Part 40

Syphilis of the Liver.--In 1852, Gubler published an account of the general appearances in syphilitic disease of the liver in new-born children, which was distinguished especially by increase in size and weight. This increase depended, as might be expected in this stage--that of general cell-proliferation--upon a proliferation of cells from the connective tissue between the acini, or from the adventitia of the interlobular vessels, this growth becoming transformed into connective tissue. The change is quite analogous to what is taking place at the same time in the skin, the mucous membranes, and other tissues. Wilks has also described a form of syphilitic disease of the liver which corresponds to that of Gubler, and in which the whole organ is infiltrated by a new fibrous tissue, producing a uniform and general hardening.

{284} [Illustration: FIG. 8. Section of an old gumma of the liver. a, a. Central caseous tissue of the gumma. v', v'. Its vessels. l. Boundary between the central portion and fibrous zone; this line of demarcation is marked in places by an opening or cleft. t, t. Connective tissue of the fibrous zone which entirely surrounds the central part. v, v. Small vessels of this zone. c. An arteriole of the fibrous zone. f, f. Quite large biliary vessels included in the fibrous zone. t'. Fasciculi of connective-tissue fibres running parallel with the surface of the caseous part. At b and d the fasciculi of fibres of the fibrous zone penetrate into the central caseous part. e, e. Tissue of hepatic cells interrupted by bands of fibrous tissue, m, m. X 12.]

As described by Gubler, the liver in such children is hypertrophied; hard, resistant to pressure, so that it cannot be indented; elastic, so that it rebounds; creaks, but does not bleed, when it is cut into, and presents the yellow color and the semi-transparence of flint. There are seen on a yellowish ground a number of small white granulations like grains of wheat, which a histological examination shows to be formed by an accumulation of embryonic cells in the spaces which separate the hepatic acini. Injections reveal the fact that the vascular network has become almost impenetrable, the capillaries obliterated, the larger vessels diminished in calibre. Fibro-plastic matter is found throughout the organ in large quantity. In consequence of these conditions--the compression of the hepatic cells and the destruction of the vessels--the secretion of bile is stopped, and the gall-bladder is found after death to contain a pale-yellow liquid consisting of bile mixed with an excess of mucus. This form of hepatitis has thus far been observed almost exclusively in infants. Cornil {285} says that he has had frequent occasion to examine such cases of hepatic syphilis, and describes them as follows: "The hepatic acini, in the normal state, are in contact except at the prismatic spaces which are formed by their union--spaces in which the capsule of Glisson forms an envelope to the afferent portal vessels of the lobuli. It is in these spaces that the round lymph-cells form and collect into small nodules representing microscopic gummata. The cells at the centre of the new formation are sometimes granular. This neoplasm is seated about the ramifications of the portal veins, which in consequence also present thickened walls with newly-formed cells in their external tissues. The small granules above mentioned are not always visible to the naked eye, and in their places are only seen, about the perilobular capillaries of the portal vein, an excessive number of embryonic cells." In addition to this interstitial sclerosis or interstitial infiltrating hepatitis there is an inflammation of the liver depending upon the presence of gummata--gummous hepatitis--which occurs in two forms: one in which very small and very numerous nodules are present, situated along the course of the fibrous seams, the prolongation of the capsule, and another in which there are two or three large circumscribed tumors. This form of hepatitis is always accompanied by the interstitial form, although the latter may be only slightly developed. The gummata, though not infrequently found in the liver of new-born children, are more likely to develop later, at from about the eighth to the twelfth year.

Rochebonne describes the following symptoms of syphilitic hepatitis in infants: A deep wine-colored venous stain and oedema of the lower extremities, often accompanied by pemphigus; ascites due to mechanical obstruction of the circulation, as in cirrhosis; a more or less pronounced chloro-anæmic appearance of the face; and the presence in the urine of albumen and hæmato-globulin. Vomiting may occur, and constipation alternating with diarrhoea has been observed. Icterus, symptomatic of the affection, has not been observed.

Bäumler says: Implication of the peritoneal coating of the liver may be recognized by the pain in the hepatic region. In new-born children--unless, possibly, there may be some enlargement of the liver--the only local symptoms, often, are those due to peritonitis--screaming, drawing up of the legs, vomiting. In those cases it is not rare for the peritonitis to become diffuse.

Hill says: "The symptoms are mainly those of functional derangement of the organ, with alteration of its bulk."

