists, cerebral symptoms are apt to ensue, with a high degree of danger.

All serious complications--parotitis, erysipelas, dysentery, abortion, pneumonia, and, above all, peritonitis--greatly increase the risk.

It is not possible to determine in what cases the relapse will fail to occur. Motschutkoffsky's statement, that when a slight post-critical rise occurs a relapse will follow, must be applicable only to a limited number of cases.

In all cases at least one relapse must be expected; the patient in the interval must be regarded as still sick, and after the close of the relapse he must still be treated with rigid care until convalescence is permanently established. It must be remembered in hospital practice that many patients enter toward or after the crisis of the first paroxysm, so that caution is needed in estimating the effect of remedies and the period of the disease.

The undue prominence of certain conditions during the course of the disease is apt to be followed by corresponding sequelæ, and emaciation, anæmia, dyspepsia, diarrhoea, dysentery, enlargement of the spleen and rheumatoid pains may then be anticipated. The liability to ophthalmia and affections of the middle ear is not to be forgotten.

{426} CAUSES OF DEATH.--In fatal cases death occurs from exhaustion dependent on the protracted and severe sufferings of the patient; from cerebral symptoms; from hyperpyrexia; from the virulence of the toxæmia; from uræmic poisoning; from sudden collapse; or from some complication, such as hemorrhagic meningitis, hemorrhages, pneumonia, dysentery, rupture of the spleen, peritonitis, or abortion.

TREATMENT.--The indications for treatment presented by regular cases of relapsing fever seem to be--to moderate the pyrexia; to relieve distressing symptoms, especially pain, insomnia, and gastric irritability; to sustain the strength of the system; to prevent or modify the relapses; and to avoid complications and sequelæ.

It is needless to observe that until the nature of the specific cause of relapsing fever is fully determined, whether the spirillum occupy that relation or not, it is impossible to direct our efforts rationally toward its neutralization or elimination. The various remedies which have been employed for these special purposes have no clinical support to recommend them. And while experiment has shown that the activity of the spirillum is readily destroyed by the direct action of various weak solutions, as of quinine, carbolic acid, iodine, and mineral acids, no special curative effect follows the internal administration of these remedies, even in the largest doses consistent with safety. In fact, there can scarcely be any disease in which treatment is less satisfactory or its results more difficult to estimate. The marked difference between various epidemics, and the wide variation presented by the development of individual symptoms in different cases of the same epidemic, fully account for this.

Quinine, as might be expected, has been largely used, in the hope that it might control the pyrexia or prevent the relapse. Murchison[39] quotes a considerable amount of evidence from various sources to show that it does not possess either of these powers. It was administered to a considerable number of our cases, either in small and frequently repeated doses during the pyrexia or the intermission, or else in large doses repeated several times in immediate anticipation of the expected time of the relapse. Thus in some cases three grains of sulphate of quinia were given every two or three hours until tinnitus was produced, and then this was maintained during the remainder of the pyrexia and of the intermission. The amount given daily was from thirty to forty-two grains. It seemed to rather increase the discomfort in the head, and in some cases it aggravated the irritability of the stomach. The pyrexia was certainly not controlled by it. Given in the same manner during the intermission, it was usually well borne, but was not effectual in preventing the relapse. It is true that in some cases the subsequent relapse seemed to be somewhat modified.

[Footnote 39: _Op. cit._, p. 408.]

Thus in one case 30 grains were given on the 6th of April; 39 grains on the 7th; 39 grains on the 8th; 42 grains on the 9th; and 60 grains on the 10th; the critical fall had occurred during the night of the 7th, and the relapse began on the evening of the 9th, but the rise in temperature was less abrupt than usual, and the relapse lasted less than five days. It was quite severe, however, so that it is doubtful whether the apparent modification was anything more than is frequently observed in cases where no quinine has been administered.

In another case the fall in temperature at the end of the first paroxysm {427} was from 105.5° to 97° on March 26th: 35 to 40 grains of sulphate of quinine were given daily on April 4th, 5th, 6th, 7th, and 8th; the temperature began to rise on the 3d, but the severe pyrexia and the usual symptoms of the relapse were limited to a period of less than thirty-six hours. This is a less common irregularity, and yet does not afford sufficient evidence of the efficiency of quinine. In other cases, however, as already stated, no appreciable effect followed its administration in this manner.

