A system of practical medicine. By American authors. Vol. 3

Chapter LXIV: Part 64

Text size

The chief characters of the lesions in the different groups have been dealt with in the section on Symptoms. The superficial glands are most often attacked, and the cervical or axillary may form huge masses before there are any signs of internal trouble. The superficial and deep cervical groups may be uniformly affected, the muscles lifted and wasted, and vessels and trachea surrounded by a solid mass. Sometimes all distinction between the tissues is lost, and the carotids run in the midst of the new growth, which may extend far out beneath the trapezius and down into the chest or over the clavicle on to the outside. When the neck is not primarily affected the groups are more isolated, and can be traced as chains of enlarged glands along the trachea and the carotids continuous with those of the axillæ and mediastinum.

The axillary group is next involved in the order of frequency, and the masses when large grow out under the pectorals and back beneath the scapulæ and high into the fossa, compressing the axillary vessels and causing great swelling of the arm. In Case VII. the growth infiltrated the neighboring muscles and eroded the humerus and neck of the scapula, perforated the blade, and exuded on its outer surface. Though an enormous mass, the vessels were not infiltrated, and only moderately compressed. The inguinal glands when very large may obstruct the femoral artery and vein, and seriously interfere with the circulation in the legs.

{927} Of the internal groups, those of the thorax are most often affected, and we may have the chain in the posterior mediastinum along the aorta and the sides of the trachea and gullet, and along them pass into the neck (Case V.), or the bronchial group may be primarily attacked, with the formation of a great bunch at the fork and numerous small masses along each bronchus at the root of the lung, which may be extensively involved (Case VI.); or those of the anterior mediastinum beneath the sternum may be affected, with the production of large masses extending over the pericardium and passing even to the diaphragm. In these cases bulging of the sternum and ribs, with erosion and perforation, may occur. In Case II. the sternum was completely destroyed to a level with the fourth rib. The heart may be pushed aside and the aorta and its branches completely surrounded by growths (Cases II. and VI.). It is remarkable in these cases that great vessels do not suffer more from compression. When the abdominal glands are involved, the retro-peritoneal are most frequently enlarged, and form a continuous chain from the diaphragm to the internal rings on either side of the aorta and its branches, extending into the pelvis. Pressure effects are not common, but they may compress the ureter, causing hydronephrosis, the sacral and lumbar nerves, the iliac veins, and, as in the case I mentioned, may adhere to the broad ligaments and uterus in such a way as to deceive the most skilled gynæcologist. The mesenteric glands may present slight enlargement, but in my experience they are but little affected, even when the retro-peritoneal are of large size. When the glands at the portal fissure are involved they may compress the vein and duct. Phelps of Chateaugay, N.Y., sent me a specimen in which the glands of this region formed two huge masses the size of cocoanuts, and, so far as I could ascertain, they were primary lympho-adenomatous growths. The possibility of ovarian disease had been discussed by several consultants.

The chief change is an increase of the cells with or without thickening of the reticulum. The cells correspond to ordinary lymph-corpuscles; some may be a little larger, with darker granules and more pronounced nuclei. Giant cells are frequently met with, more often in the small glands. I have not seen them in the large soft tumors. In the early stage there may be simple hyperplasia and the relations of the lymph-paths are maintained, but when the glands are much developed the normal arrangement is disturbed and they cannot be injected. The reticulum varies much; in the very soft form it is expanded and can scarcely be found; the substance may be semi-diffluent. The firmer the structure the more evident is it, and in the hard forms the network of fibres in whose meshes the cells are enclosed can be distinctly seen and by pencilling very clearly brought out. It is not merely a thickening of pre-existing fibres, but probably there is a new development of adenoid tissue. In some cases of advanced fibroid change very few cells can be seen. The vessels passing to the glands are sometimes dilated.

Spleen.--In about 75 per cent. this organ is hypertrophied or presents lymphoid growths (Gowers). The enlargement is not often great, rarely approximating the colossal size of the leukæmic organ. It is due to either simple hyperplasia or to the presence of the new growths, sometimes to both. In the 75 cases of enlarged spleen new growths occurred in 56 (Gowers). Of the 38 cases in Hutchinson's table, 27 presented the splenic tumors. These are grayish-white bodies, ranging in size from a small pea to a walnut or larger, scattered irregularly through the substance, usually rounded in outline, but in some instances irregularly shaped. They contrast by color strongly with the red spleen-pulp. The numbers may vary from one or two to many dozens, the spleen-substance being a mere remnant between them. These masses often resemble the lymph-glands in appearance and consistence. {928} They are not encapsulated, but in immediate contact with the spleen-tissue. They originate from the Malpighian corpuscles, and may be regarded as the enlarged and developed lymph-elements in the spleen. The larger ones probably arise from the fusion of several small ones. When uniform in size and scattered throughout the organ, they may resemble coarse tubercles, but the absence of any caseation may serve to distinguish them. Their histological characters are those of the glands, lymph-corpuscles in a fibrous reticulum; the consistence depends on the preponderating element.

