Chapter XVII: Leprosy

DEFINITION AND SYNONYMS

=Definition.=—Leprosy is a very chronic, almost incurable disease, with a protracted period of incubation (two to ten years), which sets in with indefinite prodromata of malaise, and irregular febrile attacks associated with sweating and somnolence. In nerve leprosy there may be vague manifestations of neuritis as prodromata. There are two well-recognized types of the disease. The type characterized by granulomatous proliferations in corium and subcutaneous tissues, as well as lymphatic glands, is known as nodular or skin leprosy. It shows spots and nodular infiltrations, chiefly about lobes of ears, alae of nose and region of eyebrows, with falling out of hairs of eyebrows and bearded region, and also involves extensor surfaces of forearms, dorsal surfaces of hands and feet. The palms of hands and soles of feet are almost never invaded. The other type is known as nerve or maculo-anaesthetic leprosy and is characterized by nerve thickenings, flat anaesthetic spots, chiefly of the covered region of the body, muscular palsies and atrophies, with trophic changes leading to contractures and mutilations. When the two types are associated we have mixed leprosy.

The disease is caused by an acid-fast bacillus, which has not
surely been cultivated or inoculated into animals with pathogenic
result, and which is found in extraordinary abundance in the
granulomatous subepithelial tissues of nodular leprosy and in
scanty numbers or not at all in the perineurium and endoneurium of
the ulnar, facial or perineal nerves.

=Synonyms.=—Lepra. Elephantiasis Graecorum. Leontiasis. Satyriasis. French: La Lèpre. German: Aussatz.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—There are those who consider India as the home of
leprosy, a condition corresponding to the disease having been
described in the Rig Veda, of date of 1400, B. C.

Others regard Egypt as the original focus, a disease similar to
leprosy having been described in the “Ebers papyrus” of date of
about 1300, B. C.

Any one reading chapter xiii, Leviticus, must be convinced that
the disease there described as leprosy was of a different nature.
We find statements to the effect that where the hair in the spot
is white and the spot deeper than the skin of the flesh that it
is leprosy; again, if there be a white or red rising it is not
leprosy, but if lower than the skin it is leprosy.

According to Unna the term Zaarath had a theological rather than
a medical meaning. At the same time other references in the Bible
would indicate that leprosy was more or less prevalent among the
Jews of that period.

It is very probable that the ancients confused leprosy with many
other diseases where ulceration and nodular disfigurement were
conspicuous features.

From the fact that leprosy was called the Phoenecian disease it
would seem that Asia was the real home of the disease.

It is well established that leprosy was introduced into Europe,
from Egypt, in the first century, B. C., by the returning legions
of Pompey.

As a result of the crusades, leprosy was spread widely over Europe
by the crusaders, so that in the 14th century the disease was so
prevalent, that it required approximately 20,000 leper asylums to
care for the lepers. In France alone there were about 2000 such
leprosaria.

As a result of the most drastic measures of isolation the disease
began to decrease in the 14th century and had practically
disappeared from Europe, as a whole, by the 15th century.

=Geographical Distribution.=—With the exception of a limited and
steadily diminishing number of cases in Norway and Sweden, with
an uncertain number in the Balkan region and Turkey, leprosy has
almost disappeared from Europe. Parts of Brittany and Provence in
France show cases and there are a considerable number in Portugal
and Spain.

Africa is heavily infected with the disease, especially in Central
and East Africa. In certain portions of the Cameroons (Banyang) it
is so common that one in every four persons suffers from leprosy.

Asia has many important leprosy centers, there being a very great
number in China and India. There are about 100,000 lepers in Japan
and about 3000 in the Philippines.

In 1902 there were 278 lepers in the United States, of which number
145 were native born. In 1912 there were only 146 distributed
chiefly in three centers: (1) That of the Great Lakes, there
being now 13 cases in Minnesota as against 27 in 1900; (2) among
the Orientals of the Pacific Coast, and (3) in the Gulf region,
especially about Louisiana and Florida.

There are 696 lepers in Hawaii and 28 in Porto Rico.

In South America, the disease is found in Columbia, Venezuela and
Brazil as is also true of Mexico and Central America.

In Australia the disease is found in Queensland and New South Wales.

It also prevails in New Caledonia and the islands of the Pacific.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—Leprosy is caused by an acid-fast bacillus, _Bacillus leprae_, which rather closely resembles the tubercle bacillus morphologically as well as tinctorially. It was first discovered by Hansen in 1871 and fully reported in 1874. Much of our knowledge of its characteristics is due to Neisser (1879).

