THE 
PRIMARY OR ESSENTIAL ANAEMIAS. 
BY 
JAMES TYSON, M.D., 
Professor of Clinical Medicine in the University of Pennsylvania, and Physician to the Hospital of the 
University. 
Reprinted from the International Medical Magazine for February, 1893. THE PRIMARY OR ESSENTIAL ANEMIAS. 
The results of the application of staining methods to the study of the 
blood by Ehrlich and his pupils, supplemented by the more recent studies 
of Von Jaksch, Lowit, Limbeck, Muller, Rieder, and others, have already 
modified to some extent our views as to the constitution of the blood in 
various diseases, and it is probable that there will be further changes. It 
seems, however, not an inappropriate time to review the conditions consti- 
tuting the anaemias and the management which modern clinical experience 
has determined to be most successful, even though it may involve a repetition 
of some existing knowledge. 
The broadest definition of anaemia—impoverished blood—is correct, 
but, more definitely, it is any state of the blood in which there is a diminu- 
tion in its total bulk, its haemoglobin, its albumen, or the latter two. The 
first is the condition which ensues from a large hemorrhage of any kind, as 
from the bursting of an aneurism, erosion of a blood-vessel in an ulcer of 
the stomach or in a tuberculous lung, as well as from traumatism. In all 
of these instances, however, where the hemorrhage is not fatal, the original 
bulk of the blood is rapidly restored by the absorption of water and salts 
from the tissues, while the haemoglobin and albumen remain deficient. 
The haemoglobin in blood may be diminished by a reduction in the total 
number of red corpuscles, or in the proportion of coloring-matter in each 
corpuscle. 
Anaemias are further divided into 'primary or essential and secondary 
anaemias. The former are the direct result of a defect in the blood-making 
apparatus, while secondary anaemias are those resulting from the loss of 
blood, or some one of its important constituents, or of a defective supply of 
blood-making material. 
Among primary anaemias are commonly included chlorosis, pernicious 
anaemia, leucocythaemia, lymphatic anaemia or Hodgkin’s disease, and splenic 
anaemia. It is not conceded by all observers that pernicious anaemia is the 
result of a defect in blood-making. By some, as Quincke and Hunter, it 
is regarded as a haemolysis or disintegration of the red blood-corpuscles in 
the circulation or certain parts of it, especially in the liver. While admit- 
ting that the facts adduced by Hunter, and more recently by Griffith and 
Burr, favor such a view, the evidence to me is not sufficiently conclusive to 
demand its transfer from the essential anaemias. 2 
JAMES TYSON, M.D., ON 
The secondary anaemias are numerous, including those due to hemor- 
rhages, the action of poisons on the blood,—the toxanaemias,—viz., lead- 
poisoning, uraemia, drains of various kinds on the economy, inadequate 
food, and defects in the digestive apparatus. The present paper will be 
confined to the consideration of the primary or essential anaemias. 
I.—CHLOROSIS. 
Blood Changes.—At once one of the easiest recognized yet least distinctive 
of the anaemias in its morbid anatomy, chlorosis scarcely admits of a defi- 
nition. A disease of overworked young women occurring most commonly 
at the age of completing sexual development, sixteen to twenty years, the 
most marked and constant change in the blood is a reduction in the haemo- 
globin, associated with a moderate oligocythsemia or diminution in the red 
blood-corpuscles. The haemoglobin value of each corpuscle is therefore 
reduced. Certain cases are, however, reported in which the eruthrocytes 
have been as low as one million one hundred and ninety thousand to the 
cubic millimetre. It is, moreover, true that the number is always some- 
what below the normal, the maximum in one of fifteen cases observed by 
Limbeck being three million six hundred thousand, the normal for women 
being four million five hundred thousand. The haemoglobin I have found 
as low as fifteen per cent., but such a fall is extreme. This disproportionate 
fall in the haemoglobin, while not invariable, remains, however, a tolerably 
constant feature, producing sometimes a recognizable paleness of color when 
the blood is seen en masse. 
Along with the lowering of haemoglobin, as would be expected, since 
it is a constituent of the haemoglobin, the iron of the blood falls. An increase 
of alkalescence, announced by Graeber1 as a constant symptom, has not been 
found by Kraus2 in his more exact methods of testing. 
As to remaining changes, the red corpuscles may be altered in shape to 
a moderate extent, constituting a small degree of poikilocytosis, or they may 
be larger than in health, when they are known as megalocytes. But even 
the slighter degrees of these conditions are not constant. More frequent is 
an undue reduction in size of the corpuscles,—a microcytosis. A very slight 
degree of leucocytosis may be rarely present, while the blood-plaques in severe 
cases may also be increased. 
Morbid Anatomy.—Other than the changes in the blood there is no 
essential morbid anatomy to chlorosis. Many years ago Virchow pointed 
out an imperfect development of the circulatory apparatus as more or less 
characteristic,—that the heart was small, the aorta and its larger branches 
poorly developed and thin-walled. Such a state of affairs, when present, is 
probably an accidental coincidence. There is no enlargement of the spleen 
or lymphatics. 
1 Zur klin. Diagnostik d. Blutkrankheiten. Leipzic, 1888. 
1 Zeitschrift f. Heilkunde, Bd. ii. THE PRIMARY OR ESSENTIAL ANAEMIAS. 
3 
Symptoms.—While the blood-alterations in chlorosis are scarcely dis- 
tinctive enough to be considered diagnostic, the symptoms are quite the re- 
verse. The patient is invariably a girl, generally between sixteen and 
twenty, who, although she may have been overworked, does not seem badly 
nourished ; certainly she is not emaciated. She is, however, characterized by 
a peculiar pallor, often exhibiting a yellowish-green tinge, which is es- 
pecially marked on the mucous membranes, and is responsible for one of 
the names of the affection, green sickness. She is extremely weak, es- 
pecially on exertion, and short of breath. She is subject to vertigo, palpi- 
tation of the heart, and even irregularity of the heart’s action. Physical 
examination will sometimes discover functional cardiac murmurs. Rarely a 
compensatory hypertrophy of the left ventricle has been noted, but never 
valvular disease. Epigastric pain is also a symptom at times. 
Diagnosis.—The diagnosis is based chiefly upon the age and sex of the 
patient, the peculiar greenish-yellow color, the paleness of the lips, and the 
decidedly diminished haemoglobin, unaccompanied, as a rule, with a propor- 
tionate reduction in the number of eruthrocytes, although these are always 
somewhat diminished, and sometimes extremely so. The same lost normal 
ratio between the haemoglobin and the corpuscles is also a characteristic of 
lead-poisoning, which has, however, superadded its own characteristic symp- 
toms, and is almost restricted to adult males. 
The epigastric pain mentioned as occurring in chlorosis resembles that 
more common in ulcer of the stomach. The anaemia which so constantly 
attends ulcer of the stomach, often in a high degree, is, however, different from 
that of chlorosis, there being a corresponding decline in the eruthrocytes 
and their coloring matter. 
A not infrequent error of diagnosis in connection with chlorosis is the 
mistaking it for a “decline,” a pulmonary consumption, which it resembles 
in the pallor, the feebleness, and shortness of breath of the patient. The 
absence of cough and of the physical signs of consumption will aid in a 
diagnosis between the two conditions. 