Amyloid degeneration was found by Gowers in two cases in the growths.

The thymus has been found involved in the mediastinal growths, and is occasionally affected primarily. The thyroid may be attacked by the cervical tumors.

The suprarenals may contain secondary growths. In Case VII. both were extensively involved.

The medulla of the long bones has been found converted into red lymphoid marrow, and in a few instances into the pyoid variety met with in leukæmia. It has been found normal in other cases.

Digestive System.--In the mouth and pharynx the lymphatic elements are very commonly affected when the cervical glands are enlarged, sometimes independently. The tonsils may form large masses, and with the follicles at the root of the tongue and at the pharynx produce great obstruction. Sloughing may occur. In the gullet and stomach secondary tumors have occasionally been seen. In Case VII. there was a flat elevated mass at the cardia beginning to ulcerate.

The small intestines may be extensively involved; the glands of Peyer enlarged and even ulcerated. In Case VII. there were over twenty ulcers in the jejunum and ileum, ranging in size from a split pea to a bean, edges elevated and indurated and the bases sloughing. The large intestines may be secondarily affected, the intertubular adenoid tissue be greatly developed and compress the crypts of Lieberkühn, and lead to thickening of the mucosa.

The liver is often enlarged, and presents scattered lymphoid tumors, rarely larger than a pea, of a white or yellow-white color, and may be readily mistaken for tubercles. They are most common beneath the capsule and in the interlobular tissue. A diffuse interacinous growth may also occur. Cirrhosis has been observed in the vicinity of the growths, and fatty degeneration.

The pancreas may be the seat of secondary masses.

Genito-urinary System.--The kidneys are very often the seat of new growths, usually small and of a character similar to those in the spleen and liver. When the disease is very rapid the tumors may be large and very vascular. The texture of the kidney is usually soft, and parenchymatous change is common. The testicles may also be the seat of adenoid growths; this was the case in one of Hodgkin's patients.

The Respiratory System.--Growths in the trachea are rare. The lungs are frequently affected, either by the direct invasion at the root from the bronchial glands (Case V.), or by numerous scattered nodules through the substance. They develop about the bronchi, and may reach the size of marbles. Intense bronchitis, oedema, and congestion may be secondary changes induced by pressure on the bronchi or trachea.

The serous membranes occasionally present lymphoid growths. Pleural effusion is not uncommon.

The heart presents no very constant changes. When the anæmia is profound it may be very fatty. It may be compressed by mediastinal growths, and has been found much atrophied. Lymphoid growths may occur in it.

The Nervous System.--The brain itself is rarely affected, but growths have been found in the dura mater. In Case VI. a secondary mass compressed the spinal cord, as in Hutchinson's case, producing paraplegia.

{929} The skin may be the seat of adenoid growths, as in Greenfield's case.[155] The growing tumors may involve it (Case IV.), and ulceration may occur.

[Footnote 155: _Loc. cit._]

COURSE, DURATION, AND TERMINATION.--Trousseau and other French writers have divided the disease into different stages--the latent and period of early development, the period of generalization, and the cachectic state; but the course of the disease is very variable, and depends much upon the position of the glandular enlargements, the rapidity of development of secondary growths, and also the constitutional peculiarities of the patient. Early and rapid growth in the mediastinal groups may produce pressure effects, and cause death before any marked anæmia--much less cachexia or the development of secondary masses in important organs, as the cord, may prove quickly fatal. In some cases the glandular enlargement rapidly spreads, and group after group is involved in the space of a few months; in others there may be hyperplasia of a single set, as the cervical on one side, for months, or even years, before the glands on the other side or in other regions become involved. The most acute cases may run a course in three or four months, the most chronic in as many years. Periods of quiescence are not uncommon, and the tumors may not only cease to grow, but actually diminish, or even disappear in a region, and this without any special treatment.

