Cases appear to have got well with change of air and a better diet
after resisting all ordinary means. In other instances no benefit
whatever has been derived from residence at the sea or in the
mountains. As a rule, the cases are best treated at home. The greatest
care must be exercised in the regulation of the diet, which should be
light and nutritious. So long as the digestion keeps tolerably active
there is hope: anorexia, vomiting, and other dyspeptic symptoms are
among the most troublesome and serious features. The bitter tonics,
hydrochloric acid, and pepsin may be administered. But the stomach may
fail absolutely and reject even the smallest amount of liquid food, and
rectal alimentation must be employed. The gastric symptoms have been
specially marked in cases in which there has been found post-mortem
atrophy of the peptic glands. In certain of these cases the problem of
feeding will tax to the uttermost the resources of the physician.
Rectal injections of blood (fresh or dried), as recommended by A. H.
Smith, I have found beneficial in several cases. Intestinal
symptoms--diarrhoea, flatulence, and in some cases melæna--call for
treatment.
Of medicines, arsenic is the most important, and in the form of
Fowler's solution should be employed in small and increasing doses. We
are indebted to Bramwell[91] for pointing out the great value of this
medicine, and in certain cases it acts almost as a specific. In 8 of
the 20 cases of recovery noted by Pye-Smith the improvement seemed due
to the arsenic. Padley[92] has collected in the literature 48 cases
treated without arsenic, of which 42 were fatal, while of 22 cases
treated by arsenic 16 recovered, 2 improved, and only 4 proved fatal.
The testimony of recent observers is very strongly in favor of this
drug as the most efficacious we possess in this grave disease. The use
should be continued long after the convalescence is apparently
established; indeed, it should be given at intervals for many months
after recovery, as there are dangers of relapse. There are cases which
are not benefited by arsenic, even when well borne. Finlay[93] has
recently reported a case which was cured by iron after the failure of
arsenic.
[Footnote 91: _Edinburgh Med. Journal_, 1877.]
[Footnote 92: _Lancet_, 1883, ii.]
[Footnote 93: _Lancet_, 1885, i.]
Iron, as a rule, seems quite useless in the majority of these cases. I
have frequently seen the percentage of red corpuscles gradually sink
under its administration, and then rise in a remarkable way when the
arsenic was employed. This is in curious contrast to the effect of this
drug in the various secondary anæmias and chlorosis in which it is
rightly regarded as a specific. The cases which are benefited may have
a different etiology, and where the arsenic does not succeed some form
of iron should be given, as Finlay's case, just mentioned, shows that
there are instances where it cures after the failure of the arsenic.
Broadbent advises the use of manganese when the anæmia is associated
with uterine or menstrual trouble. Phosphorus has been extensively
employed, and occasionally with benefit.
When all remedies have been tried in vain the question of transfusion
of blood arises. As a substitute for the intravenous transfusion the
blood has been injected into the peritoneum: this has been practised in
Italy with success.[94] The subcutaneous injection has also been used,
and lately the inhalation of a spray of blood has been recommended.[95]
In four or five instances intravenous injection has succeeded, but in
the majority of cases it has proved useless. Von Ott's[96] interesting
researches show that the injected blood-corpuscles and albuminous
materials always undergo destruction in the blood, and a 6/10 per cent.
solution of common salt seems to answer just as well, and is much more
available and less dangerous.
[Footnote 94: _Practitioner_, vol. xxxi.; Ponfick, _Berl. klin.
Wochenschrift_, 1879.]
[Footnote 95: _Med. News_, 1885, i.]
[Footnote 96: _Virchow's Archiv_, Bd. xciii.]
{908} The injection of milk, as first practised in cholera by my
preceptors, Bovell and Hodder[97] of Toronto, has also been employed in
anæmia (Pepper, Wulfberg).
[Footnote 97: _Canadian Journal of Science_, 1854.]
LEUKÆMIA.
DEFINITION.--A disease characterized by a great and persistent increase
of the colorless corpuscles of the blood, associated with enlargement
of the spleen, lymphatic elements, and bone-marrow.
SYNONYM.--Leucocythemia (Bennett).
HISTORY.--Our knowledge of this affection dates from the description of
two cases by Craigie and Bennett in the October number of the
_Edinburgh Medical Journal_ for 1845. The altered state of the blood
was thought to be due to the presence of pus--a suppuration of the
blood. In the November number of Froriep's _Notizen_ for 1845, Virchow
described a case in which the proportion between the red and white
corpuscles seemed reversed, and the blood had in consequence a
grayish-white appearance. He attributed the condition to an increase in
the colorless corpuscles. A case of Rokitansky's is referred to in this
article. In 1846, Fuller described a case before the Medico-Chirurgical
Society of London, in which the increase in the colorless corpuscles
was noted during life and after death.