Prognosis.—The prognosis is nearly always favorable when the disease 
is recognized and the proper treatment afforded. There are few results 
more satisfactory in therapeutics than those of a properly-treated case of 
chlorosis. Time is, however, required, and too rapid a cure must not be 
promised, several months to a year being usually required. The question 
whether a chlorosis will be transformed into that more serious variety of 
anaemia known as pernicious anaemia has been raised. This seems not im- 
possible. Both are failures in the cytogenetic apparatus to produce a proper 
cellular blood. In the one, chlorosis, the coloring-matter is chiefly wanting, 
although associated with this is usually found a less degree of cell-defect. 
In pernicious anaemia both cells and coloring-matter are defective. Both 
embarrass the oxygen-carrying office of the blood, and thus interfere with 
important vital processes, the total suspension of which must be fatal. 
Treatment.—The treatment is pre-eminently by iron, and it matters not 4 
JAMES TYSON, M.D., ON 
very much what preparation is used. The carbonate of iron, in the shape of 
Bland’s pill, made by a double decomposition between the carbonate of potas- 
sium and the sulphate of iron, is at this day very popular, one to three being 
given at a dose three times a day. But the tincture of the chloride of iron or 
reduced iron or one of the vegetable salts may be given. Iron is given in too 
large doses in the majority of cases for which it is prescribed. Most of it is 
unabsorbed, and therefore wasted; nay, worse, that which is unabsorbed 
locks up the intestinal secretions by its astringency, produces headache, and 
makes the patient otherwise uncomfortable. But chlorosis is one of the 
few diseases in which large doses of iron are well borne. The reason is plain. 
It is the iron-holding constituent of the blood which is wanting, and the 
iron is needed to replace it. The blood is, as it were, hungry for it. Next 
to iron comes arsenic. The efficiency of iron is greatly aided by union with 
arsenic, which should be given in increasing doses, but short of toxic effect. 
But to give these drugs is not alone sufficient. Best in bed, at first con- 
tinuous, is imperative to secure a rapid result, and this must be associated 
with an abundance of good food. Daily massage, except during menstru- 
ation, is also a useful adjuvant. There is no condition in which the so-called 
“ rest cure” is more efficient than in chlorosis. With a return of color to 
the lips, or, better, with the growing increase in the haemoglobin as meas- 
ured by the haemoglobinometer, the patient should be permitted to be out 
of bed at first a half-hour to an hour only, but this should be gradually 
increased until she is up most of the day. For a long time, however, 
fatigue should be avoided. To those who can afford it a residence at the 
sea-side materially aids convalescence. Indeed, I know of no condition so 
rapidly improved at the proper time by sea-air as chlorosis. To the poor 
a well-regulated hospital treatment is a boon for which there is scarcely a 
substitute. 
A second variety of essential anaemia is pernicious or idiopathic anaemia, 
originally described by Addison in 1855, in his celebrated paper on “ Diseases 
of the Supra-Renal Capsules.’’ Biermer again drew attention to the subject 
in 1868, and since then numerous others have studied it anatomically and 
clinically. It is, however, still the least understood of all the anaemias. 
Fortunately, it is a rare disease. 
Etiology.—The etiology of pernicious anaemia is almost unknown. The 
pregnant state seems to be responsible for a certain number of cases of 
true pernicious anaemia, the first of which were described by Channing and 
Gusserow. Other causes are cited, such as atrophy of the stomach, but 
I prefer to include under pernicious anaemia what Addison has characterized 
as a “general anaemia, occurring without any discoverable cause whatever, 
—cases in which there had been no previous loss of blood, no exhausting 
diarrhoea, no chlorosis, no purpura, no renal, splenic, miasmatic, glandular, 
strumous, or malignant disease.” It can be best explained as a primary 
defective haemogenesis, although some, led by Quincke, ascribe the state 
II.—PROGRESSIVE PERNICIOUS ANAEMIA. THE PRIMARY OR ESSENTIAL ANAEMIAS. 
of the blood to a haemolysis, in proof of which they point to the enormous 
accumulation of iron in the liver noted by Quincke in 1876, and confirmed 
by Rosenstein in 1877. To these Hunter added a pathological increase of 
the urobilin in the urine. In a recent noteworthy paper Griffith and Burr 
take the same view.1 
The disease affects mostly those beyond middle age, but children also 
have it, and Griffith mentions ten cases occurring under twelve. It is also 
more frequent in males. 
Symptoms.—The symptoms of pernicious anaemia are most insidious, 
and begin with a gradual progressive weakness. What is first interpreted 
as a causeless weariness or languor grows slowly into an extreme debility 
with faintness on the slightest exertion, and thence into a state of thorough 
muscular weakness, which ultimately prostrates the patient, rendering him 
unable to rise from bed. To this succeeds a mental hebetude and state of 
general torpor. Yet there is no emaciation. The body-bulk is well pre- 
served. The skin acquires gradually a yellowish hue, and sometimes an 
actual jaundice, whence, in connection with the symptoms, the disease has 
been mistaken for the slower form of yellow atrophy of the liver. In fact, 
the jaundice is similarly caused. It is a haematogenous jaundice, although 
it has also been ascribed to defective action of the liver-cells due to the 
accumulation of pigment in them. The mucous membranes, on the other 
hand, are blanched, as may be noted in the lips, gums, and mouth. 
Cardiovascular symptoms are especially conspicuous in progressive per- 
nicious anaemia. Haemic murmurs, visibly pulsating and throbbing arte- 
ries, even pulsating veins, have been noticed. The large but soft jerky 
pulse was mentioned by Addison. The capillary pulse is also frequently 
seen, and hemorrhages, cutaneous and retinal, occur. 
Digestive derangements also form a part of the symptomatology of per- 
nicious anaemia. Indisposition to take food, nausea, vomiting, and diarrhoea 
are troublesome symptoms. Moderate elevation of temperature, irregular 
and intermittent, is also noted, while nervous symptoms, including numb- 
ness, languor, and even paralysis, sometimes occur. 
The urine exhibits no constant changes, being sometimes pale and some- 
times dark-hued. The dark color is ascribed by Mott and Hunter to an 
excess of urobilin. 
Blood Changes.—The changes in the blood are more distinctive than in 
chlorosis, although it is true also that there is no single constant character- 
istic feature. The most constant is, however, a very decided oligocythaemia 
unaccompanied by a proportionate reduction in the haemoglobin, although 
the haemoglobin, as a whole, may still be less than in health. On the other 
hand, it is sometimes increased. Quincke found as few as one hundred and 
forty-three thousand corpuscles in a cubic millimetre of blood, while it is 
1 Pathology of Pernicious Anaemia, Transactions of the Association of American 
Physicians, vol. vi., 1891. 6 
JAMES TYSON, M.D., ON 
not uncommon to find them less than half a million. Frederick P. Henry 
found three hundred and fifteen thousand a few hours before death, and 
Laache three hundred and sixty thousand. 
The inevitable conclusion from such a state of affairs is that either the 
haemoglobin value of each corpuscle must be increased or there is a haemo- 
globinaemia which has its seat in the plasma. This latter view Silbermann1 
has adopted, because he has been able to produce in animals by the ad- 
ministration of blood-corpuscle dissolving substances, as pyrogallol, a com- 
plex of symptoms like those of pernicious anaemia. If pernicious anaemia 
be a haemolysis, as held by Hunter, rather than a defective haematogenesis, 
we would expect such a haemoglobinaemia to result. 
