CHAPTER V.. Pathological Anatomy of the Maculo-anæsthetic Form.

PATHOLOGICAL ANATOMY OF THE MACULO-ANÆSTHETIC FORM.

The maculæ exhibit generally the same anatomical characters as do the nodular lepromata, viz., infiltrations with round cells, epithelioid and spindle cells. The difference between them is quantitative; in the macular infiltration the number of bacilli are less. We will describe the microscopical appearance of macules of different duration.

In a recent (three weeks old) macule, microscopical examination showed cord-like and rounded infiltrations of the cutis, with round and epithelioid cells, mostly arranged around the vessels. There were pretty numerous bacilli lying between and also definitely in, the cells; here and there were found little collections of bacilli or bacillary granules, with one or more nuclei--small globi--in their neighbourhood, which in size could not be compared with those found in the tuberous form. Specimens hardened in perosmic acid showed unaffected nerve fibres, which the leprous infiltrations did not implicate. Gold preparations showed a marked increase in the number of Langerhans’ cells in the epidermis, which, indeed, we expected, since we agree with Ranvier in considering them as wandering cells, and not as nervous elements. Definite changes in the cutaneous nerves were not evident.

Microscopical sections from an older spot (perhaps two years old) show here and there infiltrations in the cutis--especially around the vessels, consisting of epithelioid, round and spindle cells. Bacilli were found here and there--one or two in each infiltration. In the lumen of one small vessel we found a collection of round cells, with a bacillus among them; and on the inner side of the wall of another vessel we saw a similar appearance. Gold preparations of this macule, which was definitely anæsthetic, showed slight changes in the small nerve twigs in the cutis, less marked precipitation of the gold salt in the nerve fibres, and a number of Langerhans’ cells.

Sections from a very old anæsthetic macule showed only very slight infiltration along the vessels; the cells were mostly spindle-shaped; only a few were round or epithelioid. In most of the sections no bacilli were found; in some, one or two distinct bacilli and some granules, taking the same stain.

The maculæ are therefore like the nodules, leprous infiltrations of the cutis, consisting of round epithelioid and spindle cells, the latter being more numerous the greater the age of the macule. These infiltrations appear to proceed from the vessels. Lepra bacilli are always present, but are most numerous in the younger macules. In young, not as yet anæsthetic, macules, the nerve twigs appear unchanged; in the older ones they are usually affected. Langerhans’ cells are, according to our view, wandering cells, and their number is probably dependant on the inflammation.

We have only had the opportunity of examining the nerves in this form of the disease in old cases, and have not found bacilli in them, but merely great increase of the interstitial connective tissue and disappearance of the nerve fibres. Dr. Arning has, however, as is well known, found bacilli in a piece of ulnar nerve which he removed during life from an anæsthetic patient. Our results, therefore, correspond with the proposition put forward above, that the leprous affection disappears, and that the anæsthesia is a result of the atrophy of the nerves caused by secondary shrinking. We found on a mutilated finger the collateral nerve almost completely transformed into fibrous tissue, not a single medullary fibre being evident. In a case where on account of joint disease (which proved to be tubercular) we amputated, the small periosteal nerve twigs were much degenerated; in another, where the foot was amputated for gangrene, the small peri-articular nerves also showed degeneration.

Danielssen found, in some cases, changes in the spinal cord which, using the methods of investigation then at his disposal, he regarded as degenerations and inflammations of leprous origin.

Armauer Hansen, Neisser and Leloir have not been able to find any leprous affection of the cord. The cases with changes in the cord, described by Langerhans and Steudener, were, in our view, not leprosy. Tschiriew’s case, Lepra tubero-anæsthetica, presented no marked changes.

Looft has found, in two cases of maculo-anæsthetic leprosy, degeneration of the posterior columns, atrophy of the posterior roots and fibrous degeneration of the spinal ganglia, with disappearance of the medullary fibres, and changes in the nerve cells. In these two cases the affection appeared to be primary in the ganglia, and secondary in the cord. Lepra bacilli were not found in either case, but Chariotti found them once in the cord, and Suderkowitsch in the spinal ganglia.

From all this we can only conclude that the cord is affected in some cases, in others not; definite clinical symptoms are absent, and where they suggest a central cause, they may be equally well ascribed to a peripheral neuritis.

The lymphatic glands related to the affected skin are swollen, but not nearly so much so as in nodular leprosy. After death one usually finds the glands but little swollen, and their appearance presents nothing characteristic. In only one case of maculo-anæsthetic leprosy have we found the inguinal glands distinctly leprous, and that two years after the disappearance of the macules. This indicates in the first place that the affection of the glands is due to the same cause in this as in the nodular form, and secondly, that the leprous affection of the glands may last longer than that of the skin. In the same case we found indefinite traces of leprous affection of the liver and spleen, unfortunately so indefinite that we cannot say with certainty whether the liver and spleen are affected with leprosy in this form of the disease. The case occurred in the pre-bacillary era.

