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 {919} 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.
[Footnote 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 {920} 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 case[143]
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 Fleischer[144] 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.
[Footnote 143: _Berliner klin. Wochenschrift_, 1877.]
[Footnote 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.
[Footnote 145: _Gazette des Hôpitaux_, 1877.]
The PROGNOSIS is in the highest degree unfavorable, and in those cases,
few, indeed, in number, in which there were symptoms like leukæmia and
which disappeared under treatment, the doubt remains whether they were
true examples of the disease. When once established, the spleen and
glands enlarged, the hemorrhages and dropsies present, and the blood
condition marked, death is the only termination to be expected.
Specially unfavorable signs are a tendency to hemorrhage, persistent
diarrhoea, early dropsy, rapid increase in the splenic tumor, great
excess of colorless corpuscles, and high fever. Temporary improvement
may occur for weeks or even months, and the white blood-corpuscles
reduce in number, but such breaks are usually transient.
TREATMENT.--If, as some writers hold, chronic malarial poisoning is an
important factor in the induction of leukæmia, we should take special
pains with patients so affected, and endeavor by the use of quinine and
arsenic to free the system and reduce the volume of the spleen. There
certainly may be danger of the development of leukæmia in any case of
chronic splenic tumor, though my own experience has been that in these
cases the production of anæmia of high grade, without increase in the
white blood-corpuscles, is more common. It is a mistake to suppose that
anæmia always accompanies chronic splenic enlargement: it may persist
for years with a percentage of red corpuscles little if at all below
normal, but grave anæmia or leukæmia are probabilities to be dreaded.
In an early stage, when the spleen is moderately enlarged, the
lymph-glands scarcely swollen, and the leucocytosis not intense, there
is a hope that by the persistent use of quinine, iron, and arsenic a
cure may be effected; but when the disease is fully established and the
leukæmia marked, a recovery {921} is rarely if ever witnessed, and the
treatment is largely palliative and symptomatic. To reduce the volume
of the spleen various remedies are recommended, and so long as the
organ is only moderately enlarged and hardened some of them may be
beneficial. Quinine should be given a full and prolonged trial, as
undoubtedly under its use the organ may reduce in size. As anæmia is
almost always present, iron may be administered at the same time. That
the quinine has any special influence over the production of the white
corpuscles, as some think, I have not been able to satisfy myself. To
be of use, it must be employed early and in large doses. Ergotin
internally and by injection into the spleen has been recommended. I
have not seen any permanent benefit from its use. Local measures, such
as inunction of biniodide of mercury ointment over the spleen, the
interrupted voltaic current, the application of cold, either ice or the
cold douche, may be employed. Moderate reduction in the volume may be
effected by these means--most effectually by the electricity and
mercurial inunction.
Arsenic should always be given a trial, and pushed for several months
in increasing doses. Several cases are reported in which the
improvement lasted for many months. Direct injections into the spleen
are also of service. Phosphorus, from which much was expected after the
favorable reports of Broadbent and Wilson Fox, has not proved of much
value. There are very curious remissions in the course of the disease
which render therapeutical deductions somewhat fallacious. I have seen
the most marked improvement occur without any special treatment:
ascites and dyspnoea disappear, the white corpuscles decrease in
number, and the patient from a bed-ridden, wretched condition get up,
attend to light duties, and walk half a mile to hospital (Case IX.). In
Case VIII. there were also during eighteen months remarkable
variations, depending more on the state of the gastro-intestinal canal
than the blood condition.
Transfusion has proved useless. Leukæmic blood to the amount of several
ounces has been withdrawn and other healthy blood substituted.
Excision of the spleen has been frequently practised in leukæmia.
Collier[146] gives a résumé of 16 cases, and concludes that it is a
useless and unjustifiable operation, as all of them proved fatal. A
successful case, however, is reported from Italy. If performed early,
there is a possibility of success, but when the organ is enormously
enlarged and the blood intensely leukæmic, the conditions are most
unfavorable.
[Footnote 146: _Lancet_, 1882, i.]