The mode of death is commonly by asthenia; cachexia is gradually developed, the anæmia becomes more profound, and finally, with local or even general dropsy, the end comes from heart failure. Very frequently the patient is cut off before grave constitutional disturbance is established, particularly by asphyxia from the pressure of enlarged glands on the trachea and bronchi or occlusion of the pharynx. Hemorrhage and diarrhoea, such common symptoms in leukæmia, are rarely seen. Coma has been the cause of death in a few cases. Oedema of the lungs, pneumonia, extensive pleuritic effusions, may hasten, and in some instances cause, the fatal result.

The DIAGNOSIS is in most cases easy; in others time alone will decide the true nature of the glandular enlargement. Of the chronic forms of adenitis which are liable to be confounded, the scrofulous is the most common. The points to be attended to in the diagnosis are--the age; scrofulous glands affecting chiefly the young and individuals presenting other signs of the so-called scrofulous habit, or there may be a well-marked family history of phthisis. In the question of age, however, it is to be remembered that there is a condition known as adult or senile scrofula, in which there may be general enlargement of the glands. Of all groups the cervical are most frequently involved in scrofula, and the submaxillary set more often than those of the anterior and posterior triangles, while in Hodgkin's disease the latter are usually affected first. The enlargement in scrofula is rapid at first, and may last for years in a group without extending; the bunches are often, even when small, welded together, and, most important of all, they tend to suppurate--a feature scarcely ever seen in true lymphadenosis. Size is an uncertain criterion. I have seen masses of scrofulous glands in the neck as large as two fists and without suppuration. A single large bunch in the neck, particularly if submaxillary, persisting for over a year or eighteen months without involvement, however slight, of the glands in the same or the opposite side or in the axillæ, is almost certainly not malignant lymphoma. On the other hand, a group of slowly-enlarging glands in the anterior cervical triangle, with gradual affection of those of the opposite side of the axillæ, particularly if in a person between twenty and thirty and becoming anæmic, would render the suspicion of Hodgkin's disease strongly probable.

In connection with this it may be mentioned that occasionally in acute {930} phthisis there may be great swelling of the glands, from a growth of miliary tubercles in them. A case of the kind was admitted into my wards in the General Hospital, Montreal: a man aged twenty-four, with great swelling of the cervical glands in both sides, tonsillitis, and sloughing pharyngitis, irregular fever, and diarrhoea, and for a time the case was believed to be one of Hodgkin's disease.

PATHOLOGY.--Local benign lymphomata occur, identical in histological characters with the tumors of Hodgkin's disease, and differing only in the absence of any tendency to extend in the neighborhood or to generalize. They are not uncommon about the neck, may grow slowly, and last for years.

The lymphatic growths of leukæmia are not in any essential particular different from those of Hodgkin's disease, and the diagnosis rests upon the examination of the blood. There are, however, certain broad differences when any considerable number of cases of the two diseases are compared. Thus the lymphatic element in leukæmia is less pronounced, the splenic and medullary forms predominate; in Hodgkin's disease exactly the reverse prevails. It is rare in leukæmia for the internal glands to be much involved, and patients do not often die from the pressure effects of the tumors. The hemorrhages so common in leukæmia, and the diarrhoea, are rare symptoms. The bone-marrow is more generally affected, and, lastly, the tendency to generalize seems greater in the growths of Hodgkin's disease.

From other forms of malignant growths in the lymph-glands there may be difficulty in the diagnosis, and even a microscopical examination may not serve to make the distinction.

Thus there is a true lympho-sarcoma, a small-celled growth of the lymph-glands, which must be distinguished, though it is hard in some cases, from the general lymphadenoma. The distinctions laid down by some writers, such as a special tendency to attack contiguous parts, and a more general distribution of the metastatic growths, will not hold, as we have seen that cases of lymphadenosis or Hodgkin's disease may attack neighboring structures, and the secondary tumors, though preferably in lymphatic textures, may occur in every organ. In the retro-peritoneum, for example, true lympho-sarcoma is not uncommon, forming large tumors which may press forward the viscera and produce a very prominent mass in the abdomen. They are not uncommon in children, and with renal sarcomas make up three-fourths of the abdominal growths of early life. But they may occur in adults and attain large size, involving adjacent organs, such as the kidneys, or, as in a case I saw a short time since, grow into the colon and cause death by gradual hemorrhage. These are local growths as regards the lymphatic system, not involving distant glands, and not often, indeed, producing metastasis.