The leprosy bacilli are found in profusion in the granulomatous
tissue of the corium and subcutaneous structures of the leprous
nodules, chiefly within cells called “lepra cells” and also within
endothelial and connective-tissue cells as well as lying free,
packed in lymphatic channels, the so-called “globi.”

The leprosy bacillus may be distinguished from the tubercle bacillus by the following points:

1. The presence ordinarily of huge numbers of bacilli often grouped
in packets like a bundle of cigars tied together.

It will be remembered that it is very difficult to find even a
single tubercle bacillus in a skin lesion. Leprosy bacilli form
palisade groups but not chains.

2. The leprosy bacilli stain more solidly and when granules are
present they are coarser and more widely separated than the fine
granulations of the tubercle bacillus.

3. They do not stand decolorization quite as well as the tubercle
bacillus. With 20% sulphuric acid in water they hold their color
almost as well as tubercle bacilli but with 3% HCl in alcohol they
decolorize in about two hours as against twelve to twenty-four
hours for the tubercle bacillus.

4. Leprosy bacilli have neither been surely cultivated nor surely
inoculated with pathogenic results into guinea pigs or other
experimental animals and it is by the negative results upon
cultivating or animal inoculation that we have our surest method of
differentiation from tubercle bacilli.

Leprosy bacilli are chiefly spread through the lymphatics, but
in nodular leprosy, their occurrence in the blood stream during
the febrile accessions is so constant that this route may also be
of importance. Next to the corium they are most abundant in the
lymphatic glands. They stain readily by Gram’s method.

A great amount of work has been done within recent years in
attempting to cultivate the leprosy bacillus.

In 1900 Kedrowsky culturing material from 3 cases of leprosy
obtained diphtheroids from two and a streptothrix from one.
A rabbit was inoculated first intracerebrally and later
intraperitoneally with this nonacid-fast streptothrix and, when
killed six months later, showed peritoneal nodules, from which
both diphtheroids and acid-fast bacilli, but not a streptothrix,
were recovered culturally. Injections of cultures of the acid-fast
bacilli and diphtheroids into rabbits and mice produced nodules
which when cultured showed acid-fast organisms or diphtheroids.

In 1901 he cultivated a diphtheroid from a fourth case of leprosy.

Fraser and Fletcher working with Kedrowsky’s culture produced
peritoneal nodules with the killed as well as the living organism.
They were able to produce the same results with _B. phlei_. With
emulsions of leprous nodules, rich in leprosy bacilli, they could
not produce similar lesions in the experimental guinea pigs.

Rost obtained a culture on a salt-free medium from which he
prepared his _leprolin_ by a process similar to that used for
old tuberculin. It was claimed that leprolin had marked curative
power in leprosy. Recently Williams and Rost have cultivated a
streptothrix on a medium containing milk.

Clegg, by inoculating his medium with cultural amoebae, obtained
growth of a diphtheroid organism, with acid-fast tendencies, from
the spleen pulp of lepers.

Duval, by using media containing amino-acids, as result of tryptic
digestion, brought forward two organisms, one of which was a
diphtheroid and grew luxuriantly while the other showed a slow
scanty growth and was acid-fast.

Bayon, by using placental media, isolated an organism rather
resembling that of Kedrowsky. These organisms alone responded to
immunity tests when such were made by Bayon and they alone gave
rise to tissue changes resembling those of leprosy when injected
into animals.

Professor Deycke obtained a streptothrix-like growth from the
granulomatous tissue of excised leprous nodules. The ethereal
extract from this culture gave a neutral fat which he called
_nastin_ and which is the basis of a leprosy treatment.

Quite recently and after working for eighteen months, with material from 32 nonulcerative cases of nodular leprosy, not only with media as recommended by Duval, Rost and Bayon, but with blood and serum culture media, both by aerobic and anaerobic procedures, Fraser has been unable, in a single instance, to obtain any evidence of growth from this wealth of leprosy material.

As being opposed to the possibility of culturing the human leprosy
bacillus, it may be stated that most of the experiments along this
line with rat leprosy, a disease occurring naturally in rats and
caused by an organism almost identical, as to lesions produced,
with the leprosy bacillus, have been negative. Bayon, however,
states that he has cultivated the bacillus of rat leprosy.