A further striking peculiarity in the blood of pernicious anaemia is the 
increase in the size of the red corpuscles. They become megalocytes, from 
ten to fifteen micro-millimetres in diameter, as compared with a normal of 
from six and five-tenths to nine and four-tenths. The majority may be so 
enlarged. On the other hand, there are also microcytes and poikilocytes, 
characterized by great irregularity in shape, being crescentic, conical, and 
otherwise distorted. While these irregular shapes were first demonstrated 
in connection with pernicious anaemia, and although they are more or less 
characteristic, cases of the disease have been described by Grainger Stewart, 
Lepine, and Hermann Muller in which poikilocytosis was absent. 
There are also sometimes found in the blood numerous minute highly- 
colored spherical bodies, called Eichhorst’s corpuscles. Eiehhorst regarded 
them as pathognomonic, but they, too, are sometimes absent. When present 
they contribute to the haemoglobin in the blood, but as they are not included 
in the blood-count they get no credit for their effect. The relative excess of 
the haemoglobin may, in a measure, be thus accounted for. Nucleated red 
corpuscles are a constant constituent of the blood of pernicious anaemia, and 
have also been regarded by their discoverer, Ehrlich, as almost distinctive. 
Two kinds are found : first, the small normal-sized corpuscle with its deeply- 
stained nucleus, and certain large forms with pale nuclei. Blood-plaques, 
according to Osier, are either absent or very scanty. Leucocytes are usually 
slightly diminished in number, while there is a tendency to an increase of 
the mononuclear white cells as compared with health. 
F. P. Henry2 has called attention to a fact which, while it does not aid 
us in the solution of the problem of pernicious anaemia, is interesting and 
deserves to l>e mentioned. He says that in this disease the red corpuscles 
“approach those of the lower animals in many, if not all, of their chief 
characteristics, namely, in their number, their size, their shape, and the 
amount of haemoglobin they carry.” 
Morbid Anatomy.—Various tissues have been studied in the effort to find 
a morbid anatomy for pernicious anaemia. In the absence of lymphatic or 
1 Berliner Klinisclie Wochenschrift, 1886, page 472. 
2 Anaemia, Philadelphia, 1887. THE PRIMARY OR ESSENTIAL ANAEMIAS. 
7 
splenic enlargement, the marrow of bones has claimed close study. H. C. 
Wood described the red condition of the marrow of long bones in 1871. 
In October, 1875, William Pepper1 described changes in the medulla of 
the sternum and radius from a case of pernicious anaemia, consisting, first, 
of a paleness as compared with health, and, second, in being made up for 
the most part of pale granular cells with single nuclei. Just a year later, 
Cohnheim2 described changes in the medulla, characterized by the absence 
of fat-cells, by the presence of colorless cells of epithelial habitus and of 
various sizes very closely resembling lymph-cells, and containing one and 
two nuclei, a few multinuclear giant cells, and a very few blood-corpuscles 
holding marrow-cells. There was about an equal proportion of colored 
elements, among which the biconcave red discs were in a decided minority. 
More numerous were the spherical non-nucleated corpuscles of different 
sizes, while most numerous were the red nucleated cells. 
In 1877 Pepper and the writer published a note in Virchow’s Archiv3 
containing the results of the study by the latter of the marrow from the 
shaft of a femur from a case of pernicious anaemia. This marrow resem- 
bled a fresh blood-clot in appearance, but on examination was found to be 
made up of about equal proportions of red blood-discs and of granular cells of 
epithelioid character, for the most part larger than white blood-cells, but 
otherwise similar. The largest were one one-thousandth of an inch (.0254 
millimetre) in diameter, the smallest one three-thousandth of an inch (.0084 
millimetre). Most of these contained a single comparatively large nucleus. 
A few contained two nuclei. Some contained granular fat particles, while 
others were completely filled with granular fat (compound granule-cells), 
but there were no true adipose vesicles. 
About the same time I also examined the medulla from a clavicle and 
radius sent from Montreal by William Osier. The mass was dark red 
and diffluent, being slightly decomposed. There was a relatively small num- 
ber of red corpuscles, but a very large number of granular cells resembling 
colorless blood-corpuscles, but of larger average size, ranging from 
inch (.0084 millimetre) to Tlfair inch (.016 millimetre). While many of 
them were nucleated and epithelioid, containing one, two, and rarely even 
more nuclei, in many no nuclei could be brought out even by aid of acetic 
acid. In addition to these two sets of cells were a number of nucleated 
colored cells, usually -f oVtr inch (.016 millimetre) in diameter and oval in 
shape, containing from two to five nuclei. These were presumably the red 
nucleated cells described by Cohnheim. Finally there were found free oil- 
globules, compound granular cells, fat crystals doubtless from decomposition, 
and undetermined granular matter probably from the same source. 
1 Progressive Pernicious Anaemia, American Journal of the Medical Sciences, 
October, 1875. 
2 Virchow’s Archiv, October, 1876. 
3 Die Betheiligung des Knockenmarkes bei Pernicioser Anaemia, Virchow’s 
Archiv, 1877, lxxi. 118-126. 8 
JAMES TYSON, M.D., ON 
These reports do not differ essentially, and, although the appearances 
described are not identical, they are sufficiently constant to justify their 
association as more than accidental. Summed up they amount to this: 
marrow dark-red, consistence less soft, fat-vesicles absent, specific cellular 
elements increased, numerous nucleated red corpuscles present. 
The deposition of iron in the liver-cells has already been alluded to. It 
is found in the outer and middle zones of the lobules, and in two specimens 
examined by Osier was so distributed as to outline the bile capillaries. The 
iron is in like manner sometimes increased in the kidney, but not in the 
spleen, but these organs are not otherwise essentially changed. 
The heart-muscle is fatty, while the other muscles are unusually red. 
Other morbid changes are described, but they cannot be regarded as essential. 
Such are changes in the ganglion-cells of the sympathetic, and sclerosis of 
the posterior columns of the cord. Osier and Henry describe a complete 
atrophy of the secreting tubules of the stomach in one case. But I should 
not regard this as a case of pernicious anaemia, but rather one of anaemia 
secondary to the atrophy of the gastric tubules, whereby the preparation of 
a suitable blood-making material is interfered with. 
Diagnosis.—The diagnosis of pernicious anaemia may be uncertain at 
first, but its true nature soon declares itself. The intense anaemia, extreme 
weakness, digestive derangements, and cardio-vascular symptoms, in con- 
nection with a blood-count of two million or below, with a corresponding 
haemoglobinaemia, and an admixture of megalocytes, microcytes, and poiki- 
locytes, point to a condition scarcely mistakable. 
Prognosis.—The prognosis is to-day regarded as less unfavorable than a 
few years ago, since recent experience has developed the fact that temporary 
improvement is not uncommon, and it is said that recovery sometimes takes 
place. Still, Addison’s original prognosis, of a termination sooner or later 
fatal, is not often a wrong one. 
Ti'eatment.—Treatment of this form of anaemia is, however, not fruitless. 