We may recognize in the lymphatic glands--1st, the local benign growth which seems nothing more than hypertrophy, lymphadenoma, and which may persist for years; 2d, a local malignant growth, lympho-sarcoma, which invades contiguous structures and may be followed by metastasis, but there is not general involvement of the lymphatic tissues; and 3d, there is a generalized lymphoma involving groups of glands in succession, and the adenoid tissue throughout the body, usually accompanied by anæmia alone, in which case we term it Hodgkin's disease--sometimes by an excess of colorless corpuscles as well, when we call the affection lymphatic leukæmia.

PROGNOSIS.--When established sufficiently to make a sure diagnosis, the prognosis is in the great majority of cases bad; true examples of the disease rarely if ever recover. A hopeful prognosis may be given in those cases in which only a few glands are involved, and where there is any suspicion of a scrofulous habit or where the enlargement has persisted for years without {931} extending. The presence of profound anæmia, the existence of swelling in distant groups and in internal glands, are grave indications. High, irregular fever, rapid growth, and the development of cachexia are symptoms of the full establishment of the disease. The physician must not be deceived by intervals of improvement, with perhaps subsidence of the glandular swelling in places. Such breaks in the onward progress are not uncommon.

TREATMENT.--When small and localized, the question of the removal of the glands may be raised. If they persist after appropriate remedies, and if there is not grave anæmia, and other groups and the spleen are not affected, excision should certainly be performed. Circumscribed lymphadenoma, particularly of the neck, may exist for years before the glands in other regions become involved; and in such cases removal affords the best guarantee that the disease will not extend.

Local applications are of doubtful benefit. I have never seen any permanent improvement follow the persistent use of iodine, biniodide of mercury ointment, or friction with oil. Galvano-puncture has not been successful, and the same may be said of the various substances injected into the glands--iodine, arsenic, chromic acid, etc.

Internally, iodine and iodide of potassium have been extensively used, but without much benefit. Quinine, iron, and cod-liver oil are useful as tonics, but have no influence on the size of the tumors. Arsenic is the only medicine which has seemed to me of positive value, and under its use I have seen the gland-tumors decrease greatly in size. It should be given in increasing doses until some of the unpleasant effects of the drug are manifested, when a return should be made to a small dose, and again gradually increase. When well borne, large doses, 20 or 25 minims, of the liquor arsenicalis should be taken three times a day for many weeks. In two cases with moderate enlargement of the cervical and axillary glands the progress of the disease seemed arrested, and the glands certainly became smaller and softer. In the history of these cases the patients will often speak of changes in the volume of the gland quite uninfluenced by any treatment; and these fluctuations must be taken into account in estimating the value of a drug; but, making due allowance for this, the beneficial effects of the arsenic are unquestionable when given early in large doses and the administration kept up for months. Many recent writers have borne testimony to this, among them Karewski,[156] who reports three recoveries.

[Footnote 156: _Berl. klin. Wochenschrift_, 1884, 17 and 18.]

Phosphorus has been of service in the hands of Gowers and Broadbent, and when arsenic is not well borne it should be tried.

Change of air and scene has benefited some cases. The patient's strength must be supported by every possible means; fortunately, gastro-intestinal disturbance is not so marked as in leukæmia, and even with most extensive and progressive enlargement of many groups of glands the appetite may be good and the digestion excellent.

When the glands of the neck compress the trachea, or when the lymphoid elements of the tonsils and pharynx obstruct the orifice of the glottis, tracheotomy may be necessary.

HÆMOPHILIA.

DEFINITION.--An hereditary or congenital fault of constitution, characterized by a tendency to bleeding, spontaneous or traumatic, and often associated with swelling of the joints.

{932} SYNONYMS.--Hæmatophilia; Hereditary hæmorrhage; Hæmorrhagic diathesis; Idiosyncrasia hæmorrhagica. _Ger._ Bluterkrankheit, Blutsucht; _Fr._ Hémophilie. The term bleeder is applied to a patient.

CLASSIFICATION.--In this article the congenital or hereditary disease will alone be considered, to the exclusion of cases of transient hemorrhagic diathesis, the hemorrhages of scurvy, fevers, anæmia, purpura simplex, and purpura hæmorrhagica.

HISTORY.--So far as is known, the classical writers make no mention of the disease, though in the _Pharsalia_ of Lucan there is a passage, quoted by Legg,[157] which well describes the hemorrhagic diathesis. The first positive reference is in the writings of Alzaharvi, a physician of Cordova who died in 1107 A.D. A doubtful case is mentioned by Benedictus in 1539, who relates the history of a barber who bled to death from slight wounds of the nose caused by clipping the hairs. Hochstetter described a case in 1674 to which Virchow has called attention.[158] Legg[159] found a well-recorded case by Banyer in the _Philosophical Transactions_ (1743). Fordyce in 1784 described a Northamptonshire family the members of which suffered from hemorrhages.[160] With brief references to the disease by two German writers in 1793 and 1798, these scanty materials comprise the facts known at the beginning of this century.