The muscular affections, paralysis and atrophy, play a prominent rôle in the maculo-anæsthetic form of the disease, and the anatomical examination of the muscles is of great interest since some (Neisser) regard it as a specific leprous process, while G. and E. Hoggan had previously described it as secondary, and due to the neuritis. In our examination of various stages of muscular atrophy, we have found that the changes begin with a multiplication of the nuclei of the Perimysium intern., which becomes thicker and thicker; at the same time the muscle fibres become thinner, they retain their transverse striation, and some break up into discs. The greater the thickening of the perimysium the thinner become the muscle fibres, so that one must regard the process as an atrophy due to pressure. The intra-muscular nerves showed interstitial neuritis.

Virchow’s Archiv, Bd. C. III.

Archive de Physiologie, Bern. 1882.

Zeitschrift, par D. C. Danielssen, Bergen, 1891.

Where the atrophy was very pronounced, as in the small muscles of the hands and feet, the muscular fibres had completely disappeared, and only fat and connective tissue remained. We found no bacilli, not even in sections of very early stages of the process, where the larger nerve branches, relating to the part, contained numerous ones, either in so-called mixed or in true tuberous cases. We must therefore with Hoggan regard the muscular affection in leprosy as a secondary one, caused by neuritis. We have tabulated at the end of this work the results of thirty-six post-mortems on maculo-anæsthetic lepers (see TABLE II, page 138).

In those thirty-six cases we find simple meningitis twice, tubercular meningitis once, solitary tubercle in the cerebellum once, and hydrocephalus internus twice. The protocol notes nothing further.

The spinal cord twice showed macroscopic changes (thin and atrophic once, thickening and hyperæmia of the lumbar cord once).

The most of these brains and cords, which are entered as normal, were unfortunately only examined macroscopically.

Two cords thoroughly examined by Weigert’s method showed degeneration of the posterior columns.

The peripheral nerves were probably examined in all cases, but only the results of a few of the examinations are noted.

The lungs were found tubercular thirteen times, the intestine four times, once without the presence of pulmonary tuberculosis being noted, this making fourteen cases of tuberculosis out of thirty-six--almost exactly 39 per cent. In the nodular form we had thirty-six undoubted tubercular cases out of eighty-nine--rather over 40 per cent. Possibly, and indeed probably, some insufficiently described cases in this form were also tubercular, but the frequency of tuberculosis is so nearly equal in both forms, that there is no ground for supposing that the particular form of leprosy has any relation to the development of tuberculosis. Under precisely similar conditions, in our institution, the nodular and maculo-anæsthetic cases were pretty equally attacked by tubercle. If Leloir means to say that tuberculosis is much rarer in the maculo-anæsthetic form, than in the nodular, it is certainly not the case in our leper hospitals.

So far as concerns the necrosis of the bones, the panaritii and periostitides, we have found in them nothing specific; we have often sought for bacilli, but always in vain. Pyogenic cocci, usually the staphylococcus aureus, we have found both microscopically and in cultivations.

The mutilation of the bones may occur from concentric atrophy alone, as demonstrated by Prof. Hjalmar Heiberg (Klinisk arbog, III). The phalanges of the hands and feet, the bones of the metacarpus and metatarsus, and even the carpal and tarsal bones, diminish in all their dimensions, evidently from trophic changes, the result of the neuritis.

We have been able to examine anatomically a few of the cases of articular affection referred to above, but we have not seen instances of the acute affections on the post mortem table. R. Thoma has described clinically and anatomically a case of lepra tuberosa (Virchow’s Archiv, Bd. 57), in which first the elbow, and later the knee joint, was affected. Examination of the knee joint showed an inflammatory irritation of the nature of hæmorrhagic gonitis. Where we have noted joint affections in the maculo-anæsthetic form we have only noted a condition of hydrops. The chronic affections we may indicate as tubercular and tropho-anatomical. Tuberculosis attacks the joints of lepers by no means infrequently, as is easily explainable in the case of those already tubercular, by the frequent traumata to which the anæsthetic and paretic lepers are exposed. The carpal and tarsal joints are most frequently affected; but we have also seen the knee and elbow tubercular. The process is exactly the same, as in those who are not lepers. Chronic trophic joint affections are by no means so rare as was formerly believed. Prof. H. Heiberg has (loc. cit.) drawn attention to this, and has described a foot which resembles that described by Charcot as pied tabétique. According to Heiberg a characteristic of these leprous tropho-neurotic joint affections is swelling and laxness of the capsule of the joint, a wearing away and atrophy of the ends of the bones, or periostitis ossificans, and hypertrophy of the ends of the bones, which is especially seen in the tarsal and metatarsal joints. We have been able to confirm these results of Heiberg’s, and have also seen in such an ankle, growth of the synovial membrane with villous projections; the capsule of the ankle joint was loose and lax, the talus smooth and oblique, the cartilage worn away; and marked outward subluxation of the foot was present. Other older spirit preparations showed changes in the joint capsule, which was flabby and loose or thickened, and further, slight irregular thickening of the synovial membrane, and thickening of the ends of the bones.