In the August and September numbers of _Medicinische Zeitung des
Vereins für Heilkunde_ (1846) Virchow reviewed these four cases, and
insisted upon the fact that the colorless cells in the blood were not
pus, and vindicated a place in pathology for the white blood-corpuscle.
In the January number (1847) of the same journal he gives further cases
of white blood which he had collected in the literature--cases of
Bichat (1801), Velpeau (1827), Caventon (1828), Andral (1839), Barth
(1834),[98] and several others--and discussed the conditions under
which the colorless elements might increase and the relation of the
spleen to the white cells. In the same year (1847), in the first volume
of his _Archiv_, Virchow proposed the name leukæmia. Vogel in 1849
diagnosed a case during life.[99]
[Footnote 98: Donne (_Cours de Microscope_, 1844), who examined Barth's
case, seems to have been the first to recognize that the colorless
cells were blood- and not pus-corpuscles. See note by Gowers in
_Lancet_, i., 1878.]
[Footnote 99: _Virchow's Archiv_, Bd. iii.]
Bennett in 1851 collected additional cases, and gave the name of
leucocythemia to the disease, and in 1852 published a monograph
entitled _Leucocythemia; or, White-celled Blood, in Relation to the
Physiology and Pathology of the Lymph-gland System_. He claimed
priority in the discovery of the condition, and for several years a
lively paper war raged between the Edinburgh and the Berlin professors.
At this distance of time and place we can, now that the clouds of
controversy have blown away, see the truth. Bennett certainly described
cases before Virchow, but only in a manner similar to that in which
Bichat, Velpeau, and others had previously done, and he distinctly
stated his belief that the grayish-white color of the blood was due to
pus. Virchow from the first grasped the idea that the altered state of
the blood was due to an increase in the colorless cells, and he first
suggested the relation between their increase and the condition of the
spleen and lymph-glands, and he first gave a satisfactory name to the
disease; so that, while acknowledging the great and valuable services
of Bennett, we must, perforce, recognize the greater merit {909} of
Virchow, and recognize his priority in the scientific description of
the disease and in giving to it a suitable name. The further
investigations of Virchow enabled a splenic and a lymphatic form to be
recognized, and many years later Neumann[100] described the myelogenous
variety.
[Footnote 100: _Archiv der Heilkunde_, Bd. xi.]
FORMS OF THE DISEASE.--According as the pathological changes are
located in the spleen, lymph-glands, or marrow we speak of splenic,
lymphatic, and medullary or myelogenous forms; but it is very
exceptional for pure unmixed varieties to occur. More commonly, the
spleen and marrow, or these with the lymph-glands, are involved. The
disease may begin and make great progress in one of these regions, or
be confined to it for months, before appearing elsewhere. The spleen is
most often affected, and with it the marrow. According to many recent
writers, the myelogenous form is the most general, and certainly the
marrow is rarely found unchanged. The unmixed lymphatic variety is not
of frequent occurrence. An intestinal form, characterized by swelling
of the solitary and agminated lymph-glands and the general adenoid
tissue of the bowel, has been described by Behier.[101] In a few
instances the tonsillar and pharyngeal lymph-elements have been early,
perhaps primarily affected, and Kaposi has recently recorded a
case[102] under the name lymphoderma perniciosa, in which the lymphatic
elements of the skin were first involved.
[Footnote 101: _L'Union médicale_, 1869.]
[Footnote 102: _Wiener Med. Jahrbücher_, 1885.]
ETIOLOGY.--We know scarcely anything of the causes of the disease, but
it is usual to take into account certain factors which may possibly
influence its production, such as climate and country, age, sex, etc.
Climate and Country.--The disease appears to be more common in
temperate regions; not many instances are reported from the tropics. It
does not appear to be often met with in India. It is, I think, more
common in Europe than in this country. The determination of its
prevalence is rendered difficult by the fact that many cases reported
simply as enlarged spleen, without any examination of the blood, have
possibly been leukæmia. It does not seem to be more common in the
southern part of this continent.
Age.--No age appears exempt. Cases are recorded in infants of eight or
ten weeks and in men of sixty-nine and seventy years of age. The
youngest case I have seen was in a suckling of eight months. The
majority of cases occur at the middle period of life, from thirty to
forty. After the fiftieth year the cases diminish very much in number.