[Footnote 157: _Hæmophilia_, London, 1872.]

[Footnote 158: _Virchow's Archiv_, Bd. xxviii.]

[Footnote 159: _Loc. cit._]

[Footnote 160: _Fragmenta Chirurgica et Medica_, London, 1784.]

To American physicians belongs the credit of the full recognition and description of the disease and the discovery of its remarkable hereditary nature.

Otto[161] gave an account of a New England family members of which had been bleeders for several generations. He also referred to a Maryland family observed by Rush. Otto appears to have been the first to note the immunity of females in bleeder families, and their tendency to transmit the disposition. In the _Philadelphia Medical Museum_, vol. i., 1805, a letter of E. H. Smith is published, written in 1794, in which he gives an account of a boy affected with the disease. Hay[162] reported the Appleton-Swain families of Reading--one of the most remarkable histories ever published of the disease. In 1817 the Buel Brothers described the Collins family,[163] and Coates[164] a family in Delaware county, Pa. Hughes[165] and Gould[166] also described notable examples. Holton, Harris, and Dunn have studied other American bleeder families, and a brief record of the local literature of the subject will be found at the end of this article.

[Footnote 161: _Medical Repository_, New York, 1803, vol. vi.]

[Footnote 162: _New England Medical Journal_, 1813, vol. ii.]

[Footnote 163: _Transactions of the Medical and Physical Society of New York_, 1817.]

[Footnote 164: _North American Medical and Surgical Journal_, Philada., vol. vi., 1828.]

[Footnote 165: _Transylvania Journal_, 1831, vol. iv., and _American Journal Med. Sciences_, 1833, vol. xxi.]

[Footnote 166: _Boston Medical and Surgical Journal_, 1857.]

In Germany, Nasse (1820), Rieken (1829), Schönlein, Canstatt, Wachsmuth, Lange, Virchow, and others added greatly to our knowledge of the disease. Grandidier published a monograph in 1855, a new edition of which in 1877[167] contains a most exhaustive account of the disease and a statistical résumé of all cases to date. In England the disease has not attracted much attention. Legg published an important monograph in 1872, and many papers of value are scattered through the _Transactions_ and journals.

[Footnote 167: _Die Hämophilie_, Leipzig, Zweite Auflage, 1877.]

In France the articles in the encyclopedias and a few theses--of which Gavoy's (1861) and Simon's (1874) are the most important--comprise the chief literature.

ETIOLOGY.--The disposition is, in the majority of cases, hereditary, but there may be a spontaneous origin, the disease appearing in the child of a family in which no previous cases had occurred. Nothing is known of the {933} conditions under which the disease may thus arise in a healthy stock. Many of such cases die early, but others live and may become the starting-points of new bleeder families. In the history of sixty families Grandidier[168] found statements of this mode of origin of the affection.

[Footnote 168: _Op. cit._, p. 136.]

The two most interesting features in the etiology relate to sex and heredity. The disease is much more common in males than females, the proportion being variously estimated at 11 to 1, or even 13 to 1. In 64 bleeder families, in 5 were sons and daughters alike affected; in 27 all the sons were bleeders; and in 6 of these there were no daughters.

There is no disease with so marked a tendency to transmission, and it may appear in four or five generations in succession. In the Appleton-Swain family of Reading, Mass., there have been cases since the early part of the last century, and F. F. Brown of that town writes me that cases still occur in the descendants.[169] Legg gives a chart of the Clitherow family, in which it has existed for the past two hundred years.[170]

[Footnote 169: The last case Brown has been able to ascertain was in a lad, Warren Coburn, aged seventeen, who died about twelve years ago. His mother's brother was a bleeder, and died of hemorrhage from a slight scalp wound after having been brought to death's door on three or four other occasions by trivial wounds. Mrs. Coburn was a daughter of Daniel Hart, whose wife was a Norton. Her mother was a Bacheller and a granddaughter of Oliver Appleton's daughter. This lad is an instance of the transmission of the disposition to the seventh generation within a period of two hundred years. Brown further states that there do not appear to be in the vicinity of Reading any Appleton or Swain families in which bleeders exist. As the tendency is chiefly transmitted through the female members of a family, who lose the patronymic by marriage, it is often difficult to trace the relationship. I think if we had fuller genealogical details we should find that several of the bleeder families now thought to be distinct belonged to the same stock.]