To illustrate the other method of giving quinia, a case may be quoted in which 20-grain doses every three or four hours were given from April 25th to April 29th, so that in four days 575 grains were taken. The initial paroxysm was of average severity, and terminated at the end of the seventh day, April 20th. The quinine did not postpone the relapse, which occurred on April 28th, but was of much less than the usual duration.

In no other case in which these large doses were given was there even as much reason as in the above instance to attribute to quinine any positive influence upon the course of the disease.

In order to demonstrate that the failure of quinine was not dependent upon a want of absorption, Muirhead injected large amounts subcutaneously with no better results.

In conclusion, it may be said that the evidence shows positively that quinine possesses no specific influence whatever upon relapsing fever; that in only occasional cases, if at all, will even enormous doses given during the intermission postpone or modify the subsequent relapse; and that it is not effective in reducing the temperature. In view, therefore, of the usual gastric irritability and tendency to vertigo and headache, which seem to be increased by large doses of quinine, and, further, in view of the small mortality, and of the fact that when death occurs it usually comes from causes over which large doses of quinine could exert no influence, it seems clear that this drug should be prescribed only in tonic doses and only in cases where it is well tolerated by the stomach.

Arsenic was used in a considerable number of our cases with the view of determining if it possessed any power of relieving the severe pains or of influencing the relapse. It was administered in the form of Fowler's solution (Liq. potassii arsenitis), and was given exclusively by the mouth. If given during the intermission, it was well borne in doses of five to ten drops every four or even every three hours, given freely diluted with water and immediately after food. In several cases it quickly induced puffiness about the eyes, but no effect whatever was produced on the pains or on the succeeding relapse. In more than one such case there was an unusually profuse crop of sudamina during the relapse, many of the vesicles breaking and being followed by brownish stains. When given during the pyrexia it aggravated the nausea and vomiting, so that it had to be suspended. In one unfortunate case, indeed, although promptly suspended, the arsenical solution seemed to have assisted in the establishment of vomiting and purging, which proved uncontrollable and contributed greatly to the fatal result. Hypodermic injections of arsenic have been used considerably with no better results. There seems, therefore, to be no reason whatever for any further use of this drug in relapsing fever.

{428} The high pyrexia and the severe rheumatoid pains have naturally suggested the use of salicylic acid and the salicylate of soda. We were not sufficiently aware of their antipyretic properties in 1869-70 to have recourse to them, but in more recent epidemics Unterburger[40] and Riess[41] have found that large doses of the latter substance (one hundred grains or more daily) will reduce the temperature either in the initial paroxysm or in the relapse, but that the disease is not cut short nor are the lesions of the blood or solids prevented.

[Footnote 40: _Jahrb. f. Kinderheilk._, v. x., 1876.]

[Footnote 41: _Deutsch. Med. Wochnsch._, Dec., 1879.]

It must be borne in mind here, as in connection with the action of quinine, that apparent modifications of the relapse are to be viewed with great distrust, since such great irregularities therein naturally present themselves. Care must further be taken lest such attempts to reduce the temperature aggravate the irritation of the stomach, and by lessening the power of taking food induce more serious exhaustion than would have resulted from the unchecked pyrexia. The evidence in our possession is not sufficient to justify a positive decision as to the therapeutic value of the salicylates in relapsing fever, but, apparently, they are applicable to only a portion of the cases, and in these are of but limited utility.

The same failure which has followed the use of quinine, of arsenic, and of salicin and the salicylates has attended the effort to prevent the relapse by berberine, benzoate of soda, tincture of eucalyptus, and other reputed antiperiodics.

Digitalis, veratrum viride, and aconite were used by us quite freely as antipyretics. The first two of these were often suspended on account of the irritability of the stomach, and no valuable results followed their use when well tolerated. Aconite in small doses, frequently repeated, as one drop every two hours, seemed to aid in allaying nausea and to exert some slight influence upon the fever. In cases where there was a distinct tendency to heart-failure, digitalis was given freely with advantage.