Sex.--Males are more prone to the affection than females, in the
proportion of at least 2 to 1. Of 11 cases which I saw in Montreal,
only 3 were in females; of 200 cases collected in the literature, 135
were in males and 65 in females (Birch-Hirschfeld[103]).
[Footnote 103: _Lehrbuch der Path. Anatomie_, 2te Auf., 1883.]
Social and sanitary conditions do not appear to have much influence,
though the lower and middle classes furnish the majority of the cases.
Mental worry and depression are specially mentioned as predisposing
causes in some cases.
Previous Disease.--In women it has frequently been noticed that
disturbance in the menstrual and sexual functions has preceded the
onset of the disease. The climacteric period has the greatest number of
cases, and in a few instances the disease had developed during
pregnancy.
The hemorrhagic diathesis has been noted in many cases, and the patient
may have been the subject of slight hemorrhages for years. In one case
of Howard's[104] the lad had been subject to nose-bleeding as a child,
and his mother and one sister had been much troubled in the same way.
[Footnote 104: _Montreal Gen. Hosp. Reports_, vol. i., 1880.]
Malaria.--On account of the frequency of chronic splenic tumor in
malarial infection, inquiries are always carefully made in any
suspected case as to the occurrence of intermittent fever. An intimate
connection is believed by {910} certain writers to exist between the
affections, and a few cases seem to have followed directly upon chronic
malaria. In Mosler's statistics of 112 cases there were only 4 in which
the sequence was well marked.[105] In Gowers' 150 cases there was a
history of malaria in 30.[106] In the Montreal cases there was an
account of malaria in 3 certainly--possibly in a fourth. In the reports
of 33 American cases there were only 6 with a history of malarial
attacks within twelve years from the date of the onset of leukæmia.
Guiteras of Key West (now of Charleston, S.C.) states that it is a rare
affection in the South. Schmidt of New Orleans writes me that it is not
uncommon in Louisiana, but there are very few cases reported in
Southern journals.
[Footnote 105: _Die Leukæmie_, Berlin, 1872.]
[Footnote 106: _Reynolds's System_, art. "Leucocythæmia."]
Syphilis appears to have been in a few cases closely connected with the
onset of the disease.
Injury.--Many patients give an account of a blow or strain in lifting.
In 3 cases which I have seen the patients laid great stress on this.
One had received a kick in the side from a horse, and the two others
had strained themselves in lifting. De Chapelle[107] has dealt
specially with this feature in the etiology of the disease.
[Footnote 107: _De la Leukémie dans ses Rapports avec la Traumatisme_,
Paris, 1881.]
Previously-existing splenic enlargement does not seem, as we might
expect, to predispose to leukæmia. It is rare for a case of simple
chronic hyperplasia of the spleen--from malaria, for instance--to
terminate in leukæmia.
The disease occurs in the lower animals, and cases have been described
in horses, dogs, oxen, cats, swine, dogs, and mice. The majority of
cases have been in dogs.[108] A study of the comparative pathology of
the disease has not thrown any light on the etiology.
[Footnote 108: Siedamgrotzky, _Ueber die Leukæmie bei den Hausthieren_,
Leipzig, 1878; Bollinger, _Virchow's Archiv_, lix.; _London Med.
Record_, vol. ii., 1874.]
SYMPTOMS.--A division of the disease into two or three stages has been
made by some writers, but as no special regularity is observed in the
sequence of events, we need only recognize a period of development, in
which the disease gradually becomes established, and a final period of
cachexia, when there are symptoms of profound blood-change and the
viscera are involved.
The mode of onset is insidious. In the majority of cases there is
failure in health and strength, and the patient seeks advice for
progressive enlargement of the abdomen with dragging pain in the side,
or for the shortness of breath, the enlarged lymph-glands, the pallor,
or the various symptoms of anæmia, as headache, palpitation, and
dizziness. Bleeding at the nose is common. Vomiting and diarrhoea may
be early symptoms, and in a few cases oedema of the face and feet has
been noted early in the disease. Occasionally the first symptoms to
attract the attention of friends or physician are of a serious
nature--a sudden hemorrhage, for example. In one of Howard's cases the
lad had played lacrosse two days before the onset of the fatal
hæmatemesis, and in another case, a girl, there was early and fatal
hemorrhage from the stomach before the condition of splenic enlargement
was suspected.
Digestive System.--Gastric symptoms are rarely absent in the form of
oppression after eating, nausea, and vomiting; the latter may be an
early and troublesome feature. The appetite is variable, and when the
spleen is greatly enlarged the mechanical pressure is apt to cause
uneasy feelings after eating.