[Footnote 170: _St. Barth. Hospital Reports_, 1881.]

In the celebrated bleeder families of Tenna, Switzerland, five generations have been affected. The modes of transmission are as follows: (1) Father {934} to son, grandson, etc. This is rare, but instances are on record. (2) Father not a bleeder, but of bleeder stock, transmits the tendency to son--very uncommon. (3) Father to daughter, granddaughter, etc.--not common. The daughters of a bleeder are usually free, though their brothers may be affected. (4) Mother a bleeder, transmits to sons and daughters. (5) Mother not a bleeder, but daughter of one, transmits to her sons, the daughters remaining free, but their sons affected. This is the most common mode of inheritance. Atavism by transmission through the female line is almost the rule, and the daughters of a bleeder, though healthy and free from any tendency, are almost certain to transmit the disposition to their male offspring. The 657 cases analyzed by Grandidier occurred in two hundred families. The chief facts of heredity are well illustrated by the preceding chart of the Yeaton family, given by Gould in the _Boston Medical and Surgical Journal_, 1857.

The Anglo-Germanic nations appear especially prone to the disease. Of 194 families in Grandidier's table, 154 were of the Teutonic stock. Records of the disease among the Latin races are rare. Jews are probably not more liable than other people, but the rite of circumcision gives an unusual opportunity for its manifestation at an early age.

The age at which the bleeding tendency first appears was determined by Grandidier in 113 cases as follows: in 63 during the first year; in 17 during the second, and up to the end of the second year in 93. It is rare for the first manifestation to occur after the twelfth year, and there was only one case in which the first bleeding appeared after the fifteenth year.

The constitution and temperament of bleeders, about which the older writers had much to say, probably present no peculiar characteristics. Some persons claim to be able to recognize bleeders even before they have manifested any tendency to hemorrhage. They are usually fresh, healthy-looking persons, with fine, soft skins, through which the superficial veins may show with more than usual distinctness. A division of cases into erethetic and atonic forms has been made by Wachsmuth and Grandidier. The mental activity of bleeders has been noted to be above the average, due, doubtless, to the fact that the liability to bleed from slight blows and cuts has made sedentary and studious habits preferred to out-of-door employments and amusements.

Families in all conditions of life are affected. Much interest was excited in the disease in England from the fact that the late Prince Leopold was a sufferer.

Climate appears to have an influence in determining attacks. Cold, damp, changeable weather is favorable, while a residence in a warm, equable climate diminishes the tendency in a very marked manner. Some patients have an extraordinary susceptibility to changes in the weather.

All observers have noted the great fertility of bleeder families. Those first born seem less liable to bleed than subsequent ones.

SYMPTOMS.--The existence of the defect of constitution may not be suspected until an uncontrollable hemorrhage follows some trivial injury or operation, or a spontaneous bleeding may occur and present great or insuperable difficulties in its arrest. The symptoms usually occur in the first years of life, and in the great majority of cases, as mentioned above, the first bleeding occurs before the fifth year. The symptoms may be grouped under three divisions (Legg, Grandidier): external bleedings, spontaneous and traumatic; interstitial bleedings, petechiæ, and ecchymoses; and the joint affections. Legg recognizes three grades of the disease. The first and most severe is characterized by bleedings of every kind, external and internal, and by troublesome joint affections: this form is most often seen in men. The second grade is less severe; there are spontaneous hemorrhages from the mucous surfaces, but no traumatic bleeding or ecchymoses and no joint {935} troubles: this form is most often seen in women. The third and lowest degree is when there is a tendency simply to ecchymoses; no dangerous bleedings occur: this form is often seen in members of bleeder families, and if in women the menstruation may be early and profuse.

