141 "On the Histology of Leucocythæmia," Canada Medical and Surgical Journal, 1876.
The COURSE OF THE DISEASE is slow and chronic, a matter of months and years. There are exceptional instances in which the disease has proved fatal in a few weeks; this occurs sometimes in children,142 but acute leukæmia is very rare. In a table of 63 cases collected by Gowers, in which the date of the first symptoms was fixed with tolerable accuracy, the duration was less than one year in 13 cases; from one to two years in 16; from two to three years in 19; from three to four years in 9; from 4 to 5 years in 3; and five years and upward in 3 cases. The course is rarely uniform, but periods of improvement occur in which the fever subsides, the painful sensations in the abdomen diminish, the appetite improves, and the spleen reduces in volume. Such intervals, corresponding to the administration of certain drugs, are apt to lead to therapeutic errors. A patient may sometimes get about for months, and even attend to a light business, with an enormous spleen and a ratio of white to red corpuscles of 1 to 6 (Case VIII.). Hemorrhages, high fever, profuse diarrhoea, and the occurrence of dropsy shorten the course. Toward the close there is great muscular debility, and usually a wandering delirium.
142 Golitzinsky, Jahrb. f. Kinderheilkunde, 1860–61.
In the majority of cases death is by asthenia—a gradually progressive weakness and ultimate failure of the heart. Diarrhoea and hemorrhage hasten the fatal result. A profuse hemorrhage may cut off a patient early or after the disease is well established. Cerebral hemorrhage was noticed in 6 of 60 cases in which Gowers was able to ascertain accurately the cause of death. A few are carried off by pleurisy or pneumonia or peritonitis after tapping.
Pyæmia and rupture of the spleen are mentioned as causes of death in some cases.
The DIAGNOSIS of leukæmia rests upon the determination of a great and persistent increase in the colorless elements of the blood. Cases of Hodgkin's disease and of splenic anæmia, almost identical in general features, can only be distinguished by an examination of the blood. I should say that in any case we can speak of the blood as leukæmia when the ratio of white to red cells falls below 1 to 50. Some writers hold that to determine leukæmia the ratio should be at least 1 to 20, but when the study of the variations in the proportion of the corpuscles in any case extends over weeks or months, we not uncommonly find that the ratio, which, at one observation may be 1 to 8, or 1 to 10, a week later may be 1 to 60 or 80, or even 150. Indeed, the state of the blood is a variable factor, and too close attention to it has diverted our minds from the broad features which this disease has in common with others. For practical clinical purposes we have to distinguish ordinary lieno-lymphatic leukæmia from—(1st) chronic malarial infection with splenic hypertrophy; (2d) from cases of non-malarial splenic enlargements with anæmia; (3d) from general lymphadenoma or Hodgkin's disease. The history in malarial cachexia, the absence of lymphatic enlargement, and the blood-condition will usually be sufficient for purposes of a diagnosis. Great increase in the white blood-corpuscles is not often seen in the chronic splenic tumor of malaria; indeed they may be much diminished in number. Toward the end in very chronic cases the clinical picture may be very similar: the large abdomen, possibly ascites, dropsy of the feet, and irregular fever may resemble closely splenic leukæmia, and the absence of an increase in the colorless corpuscles may be the only marked difference. From anæmia splenica there is still greater difficulty, and I have seen instances in which the absence of an excess of the colorless corpuscles in the blood formed the sole criterion: the hemorrhages, the dropsy of feet and abdomen, retinal extravasations, the general cachexia, and the fever were identical with those of leukæmia. Still greater may be the difficulty of separating certain cases of lymphatic leukæmia from general lymphadenoma or Hodgkin's disease; but in the latter affection the glandular enlargement is usually greater and altogether a more prominent feature, and the spleen is not so often increased in size. There may, however, be a considerable increase in the number of the white corpuscles, 1 to 150 or 1 to 100 red, and cases do occur which appear intermediate or transitional in character, and upon which judgment must be reserved until the progress of the case decides the question.
Pure cases of myelogenous leukæmia are almost unknown; if the osseous symptoms are not marked the course is very like that of pernicious anæmia. Indeed, there are two interesting cases on record in which the progressive anæmia seemed to pass into leukæmia. In Litten's case143 the patient presented the symptoms of profound anæmia, and five days before death the blood became markedly leukæmic. There was no enlargement of spleen or lymph-glands, but the bone-marrow was intensely leukæmic—i.e. of the pyoid form. In the case reported by Leube and Fleischer144 the patient, aged thirty, four months after her confinement became anæmic and the left leg was swollen. Though at first only anæmic, subsequently the ratio of white to red corpuscles rose to 1 in 10. Gangrene of the leg supervened, necessitating amputation, from the effects of which she died. There was no affection of spleen or lymph-glands, but the marrow was of the red lymphoid variety. A gastric ulcer was also present. This was no doubt a case of post-partum anæmia aggravated by the presence of ulcer of the stomach, and the great interest of the case lies in the transition of the anæmia into leukæmia.
143 Berliner klin. Wochenschrift, 1877.
144 Virchow's Archiv, lxxxiii.
There are certain general conditions, accompanied by an increase in the colorless corpuscles, which must be distinguished from leukæmia. In suppuration there may be marked leucocytosis; so also in cancer and protracted cachectic states, as phthisis. In cases with large cancerous masses about the stomach and omentum, or where, as occasionally happens in chronic phthisis, there is a greatly enlarged amyloid spleen, if the white blood-corpuscles are much increased, care may be necessary to escape a mistake in diagnosis. In diphtheria the colorless elements may be much increased. Bouchat says that in some instances there may be an acute leukæmia.145 In puerperal fever also the condition of leucocytosis is not uncommon.