=Epidemiology.=—There is a consensus of opinion that every case of leprosy owes its origin to contact, direct or indirect, with some other case, but evidence as to the manner in which the disease is transmitted, or even the proof of transmission, is to a great extent lacking.

Every book refers to the inoculation experiment by Arning, of a
freshly excised leprous nodule sewn into a skin incision of the arm
of a condemned criminal. In this case a neuritis developed shortly
after the inoculation and the patient showed fully developed
leprosy three years later. Unfortunately for the value of the
experiment the man was a native of Hawaii and had lepers in his
own family. Against this experiment are the numerous instances
where physicians have inoculated themselves and others with leprous
material with invariably negative results.

Danielson inoculated himself and nine others with leprous material and later Profeta repeated the same, but without success in a single instance.

As regards those living for a long time in attendance on lepers
there have been a very few instances of the contraction of leprosy
as in the case of Father Damien at Molokai, and two instances in
Sisters of Mercy. Such cases however are most exceptional, as the
hundreds of attendants on the unfortunates continue their work for
years without showing any signs of leprosy.

It is stated that there has never been an instance of transmission of leprosy to any attendant at the Saint Louis Hospital, Paris.

There are two cases which show that those who live in close
relation to lepers may develop the disease; in one, a leper
returned to Ireland and his brother, who had never been in a
leprosy country, but who had occupied the same bed with the leper
and worn his clothes, developed the disease in about five years. A
similar case is reported from Germany.

As showing that even with intimate contact, infection is rare, it is stated that of 225 healthy Hawaiians, living in the same houses with lepers, only 4½% contracted leprosy. Even when married to lepers only 9 out of 181 healthy people contracted leprosy from their leprous mates.

In Japan, 7% of children of lepers contract the disease, 3.8% of
those married to lepers and 2.7% of people living in the same house
with lepers.

Just as with tuberculosis, in which all evidence points to the
predominance of infection in early life and its infrequency in
adult life, so does it seem to be true of leprosy. Among 10,000
lepers in the Culion leper colony, Denny notes that 35% were
brothers and sisters, 27% were cousins, 11% were children of
lepers, 7% parents of lepers, and only 1% husband and wife. This
would indicate that the relationships involving intimate contact in
childhood are etiologically most important.

One of the strongest proofs that leprosy is at least feebly contagious is that based on the disappearance of the disease following isolation of the lepers. The best instance is that of Europe, in the thirteenth and fourteenth centuries, where, with 20,000 leper asylums for isolation, the disease disappeared by the fifteenth century. In Norway, there were 2833 cases in 1856, while in 1907, there were only 438 left.

At the end of 1913 there were only 285 cases, 181 of these being interned and 104 in their own homes. The reduction is attributed to isolation.

This might have occurred without isolation because Hansen in
investigating the descendants of 160 known Norwegian lepers, who
immigrated to the North-western States of America, was unable to
find trace of a single leper among their descendants.

This and other facts militate against the views that leprosy may be inherited and the idea is generally held that if a child be taken away from its leprous surroundings after birth there is little or no likelihood of its developing leprosy.

Again, it is a well-recognized fact that leprosy is more than
twice as common among men than among women. It is probable that
the greater opportunity for contact with lepers by man is the
explanation of the greater frequency.

_Views as to Mode of Transmission._—It may be stated that nothing definite is known. There has been an idea that itch mites might transmit the disease but no proof has been advanced. Lebouf found leprosy bacilli in the stomachs of flies, which had been feeding on leprotic ulcerations, and did not find acid-fast rods in flies which had fed on persons with nerve leprosy or upon those not showing open lesions. He thinks that flies may deposit faeces containing bacilli about the nasal orifices or upon wounds of well persons, bringing about thereby their infection.

Skelton was unable to find evidences of leprosy bacilli in bedbugs
living in the beds of lepers. Paldrock also was unable to find any
evidence of leprosy bacilli in bedbugs a few hours after feeding on
leprous tissue, but did find acid-fast rods in cockroaches which
had fed on leprosy nodules, even fourteen days after the feeding.

A. J. Smith fed bedbugs on Duval’s organism and recovered acid-fast
bacilli for considerable periods. The question arises, however, as
to the significance of Duval’s bacillus for leprosy.

Acid-fast bacilli have been reported from head lice and mosquitoes,
when the insects have been feeding on leprous tissue, but little or
no evidence of any multiplication has been obtained.