External Bleedings.--The spontaneous bleedings may occur from the skin, the mucous, and in rare instances the serous, membranes. There are frequently preliminary symptoms--prodromata--such as flushing, fulness of the head, and throbbing of the arteries--signs of so-called plethora; often there is irritability of temper, but sometimes, in children, extra cheerfulness has been observed. The localities affected and the frequency are shown by the following analysis of 334 cases by Grandidier: Epistaxis, 169 times; from the mouth, 43; stomach, 15; bowels, 36; urethra, 16; lungs, 17; cerebral hemorrhage, 2; skin of head, 4; tongue and finger-tips, 4 each; tear-papilla, 3; eyelids, 2; external ear, 5; female generative organs, 10; ulcer of skin, 2; navel (long healed), 2. An odd situation for spontaneous bleeding is mentioned by Townsend,[171] in which a child bled to death from the scrotum. In many cases these spontaneous hemorrhages prove fatal--most frequently the epistaxis. The traumatic bleeding may result from blows, cuts, scratches, etc., and the blood may be effused into the tissues or discharged externally. Fatal hemorrhages have occurred from the following wounds: blow on head, 11 times; slight scratches on skin or abrasion of dermis; laceration of the frænum of the lip, slight cut (two lines deep) in a duel wound; bite of the tongue (7 cases); fall on the mouth; blow on the nose; blow of a stone on the finger; cut in paring the nail; fall on the head with meningeal hemorrhage (2 cases, brothers); and rupture of the hymen on the wedding-night.

[Footnote 171: _Boston Med. and Surg. Journal_, lv.]

After operations, trivial and severe, many fatal cases have occurred, and the statistics of the same author give the following: cutting of the frænum linguæ, 1; leeching, 5; venesection, 4; blister, 2; extraction of tooth, 12; circumcision, 8; cutting umbilical cord, 4; vaccination, 2; fistula, stone, ligation of carotid, of radial, of ulnar, of femoral arteries, amputation of arm and of thigh, 1 each; phimosis, 2. Leeching, extraction of teeth, and circumcision are most dangerous operations in bleeders.

The bleeding is always a capillary oozing, and the vessels are not seen. It may last for hours, or even many days and weeks, and the amount of blood lost may be enormous. Epistaxis may be fatal in twenty-four hours. In Coates' case a medical student lost half a gallon of blood in twenty-four hours, and in the ten days which the bleeding continued it was estimated that he lost about three gallons.

The healing of a wound in a bleeder may take place rapidly, either with or without suppuration. When the hemorrhage is large or prolonged, severe anæmia follows, from which, as a rule, the patients recover with remarkable rapidity.

The interstitial hemorrhages--petechiæ, ecchymoses, hæmatoma--may be spontaneous or the result of injuries. The petechiæ occur most frequently in the skin, particularly of parts distant from the heart--the legs and arms, less often the face. On the mucous and serous surfaces they are less common. They resemble ordinary purpuric spots, and crops may come out with symptoms of swelling and pain in the joints. Large extravasations--hæmatoma--are most frequently of traumatic origin and may follow the slightest blow, as in a case of Sir Wm. Jenner's, in which from the fall of a rubber ball on the thigh an enormous extravasation took place between the knee and trochanter.[172] They are blue, black, or reddish-black at first, and in their absorption go through the various changes in color which we notice in a bruise. These blood-tumors may occasionally arise spontaneously.

[Footnote 172: Legg, etc., p. 68.]

The arthritic affections in hæmophilia are very remarkable, and so {936} common as to form prominent features in the disease. There may be simple pain in and about the joints, or swelling with redness and signs of intense inflammation. The attacks may come on suddenly with fever, resembling closely acute rheumatism. The large joints are usually affected, the knees most often, then the elbows, ankles, and shoulders. There may be repeated attacks, and at last great crippling and deformity. The small joints are rarely affected. In cold, damp weather the attacks are most common; occasionally they follow traumatism. In addition to the joint troubles, bleeders suffer much with irregular pains in the limbs, particularly during change of weather, or these pains with arthritis may usher in an attack of hemorrhage.

Many other irregular symptoms are described in the monographs, some of which have no intimate relation with the disease. The anæmia has, of course, all the features of the traumatic form. Digestive troubles, after the bleeding, are common, and are due to the anæmia. The Buel Brothers[173] mention that in two of their cases the patients showed a marked inclination to eat sand and earth. Children with the hemorrhagic tendency pass through the ordinary diseases of infancy like others. Whooping cough is very liable to cause epistaxis. Rheumatism and scrofula are said to be common in bleeder families.

[Footnote 173: _Op. cit._]

The blood in bleeder cases is, as a rule, normal, so far as our present means of investigation enable us to decide. When a hemorrhage has continued for some time, it is thin and watery, but at the beginning of the bleeding the blood is usually rich in corpuscles and fibrin and coagulates firmly. The salts have been found increased in quantity. No change has been noted in the corpuscles, the number of which is stated by several observers to be increased. Prior to a hemorrhage there may be, according to some writers, a state of plethora or increase in the total quantity of blood, and the tolerance of the loss, so much greater in bleeders than in ordinary persons, is adduced in support of this view.