We have also in some cases examined the tendon sheaths; but never, even when contraction had existed for a long time did we find any anatomical changes, which pointed to a tendo-vaginitis. Leloir and Wolff have noted this clinically, but we have been unable to confirm their observation.

The pemphigoid bullæ we have repeatedly examined, and never found lepra bacilli in their contents; both microscopically and on culture we have found only pyogenic cocci, usually the staphylococcus aureus. Müller found (according to Neisser, Virchow’s Archiv, Bd. 103) lepra bacilli in the contents of a pemphigoid bulla. This was probably a mere accident. For other morbid changes found in maculo-anæsthetic leprosy the reader is referred to TABLE I, page 128.

Maculo-anæsthetic leprosy is therefore characterized by an infection of the skin and nerves directly caused by the lepra bacillus, and by secondary tropho-neurotic affections of the muscles, bones, and joints, the skin and organa sensus.

As is clear from the description of the two forms, the leprosy bacillus is found in the leprous products in both, though in much greater quantity in the nodular than in the maculo-anæsthetic form. The course of the two differs; in that in the nodular form eruptions constantly recur, and thus the affected areas are much more numerous than in the maculo-anæsthetic. Whether the liver, spleen, and testicle are attacked in the latter form we cannot as yet say with certainty. In one case of maculo-anæsthetic leprosy, we noted an affection of the throat exactly corresponding to that constantly present in the nodular form, and in another we found the inguinal glands affected with leprosy in a manner similar to that in the nodular form. In the maculo-anæsthetic form eruptions are also present, but they are by no means so frequent or so severe as in the other. Both forms may recover. As we have frequently noted in the description of nodular leprosy, the bacilli in the leprous products break up into granules which finally disappear, and there remains of the leprous products only a scar in which nothing leprous can be recognised. Occasionally this takes place in all the affected parts, and there remains only a widespread anæsthesia, the result of the nerve affections; and in the maculo-anæsthetic form this is the regular termination of the disease. In both cases the leprosy is completely healed.

We are thus enabled to see how complete is the parallel between the two forms. The course of the disease, especially the eruption, gives to it evidently the character of an infectious disease. In the nodular form, where the bacilli are present in millions or milliards, the eruptions or auto-infections are frequent; in the maculo-anæsthetic form, where their number is comparatively insignificant the eruptions are rare.

Does this difference between the two forms depend on a difference in the virulence of the bacilli? This readily suggests itself. But if so, this virulence is capable of very rapid changes. We have seen a case of maculo-anæsthetic leprosy, which probably arose by inoculation from a very severe case of nodular leprosy, since the patient some years before the outbreak of the disease had for a long time shared the bed of a nodular leper. In this case the virulence of the bacilli must have been at once diminished on their inoculation on another organism. And since it also happens that a maculo-anæsthetic case may on a fresh eruption become nodular, the bacilli must be able by cultivation in the organism to re-acquire their power. Both are possible, but the virulence of the bacilli seems to depend, not so much on any constant character of their own, as on the soil in which they live.

Now it is a remarkable fact that in certain regions in Norway the nodular form predominates; in others the maculo-anæsthetic does not indeed predominate, but is present almost as frequently as the nodular. The maculo-anæsthetic cases are more numerous in the eastern districts, where the climate is dry; the nodular in the western, along the coasts where the climate is moist. And in this western division there is a region where the climate is not nearly so moist as in the division generally, and here the proportion of maculo-anæsthetic cases is distinctly higher, as may be seen by referring to TABLE III, page 144.

Sogn lies in Nordre Bergenhus, and is an inland fjord with a rather dry climate. Söndfjord and Nordfjord lie nearer the coast, and have, especially the former, very damp climates.

We have already noted that the leprous nodes are most frequently found on the exposed parts of the skin, and it is quite possible that the form is determined by climatic influences.

As the TABLE shows, males are more affected than the opposite sex, and this too may depend on climatic influences.

It is also possible that the bacilli always possess the same virulence, and that it is solely dependant on the soil in which they live, whether they multiply freely or no. But it is impossible to say anything definite on this, so long as we are unable to cultivate the bacillus, and so long as we can only refer to the conditions in Norway; and nowhere else have we such definite statistics of the disease and its form as to justify us in drawing any conclusions.

We must, therefore, for the present leave in suspense this most important and interesting question of the virulence of the Lepra bacillus, since we possess no experimental proof of any attenuation.