Cold baths were not used to reduce the temperature in any of the cases under our observation. They have been employed in other epidemics, but, as far as we know, with no other effect than to cause merely temporary lowering of temperature, without any decided relief to the other symptoms and without any apparent influence upon the course of the disease. Frequent spongings with cool water and the application of ice to the head gave only slight and temporary relief.

Simple febrifuge remedies, such as effervescing draught or spirit of nitrous ether with solution of acetate of ammonium, were well received by the stomach, and appeared to promote perspiration and the more free secretion of urine.

Finding all our efforts to control the pyrexia so unsuccessful, recourse was had in a large proportion of our cases to the hyposulphite of soda, given, dissolved in two ounces of water, in doses of twenty grains every two or three hours. In two cases it seemed to increase nausea, and at times it caused some purging, but otherwise it was well borne by the stomach, and, indeed, frequently appeared to aid in controlling vomiting. The records show that this drug was given in only two or three of the fatal cases, so that although the patients who took it regularly presented every grade of severity of the disease, they did well uniformly. It is certain, however, that the hyposulphite of soda exerted no specific effect {429} upon the disease; it did not reduce temperature, it did not prevent or modify the relapses nor relieve the severe pains; it may have promoted more free and healthy secretions, and, by tending to prevent vomiting, may have aided in maintaining nutrition; but, on the whole, it may fairly be doubted whether this remedy merits any more extended trial.

One chief reason of the failure of antipyretics in relapsing fever is to be found in the existence of widespread irritative lesions of the glandular and mucous tissues, which combine with the specific blood-changes in causing and maintaining the high temperature. It is not surprising, therefore, that the remedies which afford the greatest relief in this disease are opiates and sedatives to the gastro-intestinal mucous membrane. Opium, or morphia, must indeed be regarded as the basis of the rational treatment of relapsing fever. It is called for by the insomnia, the severe headache and the pains in various parts of the body, the nausea and vomiting, and the pyrexia. It does not appear to have been as prominent a feature in the treatment of other epidemics as we found it necessary to make it in Philadelphia. Parry[42] used it very freely, chiefly in the form of opium, by the mouth, and found a singular tolerance exhibited by his patients, several of whom took as large a dose as three grains every two hours during the afternoon and night without producing any sleep or even any contraction of the pupils. This resistance to the action of opium was observed chiefly in the early part of the epidemic, and we may add that it was exhibited chiefly when opium was given by the mouth. When morphia was used hypodermically we found that one-fourth of a grain, given at intervals of six to twelve hours, afforded very great relief to the pains, aided and relieved vomiting, and often induced quiet, refreshing sleep. Its use was not contraindicated by jaundice, by cough or pulmonary congestion, or by moderate contraction of the pupils. It was frequently given so as to maintain decided drowsiness throughout the pyrexia. When the pains persisted during the intermission the morphia was continued in smaller doses or at longer intervals. It occasionally happened that when patients were thus kept continuously under opium influence no relapse occurred; but here, as in regard to the action of quinine, it may safely be asserted either that what was regarded as the initial paroxysm was in reality the relapse, or else that the absence of a relapse was a mere irregularity, and in no way to be attributed to the action of the opium. On the other hand, in cases presenting a tendency to the typhoid state, with a disposition to stupor, or where the urine was scanty and albuminous, no opiate was administered.

[Footnote 42: _Loc. cit._]

We have already stated that in our cases quinine in acid solution was frequently ordered, and it answered very well to add to each dose of this a suitable amount of morphia.

Atropia, in the dose of gr. 1/60 to gr. 1/40, was usually associated with the hypodermic injections of morphia. This was done particularly in cases where the pains were very severe, when the pupils were disposed to be contracted, or when there was continued profuse sweating. In addition to this, atropia was continued without morphia during the intermission in a few cases. The patients proved susceptible to its influence, and dryness of the mouth with dilatation of the pupils was readily {430} produced by gr. 1/60 every six hours. In one case gr. 1/40 every four hours for two days caused delirium, with the usual symptoms of belladonna action, all of which passed away quickly after withdrawal of the drug. But in none of these cases was the relapse influenced in the least.

