characterized by extensive cutaneous ecchymoses, mucous hemorrhages,
but not dependent on any local disease, or, so far as is known, on any
specific poison. The bleedings in scurvy may be mentioned here, but
there could be little difficulty in determining their nature.
(5) Infective purpura, due to the action of some specific
poison--small-pox, measles, scarlet fever, cerebro-spinal fever, etc.
The hemorrhages may be cutaneous and trivial, or may be in the most
aggravated form of interstitial and mucous bleedings, as seen, for
example, in black small-pox.
(6) Toxic purpura, as in snake-bites and many poisons, such as
phosphorus.
(7) Simple hemorrhagic diathesis, under which may be included those
cases in which, without any hereditary disposition or previous
hemorrhagic history, there is a tendency to uncontrollable hemorrhage
from a slight wound.
{938} (8) Hæmatidrosis, bloody sweats, which occur usually in
hysterical or epileptic females, and are in rare instances accompanied
with mucous hemorrhages.
In considering the PROGNOSIS it is well to remember that the patients
rarely die in the first bleeding. The younger the individual the worse
is the outlook. As above stated, the attacks are most frequent under
five years of age, and of 152 boys the subject of the disease, 81 died
before the termination of the seventh year (Grandidier). Legg, however,
states that it is rarely fatal in the first year. The longer a bleeder
lives, the greater the chance of his outlasting the tendency; but that
it may persist to the end of a long life, and then prove fatal, is
shown by the case of old Oliver Appleton, the first recorded American
bleeder, who died at an advanced age of hemorrhage from a bedsore and
from the urethra. A bleeder may have years of existence, in which the
tendency seems lessened or even absent. The prognosis is always worse
in a boy than in a girl. In the latter menstruation is sometimes early
and excessive, but, happily, in the female members of hæmophilic
families neither this function nor the act of parturition bring with
them special dangers.
TREATMENT.--The prophylaxis is all-important. The members of a bleeder
family, particularly the boys, must be guarded from injury as much as
possible, and operations of all kinds must be avoided, except when life
itself is in jeopardy. The extraction of a tooth should be absolutely
prohibited. Occupations must be sought which will give the least
possible risk of injury. Daughters of bleeder families should not be
permitted to marry, as it is through them that the tendency is chiefly
propagated, and, even if not bleeders themselves, some of their male
children are certain to be affected. The question of the marriage of
male bleeders is more difficult to decide, but in any case where the
tendency is marked it should be prohibited.
When an injury or wound has occurred, absolute rest, cleansing the
wound, and compression should first be tried. If in a favorable
locality pressure on the artery may be employed, failing in this, the
various styptics may be used. In epistaxis, ice, tannin, and gallic
acid may be tried before plugging.
Internally, ergot seems to have been of use in several cases. Otto[180]
speaks of the value of sulphate of soda in purgative doses. The
perchloride of iron, 30-40 minim doses, every two hours, is advised by
Legg, with a purge of sulphate of soda if there is no bleeding from the
bowels. Venesection has been resorted to in several instances.
Transfusion has been employed, but without benefit. The diet should be
light and supporting. After the attacks the patients should take iron
and cod-liver oil until the health seems restored. When possible, a
residence in the South during the winter is advisable, as most cases
are aggravated by the cold weather, and in any case care must be taken
to protect patients against cold and wet.
[Footnote 180: _Loc. cit._]
The joint troubles must be treated on general principles.
AMERICAN LITERATURE OF HÆMOPHILIA.
Buel: _Transact. of the Med.-Physic. Society of New York_, vol. i.,
1817; 1 F., 4 cases.
Coates: _North Am. Med. and Surgical Journal_, Philada., 1828, vi. p.
37; 1 F., 5 cases.
Dunn: _Am. Journal Med. Sciences_, 1883, vol. lxxxv. p. 68; 4 F.
Felt: _History of Ipswich_, 1834--Appleton family referred to.
Gould: _Boston Med. and Surgical Journal_, 1857, p. 500; 1 F., 11
cases.
Harris: _Philada. Med. Times_, 1872; 2 F., 7 cases.
Hay: _New England Journal of Med. and Surgery_, 1813, vol. ii. p. 221;
1 F., 15 or 16 cases (accurate number rather difficult to make out).
{939} Holton: _Am. Journal of Med. Sciences_, April, 1874; 1 F., 7
cases.
Hughes: _Transylvania Med. Journal_, 1831, vol. iv. p. 518, and _Am.