The same measures which are almost a specific for chlorosis are not without 
effect in pernicious anaemia. Accordingly arsenic, to a less degree iron, good 
food, and favorable hygienic surroundings are to be adopted. The arsenic 
treatment has been followed by results which justify the words “ temporary 
cure,” and it is said that permanent cure has followed. Such temporary 
cures have covered a period of three years. The best preparation appears 
to be Fowler’s solution in gradually increasing doses, until twenty and 
even thirty minims are reached, and this three times a day. The drug 
thus administered is wonderfully well borne, nausea and vomiting being rare. 
Rest in bed is indispensable, but may be supplemented with massage. 
Food should be in easily assimilable shape, such as beef-juice, beef-pep- 
tonoids, and peptonized milk. 
Transfusion of blood and of milk, which seemed at one time to give 
promise of favorable results, have been discontinued. THE PRIMARY OR ESSENTIAL ANAEMIAS. 
9 
III.—LEUKAEMIA. 
The third of the essential anaemias is leucocythsemia, or leukaemia, the 
former of these words meaning white-cell blood, the latter simply white 
blood. From the etymological and histological stand-point, leucocythaemia, 
suggested by Hughes-Bennett, is the more accurate term, but, as the German 
mind leads the medical thought of the day, Virchow’s term leukaemia has 
become the more usual one. 
The extremely rapid course of certain cases of leukaemia justifies its 
division into an acute and a chronic form. An instance of the former was 
a fatal case reported by Ebstein, in which the whole course of the disease, 
including a prodromal stage, was but six weeks. Similar cases are reported. 
The duration of the chronic form may extend over years. Leukaemic 
women have had multiple pregnancies and have borne children at term.1 
Etiology.—Nothing definite is known of the cause of leukaemia. It 
occurs in all countries, in both sexes, and at all ages, although more com- 
mon in middle life and more frequent in males. The eighth \Veek and sev- 
entieth year have found cases. It is sometimes hereditary. Malaria has 
been assigned as a cause, and certainly its association with this disease has 
been seemingly more than accidentally frequent. To a less degree this is 
true of syphilis. It is said to have followed a blow or injury, and to have 
been found in the lower animals. 
Morbid Anatomy.—Leukaemia has a definite morbid anatomy, consisting 
in alterations in the blood and in the haemogenic apparatus, including the 
spleen, the lympathic glands, and the marrow of bones, and it is called ac- 
cordingly splenic, lymphatic, myelogenic, while a compound word, as splenic- 
myelogenous, is used when two of these agents are at fault. 
The splenic changes exhibit three stages in their development. In the 
first the spleen is simply hyperaemic, soft, and swollen even to the extent of 
rupture. The Malpighian bodies share in the hyperaemia and may be 
slightly enlarged, but are overshadowed by the swollen pulp. In the second 
stage hyperplastic changes make their appearance in the Malpighian bodies, 
and as these grow the pulp is intruded upon. They may reach such size as 
to be recognized by the naked eye as spherical gray nodules one to three 
lines in diameter, or they may be elongated, or forked, following the course 
of the blood-vessels. The third stage furnishes the granitic spleen, in which 
white dots are separated by dark streaks representing the destroyed pulp, 
pigmented by the disintegrated blood. The spleen is now hard and is cut 
with resistance. Its size may be enormous and the organ weigh from two 
to eighteen pounds. 
The lymphatic enlargement is a true hyperplasia. Not only do the 
glands enlarge, but new foci of lymphatic tissue appear in various organs, 
1 See cases reported by J. Chalmers Cameron and Saenger, Sajous’ Annual for 
1891, E. 10 
JAMES TYSON, M.D., ON 
as the liver and kidneys. These are also said to be simple extravasations 
of leuksemic blood from the capillaries. All the more prominent groups 
may share in the enlargement,—the cervical, axillary, inguinal, and perineal 
glands. The individual glands remain, however, soft. The lymphatic 
follicles in the tonsils and in the tongue, pharynx, and mouth may enlarge. 
This is also occasionally the case with the solitary glands of the intestine 
and the agminated glands of Peyer. 
In myelogenic leukaemia the marrow-changes may be described in a 
word as reversion to the embryonal type of medullary tissue. The fat of 
the adult marrow has disappeared, and a mass of lymph-cells mingled with 
nucleated red corpuscles in all stages of development takes its place. The 
lymph-cells include numerous large mononuclear cells in the act of divi- 
sion by karyokinesis, multinuclear leucocytes, and a few mononuclear cells. 
There are also numerous marrow cells, including both eosinophiles and 
myelocytes like those found in the blood. 
The liver is often enlarged, and, according to Von Jaksch,1 pari passu 
with the spleen, and it has this further peculiarity, that its edges are rounded, 
while in what he describes as pseudoleuksemia infantum the edges are sharp 
and the enlargement does not go hand in hand with that of the spleen. The 
liver is also at times infiltrated with leukaemic patches and nodules not 
unlike miliary tubercles. The same is occasionlly true of the kidney. 
The thymus gland has been found enlarged in some cases of acute 
lymphatic leukaemia, and even the skin, stomach, and gastro-splenic 
omentum have been the seat of growths presumably lymphatic. In fact 
there is no situation in which such growths may not make their ap- 
pearance. The possibility of their being blood extravasations, white 
in consequence of the large proportion of white cells, is always to be 
remembered. 
The lungs and heart alone seem free from encroachment by the lymphatic 
tissue. The heart may, however, be dislocated by a large spleen. 
The alterations in the blood constitute really a part of the morbid 
anatomy of leukaemia, but are commonly treated under the head of 
symptomatology, where I, too, will consider them. 
Symptoms.—The early symptoms of leukaemia are precisely those of the 
other anaemias, insidious onset, pallor, rapid breathing amounting to dyspnoea 
on exertion, weakness and faintness, headache, loss of appetite, and indiges- 
tion. The last two symptoms may precede all others. Moderate fever with 
rapid pulse is also present in the majority of cases, the temperature some- 
times reaching 103° F. Headache more or less continuous is also a symptom. 
Swelling of the abdomen from an enlarged spleen may be the first noted, 
lymphatic glandular enlargements more rarely. In a case recently under 
my advice the first intimation of the presence of a large spleen was an attack 
of circumscribed peritonitis, favored, doubtless, by the presence of the splenic 
1 Sajous’ Annual for 1890, vol. ii., E. p. 12. THE PRIMARY OR ESSENTIAL ANAEMIAS. 
11 
tumor and excited by exposure to cool air while perspiring. Hemorrhages 
from the nose and stomach are common, and dropsical swelling towards the 
close. Very recently Thomas Oliver reported a case terminating fatally by 
sudden post-peritoneal hemorrhage.1 Haematemesis may be an early, an 
almost initiatory, and fatal symptom. Osier has recorded two striking cases 
terminating thus. Purpura haemorrhagica sometimes presents itself as a 
manifestation of the same tendency, as may also cerebral hemorrhage, pro- 
ducing coma. Priapism is sometimes a symptom, and in a case of Edes was 
the first noted. 
The urine often contains a little albumen, is high-colored and scanty, 
and deposits a copious sediment of uric acid. 
Blood Changes.—The blood exhibits a most marked and diagnostic 
change, consisting in an enormous leucocytosis. Normal blood contains 
about six thousand colorless corpuscles to the cubic millimetre, which, with 
the red discs at four and a half million, makes the proportion one to seven 
hundred and fifty; or with the eruthrytes at five million, one to eight hundred 
and thirty-three. There is a physiological leucocytosis which after a full meal 
may reach one to one hundred and fifty, and even one to one hundred. In 
leukaemia, however, there may be one to fifty, to twenty-five, to ten, to three, 
to two, or the leucocytes may equal and in rare cases even exceed the red discs. 