Other remedies may be used for the relief of the insomnia, which is always one of the most distressing symptoms. Chloral and bromide of potassium have been found serviceable in various epidemics, and some observers have preferred them to opium for the relief of headache and insomnia. They did not prove reliable in the Philadelphia epidemic of 1869-70. Bromide of potassium, even in large doses, produced scarcely any effect, and, while in a few cases chloral in doses of gr. xx. gave positive relief, in the majority of instances 40 grains failed to cause sleep or relieve suffering. It must not be forgotten also that, as there is a special tendency to cardiac failure in this affection, the action of chloral must be closely watched.

In a small series of our cases where muscular pains, hyperæsthesia, and twitching were marked succus conii was given quite freely, but without any apparent benefit.

The condition of the stomach required attention in almost every case. Nausea, vomiting, and epigastric and hypochondriac soreness were the prominent symptoms. Anorexia was usually complete during pyrexia, and not rarely patients were admitted to the hospital who asserted that for one or more days they had not taken any nourishment whatever. Under such circumstances, and in a disease where the tendency to prostration and cardiac failure calls for stimulants and food, it is evident that strict care must be given to the diet. In many cases skimmed milk with lime-water, meat broths, arrowroot, or gruel, could be taken in small amounts at short intervals, and retained. But whenever these are rejected, no attempt should be made to persist in their use, but koumiss, whey, or chicken-water should be substituted, and continued until the stomach grows retentive. Equal care must be paid to the selection of a suitable form of stimulus. It may be proper to employ a mild and relaxing emetic if the patient be seen at the onset of the disease and if there is reason to suspect the presence of indigested food in the stomach, but under any other circumstances there seems no reason for its use in a disease where vomiting is so common and gastric irritability one of the most troublesome symptoms. Nor should purgatives be given save when very positive indications exist for their use.

Constipation is rarely obstinate; the amount of nourishment taken is very small; in a considerable proportion of cases there is diarrhoea, or at least a sensitive state of the bowels; and as a consequence it is preferable in nearly every case to dispense with laxatives entirely, and, if the bowels must be opened by assistance, to administer a simple enema.

When irritability of the stomach is marked, benefit may be derived from very small doses of calomel frequently repeated, as, for example, gr. 1/8 or 1/4 every one or two hours. Subnitrate of bismuth may be used in combination with this or as a substitute for it. In several instances more prompt relief was obtained from nitrate of silver given in the dose of gr. 1/12 every three or four hours, dissolved in thin mucilage of acacia.

Stimulants were remarkably well borne, and their administration in such form as was acceptable to the stomach was clearly of service, {431} even from an early period of the disease. As a rule, whiskey was employed, given in the form of milk punch. By carefully graduating the amount of alcohol, and when necessary diluting the milk freely with lime-water, the stomach usually received it well. If circumstances favored, dry champagne, or brandy or sherry in carbonated water would often prove preferable. The exhausting nature of the disease, the marked tendency to cardiac failure, and the inability to digest an adequate amount of nourishment, all indicate the early use of stimulants. In cases where a tendency to the development of the typhoid state existed alcohol was freely given, even to the extent of sixteen ounces of whiskey in twenty-four hours. Other stimulants were usually given in these cases, such as carbonate of ammonium, especially if pulmonary congestion existed; turpentine, especially if tympany was marked; or Hoffmann's anodyne or spirit of chloroform, if muscular twitchings, hiccough, or insomnia with wandering delirium were prominent symptoms. In all cases of severity the use of tonics and stimulants should be maintained in reduced doses during the intermission and for some days after the final fall of temperature.

It remains to allude briefly to certain special remedies and to certain symptoms requiring special treatment. Formerly, much diversity of opinion existed as to the propriety of venesection or local depletion in relapsing fever, but Murchison concluded, after a careful examination of the evidence, that it had not been shown to be of service; and certainly the disease as it occurred in Philadelphia in 1869-70 presented no indication whatever for even the mildest depletory measures. This corresponds with the recognized plan of treatment in all the specific fevers.

Blisters are not so objectionable in relapsing fever as in either typhus or typhoid, and there are several conditions in which they have been found decidedly useful. In cases where the headache has obstinately resisted cold applications, bromide of potassium, and opiates, a blister to the back of the neck has afforded marked relief, with no unfavorable result. Again, in cases where the vomiting and epigastric distress were severe and obstinate the application of a blister three inches square to the epigastrium is to be recommended.