Journal Med. Sciences_, 1833, vol. xxi. p. 543; 1 F., many cases.
Hutchinson: _Trans. State Med. Society of New York_, 1877, p. 208.
Otto: _Medical Repository_, 1803, vol. vi.; 3 F., 8 cases.
Pepper: _Philada. Med. Times_, 1881, vol. xii. p. 109; 1
case--Lancaster county family described by Dunn.
Sewell: _Med. Chronicle_, Montreal, 1857, vol. iv.; 2 F., 4 or 5 cases.
Smith: _Philadelphia Medical Museum_, 1801, vol. i. p. 284.
Traneus: _St. Louis Med. and Surgical Journal_, 1870, p. 535; 1 F., 4
cases.
Townsend: _Boston Med. and Surgical Journal_, vol. lv. p. 447; 1 F., 3
cases.
ADDISON'S DISEASE.
DEFINITION.--A constitutional affection characterized by asthenia
without emaciation, a depressed circulation, gastric irritability, and
usually pigmentation of the skin. In the majority of cases it is
associated with a fibro-caseous degeneration of the suprarenal
capsules, and in many there are changes in the abdominal sympathetic
system.
SYNONYMS.--Morbus Addisonii; Bronzed-skin disease. _Fr._ Maladie
d'Addison, Maladie bronzée; _Ger._ Addisonische Krankheit.
HISTORY.--In the _Halle Hospital Reports_ for 1823 Schötte describes a
case, and one is also given by Bright in vol. ii. of his _Medical
Reports_, 1831. A few other instances are also on record before 1855,
when Addison published his monograph _On the Constitutional and Local
Effects of Disease of the Suprarenal Capsules_, from which we may date
our knowledge of the affection. Following close upon the work of
Addison numerous observations were made in England, where the disease
appears to be more common than elsewhere. Wilks of Guy's Hospital,[181]
and Greenhow of the Middlesex Hospital, may be mentioned among those
who in England have specially studied the disease, and the latter
published an important monograph in 1875.[182] In France, besides
numerous minor contributions, the exhaustive articles in the
encyclopædias have been the most important publications. In Germany the
monograph of Averbeck (1869) and the abstracts of Meissner in
_Schmidt's Jahrbücher_ may be specially mentioned. Virchow, Griesinger,
Oppolzer, Bamberger, and others have made valuable contributions.
Recently Burger[183] has published a small monograph. In other European
centres contributions have been made, among which may be mentioned that
of Schmidt of Amsterdam, who brought forward cases in support of the
view that the disease was an affection of the sympathetic ganglion. In
America the first cases were reported by Ranking[184] and Taylor.[185]
[Footnote 181: In numerous communications in _Guy's Hospital Reports_
and _Trans. Path. Society_.]
[Footnote 182: "On Addison's Disease," _Croonian Lectures_.]
[Footnote 183: _Die Nebeunieren und der Morbus Addison_, Berlin, 1883.]
[Footnote 184: _Am. Journ. Med. Sci._, 1856.]
[Footnote 185: _New York Med. Journal_, 1856.]
ETIOLOGY.--The causation of the disease is unknown. Cases are more
frequent in hospital than in private practice. Males are more often
attacked than females; the proportion in Jaccoud's table[186] is 79 to
48, and in Greenhow's[187] analysis of 183 good cases, 119 were males
and 64 females. Under ten and over fifty years of age the disease is
very uncommon; the majority of the cases occur between the twentieth
and the fortieth year. Greenhow {940} has called attention to the fact
that in a number of instances the disease appears to have followed an
injury, such as a blow upon the abdomen or back, and in several cases
caries of the spine has preceded the attack. He refers also to the
greater frequency of the disease in the laboring classes and those
exposed to injury from over-exertion. The disease does not seem to be
more prevalent among members of phthisical families, although the
morbid process in the glands has been regarded as of a tuberculous
nature, and it is common for other tuberculous lesions to occur in the
course of the disease.
[Footnote 186: _Dictionnaire de Médecine_.]
[Footnote 187: _Op. cit._]
The disease is rare in America--apparently much more so than in
England.
SYMPTOMS.--In the words of Addison, the leading and characteristic
symptoms are: "Anæmia, general languor and debility, remarkable
feebleness of the heart's action, irritability of the stomach, and a
peculiar change of color in the skin occurring in connection with a
diseased condition of the suprarenal capsules."