Gastric symptoms and diarrhoea call for careful treatment, as the
comfort of the patient depends largely on the condition of the primæ
viæ. Hemorrhage is frequent, and is a dangerous symptom, particularly
when it depends upon engorgement of the portal system, and calls for
appropriate remedies. Purgatives are to be employed with caution. The
dragging pain in the left hypochondrium, and the sense of weight and
distension after eating, are very distressing, and the splenic pain may
require sedatives. Inhalations of oxygen relieve the dyspnoea and have
been found to check the progress of the disease.
HODGKIN'S DISEASE.
DEFINITION.--A disease characterized by progressive hyperplasia of the
lymph-glands, sometimes also of the spleen, with anæmia and the
development of secondary lymphatic growths in various parts of the
body.
SYNONYMS.--Pseudo-leukæmia; General lymphadenoma; Malignant {922}
lymphoma (Billroth); Lympho-sarcoma (Virchow); Adénie (Trousseau);
Desmoid carcinoma (Wagner); Anæmia lymphatica (Wilks); Lymphatic
cachexia (Mursick); Adenoid disease (Southey).
HISTORY.--Morgagni and other writers mention cases of enlargement of
the lymph-glands proving fatal, but Hodgkin of Guy's Hospital first
called special attention to the subject in a paper before the
Medico-chirurgical Society of London,[147] entitled "On Some Morbid
Appearances of the Absorbent Glands and Spleen." Some of the cases then
described were undoubtedly examples of scrofulous glands, but four at
least were instances of the disease which now bears his name; and at
the meeting of the London Pathological Society in 1878, when a
discussion on lymphatic disease took place, Wilks exhibited the
original specimens collected by Hodgkin. Other cases were recorded in
England by several observers, and in 1856, Wilks[148] reported several
examples of enlarged lymph-glands with growths in the spleen associated
with anæmia, but without any leukæmia; and again in 1865 this observer
published additional cases,[149] and gave the name of Hodgkin's disease
to the affection characterized by enlargement of the lymph-glands,
growths in the spleen and other organs, and anæmia. The cases and
discussions contained in the _Transactions_ of the Pathological Society
of London and Gowers' exhaustive article in _Reynolds's System of
Medicine_ embrace the most valuable of the English contributions. In
Germany, Virchow described the cases under the term lympho-sarcoma, and
in his work on tumors gave a full account of the histology. Billroth
gave the term malignant lymphoma to these growths to distinguish them
from local non-infective lympho-sarcomas. Cohnheim and Wunderlich used
the term pseudo-leukæmia to express the distinction between these cases
and leukæmic enlargements.
[Footnote 147: _Transactions_, vol. xvii., 1832.]
[Footnote 148: _Guy's Hospital Reports_, 3d Series, vol. ii.]
[Footnote 149: _Ibid._, vol. ix.]
In France, Trousseau described it under the term adénie, and Ranvier
used the term lymph-adénie. In America many cases have been described,
and one of the first and fullest analyses of recorded observations is
by J. H. Hutchinson in the _Transactions_ of the College of Physicians
of Philadelphia, Series 3, vol. i.
ETIOLOGY.--No satisfactory etiological relations have been determined
in the disease.
Age has an important predisposing influence. The majority of the cases
are young persons. In Gowers' table of 100 cases, 30 were under twenty
years, 34 between twenty and forty, and 36 above forty. Most of the
cases I have seen have been in young adults.
Sex has a still more marked influence; at least three-fourths of all
cases are in males, the proportion being considerably higher than in
leukæmia--75 per cent. in Gowers' tables, and 40 out of 58 in
Hutchinson's tables.[150]
[Footnote 150: _Loc. cit._]
Heredity has in a few instances been adduced as a possible cause, but
not, I think, on very reliable grounds. In two cases (II. and
III.[151]) the patients were each a twin. It might be supposed that
members of tuberculous families, or those who had suffered from
scrofulous enlargements when young, would be more liable to the
disease, but the cases in which such connection can be traced are very
few in number.
[Footnote 151: These figures refer to cases of which I have notes.]
Antecedent syphilis has been noted in a few instances.
Exposure, intemperance, bad food, etc. are possible predisposing
causes.