Chloroform has proved of value for the relief of various symptoms in relapsing fever. As already stated, it was found the most useful remedy for the hiccough which was so troublesome in a number of our cases, and especially in those where jaundice was pronounced. It also seemed serviceable in controlling the peculiar chills which in varying degrees of severity were present in a few cases, recurring at about the same hour on successive days. These rigors or chills were uninfluenced by very large doses of quinine or other antiperiodics, but were apparently controlled by full doses of chloroform given in advance of the expected hour of recurrence.

Jaundice, which, as has been stated, is partly of hæmic origin, but is probably also due in part to obstruction from catarrhal swelling of the mucous membrane of the bile-ducts, is not influenced by mineral acids, and still less should mercurials or purgatives be administered for its relief. It would seem proper, in cases where this symptom is marked, to observe special care in diet and the use of stimulants, and to employ local sedative {432} astringents, such as small doses of nitrate of silver combined with opium and belladonna.

Muscular soreness, pains, and tremor may call for special treatment on account of their severity. The only remedy which has proved useful in relieving the first two of these symptoms is opium, conjoined with the external use of anodynes. Iodide of potassium fails even in doses as large as can be borne, and the same is true of muriate of ammonium and cimicifuga, which we used thoroughly without any effect. In the muscular pains, however, which torment the patient during convalescence, the ammoniated tincture of guaiacum was found of service. Atropia hypodermically and chloroform internally have been found useful for the relief of severe muscular twitchings.

Upon the whole, therefore, it will be seen that in ordinary cases a supporting and expectant plan of treatment is all that is required. Abandoning the idea of forcibly controlling the fever or of preventing the relapse, care should be given in the first place to the diet and to judicious stimulation.

Opium or morphia should be used to control pain, excitement, and insomnia, aided, as far as the latter is concerned, by bromide of potassium or the cautious use of chloral. Cooling drinks should be allowed, cool applications made to the head, and the body should be repeatedly sponged with cooling and disinfecting lotions. If the stomach is retentive, quinine in moderate doses may be given in acid solution, alternating with a simple fever mixture; but if nausea and vomiting are present, the first purpose will be to allay them by the appropriate measures already discussed.

Epistaxis is a frequent symptom, but usually requires no special attention. Occasionally it is profuse, and then should be promptly checked, since serious exhaustion may follow its continuance. If, therefore, mild astringent applications do not arrest it, recourse must be had to the tampon saturated with diluted Monsell's solution.

The urine must be closely watched and frequently analyzed in relapsing fever. In some epidemics serious alterations in this secretion are rare; in others it is not uncommon for the urine to be scanty, and to contain albumen or blood. When this latter condition is presented, especially if at the same time uræmic symptoms exist, dry cups should be applied over the kidneys, to be followed by the use of dry heat, and free perspiration should be promoted by hot-air baths or by the hot wet pack. It is probable that jaborandi given in repeated small doses, so as to avoid any depressing effect on the heart, will be found valuable in such cases. Infusion of digitalis, with spirit of nitrous ether or with acetate of potassium, may also be used with advantage.

Absolute rest must be insisted on throughout the entire period of paroxysm and relapse. The records of every epidemic present instances of sudden death from cardiac syncope following trifling exertions. The patients should therefore be kept strictly quiet in bed from the initial rigor until their strength is fully restored after the relapse. As the danger of collapse is especially great at the time of the critical fall in temperature, the patient should be closely watched as the end of the initial paroxysm and of the relapse approaches. If there is any sudden rise of temperature, with head symptoms due to hyperpyrexia, large doses {433} of quinine, ice to the head, cold spraying, or the cold bath must be promptly used. As sweating begins the body must be covered with a warm blanket and warm stimulating drinks be administered. If any marked tendency to collapse is observed, the subcutaneous injection of strychnia or of ether and digitalis, conjoined with diffusible stimulants internally and hot applications externally, are to be employed immediately. The special remedies required for the various complications and sequelæ have already been sufficiently indicated.

