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)[5]
regard it as a specific leprous process, while G. and E. Hoggan[6]
had previously described it as secondary, and due to the neuritis. In
our[7] 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.
[5] Virchow’s Archiv, Bd. C. III.
[6] Archive de Physiologie, Bern. 1882.
[7] 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.