For many years Jonathan Hutchinson insisted that leprosy was caused
by the eating of imperfectly cured or decomposing fish, a view
which now has no supporters.

For a time it was considered that the initial lesions of leprosy were to be found in the nasal mucosa and especially in ulcerations of the nasal septum and that it was by the atrium of the nasal mucous membrane that infection occurred.

There is no question but that the examination of the nasal mucus
for leprosy bacilli is of prime importance in diagnosis and it may
be that cases showing ulcerations of the septum are especially
dangerous when sneezing, but very few believe that leprosy is to
any extent contracted through this channel. de Azevedo examined
smears from the nasal mucosa in 59 persons who were in close
contact with lepers without finding acid-fast bacilli in a single
instance.

With a period of incubation covering from two to ten years it is
of course manifestly difficult to arrive at any correct idea as
to transmission but there is a growing belief that the free and
frequent use of soap is a decided factor in preventing infection
which may, like rat leprosy, be best brought about by continued
contact with a skin surface more or less abraded. There has been a
suspicion, but no proof, that sexual intercourse may bring about
infection.

_Rat Leprosy._—A disease occurring naturally among rats was first observed by Stefansky, in Odessa, in 1903.

There are two types: (1) Of skin and muscles, and (2) of the
lymphatic glands. In the skin form areas of alopecia are present
with thickening of the site invaded. These areas are most often on
the back of the head. Just as in human leprosy the epithelium is
unaffected, the corium however being filled with cells packed with
acid-fast bacilli, exactly similar to the picture in human leprosy.
Ulceration of these subcutaneous nodules is common.

In the glandular type the glands are enlarged and the lymph sinuses
packed with the causative bacilli.

In rat leprosy it has been found that infection of other rats takes
places as readily through slight abrasions of the skin as when
material is injected subcutaneously.

The idea is that natural infection occurs by way of the skin and
through the lymphatics. There is no evidence that insects play a
part in transmission.

Rat leprosy prevails extensively in Europe, Asia and America.
Although similar etiologically and pathologically there does not
seem to be any connection between the disease in rat and in man, as
is the case with human and rat plague.

The prevalence of rat leprosy in the various parts of the world
varies greatly; thus in Odessa 4 to 5% of the rats are infected
while in San Francisco only ⅕ of 1%.

PATHOLOGY AND MORBID ANATOMY

In whatever way introduced the leprosy bacilli tend to invade and multiply in the lymphatics of the corium and subcutaneous tissues. In response to irritation, cells of disputed type, possibly plasma cells, appear and phagocytize the bacilli in large numbers, so that eventually the outline of the cell, as brought out in acid-fast staining, is that of a mass of red bacilli.

These red-staining bodies are called _lepra cells_. In addition, endothelial cells phagocytize the bacilli and these with their bacilli, together with the free lying masses of bacilli in the lymphatic sinuses, make the so-called “globi” when seen in transverse section. The toxicity of the lepra bacillus is only slight so that we may have very large giant cells of the Langhans type and this probably explains the absence of caseation in leprosy. The arteries of the leproma, as the granulomatous mass is termed, undergo an arteritis with thickening of their walls.

The leproma is a mass of cells of varying sizes and types in a
connective-tissue framework. The infiltrations are chiefly about
the hair bulbs, sweat glands and arteries. The epidermis is
separated from the leproma by a connective-tissue layer and is
uninvolved except for a thinning out of the layer and obliteration
of the interpapillary epithelial pegs.

Incision of a leprous nodule shows a smooth glistening cut of a
yellowish to slate gray color.

In nerve leprosy the cellular proliferations in the region of the blood vessels and later in the perineurium and endoneurium cause pressure on the axis-cylinder with consequent degeneration. The affected nerves are swollen and reddish-gray in color. It is now thought that an axonal degeneration involves the cells of the anterior horns so that this, as well as the peripheral neuritis, is a factor in the muscular atrophies which are features of the disease. The sensory fibres are destroyed before the motor ones.

Leprous changes are common in the anterior part of the eye,
as of conjunctiva, cornea and iris, but rare in the posterior
eyeball. The mucosa of tongue, larynx and, pharynx is often
involved. Cartilage and bone are destroyed through pressure of the
granulomatous tissue.

The ovaries and testes may show connective-tissue increase.

Nephritis is rather common in leprosy but there is considerable
doubt whether the lungs are invaded by leprosy, except most rarely.