I desire in conclusion to acknowledge the important assistance received from Drs. Geo. S. Gerhard, Louis Starr, Charles Shaffner, and R. G. Curtin, who, under the supervision of my colleague, the late Dr. Edward Rhoads, and myself, recorded the histories of most of the cases which serve as the basis of this article, and also tabulated them for statistical purposes.[43]

[Footnote 43: Reference must also be made to the interesting observations on spirilla published by Mülhaüser in _Virchow's Archiv_ for July 9, 1884, after this article had been printed. His results go to confirm the view that the spirillum of Obermeier is the essential cause of relapsing fever.]

{434}

VARIOLA.

BY JAMES NEVINS HYDE, M.D.

Variola is an acute, febrile, contagious, and systemic affection, preceded by an incubative period, characterized by the evolution of symptoms in a relatively determinate order, with a cutaneous efflorescence successively papular, vesicular, and pustular in type, followed by crusting, and terminating either fatally or by complete convalescence, with or without sequelæ in the form of multiple, circumscribed, and superficial cicatrices.

SYNONYMS.--_Lat._, Variola; _Eng._, Small-pox; _Fr._, Petite Vérole; _Ger._, Pocken; _Ital._, Vajuolo.

HISTORY.--Small-pox is a disease which, there is reason to believe, was first developed in the earliest ages of which the human family has record. Originating probably in China, India, and the adjacent countries of the Asiatic continent, its extension over Europe and America was, without question, in the line of progress pursued by the advancing centres of traffic and population. The earliest traces of its ravages can be dimly recognized in the descriptions of writers in the middle and latter parts of the sixth century. In the early years of the tenth century, however, a remarkably accurate picture of the disease was drawn by Rhazes, a physician of Bagdad. His treatise, translated by Greenhill for the London Pathological Society,[1] sets forth the views of an Egyptian physician named Ahron, who wrote in the sixth century. After these dates the remarkable political and social changes in Europe, which are to be attributed either directly or remotely to the Crusades, contributed largely to the opportunities for the spread of the disease and to the occurrence later of those decimating epidemics which became veritable scourges. In the last century the resulting mortality in some of the countries of Europe was often equal to the entire population of one of their largest cities. If a modern traveller could find himself transported to the streets of the city of London as they appeared in the early part of the present century, it is probable that no peculiarities of architecture, dress, or behavior would be to him so strikingly conspicuous as the enormous number of pock-marked visages he would encounter among the people at every turn. In the face of all cavil and sophistry, medical science will always count among its greatest triumphs the modifications which variola has undergone since its preventive treatment was established upon a satisfactory basis by the discovery of the immortal Jenner.

[Footnote 1: _A Treatise on the Small-pox and Measles_, by Abu Becr Mohammed Ibn Zacaríyá Arrází, London, 1848.]

{435} The bibliography of the disease is extensive, and the list of authors contributing to the subject is enriched by the names of such men as Boerhaave, Van Swieten, Sauvages, Willan, E. Wagner, Johanny Rendu, Hebra, and, more lately, Kaposi.

ETIOLOGY.--Respecting the etiology of variola, it can scarcely be affirmed that our knowledge has been greatly extended since the date of the experiments of Jenner. There is no historical knowledge of its generation de novo; and the earliest cases of the malady must therefore be classed with the exceedingly rare instances of spontaneous cow-pox which have proved such a boon to the vaccini-culturists. To-day every case of small-pox is justly regarded as having been directly or indirectly transmitted from one or more individuals affected with a similar disorder. It is thus recognized as specifically infectious, contagious, and inoculable, its transmission occurring, first, without contact, by atmospheric conduction of a volatile contagious principle of unknown nature; second, with contact either by (_a_) actual transference of dry or moist infectious secretions deposited upon a susceptible surface, immediately or through the medium of garments, bed-clothing, paper money, and similar material substances; or (_b_) by inoculation of unprotected persons with the pathological product of an infected organism. There is no doubt but that the contagious principle displays its greatest activities in connection with the contents of the lesions undergoing a change from the vesicular to the pustular phases, though from the beginning to the end of the disease it is probable that all the tissues and fluids of the infected body are in various degrees capable of producing the malady in those who are unprotected. Furthermore, whether associated or not with an organic substance, the contagium of the disease is known to preserve the power of reproducing itself for a period lasting for weeks, months, and even a longer time. A field for its activities once secured, there is a period of time during which few if any evidences of its progress are declared, this period being abruptly terminated by distinct and characteristic symptoms. This is known as the period of incubation.