Local irritation, which so often produces lymphatic swellings, appears
to stand occasionally in causal connection with the development of
general lymphadenoma. Trousseau lays particular stress upon this, and
gives instances in which chronic irritation of the skin, otorrhoea,
chronic nasal or pharyngeal catarrh, irritation of a decayed tooth,
gave rise to local gland swelling which preceded the general
development of the disease. But this {923} is a comparatively rare
affection, and think of the hundreds of instances met with of local
lymphatic irritation!
SYMPTOMS.--Enlargement of the lymphatic glands in the neck, axillæ, or
groins is the earliest symptom noticeable in the great majority of
cases. This may be quite painless at first, and the patient seeks
advice on account of the disfigurement or the inconvenience felt in
adjusting the collar. Occasionally the anæmic and constitutional
symptoms first attract attention. When the trouble begins in the deeper
groups--bronchial, mesenteric, or retro-peritoneal--pressure effects
are the first complaint, and there may be great obscurity and
uncertainty about the nature of the case. Thus, the first symptom may
be dyspnoea, with pain in the chest, or pain in the abdomen with
swelling of the legs and shooting pains in the course of the nerves; or
in rare cases symptoms of a totally different nature may be among the
first to attract attention. Thus in J. H. Hutchinson's case there was
paraplegia from pressure of a secondary growth, and the same was
observed in a case which I dissected at the Montreal General Hospital
(Case VI.). But such are very exceptional, and in the great majority
swelling of the superficial glands is the earliest phenomenon. In rare
instances the tonsils and pharyngeal adenoid tissue have been first
affected.
Hemorrhage is not an early symptom. Epistaxis has been noted, but not
with the frequency with which it occurs in leukæmia.
With the progressive enlargement of the glands the patient becomes
anæmic, and finally cachexia is developed.
The Lymphatic System.--In an early stage it is difficult or impossible
to distinguish the affection from syphilitic or scrofulous adenitis.
The gradual increase in the size and the involvement of other groups,
and the oncoming anæmia, will alone in certain cases render a decision
possible. In the cervical group, in which the trouble usually begins,
the chain of glands on one side becomes enlarged--perhaps only those
just above the clavicle, or in some instances the posterior ones are
also affected. They are isolated, movable, and not, as a rule, tender.
Months, or even years (three years, Case VII.), may elapse before the
enlargement becomes general or affects the other side. With their
increase in size and number the separation between the glands, at first
evident, disappears, and they form distinct groups or bunches. Thus the
submaxillary set, those of the anterior triangle, and those of the
posterior may form irregular aggregations of various sizes. Ultimately,
huge tumors may develop which obliterate the neck, extending upon the
shoulders and over the clavicles and sternum. When these grow inward,
toward the trachea, great dyspnoea may be produced, and the pressure
may be so extreme that tracheotomy must be performed.
The skin becomes involved, and ulcerates. Usually it is freely movable
over the masses. The pharynx and oesophagus may be compressed, and
occasionally the carotids. The submaxillary tumors may limit the
movement of the jaws.
Next to the cervical, the axillary glands are most frequently involved.
If small, no inconvenience is felt, but when large bunches occur there
is great pain in moving the arms, and pressure upon the brachial or
axillary veins may cause swelling of the limbs. The tumors may pass far
out, almost to the nipple.
The inguinal glands are not so often involved. In only one of the ten
cases which I have seen were they affected, but they may form large and
even pendulous tumors, as well shown in the cases of Surgeon-Major
Porter.[152]
[Footnote 152: Figured in _Path. Soc. Trans._, xxix.]
Of the internal glands, those of the thoracic cavity are most often
attacked. The chain in the posterior mediastinum may be involved and
surround the aorta or compress the gullet; or they may pass up the
trachea to the {924} neck, and involve the thyroid (Case V.). When the
bronchial group is enlarged there are signs of pressure on the tubes,
dyspnoeal attacks, and serious implication of the lung (Case VI.) In
the mediastinum there may be large masses covering the aorta, extending
over the pericardium, and producing bulging of the sternum and ribs,
perhaps pulsation, and ultimately erosion of the bones and outward
projection of the tumors (Cases II. and III.). There may be
considerable pressure upon the veins and obstruction to the flow in the
superior cava and jugulars.