MORBID ANATOMY.--Not many changes other than those of profound anæmia have been found in the bodies of bleeders. An unusual thinness of the walls of the vessels, first noted by Bladgen in 1817,[174] has been met with in a number of cases; in a few instances hypertrophy of the heart; in others a rounded foetal shape of the organ. Within the past few years careful microscopical examination has been made of the tissues and blood-vessels of bleeders. Kidd[175] found degeneration of the muscle-fibres of the middle coat of the arteries, and the endothelium of the small arteries, veins, and capillaries was swollen, proliferated, and some of the small veins were blocked with the products. Legg[176] reports a case in which Klein made a most careful examination with negative results, and he stated that of six such examinations which had heretofore been made, in only one case (Kidd's) were important changes found. At the same meeting of the London Pathological Society, Theodore Ackland also reported a case with negative results as regards histological changes.

[Footnote 174: _Medico-Chirur. Transactions_.]

[Footnote 175: _Medico-Chirurgical Society's Transactions_, vol. lxi.]

[Footnote 176: _Lancet_, Oct. 27, 1884.]

The joint changes have been studied in a number of cases. Hemorrhage has been found in and about the capsule, and the acute swelling may be due largely to it, as was shown in Hutchinson's case,[177] in which he aspirated the joint. When it lasts any time, there is great staining of the cartilages and discoloration. There may be inflammation of the synovial fringes and erosion and destruction of the articular surfaces (Legg).

[Footnote 177: _Trans. State Med. Soc. N.Y._, 1877.]

The PATHOLOGY of the disease is unknown. No doubt two circumstances combine in hæmophilia--congenital fragibility of the vessels and a defect in coagulability of the blood--but whereon these depend we are as yet entirely ignorant. There is no evidence of the nature of the anatomical changes in {937} the vessels which permits of their ready laceration, and none on the nature of the alteration of the blood which prevents the normal thrombus formation in a wound; and in the absence of information on these points theories must necessarily be unsatisfactory, and their discussion, in a work of this practical nature, profitless.

The DIAGNOSIS presents no difficulty in members of a bleeder family, in whom slight joint trouble and petechiæ are as much manifestations of the disease as the more severe hemorrhages. In a large majority of cases the tendency becomes manifest at an early date. The spontaneous umbilical hemorrhages of infants are, as a rule, to be excluded, being dependent upon, or associated with, jaundice or syphilis or a mycosis (Weigert[178]). The hemorrhagic diathesis may develop in children or members of a healthy family and prove fatal, and the question in such cases always comes up, Are they instances of hæmophilia? There seems to be a desire to limit this term to cases of an hereditary nature only; but when a child shows a marked tendency to multiple hemorrhages, spontaneous or traumatic, which tendency persists and is not merely transitory, and particularly if there are joint troubles, I think that under these circumstances we have a genuine case of hæmophilia; and such a child, if he--it is more likely to be a male--survives and marries, may be the founder of a bleeder family. These are the congenital in contradistinction to the hereditary cases. In the histories of the bleeder families we frequently come back to the origin in a person born of a healthy stock in which there have been no hemorrhagic tendencies. On the other hand, single severe uncontrollable hemorrhages in children or adults are not to be ranked as hæmophilia unless there have been other features pointing to the existence of the diathesis. The literature abounds in cases of this kind, many of which are described as hæmophilia. In doubtful cases it is very difficult to decide, as in a case of Forscheimer brought before the Academy of Medicine of Cincinnati.[179] In the review of American literature we have excluded all cases in which the hereditary or congenital characters were not well marked.

[Footnote 178: _Cohnheim's Pathologie_, i. 382.]

[Footnote 179: _Cincinnati Lancet and Clinic_, 1884.]

It may be useful to put down here for the guidance of the practitioner the varieties of bleeding commonly met with, and which must not be confounded with hæmophilia:

(1) The umbilical hemorrhages of infants, due to jaundice or to syphilis hæmorrhagica neonatorum, etc.

(2) Purpura simplex, seen often in debilitated, rarely in healthy, children, usually confined to the legs, and in some cases I have seen it associated with rheumatic pains or swellings in the knees and ankles.

(3) Peliosis rheumatica, an affection which in the large interstitial hemorrhages and the joint swellings touches hæmophilia in a curious way. It too may show itself in several members of the same family.

(4) Purpura hæmorrhagica, Morbus maculosus Werlhöfii, a grave disease, 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.

Previous Next

Comments

A system of practical medicine. By American authors. Vol. 3Chapter LXIV: Part 64

0%37 min left in chapter