The nature of the contagium in small-pox has been the subject of much speculation, careful investigation, and experiment, the results having established but few facts of any practical value. There is at present no proof that any bacteria, vegetable germs, or other minute organisms foreign to the human body are the essential causes of the disease. It is certain that in health the human body is completely enveloped in a volatile medium emanating from the secretions of the glands of the skin, which can be recognized by some of the keen-scented lower animals when it is wafted through the air at a distance of several hundred feet from a single individual. It is reasonable to conclude that not only in small-pox, but in other contagious and infectious diseases, these emanations possess a pathological character, and become capable of transmitting such maladies from diseased to healthy organisms. Certain also it is that when the subjects of these diseases are crowded together, as in prisons, hospitals and camps, this contagious element gathers an unwonted intensity. By far the larger number of all transmissions of variola occur after inhalation of the infective medium--in other words, by the avenue of the lungs. It is probably for the same reason that the disease spreads more widely and with greater virulence during the cold seasons of the {436} year, in this latitude especially from December to February--a time when the ventilation of inhabited dwelling-houses is usually much less perfect than in warmer weather.

The disease affects individuals of all ages and both sexes, not sparing the foetus in utero, and, in the case of the latter, occurring both with and without previous infection of the mother of the unborn child. Nowhere are its ravages so extensive and followed by such fatal results as among those who have long been unprotected by previous vaccination. Among the debilitated, as also among the very young and the very old, small-pox is liable to be followed by severe complications and a fatal result. Negroes, possibly in consequence of tendencies inherited through generations of unvaccinated ancestors, are particularly prone to the disease. Lastly, there is occasionally noted an individual idiosyncrasy, in consequence of which either a remarkable susceptibility to the disease exists or a no less singular immunity against its encroachment is conferred.

Thus, physicians, much exposed to its influences in the discharge of their professional duties, are known to be relatively exempt, while other individuals, few in number it must be admitted, have either had repeated attacks of the malady itself, or, after each exposure to its contagious principle, a recurrent illness of variable type. In the immense majority of all cases, however, one attack confers immunity upon the sufferer against subsequent invasion of the disease for the remainder of life. Upon a few occasions I have known variola to occur in individuals previously affected with cutaneous diseases, especially the eczematous--a fact which merely suggests that such pre-existing disorder of the integument conferred no immunity against infection.

SYMPTOMATOLOGY.--The earliest symptoms of small-pox may be occasionally recognized during the stage of incubation, which, as described above, embraces a period of from ten to fifteen days, though these limits are not absolutely fixed, since both shorter and longer incubative periods have been at times established. During the interval the patient may appear to enjoy perfect health, or, on the other hand, suffer from an ill-defined malaise, with anorexia, languor, insomnia, and allied symptoms. Close observation of the patient thus affected will often reveal the existence of a peculiar pallor of the face, accompanied by a skin-color which suggests a slight degree of sallowness of the complexion. These rather indeterminate symptoms are naturally most marked toward the completion of the period of incubation.

The latter terminated, the period of invasion follows, and extends from the conclusion of the incubative stage to the moment when the first cutaneous lesions of variola appear upon the surface. The symptoms which characterize the onset of this period of invasion are conspicuous and characteristic. There is often a sharp vespertine rigor or a more or less continuous chilliness, accompanied by sensations of "creeping" over the surface, lasting even for several hours. Meantime, the temperature rises to 103° or 105° F., the pulse running up to 120 or 130 beats per minute. In this febrile condition there is commonly complaint of a characteristic aching in the head and back, intense, scarcely intermittent, and so peculiar as to have frequently furnished a clue to the diagnosis of the approaching malady. These sensations are quite analogous to the substernal and other pains which frequently precede the first explosions {437} of syphilis, and are all, without question, due to the circulation of a poisoned blood, the influence of which is in this manner confessed by the nervous system. In the case of infants and young children the invasion of small-pox is frequently ushered in by delirium and convulsions--symptoms which are to be explained by the facts just named.