Although, perhaps, not the most essential, the symptoms pertaining to
the skin are in the majority of cases the most prominent, and have
given rise to the names bronzed skin, melasma suprarenale, etc. which
have been applied to the disease. A gradual increase in the pigment of
the rete mucosum, either patchy or diffuse, causes a gradual
discoloration, which may ultimately reach such a degree that a
previously blonde individual may have the aspect of a Malay or a
mulatto. The grades of coloration may range from a light yellow to a
deep brown, or even black. In some instances there is a greenish-brown
tinge, to which the term bronzed is peculiarly applicable. In typical
cases it is diffuse over the whole surface, but as a rule deeper on
exposed parts, face, neck, and hands, and also in those regions where
the normal pigmentation is most intense, nipples, scrotum, and penis,
or in the vicinity of cicatrices or regions of chronic irritation. It
is usually first noticed on the face, either diffuse or in spots, and
the extension may be rapid or gradual, in many instances not reaching a
high grade and not becoming universal. It may be absent, and is not to
be regarded--as was formerly the case--as an essential feature of the
disease. Patches of leucoderma may occur in connection with the
pigmentation, as beautifully delineated in Pl. xi. of Addison's
monograph. The pigmentation is not confined to the skin, but may extend
to the mucous surfaces--mouth, conjunctivæ, vagina. In the mouth the
patches may be as dark as in the dog; they are usually scattered, often
on the margins of the lips and on the edges and under surface of the
tongue and on the cheeks. The conjunctivæ are less often affected. The
vagina may be very deeply pigmented. An intensification of the
choroidal pigment has been observed. In some cases a patchy
pigmentation of the serous membranes has been found, and is figured in
one of Addison's original plates, and pigmentation of the nails, hair,
and teeth may also occur. A variation has been observed in the
intensity of the coloration with the general health of the patient. The
discoloration rarely precedes the general symptoms, but more usually
follows the asthenia.
Some observers have noted a peculiar odor of the breath and from the
skin, particularly during the last few days of life.
Anæmia of a moderate degree may exist, but it is not, as often stated,
a constant symptom. Greenhow states that "there is no real anæmia, the
blood being often rich in red corpuscles, even in excess, and there is
no increase in the white." No special alterations in the appearance of
the corpuscles have been noted. In some instances free pigment has been
found.[188] In a case recently at the hospital of the University of
Pennsylvania, Hughes found the number of red corpuscles over five
millions per cubic millimeter, and there were free pigment-granules in
the blood.
[Footnote 188: Corput, _Gazette hébdomadaire_, 1863.]
Hemorrhages are rare; extravasations into the retinæ have not, so far
as I {941} can ascertain, been observed, nor are there often the other
common features of anæmia.
The pulse is frequent and small, the heart's action weak--sounds clear;
a venous murmur may sometimes be heard. In some cases there appears to
be a special enfeeblement of the heart and a liability to fainting
attacks, and without any warning a fatal syncope may occur. Cold feet
and hands result from the weak circulation, and may be a most annoying
symptom.
Symptoms in connection with the respiratory system are not common.
There may be dyspnoea, and the complication of phthisis may give rise
to all the features of that disease. There may, however, be extensive
lung trouble with but few symptoms. The temperature is rarely elevated,
more often it is subnormal.
Gastric disturbances are very common--anorexia, nausea,
vomiting--particularly toward the close, but they may be early and
prominent features, persisting in spite of all remedies and proving the
most formidable symptoms of the malady. They appear to be of nervous
origin, and not referable to changes in the organ itself. It is
doubtful if the case reported by Gilliam,[189] in which there was
degeneration of the gastric mucosa, was Addison's disease. The state of
the bowels is variable; constipation is more frequent than the normal
condition. Diarrhoea is common, and may come on suddenly without
obvious cause, and is a not infrequent cause of death.
[Footnote 189: _Phil. Med. and Surg. Reporter_, xxiv.]
The urine is usually pale, free from albumen, not often increased in
amount. It is interesting to note, in connection with the involvement
of the abdominal sympathetic, that in a few cases there has been
polyuria. The nitrogenous elements may be greatly reduced, the urea to
13-20 grammes daily, and the amount of indican may be increased as much
as 64-75 milligrammes in 1000 c.c. (Samuel). In one case Thudichum
found the urinary pigments greatly reduced in amount, the uromelanin
not amounting to more than one-twelfth the normal quantity. A recent
observation of Nothnagel is of interest.[190] In a patient aged twenty,
who had the typical symptoms of the disease for two years, death took
place by coma and the condition of acetonuria was determined.