A case at this time under my observation has one to six. The maximum 
proportion of colorless corpuscles impresses decidedly the color of the blood 
en masse, making it pink, or even the color of chocolate and milk, while 
aggregations of leucocytes may produce white streaks, and well justify the 
notion of the older pathologists that there was pus in the blood,—a suppu- 
ration of the blood, as they called it. 
There is also a reduction in the total number of blood-cells, including 
white and colored, the quantity per cubic millimetre being sometimes reduced 
to between two and three millions. This reduction may be even more positive, 
as in a case reported by Suchannek,2 in which there were three hundred and 
one thousand six hundred red discs and three hundred and six thousand one 
hundred colorless corpuscles. 
Numerous nucleated red discs are sometimes present, and occasionally also 
poikilocytes. The haemoglobin falls below the normal proportion, so that the 
value of each disc is lowered. The blood-plaques may be slightly increased. 
An early discovery in the study of leukaemia was certain transparent 
octahedral crystals, known as Charcot’s crystals, which form in blood which 
has been kept for some time on slides. Neumann referred these crystals to 
the bone-marrow, but Von Jaksch says they are the same as those some- 
times found in the expectoration and in faeces and seminal fluid. There is 
reason to believe they are decomposition products, and that they hold no 
essential relation to leukaemia. That the alkalinity of the blood is some- 
American Journal of the Medical Sciences, November, 1892. 
2Sajous’ Annual for 1891, vol. ii., E. 12 
JAMES TYSON, M.D., ON 
times diminished is true; that it is ever replaced by acidity is not true, 
although this was at one time held. 
The further minute study of the blood in leukaemia requires a review 
of the histological characters of the colorless corpuscles in normal blood. 
These, through the studies of Ehrlich and others, have assumed a much 
greater complexity than heretofore. It occurred to Ehrlich that important 
differences in white corpuscles could be differentiated by staining-fluids, and, 
putting into practice this conception, he was enabled to discover five different 
varieties, as follows: 
1. Lymphogenous elements arising in lymphatic glands, (a) Small 
lymphocytes. (b) Large lymphocytes. 
2. Myelogenous elements arising in marrow, including eosinophile cells. 
3. Undetermined elements arising in spleen and marrow, or in marrow 
only, (a) Large mononuclear cells. (6) Transitional forms, (c) Poly- 
nuclear cells. 
I. (a) The small lymphocytes are somewhat smaller than the red blood- 
corpuscle (Fig. 1), and contain a large, round, deeply-staining nucleus, sur- 
rounded by a very scanty and almost invisible layer of homogeneous pro- 
toplasm. (Fig. 2.) 
(6) The large lymphocytes are a further development of the first, and 
differ from them only in possessing a larger and easily recognizable rim of 
protoplasm. (Fig. 3.) 
II. The eosinophile cells, originating in the bone-marrow and only 
rarely seen in normal blood, are colorless corpuscles, characterized by coarse 
granulation, containing one, two, and more rarely three nuclei. They take 
the a- or eosinophile granulation stain described below. (See plate, Fig. 8.) 
III. Undetermined elements originating in spleen and marrow or mar- 
row only, (a) The large mononuclear cells are about three times the size 
of a red blood-corpuscle, and contain a large round or ovoid nucleus and a 
large ring of protoplasm. (Fig. 5.) (6) The mononuclear transition form 
differs from these only in that the nucleus is no longer round or ovoid, but 
indented. (Fig. 6.) (c) The polynuclear elements (Fig. 7) are somewhat 
smaller, but still larger than the red corpuscles, and their nuclei exhibit 
further differentiation in that they are polymorphous. These are the more 
usual white blood-corpuscles, which have long been recognized. Except in 
the lymphocytes the protoplasm of these cells is granular, but the granu- 
lations possess different properties, which have also been investigated by 
Ehrlich, who makes five different varieties of granulation, which he 
distinguishes by letters of the Greek alphabet from a to e, as follows: 
The a-granulation, or eosinophile granulation, is characterized by large 
granules, highly refracting or oil-globule-like, and stainable by all acid 
aniline staining fluids. They are found in the myelogenous elements, 
very rare in normal blood, but strongly increased in leuktemic processes, 
and called eosinophilic by Ehrlich because of their strong affinity for eosin. 
(See plate.) PLATE II. 
Fig. 8. 
Blood from Case of Leukjemia, showing Eosinophilous Cells.—Ocular, Zentmeyer A, 
Objective, Zeiss fa, oil immersion. THE PRIMARY OR ESSENTIAL ANiEMIAS. 
13 
Fig. 1. 
Fig. 2. 
Fig. 3. 
Red corpuscle. 
Small lymphocyte. 
Large lymphocyte. 
Fig. 5. 
Fig. 4. 
Myelogenous cell-element, including 
the a-granulation, or eosinophile granula- 
tion. Seldom found in normal blood, but 
greatly increased in leuksemic processes. 
Granules stainable in acid staining fluids. 
Large, mononuclear cell. 5-granulation, or baso- 
philic granulation. In leukaemia are found large 
cells like these, but presenting the “ neutrophilic” 
granulation. Also myelogenic. 
Pig. 6. 
Fig. 7. 
Polynuclear cell, e-granulation, or 
neutrophilic granulation. Very delicate, 
neutral colors. 
Transition form. 
Tigs. 1 to 7 are diagrammatic, intended to show the relative sizes of the various cells 
compared with the red corpuscle. After a drawing by my colleague Prof. Guiteras. 14 
JAMES TYSON, M.D., ON 
The /9-granulation, or amphophilic granulation, is found especially in the 
cells of the medulla of bones, but also in blood, often in the leucocytes of 
rabbits and guinea-pigs, and is stained by acid and basic or similar fluids, 
hence called amphophilic. 
The y-granulation, or basophilic or “ mastzellen granulation,” 1 is stain- 
able by basic aniline colors, as are bacteria: The granules are coarse and 
refract light but slightly. This granulation is almost altogether wanting in 
healthy human blood, but is increased in leuksemic processes. These gran- 
ules are also found in the blood of some animals in health, as the white rat. 
The 8-granulation, also basophilic, is finer, stainable in basic aniline colors 
like bacteria, and is found in the large mononuclear leucocytes. 
The e-granulation, or neutrophilic granulation, is very delicate, and per- 
vades the polynuclear elements of normal human blood very densely, i3 
found sparingly in the transition forms of cells, and very seldom in the 
mononuclear elements. - It is also characteristic of the myelocyte found 
only in leuksemic blood. It is stained by neutral coloring-matters, and 
therefore called neutrophilic. Such is the granulation of the common 
polynuclear leucocyte. 
All these varieties of granules may become free in the blood by the 
disintegration of leucocytes, and are among the sources of error in recog- 
nizing bacteria in the blood. 
In normal blood the polynuclear cells form sixty-five to eighty per 
cent, of the colorless corpuscles, the lymphocytes fifteen to thirty per cent., 
the mononuclear and transition forms about six per cent., and the eosino- 
philes two to four per cent. 