Hutchinson has described cases in which in young persons the subjects {286} of hereditary syphilis there has been great hepatic enlargement which has subsequently wholly disappeared. He finds it difficult to believe that there is any kind of gummous growth in such cases, and feels obliged rather to fall back upon the hypothesis of mere vascular turgescence. In one such case the liver occasionally was so large as to be visible as the patient lay on his back in bed.

It seems much more likely that the enlargement is due to an exceptionally active cell-proliferation, which does not, however, go on to organization, but may be just as susceptible of absorption and resolution as are the papules or maculæ of the skin. A portion of the enlargement may be due to a passive congestion caused by the presence of this cell-accumulation.

As to the diagnosis of hepatic syphilis in infants, I am disposed to agree with Cornil, who says: "The symptoms are null, or they are identical with those of local and general troubles so often observed in children who have poor or insufficient nourishment. The only physical sign which properly belongs to hepatic syphilis is, when it exists at all, increase in the size of the liver."

Syphilis of the Bones.--Until the publication in 1870 of the researches of S. Wegner, an assistant of Prof. Virchow, diseases of the osseous system due to hereditary syphilis were either ignored or denied by the various writers upon this subject. Valleix, Bargione, Ranvier, and Guéniot had indeed recorded cases of bone disease occurring at the points of junction between the epiphyses and diaphyses and in the costal cartilages, but it remained for Wegner first fully to describe the pathological changes which occurred there, and to differentiate them from those due to rickets or scrofula. His memoirs recognized three stages of alteration in the long bones: 1st. While in the normal state the boundary of the hyaline cartilage is distinctly marked by a line which indicates the direct transformation of the cartilaginous tissue into a spongy tissue, the unaided eye being unable to distinguish a spongio-calcareous layer, in new-born syphilitic children, on the contrary, the bones are seen to have a spongio-calcareous layer interposed between the bone and cartilage, measuring two millimeters in thickness. This is a zone of calcifying cartilaginous material more extensive than in the normal state. 2d. These same changes become more distinct and more extensive. The unnaturally thick layer of calcareous material continues to grow. There is proliferation of the cartilaginous trabeculæ, abundant calcification of the cartilage, too early and irregular ossification of the intercellular substance {287} of the cartilage, and at the same time an arrest of the normal formation of bone which should be going on from the epiphysial cartilage. 3d. There is now added, by extension of these processes, a thickening of the perichondrium and periosteum at the extremities of the long bones and at the junction of the ribs with the costal cartilages. In consequence of the interference with nutrition occasioned by these changes atrophy and fatty degeneration of the cartilage-cells occur, and they form between the epiphysis and diaphysis a necrosed mass which irritates the living bone. This causes osteo-myelitis, which frequently results in a separation of the epiphyses. Occasionally pus is produced in such quantity as to perforate the periosteum, escape into the surrounding tissues, and become superficial. He terms the entire process an osteo-chondritis.

Waldeyer and Köhner, after examining twelve cases, confirm in the main these investigations of Wegner, but interpret the changes as arising rather from the formation of a gummous tissue between the epiphysis and diaphysis than from an osteo-chondritis. The tissue-death which occurs later, the atrophy of the cells, etc., they compare with the same modifications observed in syphilomata.

Parrot in a number of exceedingly valuable papers has repeated and greatly extended these observations. He places especial importance upon the formation of osteophytes, which, he says, in the first stage envelop the diaphyses of the long bones, especially at their inferior extremities. In the succeeding stage the new bony layers are more porous; a gelatinous degeneration affects the epiphysial cartilage and the spongy bones at a point where they are in contact; the epiphyses tend to separate from the diaphyses. This solution of continuity results in a characteristic pseudo-paralysis, with curvatures, abnormal twistings, and preternatural mobility of the bones, with loss of the power of locomotion. Then the osteophytes increase in size by the formation of several layers, thus enlarging the inferior extremities of the long bones. He describes the general process as consisting, first, of a periosteo-genesis--a formation of osseous tissue from the periosteum; next of a chondro-calcosis--a calcareous incrustation of cartilage; and finally of a gelatiniform degeneration and softening of the bone, with diaphyso-epiphysial disjunction.

Taylor sums up the results of his observations as follows: "In the first stage we have a simple hyperplasia of cells with irregular deposition of lime salts; in the second, an intensification of this condition; and in the third, a new element--namely, the abnormal proliferation of all the elements of the tissues, with an infiltration of granulation-tissue into the medullary spaces following the vessels."