In the abdomen the mesenteric glands are often affected, and if the
belly-walls are thin can be readily felt. The continuous chain of
retro-peritoneal glands may be greatly enlarged, and extend from the
diaphragm into the pelvis, surrounding the aorta, cava, and nerves.
When the patient is thin there may be no difficulty in detecting these,
but when there is an enormously thick panniculus the diagnosis may be
impossible, as in Case I., in which intense lumbar and sacral pain and
swelling of the legs were the only symptoms. The matting of organs in
the pelvis caused by these growths may be a source of great difficulty
in the diagnosis, as in a case in which I saw an eminent and careful
surgeon open the abdomen to extirpate a uterus for fibroids, and found
general lympho-sarcoma of the retro-peritoneal and pelvic glands.
It is probably in connection with affection of the abdominal glands
that the bronzing of the skin occurs which is mentioned in a few
instances. It was well marked in Case IV. of my series.
The glands present great variations in the rate of growth and there may
be fluctuations from month to month. They may diminish rapidly, and
almost disappear from a region to develop again in a few weeks. The
enlargements may diminish very much before death.
The spleen does not present the almost constant enlargement of
leukæmia, and in the majority of cases cannot be felt below the ribs.
Moderate hyperplasia is common, but I have never seen the large splenic
tumor. In some instances it has been found extending into the umbilical
region, and if there are secondary lymphoid growths the surface may be
very irregular.
The thyroid may be enlarged; it was so in Cases II. and IV., and in
Case V. the growth in the glands of the neck involved the right lobe.
The thymus has also been found affected; indeed, the disease may,
according to Virchow, sometimes begin in the gland.
Blood and Circulation.--The blood presents the characters of anæmia,
and as a rule the more advanced the glandular trouble the greater the
impoverishment. The red corpuscles are reduced in numbers one-half or
even three-fourths, but never, in my experience, to the extent in
pernicious anæmia. The lowest number per cubic millimeter which I have
counted was in Case II., when on one occasion the numbers sank to
2,100,000 per c.m. There may be most advanced disease without great
anæmia. In one case (IV.) with enormous enlargement of the cervical and
axillary gland there were 4,250,000 to the c.m., and during his three
weeks' stay in the hospital the numbers were never much reduced. So
also in Case III. there was not profound anæmia to within two months of
the patient's death.
The red corpuscles are usually uniform in size. I have never seen
extreme poikilocytosis, though occasionally the microcytes have been
numerous. The colorless corpuscles are not greatly increased, although
there may be moderate leucocytosis, as in Case IV., in which the ratio
of white to red kept about 1:150. A condition of actual leukæmia may be
induced. The corpuscles may be smaller than usual, and present the
characters of the blood in lymphatic leukæmia. I have not met with
nucleated red corpuscles in any of the cases which I have examined.
The granule-masses of Schultze are in variable numbers.
{925} Cardiac weakness and palpitation are common, due chiefly to the
anæmia. The mediastinal growths in some cases cause great embarrassment
from pressure. Fatty heart-muscle is an almost constant sequence of the
anæmia. The pulse is quickened--80-110, or, if much fever, 120-130.
Hæmic murmurs may be heard at the base of the heart, and the venous hum
at the root of the neck is often very distinct. Pressure of the tumors
upon the nerves may influence the heart's action, and in one case in
which sudden death took place it may have been due to interference with
the innervation of the heart by pressure on the nerve-trunks.
Respiratory System.--Shortness of breath from the anæmia is common,
particularly on exertion. When the tracheal and bronchial glands are
affected urgent attacks of dyspnoea may occur and suffocation be
induced. Pressure on the pneumogastric or recurrent laryngeal may cause
hoarseness or aphonia. The gland-tumors may invade the lung, or there
may be secondary growths. These are not usually large enough to induce
symptoms. The shortness of breath may be caused by pleuritic effusion,
which may be an early symptom and the one for which the patient is sent
to hospital (Case X.). It is due to pressure on the azygos and
intercostal veins.