[Footnote 190: _Zeitschrift für klin. Med._, Bd. ix.]
The symptoms connected with the nervous system are the most prominent
in the disease, and are more constant than the anæmia or the bronzing.
The most marked is a depression and enfeeblement of the nervous forces,
a profound asthenia out of all proportion to the general condition. The
patients complain of a lack of energy, mental and bodily; the least
exertion is an effort, and there is a feeling of tire and weariness
with which the facial expression is quite in keeping. The fainting
fits, giddiness, noises in the ears, may also be due to faulty
innervation, as they occur in cases in which the anæmia is by no means
advanced. Headache, lumbar and abdominal pains are frequent, and in a
considerable proportion of cases there is tenderness on pressure in the
lumbar region. With the advance of the disease the prostration becomes
more marked, the patient remains in the recumbent posture, the voice
gets weak and small, the intelligence dulled, and occasionally there is
delirium. Head symptoms may suddenly supervene, and death by coma or
convulsions cut short the progress even early in the disease
(Pye-Smith). In Jaccoud's series convulsions were noted in 19 cases.
The disease may be said to be invariably fatal, but the course presents
many variations. The majority of cases die within eighteen months of
the first onset of the symptoms. B. Fenwick, in an analysis of 30
recent cases,[191] calls attention to the fact that when bronzing does
not occur the course is more rapid. Thus the average duration of the
non-bronzed cases was only 4.8 months, while for bronzed ones it was
23.6 months. There are acute cases {942} in which, with great weakness,
vomiting, and diarrhoea, the fatal end may occur in a few weeks. Some
of these rapid cases resemble typhus. Syncopal attacks, coma, or
convulsions cut short not a few cases. In a few instances it is much
prolonged--six years (Niemeyer) or even ten years (Greenhow). Whether
recovery ever takes place is doubtful. Finney[192] has reported an
apparently genuine case which got well. Some French observers (Potain)
think that recovery takes place more often than is supposed. Sir Wm.
Gull mentioned a case of recovery.[193] Periods of improvement lasting
many months may occur.
[Footnote 191: _Path. Soc. Trans._, vol. xxxiii., London.]
[Footnote 192: _Dublin Med. Journ._, April, 1882.]
[Footnote 193: _Int. Med. Congress_ (London) _Transactions_, vol. ii.]
MORBID ANATOMY.--The panniculus adiposus and subperitoneal fat may be
in normal quantity. There is rarely great emaciation, nor are the
organs blanched and bloodless. The most constant lesion is in the
suprarenal organs, which present a caseo-fibrous change, more rarely
simple atrophy or other alterations. So frequent is the caseo-fibrous
condition that some writers (Wilks) hold that it is the specific lesion
of the disease. The organs are enlarged--may weigh several ounces each.
The capsules are thickened, and may present caseous or even calcareous
masses. The normal shape of the gland is lost, and it forms an
irregular nodular mass closely adherent to contiguous parts--liver,
kidney, and cava on the right side, kidney, spleen, and often pancreas,
on the left. There is usually a good deal of fibrous thickening and
matting in the vicinity, and the adhesions to adjacent structures may
be very strong. The peritoneum often shows patches of fibroid
induration. On section the diseased organ cuts with great resistance,
and to the touch has an almost cartilaginous hardness. The exposed
surface shows caseous masses of a yellow or grayish-white color,
varying in size from a pea to a walnut, imbedded in a grayish
semi-translucent fibrous tissue, pale when first cut, becoming reddish
on exposure. These caseous masses may undergo softening or
calcification, and pockets of pus are not uncommon. Definite small
miliary granulations are not often seen, though nodular grayish-yellow
bodies the size of small peas may occur. The strands of fibrous tissue
which separate and enclose the caseous masses have often a very
peculiar translucent, infiltrated appearance. When the cheesy lumps are
small, the amount of this tissue is considerable and gives a remarkable
character to the section. Wilks has described a case in which this
tissue made up the entire mass. The substance of the gland is usually
destroyed. The vessels and nerves can be traced to the organs where
they become imbedded in the fibrous tissue.