This complexus of febrile and nervous symptoms, varying somewhat in intensity and possibly interrupted by sensations of chilliness, may be recognized as continuing on the second and third days of the period of invasion. Meantime, there may be noted a dusky hyperæmia of the pharynx and tonsils, the surface of which may even display elevated points which develop later into papules. In exceptional instances the intensity of the poison is such that the system fails to rally before the violence of the onset, and a fatal result ensues before the characteristic exanthem appears upon the skin.

On the second and third days of the invasion stage of the disease, if they are displayed at all, the variolous rashes appear. Too much attention can scarcely be paid to the importance of their recognition on the part of the diagnostician. Often indeed have practitioners been deceived by their occurrence, having been either completely blinded to the serious nature of the malady in progress, or, as Bartholow[2] has well shown, having supposed that they were dealing with a concurrence of variola and scarlatina or rubeola.

[Footnote 2: "The Variolous Diseases," _Med. News_, Mar. 4, 1882, p. 232.]

Hebra was the first to point out the significance of the rash known as roseola variolosa or erythema variolosa. Occurring at about the dates named above, it is in a few patients pronounced and vivid, even in solitary instances rivalling in severity the exanthem which succeeds it. In others, the majority of all patients in some epidemics, it may be entirely wanting. The writer has certainly observed its most typical development in women who were either menstruating or in the puerperal state. It is said also to be relatively frequent in subjects of a tender age. Kaposi[3] has recognized it in all its manifestations at every age.

[Footnote 3: Consult the admirable chapter on variola in his treatise, _Path. u. Therap. der Hautkrankt_, Wien, 1882.]

It appears in the form of puncta, striæ, or diffuse and uniform blushes covering extensive areas of the integument, livid red, purplish, or brownish-red in hue, paling under pressure, but never leaving upon the skin over which the finger-nail is quickly drawn the characteristic whitish streak by which many practitioners test the scarlatinal rash. The surfaces involved may be either not raised or slightly elevated above the general level of the skin, and are usually circumscribed. The regions chiefly involved have been carefully described by Th. Simon, and are hence sometimes called Simon's triangles. Thus the groin, the internal face of the thighs, and the hypogastric region may be involved at once (femoral triangle of Simon); the surface of the axilla, the pectoral region, and the inner face of the arm (brachial triangle of Simon), as also the extensor faces of the knees and the elbows, the dorsum of the feet, and indeed every portion of the surface of the body.

In the midst of these rash-covered areas may also appear petechial or hemorrhagic, dark-red, pin-head to bean-sized maculæ, which undergo color-changes both in lighter and deeper shades as the invasion period {438} lapses. In lieu of these, however, transient wheals may come and go over the surface, and even the erythema described above may assume an erratic phase and appear in one part only to disappear and recur at another. None of these flash-light warnings of the oncoming exanthem are proportioned to the latter in the matter of extent and intensity of development. They may be followed by grave or mild manifestations of the disease. The subsequent eruption may also be much more abundantly developed in regions where the invasion rashes have not appeared, and the latter completely fade before the former have advanced to occupy the field thus deserted.

The invasion stage of variola commonly occupies three days. Rarely it extends into the fourth, fifth, and even the sixth, day after the premonitory chill and fever.

Upon its subsidence the exanthem of the disease as a rule promptly appears. Simultaneously, the temperature abates, the rapidity of the pulse diminishes, and there is marked amelioration of the general symptoms. The patient, frequently deceived by the completeness of this defervescence, is apt to conclude that he is convalescent from his disorder, and is thus often astonished at the discovery of the exanthem upon the person, usually the face. In other cases, more commonly those of a grave character, there is failure of this defervescence, the febrile symptoms continuing or even increasing in severity.

The eruption first appears in the form of pin-head sized and larger, firm, conical, discrete, coherent or confluent, reddish papules, sometimes accompanied by mild sensations of a pricking or painful character, often exciting no subjective symptoms by which their presence could be declared. To the touch they are characteristically indurated, and suggest the hardness of small shot imbedded in the skin. They appear first and in greatest abundance upon the face and scalp, involving later and progressively the trunk, the extremities, and the palmar and plantar surfaces. It is at this moment that the eruption most resembles that to be recognized in measles (the distinction between the eruptive symptoms of the two diseases will be considered later). At times a reddish areola surrounds each lesion, especially those appearing upon the trunk. All are situated about the orifices of the follicles and glands of the skin.