Diagnosis.—The diagnosis of leuksemia requires the microscope, but 
with it becomes easy. A refinement of diagnosis, thus aided, attempts with 
more or less success to separate the different varieties, which are known as 
simple or complex, according as one or more of the cytogenous organs are 
implicated. Thus, of the simple forms there would be the splenic, lym- 
phatic, and myelogenous. In his recent monograph Rieder says that, so 
far as he knows, pure splenic and pure myelogenous forms have never been 
observed, while the pure lymphatic form has.2 The latter is, however, rare, 
while a case of the pure myelogenous variety is, however, reported by 
Fraenkel, in a girl of fourteen.3 
The most frequent of all the varieties is the complex form of splenic 
myelogenous or lieno-myelogenous. In it the lymphocytes are slightly if at 
all increased. They are relatively diminished ; that is, instead of repre- 
senting fifteen to thirty per cent, of all the leucocytes, they represent a 
smaller proportion. The eosinophiles, on the other hand, which are very 
‘This word is retained because there seems to be no corresponding word in 
English. 
2 Beitrage zur Kenntniss der Leukcytosis. Yon Dr. Hermann Rieder, 1892, 8.36. 
3 Deutsche medizinische Zeitung. Berlin, 1890. Sajous’ Ann., vol. ii., E. 19. THE PRIMARY OR ESSENTIAL ANJEMIAS. 
15 
rare in normal blood, are increased and conspicuously handsome in a 
stained preparation by their bright red granules. The polynuclear neutro- 
philes are either normal, sixty-five to eighty per cent., or relatively dimin- 
ished, particularly towards the close. But the most characteristic feature of 
this variety is the presence of cells not found in normal blood, the myelocytes 
of Ehrlich, so called because of their supposed origin from the marrow of 
bone. They are mononuclear, as large as, and even larger than, the large 
mononuclear leucocytes, which they resemble also, but from which they 
differ in the fact that the protoplasm is “neutrophilic/’ while the mono- 
nuclear cells are “ basophilic.” To these forms Muller1 has recently added 
another large mononuclear cell which exhibits karyokinetic figures. It is 
found in leuksemic blood and in the marrow, and is apparently the marrow- 
cell originally described by Cornil, and which is said not to occur in normal 
blood. 
If relatively large leucocytes prevail, we may infer the presence of the 
splenic form with a relatively small involvement of the lymphatic glands 
and of the bone-marrow. 
If there are numerous transitional forms between the white and red 
blood-cells, if there are nucleated red blood-corpuscles, but especially large 
polynuclear leucocytes, containing large eosinophilic granules, we may 
infer marked alterations in the bone-marrow; in a word that myelogenous 
leukaemia predominates. 
In pure lymphatic leukaemia the colorless cells are never so numerous, 
scarcely ever exceeding one in ten, while the lymphocytes only are increased, 
all the other forms being greatly diminished, and myelocytes are altogether 
absent. In a case reported by Uthemann, ninety-three per cent, of all the 
leucocytes were lymphocytes, as compared with fifteen to thirty per cent, in 
normal blood. 
In acute leucocytosis the e-granulation or neutrophilic cells, both mono- 
and polynuclear forms, are increased, while the a-granulation or eosinophilic 
cells are apparently diminished. The reverse obtains in incipient leukae- 
mias, where the eosinophilic and basophilic cells are increased. 
Too much stress must not, however, be laid upon the diagnostic value of 
these cells, until observations multiply. Thus Von Jaksch found eosino- 
phile-cells in the blood of an adult in health, of a boy with tuberculosis, in 
a case of pneumonia, and in all forms of anaemia. Dolega and Aldehoff* 
have recently found numerous eosinophiles in the blood of malaria in 
three cases. Muller and Rieder have made similar observations, and Fink 
found numerous leucocytes of the eosinophilic-granulation type in the 
blood of asthmatics. So also Von Jaksch found the karyokinetic forms 
described by Muller in the blood of a case of sarcomatosis, as did also Weiss.2 
1 Archiv f. Klin. Med., 48, 51, 1891. 
2 For references to all the above see Von Jaksch, Klinische Diagnostik, third 
edit., 1892, p. 31. All are within the dates 1890-91. 16 
JAMES TYSON, M.D., ON 
Caution should be observed, too, in basing the presence of a leukaemia 
solely on a leucocytosis, as some remarkable instances of this condition have 
been reported wherein leukaemia did not supervene. Thus Von Jaksch, in 
his studies of the anaemia of children, found such proportions as one white 
to twelve red corpuscles, one to seventeen, and one to twenty ; and in the 
case of an adult one to eight, and still no leukaemia followed.1 The asso- 
ciation of lymphatic or splenic or myelogenous change with the leucocytosis 
is essential to a diagnosis. And especially valuable as diagnostic of leu- 
kaemia is a large number of eosinophiles, and, according to Von Jaksch, 
Klein, and others, in the beginning of leukaemia this increase in the eosin- 
ophiles is the only change. Rieder is also inclined to regard the cases of 
so-called acute leukaemia as really acute inflammatory leucocytosis rather 
than leukaemia. 
Allusion has already been made to an anaemia described by Von Jaksch 
as anaemia infantum pseudoleulcsemica, further studied by Loos and Luzet, 
which is not to be confounded with leukaemia. Its essential feature is an 
enormous falling off in the cellular elements of the blood, the red cells being 
as low as eight hundred and twenty thousand, and the white fifty-four thou- 
sand six hundred and sixty-six. The proportion of leucocytes is always 
increased, but never to the same degree as in leukaemia, nor is it so rapidly 
brought about. On the other hand, the leucocytes are characterized by their 
varied shape and unusual size. The red cells display a high degree of 
poikilocytosis, while white cells enclosing red cells and fragments of red 
cells are also found, together with occasional eosinophilic leucocytes and 
large multinuclear neutrophilic leucocytes and nucleated red cells. All of 
these modifications of the blood-corpuscles may occur in leukaemia, but in the 
latter disease there is not as marked a reduction either in the haemoglobin or 
in the number of cellular elements. The difference in the form of the liver 
and splenic enlargement in the two conditions has been referred to. 
Prognosis.—The prognosis of leukaemia is unfavorable, the best that can 
be expected from treatment being the deferring of the fatal end. Some 
rather remarkable fluctuations are noted, and cases of cure are even reported, 
especially of late by inhalations of oxygen. The lymphatic leukaemias are 
the more acute and more intractable. 
Treatment.—The treatment has heretofore been mainly with iron, qui- 
nine, and arsenic, fresh air, and good food. Large doses of arsenic, as much 
as thirty drops of Fowler’s solution, reached by gradual increment, have 
been especially recommended, and certainly should be tried. 
Inhalations of oxygen, suggested in 1887, were used by Sticker and 
Pletzer with temporary benefit, and Da Costa and Hershey report the 
apparent cure of one case, a boy of thirteen, and such marked improvement 
in a man of thirty-five that he was thought for a time to be cured. This 
treatment deserves, therefore, to be tried along with that first named. 
1 Op. citat., p. 29. THE PRIMARY OR ESSENTIAL ANAEMIAS. 
17 
Thirty to one hundred litres (about four to twelve gallons) of oxygen are 
to be used daily. 
IV.—LYMPHATIC ANAEMIA. 
The fourth of the essential anaemias is lymphatic ansemia, also known 
as Hodgkin’s disease, pseudoleukaemia, lymphadenosis, lymphadenoma, ma- 
lignant lymphoma (Billroth), ad6nie and ]ymph-ad6nie. Hodgkin’s paper, 
to which we are indebted for our first definite knowledge of the disease, 
appeared in 1832. 