Diarrhoea is common, and may come on very early in the disease (Case
I.[109]), and it is a frequent cause of death. The stools are usually
thin and catarrhal, not often dysenteric, but melæna occurs in many
cases. The diarrhoea may be due to a dysenteric process in the colon
(Case II.), and tenesmus may {911} be present. It has not been noted
that the diarrhoea is more frequent when the lymph-glands of the
intestines are involved.
[Footnote 109: These figures refer to Montreal cases, some of which I
saw with my colleague, Palmer Howard, others with John Bell,
Lachapelle, and G. T. Ross.]
The liver shows no alterations in the early stage, but as the disease
advances it is almost invariably enlarged. Jaundice is not often
present, but there may be recurrent attacks (Case II.), due either to
catarrh of the ducts or to pressure of glands in the hilus. Ascites is
a variable feature; a slight degree is not uncommon as part of a
general dropsy dependent upon the blood-condition, but in some cases it
is a prominent symptom and calls for frequent tappings (Case IX.). In
some cases it is due to pressure of leukæmic growths in the branches of
the portal vein or the liver, or of enlarged glands upon the trunk at
the hilus. The ascites is not always hepatic; like the hæmatemesis and
melæna, it may be of splenic origin and occur without any disturbance
in the portal vein or liver. Leukæmic peritonitis has been met
with.[110]
[Footnote 110: Willcocks, _Proceedings of Conn. Med. Soc._, 1874.]
Nervous System.--Headache, dizziness, and attacks of fainting are
common, and due chiefly to the anæmia. In some cases the headache is
severe and persistent. The intelligence is well preserved; only toward
the close is there rambling delirium. Mental disturbance may occur, and
in one case the patient committed suicide. Some writers speak of
special sadness and moroseness. This I have never noticed; on the
contrary, in most of the cases I have seen the patients seemed
specially tranquil and resigned. Coma may come on suddenly from
cerebral hemorrhage (Case X.).
Sleep is not usually disturbed; some patients doze incessantly.
Special Senses.--Weak vision is often complained of, due to the anæmia,
sometimes to the leukæmic retinitis. Blindness rarely supervenes, even
when the retinal changes are extensive. Marked intolerance of light may
be present.
The condition of the retina is variable. There may be simply turbidity
and swelling of the retina, with large and tortuous veins, or more
commonly with the opacity there are hemorrhages, such as occur in
profound anæmia from any cause. A peculiarity, however, of the
extravasations in some cases of leukæmic retinitis is the appearance
produced by the aggregation of colorless corpuscles, often in the
centre of the hemorrhage, so that there is a yellow or white nucleus
and a zone of red. The collections of colorless corpuscles may indeed
have the characters of small leukæmic growths. In one case (XI.)
throughout the retinæ were numerous small raised opaque white bodies
one to two millimeters in diameter, some of them surrounded by rings of
extravasation. There was no swelling of the disk.
Deafness has been frequently observed, and may appear early. It was
specially noted in the cases of Edes,[111] Morrill,[112] Seguin,[113]
and Pepper,[114] and DaCosta.[115] No satisfactory explanation has been
given, and the suggestion that it is due to hemorrhage has not, so far
as I know, been confirmed by autopsy. Noises in the ears may be very
troublesome, and even be so bad as to disturb hearing and necessitate
the writing of questions (Case XI.).
[Footnote 111: _Boston Med. and Surg. Journal_, 1871.]
[Footnote 112: _Loc. cit._]
[Footnote 113: _Archives of Scientific and Practical Medicine_, New
York, 1873.]
[Footnote 114: _Med. and Surg. Reporter_, 1883, 48.]
[Footnote 115: _Ibid._, 1874.]
Blood-vascular System.--In a well-marked case the blood-drop squeezed
from the finger-tip is more or less turbid, of a reddish-brown or in
extreme cases chocolate-brown color.
The blood should be examined in a thin layer, and for this purpose it
is better to take a small than a large drop. A rough estimation of the
proportion of white corpuscles can be much better obtained when a
uniform thin layer is beneath the top cover. The red corpuscles, as a
rule, present no striking changes, no special alterations in size or
shape. Microcytes are {912} occasionally seen, and now and then larger
forms, but the extreme variations of pernicious anæmia are rarely met
with. They are reduced in number, but not often to a great extent. A
reduction below 2,000,000 to the cubic millimeter has been exceptional
in cases which I have examined. In only one did the number sink to
1,500,000 per c.m. Laache[116] has noted a case in which, with
enlargement of the spleen and a ratio of white to red of 1:17, the
number of red corpuscles was little if at all reduced.