{288} We see, then, that, setting aside minor points of difference, these observers all coincide in describing this condition as one essentially of the nature of syphilitic bone troubles with which we are familiar in the acquired form of the disease, consisting primarily and throughout of an unnatural accumulation of cell-elements, which in the later stages by their pressure produce various degenerations of surrounding structures, and which, as they occur during the process of bone-formation, are accompanied by irregular and abnormal deposition of lime salts. They especially affect the regions mentioned--the junctions of the epiphyses and diaphyses--because at that time those points are the seat of great physiological activity. Syphilis, indeed, throughout its entire course is notably subject to similar influences, as one example of which I may instance the preference displayed by the periostitis which results in nodes or in caries for the subcutaneous bones, the tibia, clavicle, cranium, etc.; or, in other words, for those which are subject to frequent traumatisms--trifling, perhaps, but sufficient to determine a slight hyperæmia, which is followed by abnormal cell-proliferation or accumulation.

The symptoms which obtain in this condition of syphilitic osteo-chondritis are as follows: The child may be attacked during intra-uterine life, and in that event the osseous lesions will probably be coincident with other syphilomata and with placental disease of sufficient gravity to destroy life. If the child is born alive, the first development of the disease will probably be noticed as a swelling at the diaphyso-epiphysial junction of one of the long bones, which in the emaciated subjects of hereditary syphilis is often visible, and can always be discovered by palpation. The bones most frequently attacked are the humerus, radius and ulna, tibia and femur, but the clavicle, ribs, sternum, and bones of the metatarsus and metacarpus are also often involved, and much more rarely the frontal and parietal. The more pronounced the syphilis of the parents, or the nearer the date of conception to the time at which their infection occurred, the more probable is it that several bones will be affected, and the more unfavorable the prognosis as respects the life of the child. Indeed, it has been noticed that "in stillborn infants and in those dying soon after birth the majority, or even all, of the long bones are affected."

The swelling is found to consist of a ring or collar which more or less completely surrounds the bone, is apt to be smooth rather than irregular, and when two bones situated near to each other are simultaneously affected may conjoin them. This condition persists during the first stage of pathologists, and passes with greater or less rapidity into the second stage, in which the swelling, the cell-proliferation, reaches its height. This may take, in cases uninfluenced by treatment, several weeks or even months. Under the use of mercurials and iodide of potassium they usually subside rapidly. During this second stage, however, owing to the proximity of the swellings to the joints, a moderate amount of synovitis is often present. This affects chiefly the elbow and the knee, but may appear in any joint. It is also readily influenced by specific treatment and well-regulated pressure.

{289} When the third stage is reached, or that of the formation of granulation-tissue, with degenerative changes of the cartilages and of the bones themselves, deformity often becomes more marked. There are unnatural curves or angles in the bones, with more or less complete separation at the point of junction. Where many bones are affected in this way, the resulting deformity is extreme and the patient may be absolutely powerless, a condition of pseudo-paralysis supervening in which the limbs lie motionless or swing about like the arms or legs of a doll when the child is carried.

When the swelling does not undergo absorption, the superjacent tissues sometimes become involved, abscesses form and make their appearance externally, extensive necrosis of the shaft of the affected bone takes place, and the little patient usually dies of hectic, pyæmia, or exhaustion. When the cranial bones are involved, the disease is apt to limit itself chiefly to the stage of osteophytic formation, the immovability of the bones probably favoring the organization of the new cell-growth rather than the production in it of inflammatory changes. The growths are met with chiefly in older children than those affected with the form of osteo-chondritis just described; they affect the periphery of the liver, and are found most usually around the anterior fontanel, and later on the parietal and frontal eminences. The sutures are sometimes completely soldered together. The osteophytes vary in thickness from a quarter of an inch to an inch, or are even larger.

The most important differential diagnosis to be made in these cases is between the rachitis of young children and the form of syphilis in question. Much difference of opinion still exists as to the relation between these diseases, syphilis being claimed, on the one hand, as having in the majority of cases a definite causative influence, while, on the other, the existence of this relation is denied. When we come to contrast the pathology of the two diseases, we can readily understand why they should be confounded, the minuter changes which occur being essentially the same--viz. cell-proliferation and accumulation, with subsequent inflammatory changes, associated with irregular deposits of lime salts.

Compare, for example, the description of the pathology of bone diseases in inherited syphilis already given (pp. 287, 288) with the following terse summary of the changes which take place in rickets in cases where no suspicion of syphilis exists, either ancestral or acquired: "The changes are more distinctly noticed at the epiphyses than in the diaphyses. Instead of the regular stages and distinct boundaries observed in the normal development of bone, there is a singular disorderly commingling of the exaggerated cartilage-proliferation and transition substance, with calcification. The cartilage-cells, stimulated to excessive multiplication, are transformed, some into bone-corpuscles, some into medullary cells, {290} and others into connective-tissue forms. The same process is in active operation in the deep periosteal layers, the material accumulating to such a degree as to add much to the thickness of the shaft."