The disease consists essentially in an anaemia unassociated with an in- 
crease in the colorless corpuscles of the blood, accompanied bv a fibro-adenic 
enlargement of the lymphatic glands, and the formation of lymphatic foci 
in the spleen, and occasionally in other glandular organs. 
Etiology.—Its etiology is as undetermined as that of leukaemia. De- 
pressing influences of all kinds are believed to favor it. Scrofulosis has 
sometimes preceded it. The presence of an irritating substance in the blood 
has been suggested, and the necessity of local irritation, associated with a 
lymphatic diathesis, has been insisted upon by Trousseau. 
Morbid Anatomy.—Its morbid anatomy is, however, definite. There is 
both lymphatic and splenic involvement, the latter secondary to the former. 
The tonsils, intestinal lymphatic structures, and even the liver and kidneys, 
may be invaded. There is, moreover, a deposition of new foci of lymphatic 
tissue decidedly more marked than in leukaemia. The enlargement usually 
begins first in the more superficial groups, as those of the submaxillary 
region, neck, axilla, and groin, but the entire lymphatic system may be 
involved, including the retroperitoneal glands, resulting sometimes in 
marked abdominal enlargement. Occasionally the overgrowth is limited to 
the deep-seated glands. Of the abdominal, the retroperitoneal are most 
frequently involved, producing tumors which have been mistaken for myo- 
mata of the uterus. The bronchial glands may also be involved, and by 
their pressure produce dyspnoea. 
The process is a hyperplastic one, shared by the cellular and trabecular 
tissue in varying degrees. When the former predominates the product is 
soft and exudes a milky juice on section; when the latter, it is firm and 
resisting. The individual glands are not disposed to fuse, nor to become 
adherent to adjacent tissue, differing in this respect greatly from glands en- 
larged by the tubercular process. The lymphatic enlargement exceeds also 
that in leukaemia, while the splenic involvement is more limited, the organ 
rarely exceeding ten inches in length, as contrasted with the colossal size of 
the leukaemic spleen. 
The alteration in the spleen is hyperplastic, involving the pulp and 
Malpighian bodies jointly, or alone. The enlarged Malpighian bodies furnish 
the most characteristic feature. They form grayish-white masses, varying 
in size from that of a barley-grain to a walnut, a couple of millimetres to 
as many centimetres in diameter, and contrast strongly with the dark-red 18 
JAMES TYSON, M.D., ON 
parenchyma. The process in the Malpighian bodies is a true hypertrophy 
of the adenoid tissue, while in the pulp it is rather the trabecular tissue 
which is overgrown. The spleen, however, is not always involved. Thus, 
GowTers found splenic enlargement in seventy-five per cent, of the cases 
collected ; the organ contained lymphoid growths in fifty-six of these. 
There are, likewise, at times changes in the marrow of bones, which is 
converted into lymphoid tissue, sometimes pyoid in consistence. 
The liver and kidney, and even the thymus gland and lungs, are some- 
times the seat of lymphoid deposits; in fact, all organs and tissues may be 
invaded, including the nervous; and paraplegia has resulted from pressure 
on the cord of growths in the spinal canal. The posterior nares may be 
occluded by invasion of the tonsils and the numerous lymphoid follicles in 
the pharynx. In like manner the intestinal walls may be invaded, pro- 
ducing thickening, while even serous surfaces do not escape. 
Symptoms.—The symptoms of Hodgkin’s disease are again the pallor, 
weakness, dyspnoea, palpitation, and other signs of anaemia, concurrent, or 
even sometimes in advance of the glandular enlargement. There is quite 
often fever, very irregular and variable in degree, and cases have been ob- 
served by Murchison and De Renzi in which there was paroxysmal glan- 
dular enlargement, coinciding with fever, the enlargement subsiding with 
the decline of the fever, but not reaching the degree present prior to the en- 
largement. In a case of Laache’s the glands diminished in size during the 
fever. In a case under my care in the wards of the Hospital of the Uni- 
versity of Pennsylvania, in which the glandular enlargement was not con- 
spicuous, there occurred an intermittent rise of temperature ascribed to a 
concurrent peritonitis, but the autopsy discovered this to be so limited that 
it is perhaps more reasonable to ascribe it to the feverish tendency charac- 
teristic of the disease. 
The glandular enlargements themselves contribute further to the symp- 
toms by their effects. Thus, in the case of the bronchial glands, dyspnoea 
from pressure on bronchi or trachea may occur, and is apt also to be inter- 
mittent. Pressure elsewhere may lead to pleuritic or abdominal effusions, 
while the entanglement of nerves in the growth may cause pain. Bronzing of 
the skin has been found associated with enlargement of the abdominal glands. 
The external glandular growths are variously conspicuous ; occasionally, 
however, they are wholly absent. There is no fixed order of involvement, 
although the submaxillary commonly enlarge first, and with the acme of 
their growth produce a striking picture. Extreme dyspnoea may arise from 
encroachment upon the trachea. The enlargement is not uniform, but at 
times remits and even ceases. It is said it may even disappear altogether 
for a time. The glands are usually soft, sometimes even to a sense of fluc- 
tuation. On the other hand, erosion of bone may result from pressure. 
Macroscopically the blood appears thin and pale, and generally the red 
corpuscles are diminished in number, although not always. Minimum THE PRIMARY OR ESSENTIAL ANiEMIAS. 
19 
counts make nine hundred and sixty thousand 1 to the cubic millimetre, 
while in a case reported by Henry,2 that of a boy of five, with enormous 
enlargement of the right cervical glands, there were five million four hun- 
dred and sixty-two thousand to the cubic millimetre. Osier has never 
counted less than two million. Thus the diminution is less than in per- 
nicious anaemia. The haemoglobin is, however, reduced to at least sixty per 
cent., furnishing thus one of the conditions essential to anaemia. 
There are few nucleated red corpuscles and poikilocytes, and especially 
microcytes. The leucocytes may be slightly increased, occasionally decidedly 
so, but this is rare, and there is no approximation to the leukaemic state of 
the blood, and the two states are distinct and separate. A combination of 
the two may be possible. 
Diagnosis.—The diagnosis requires some care, as more than one condition 
is attended by similar glandular outgrowths. Chronic and even acute 
adenitis have been mistaken for the early manifestations of Hodgkin’s dis- 
ease, while the converse has obtained perhaps more frequently. Time is 
the arbiter of such uncertainty. 
A group of tubercular glands resembles more closely the disease under 
consideration, but it is not usually difficult to distinguish the two. Tuber- 
cular glands are adherent to each other and adjacent tissues, while the 
lymphadenoid growths are loose and easily movable. Tuberculosis rarely 
involves more than one group of glands, is characterized by caseation and 
suppuration, while the lymphadenoid growths almost never suppurate. 
Yet the tubercular process is the slower. Tuberculosis is commonly found 
in young persons under twenty. Hodgkin’s disease may occur at any age, 
and is more common in males. In Gowers’ one hundred cases, seventy-five 
were males and fifty females; fifty were under thirty, and sixty-four under 
forty. 
Simple lymphoma, affecting as it does a group of glands, resembles most 
closely lymphadenoma. But it is harder and slower-growing than the 
lymphatic growth of Hodgkin’s disease, while it does not affect the system. 