[Footnote 116: _Die Anämie_, Christiania, 1883.]
The colorless corpuscles are enormously increased. Instead of eight to
ten millions per c.m., as in normal blood, they may reach 500,000 per
c.m. or even 700,000 per c.m. The ratio of white to red cells may be
1:20, 1:10, 1:4, or they may even equal or exceed the red. Without a
proper apparatus (Gowers, Malassez, or Zeiss) an accurate estimate is
impossible, and it is chiefly upon the rough-and-ready method that the
statements are made of the white exceeding the red in numbers. It is
very seldom indeed that this is the case, and even in extreme leukæmia
the ratio does not often reach 1:3 or 1:2. In none of my observations
did the ratio rise to 1:1; the highest was 1:2. Cases are on record in
which the white have exceeded the red: Sörensen's,[117] where the red
per c.m. were 470,000 and the white 680,000, and in an interesting
observation of Fleischer and Penzoldt,[118] as a mean of 57 accurate
counts, the ratio of white to red was 115:100. The corpuscles have the
natural grayish-white appearance of leucocytes, but differ in certain
points from normal white blood-cells. The variations in size are
greater: in normal blood only a few may be seen less than 1/2800 or
1/3000 of an inch, but in leukæmia on a single slide there may be
colorless cells with the extreme measurements of 1/2000 and 1/3500. In
ordinary cases we meet with--(1) cells of the average size, about
1/2800 of an inch in diameter, like normal corpuscles, with two or
three nuclei and fine granular protoplasm; (2) smaller forms, 1/3000 of
an inch and under, with single nuclei, resembling rather lymph-cells,
and they were believed by Virchow to indicate special involvement of
the lymph-glands, but they are present in all forms, though possibly
more prevalent in the lymphatic variety; (3) large forms, 1/2000 to
1/1500 of an inch, with bold nuclei and bearing a close resemblance to
the marrow-cells. They are not always present, and are believed to
originate in the marrow.
[Footnote 117: _Virchow-Hirsch's Jahresber._, 1874.]
[Footnote 118: _Deutsches Archiv f. klin. Med._, Bd. xxvi.]
Cafavy states[119] that the colorless corpuscles of leukæmia do not
display active amoeboid changes, indicating thereby a diseased and
enfeebled condition of protoplasm. I find a note made in Sanderson's
laboratory in 1873 on the very sluggish and imperfect movements of the
colorless corpuscles in a case of leukæmia in University College
Hospital. In Case V. the note on one day is, "Active amoeboid changes,"
and in two other cases since Cafavy's paper I have seen the
protoplasmic movements tolerably active, but not in all equally.
Possibly the leucocytes from the marrow do not move so freely as the
others; normal marrow-cells have very feeble amoeboid powers.
Ehrlich[120] has observed that the number of leucocytes in leukæmic
blood which contain granules reacting with eosin is very great, whereas
in normal blood very few occur.
[Footnote 119: _Lancet_, ii., 1880.]
[Footnote 120: _Zeitschrift f. klin. Med._, Bd. i.]
Nucleated red blood-corpuscles, such as occur in the blood of the
foetus and in the red marrow of the adult, have been found in leukæmic
blood by Klebs, Mosler, and others. I have observed them in four cases.
They are scanty, usually isolated, rarely more than one or two in a
field; often, indeed, many fields must be searched before finding one.
On two occasions (Case IX.) they might be called numerous--three or
four in each field of the No. 9 immersion lens.
Schultze's granule-masses, the aggregations of the discoid
hæmatoblasts, are {913} present in variable numbers, sometimes very
numerous. I have examined slides in which they were absent. A curious
mistake was made by a writer in the _Lancet_ (1878, ii.) when he
described these as a hitherto unnoticed feature of the blood in
leukæmia.
The fibrin network which separates between the corpuscles is usually
very thick and dense.
Peculiar crystals, elongated octahedra or spindles, of variable size
and bright-white appearance, separate very commonly on a slide of
leukæmic blood, particularly if kept surrounded with oil or paraffin
for twenty-four hours. They are known as Charcot's crystals, and are
identical with those which occur in the bone-marrow, in semen, and in
sputum in some cases of bronchitic asthma. White of Boston described
them well in 1859,[121] and believed they were produced by the
separation of a neutral principle which he named leukosin. I can
confirm Zenker's observation,[122] that they form sometimes in the
colorless cells.
[Footnote 121: _Boston Medical and Surg. Journal_.]