The points of resemblance are manifest, just as they are between a syphilitic and a variolous pustule, but they end in both cases when we come to study the evolution of the phenomena either from an anatomical or from a clinical standpoint. They may be expressed as follows in tabular form:

OSSEOUS LESIONS DUE TO INHERITED | RICKETS. SYPHILIS. | | The swellings, particularly those| Rarely appear before six months, of the long bones, show | generally still later. themselves at or soon after | birth. | | A history of syphilis or evidence| No such history necessarily. of existing syphilis in one or | both parents. | | Preceded or accompanied by | No such prodromata. snuffles, coryza, and cutaneous | and mucous lesions. | | No such prodromata in most cases.| Pallor, restlessness, sweating, | nausea, diarrhoea, etc. | constitute a combination of | symptoms which often precede the | bone disease. | Cachexia absent or moderate. | Cachexia marked. | Physiognomical peculiarities of | Not present as a group. syphilis present. | | Circumscribed tumors on frontal | Cranial bones thickened in spots, and parietal bones, rarely on | usually upon the occiput. occiput. | | Ribs not markedly affected. | All or nearly all involved. | Swellings on long bones or | Extremities symmetrically extremities irregular. | enlarged. | Disease of ribs, when existent, | Nearly always so. not ordinarily coincident with | that of other bones. | | Fontanels close at usual period. | Closure delayed. | Other syphilitic symptoms | Syphilitic symptoms absent. present; enlargement of | phalanges, metatarsal bones, etc.| | Often accompanied by sinuses, | Little external or surrounding synovitis, abscesses, cutaneous | involvement. ulcers, etc. | | Generally disappears by | Usually leaves some bending of resolution, without leaving any | shaft and distortion of the permanent change. | neighboring joint. | Mortality among children in whom | Much less. many bones are involved is very | great. | | Specific treatment useful. | Of no benefit. | In the first stage there is an | This is less marked. There is exuberant calcification of the | formed, instead, a soft and ossifying cartilage, causing | non-calcified osteoid tissue. necrosis of the new-formed tissue| and a consecutive inflammation, | which terminates in the | separation of the epiphyses.|

The diagnosis of the bone lesions of hereditary exostosis can readily be recognized in a short time by noting the fact that they are stationary, {291} even if their later appearance, larger size, the absence of syphilitic history or symptoms, and the resistance to specific treatment left us in doubt.

The diagnosis from accidental separation of the epiphysis, or from fractures, may be made from the history of the case.

In cases of separation of the epiphysis, complicated with suppuration, sinuses, etc., the trouble may be mistaken for a similar condition due to non-specific inflammation. In all the recorded instances, however, the latter has occurred much later in life, is attended with much more acute inflammatory symptoms, lymphangitis, etc., and is of course without concomitant symptoms of syphilis. In both these cases there is a decided osteo-periostitis, and as so much depends on the early and vigorous use of specific treatment, it may be worth while to contrast the two forms of the disease.

SYPHILITIC OSTEO-PERIOSTITIS. | NON-SPECIFIC OSTEO-PERIOSTITIS. | Occurs in infants under three | No instance of its occurrence in months of age. | children under one year of age. | History of syphilis in child and | No history of syphilis; sometimes its parents. | a history of traumatism. | Implication of other bones. | Usually confined to one bone. | Coincident with the development | Coexists with the ossification of of the shaft of the bone. | the epiphyses. | Other lesions of syphilis: nodes,| No such symptoms. skin eruptions, etc. | | All the local symptoms | Pain, redness, and swelling very comparatively mild. | marked. | Disease sharply localized. | Involves neighboring parts. | Lymphatics of limb unaffected. | Lymphangitis present. | Beneficial effect of specific | No such effect. treatment if employed early.|

Syphilitic dactylitis in the inherited variety of the disease, as in the acquired, consists of two varieties. The one of these which usually appears earlier involves chiefly the periosteum and the fibrous and integumentary structures surrounding a joint, usually a metacarpo- or metatarso-phalangeal articulation, involving a phalanx, and is characterized by slow, almost painless, swelling and discoloration of the affected member. (Fig. 9.) This is due to a gummous infiltration which, after absorption under proper treatment, leaves the toe or finger temporarily stiff, but not permanently disabled.

The second form is a specific osteo-myelitis, with periostitis, coming on later, and often destroying the bone or the articulation involved. (Fig. 10.)