Histologically, the soft translucent tissue consists chiefly of
spindle-shaped fibre-cells, and in firmer older parts of ordinary
fibrous stroma. In the immediate neighborhood of the cheesy masses
there are round corpuscles--about the size of or a little larger than
white blood-cells--imbedded in a fine reticulum of fibres. Giant-cells
are sometimes found, but they have not been common elements in the
specimens which I have examined. The caseous substance consists of
granular débris in which the remains of cells and fibres can be seen.
In coarse and microscopical features the lesion resembles closely local
tubercular affections. The extension is by a small-celled growth, which
gradually invades the adjacent parts, extending peripherally as the
central portions caseate. Distinct miliary granulations are not often
met with. The relation of this local growth to tuberculosis is a very
interesting question. It is usually regarded as a scrofulous or
tuberculous process, to which in its general features it quite
conforms. I have been interested in ascertaining whether the bacillus
tuberculosis existed or not in the local lesion. In Cohnheim's
laboratory Karl Hüber kindly gave me an opportunity of examining the
adrenals in two cases, in only one of which were the {943} bacilli
evident. Since then I have re-examined the fibro-caseous tissue in
Ross's case,[194] which was a most typical one, the suprarenals alone
involved, and in the recent case reported by Pepper,[195] and in
neither have I been able to demonstrate bacilli. Future examinations
must decide whether the local affection is inflammatory or whether it
belongs to the infective granulomata.
[Footnote 194: _Can. Med. Assoc. Trans._, vol. i., 1877.]
[Footnote 195: _Phila. Med. Times_, 1885.]
That other alterations may occur in cases of Addison's disease appears
well established, though some still regard the caseo-fibrous change
essential and specific. Atrophy of one or both glands has been
frequently seen. Jaccoud gives 7 cases in his tables. Good recent cases
have been described by W. B. Hadden,[196] Hebb,[197] and Goodhart.[198]
The atrophy is due to a chronic interstitial process similar to
cirrhosis of the liver. Hadden[199] states that the lesion is identical
with that in the thyroid gland in myxoedema.
[Footnote 196: _British Medical Journal_, 1885.]
[Footnote 197: _Lancet_, 1883, i.]
[Footnote 198: _Path. Soc. Trans._, 1882.]
[Footnote 199: _Loc. cit._]
Absence of one or both the capsules has been noted by Legg, Spender,
Borland[200] and Hubbard.[201]
[Footnote 200: _Boston Med. and Surg. Journal_, 1867.]
[Footnote 201: _Proceedings of Conn. Med. Society_, 1868-71.]
Cancer of the adrenals, by no means uncommon as a secondary process,
rarely produces any special symptoms; but there are cases which are
difficult to exclude from the category of Addison's disease. Jaccoud
gives several, and in the case of Edes, often quoted,[202] the asthenia
and discoloration may have been due to the capsular affection, but
there was also extensive peritoneal cancer.
[Footnote 202: _Boston Med. and Surg. Journal_, 1878.]
By far the most constant morbid change after that in the adrenals is a
more or less widely distributed tuberculosis, particularly of the
lungs. A very considerable proportion of the cases are complicated with
chronic phthisis. Regarding the disease of the suprarenals as primary,
the general tuberculous affection may be secondary; and it is just in
these organs, as Weigert has shown, that the veins are apt to be
perforated by tubercles and systemic infection induced. The
retro-peritoneal and mesenteric lymph-glands may also be tuberculous.
Ulcers of the ileum may occur, and swelling of Peyer's glands and the
solitary elements in the bowels is very common. In Ross's case there
were numerous lymphoid infiltrations of the mucosa of the stomach,
chiefly about the pylorus and cardia. The changes in the skin are
confined to an increase of the pigment in the cells of the rete
mucosum, most pronounced in the deeper layers and in the deeper parts
in the connective-tissue cells of the papillæ and subcutaneous tissues.
The condition is not to be distinguished from a deeply-pigmented
scrotum or from the dark skin of the negro. The pigment resembles the
ordinary coloring matter of the skin, but is possibly different from it
in containing no iron.[203] Nothnagel has made[204] an exceedingly
interesting study of the pigmentation in Addison's disease, and
concludes that it is identical in distribution with that in the skin of
the dark races; that it does not originate in the cells of the rete
mucosum, but is elaborated in deeper cells, about the vessels of the
cornium, and transported by them to the more superficial layers--a mode
which recent observations seem to show is the normal one; and, lastly,
that it is a process induced through the nervous system in some way as
yet unknown.
[Footnote 203: Arnold, _Virchow's Archiv_, xxxv.]
[Footnote 204: _Loc. cit._, Bd. ix.]