Sarcoma also involves groups of glands, and in the beginning the con- 
sistence of the glands is similar to that in Hodgkin’s disease. But this 
disease rapidly invades surrounding tissues, fusing with them, and destruc- 
tive ulceration soon makes its appearance. 
Carcinoma of lymphatic glands should also be mentioned as producing 
a somewhat similar growth associated also with cachexia, but it is for the 
most part secondary to cancer somewhere else. 
Finally all the conditions named as possible to be mistaken for Hodg- 
kin’s disease are limited to single groups, while the latter always extends, 
and the fact of such limitation is of itself sufficient to preclude the disease. 
1 Case reported by Richard Geigel, quoted by Henry (Anaemia, Philadelphia, 
1887), from Deutches Archiv fur Klinische Med., 1885, Bd. 37, p. 59. 
2 Op. citat., p. 67. 20 
JAMES TYSON, M.D., ON 
From leucocythsemia the disease is easily distinguished by the leucocyto- 
sis characteristic of the former. 
Prognosis.—While the prognosis is ultimately fatal, the course of the 
disease varies greatly, and death seldom results in less than a year. F. P. 
Henry puts the average duration of life at two years, but admits it is greatly 
modified by such circumstances as age and previous health of the patient. 
Treatment.—Treatment, too, may avert the fatal termination for a long 
time. Extraordinary results in this respect have followed the administra- 
tion of arsenic, and even recoveries have been reported. Large doses ar- 
rived at by gradual increment should be attained and kept up until some 
physiological effects are observed. Such doses are fifteen to twenty minims 
of Fowler’s solution. Particularly happy results are claimed for the in- 
jection of arsenic into the lymphoid masses. Especially is this recommended 
when arsenic is not well borne by the stomach. From eight to thirty min- 
ims of Fowler’s solution have been injected daily in divided doses. In- 
unctions of iodine and iodide of potassium are also recommended. Sup- 
porting treatment of all kinds, including quinine, cod-liver oil, and the best 
of food, is necessary. 
Operative interference is sometimes necessary to avert danger to life 
threatened by the encroachment of enlarged glands on vital organs and 
functions, such as respiration. It has even been claimed that the removal 
of a group of primarily enlarged glands has cut short the spread of the dis- 
ease, but while such an apparent result is rather an evidence of error in 
diagnosis, in view of the fact that at an early stage a diagnosis is impossi- 
ble, the removal of a local group of glands should be recommended. 
This terra is applied to a condition in all respects analogous to Hodg- 
kin’s disease, where there is splenic enlargement only, and no involve- 
ment of the lymphatic glands. Attention was first called to it as a separate 
variety of pseudoleuksemia, by Horatio C. Wood,1 in 1871, although 
reports of cases corresponding to it had been previously made by others. 
It has been more recently studied by Strumpell and Banti. It occurs alike 
in old and young without assignable cause. 
Morbid Ancdomy.—Its morbid anatomy consists in the splenic changes. 
The organ is greatly enlarged, approaching that of the leuksemic spleen 
rather than the spleen of Hodgkin’s disease. It is three to four times its 
normal size, but retains its normal shape. It is indurated, and its incisures 
are deep. Its capsule is thickened and opaque in spots, and sometimes ad- 
herent to adjacent tissues, as is often true of any large spleen. The his- 
tology of the organ differs from that of the leuksemic enlargement and that 
of the enlarged spleen of Hodgkin’s disease. There is no true overgrowth 
V.—SPLENIC ANiEMIA, OR SPLENIC PSEUDOLEUKAAIIA. 
1 Relations of Leucocythsemia and Pseudoleuksemia, American Journal of the 
Medical Sciences, October, 1871. THE PRIMARY OR ESSENTIAL ANiEMIAS. 
21 
of the lymphatic tissue in the Malpighian body, but rather a destruction, it 
being replaced by an overgrowth of the reticulum, producing a white body 
as large as a pea. In addition to this the organ is often traversed by 
bands of thickened reticulum, visible to the naked eye. The change cor- 
responds rather with that in the harder lymphatic glands of Hodgkin’s 
disease than that in the spleen. In a word, as well stated by Banti, the 
histological alterations of the spleen consist of an atrophy and sclerosis of 
the Malpighian corpuscles. Marrow changes like those described under 
pernicious anaemia are also sometimes present. 
The blood exhibits the changes one would expect where there is destruc- 
tion of the tissue devoted to its reproduction. It is anaemic. The red 
discs are notably diminished, from five million to as low as even one mil- 
lion. There are found also the other changes of the eruthrocytes charac- 
teristic of pernicious anaemia. There are poikilocytosis, megalocytosis, and 
microcytosis. Nucleated red blood-cells are also sometimes present. The 
leucocytes are sometimes slightly more numerous, at others they are in 
normal proportion, and are said to be generally mononuclear. 
Symptoms.—As the blood-changes are analogous to those of pernicious 
anaemia, so are also the symptoms, which include pallor, weakness, dyspnoea, 
palpitation associated with the signs of enlarged spleen, evidence of which 
is sometimes shown by its weight and the pressure it exerts, before other 
symptoms show themselves. Finally, there results the cachectic state char- 
acterized by emaciation, a deeper yellow color of the skin and mucous 
membranes, a tendency to hemorrhage and pyrexia, oedema, serous effusions, 
extreme muscular prostration, and mental hebetude. There is also said to 
be at times, as in lymphatic pseudoleukaemia, an intermittent or per saltern 
course in the symptoms to the extent of apparent complete restoration to 
health in the intervals. 
An increase in the urea of the urine has been noted by Strumpell, and 
is regarded as evidence of increased albuminoid metamorphosis. 
All clinical facts go to show that the spleen is responsible in some way 
for a destruction of eruthrocytes and of their capacity for carrying oxygen. 
The duration of the disease is from five or six months to three years. 
Diagnosis.—The diagnosis of splenic leukaemia depends upon the pres- 
ence of splenic enlargement associated with the phenomena of anaemia above 
described, and the absence of glandular enlargement so conspicuous in 
Hodgkin’s disease. Anaemic symptoms attend the chronic malaria so often 
associated with enlarged spleen, but the history of malaria in such cases is 
invariably present, while the degree of anaemia is not so deep. 
Prognosis.—The prognosis has been unfavorable, but may be modified 
by the results of splenectomy, which in the cases collected by Banti appears 
to have been successful in three out of four. 
Treatment.—The treatment is that for the other anaemias, by iron and 
arsenic and nutritious food. The propriety of splenectomy must be deter- 
mined on the merits of each case. International 
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The department of Forensic Medicine, dealing with medico-legal 
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incidental to, the relation of physician and patient, as ascertained and 
defined by courts of last resort, has proved an interesting and valuable 
feature of the Magazine, and called forth many expressions of apprecia- 
tion and approval from its readers. 
The department of Book Reviews furnishes a brief critical analysis 
of all the more important medical books and periodicals as soon as they 
are published. 
The Magazine becomes, therefore, the medium by which all that 
is settled as best, in every department of medical and surgical science 
throughout the medical world, is placed within the means of every 
practitioner. And it is the purpose of the publishers to spare neither 
pains nor expense to keep the Magazine where it has already taken its 
stand,—at the very head and front of medical periodical literature. 
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