Next to skin, mucous membrane and nerves, the lymphatic glands show
the greatest involvement.

The liver not uncommonly in nodular leprosy and more rarely the
spleen may show connective tissue or cellular infiltrations.

SYMPTOMATOLOGY

The period of incubation of leprosy is peculiarly prolonged and is at any rate from two to five years and may extend over many years, Hallopeau having recorded a case where the disease did not develop for twenty-seven years after the patient left the infected district. The early manifestations are vague and indefinite, consisting chiefly of malaise, weariness and mental depression.

There are often noted (_a_) irregular accessions of fever (leprotic
fever), attended with rather profuse sweating, so that the onset
may be mistaken for a malarial infection; (_b_) progressive
weakness, the patient being easily fatigued with a tendency to
somnolence; (_c_) alternating attacks of dryness and hypersecretion
of the nasal mucous membrane, with frequent attacks of epistaxis,
and (_d_) various neuralgic manifestations or paraesthesias as well
as headache. These prodromal manifestations usually precede but may
accompany the outbreak of the spots.

It is the prominence of the nasal manifestations that has caused
Sticker to insist that the primary lesion of leprosy is of the
nasal mucosa, the general view, however, being that this view
is without sufficient foundation and as a matter of fact some
have recently suggested that the disease first manifests itself
in the lymphatic glands, punctures of such structures showing
bacilli rather frequently, although in less proportion than upon
examination of the nasal mucosa.

All authorities recognize two well-separated clinical types of leprosy, one the nodular, skin, hypertrophic or tubercular form and the other the smooth, nerve, maculo-anaesthetic or atrophic form.

These fairly distinct types tend to run into one another and in
such cases we have the mixed form of the disease.

Following Manson I use the terms nodular and nerve leprosy. It is usually stated that in Northern climates nodular leprosy forms about 70% of cases while, in the tropics, the larger proportion is made up of nerve leprosy.

At one time a classification of the 239 lepers at San Lazaro
Hospital, Manila, P. I., showed 97 cases of nodular, 42 of nerve
and 93 of mixed leprosy, with two cases of doubtful nature.

NODULAR LEPROSY

_A Typical Case._—After more or less indefinite and uncharacteristic prodromata the definite onset is by an outbreak of brownish red spots which later become pigmented and thickened. These spots are at first erythematous and tend to come out in crops, attended with attacks of irregular fever. They soon have the appearance of limited areas of sunburn. They vary in size from 1 or 2 millimeters to a blotch the size of the palm of the hand.

They are raised and have a preference for appearing on the lobes of
the ears, the nasal alae, the forehead, eyebrows, cheeks and chin.

The extensor surfaces of the forearms, thighs and buttocks are also
favorite sites for the indurated spots. The palms of the hands,
soles of the feet, hairy scalp, groin and axillary regions are
almost never attacked.

These spots may be hyperaesthetic at first but soon show loss
of pain and temperature sense with retention of touch sensation
(dissociation of sensation). These spots do not sweat, they remain
dry even in a general perspiration.

Following successive febrile accessions and reappearances of spots we have developed reddish-brown nodular masses, usually on the sites of the spots.

When the nodules are grasped between the fingers one usually finds
them elastic to touch. As the result of active sebaceous secretion
these nodules have a greasy appearance.

These protruding nodules may give the face a leonine appearance, hence the name leontiasis, or that of a satyr, hence satyriasis. With the development of the nodules the hair falls out of the eyebrows and bearded face. Nodules develop in the mucous membranes of the nose, mouth and larynx, giving rise to foetid discharges and obstruction of the nares, difficulty in mastication as well as in breathing and a raucous voice.

The eye is involved with frightful frequency in this form of
leprosy, there being infiltrations of the eyelids, conjunctivae,
cornea and iris, with subsequent ulcerations and loss of sight.

The nodules on face, backs of hands, buttocks, etc., may disappear by resolution but the tendency is for them to ulcerate and produce various contractions and deformities.

The glands in the region of the lesions become enlarged but do not
tend to suppurate.

Visceral involvements are not common but serious lesions of the liver have been reported.

The course of the disease is essentially chronic and if some
intercurrent affection does not carry off the patient, the end
comes in a cachexia in about ten years, the temperature gradually
falling and a state of somnolence ushering in the end.

When nerve leprosy sets in upon a nodular type the life of the
patient seems to be prolonged.

Nerve Leprosy

_A Typical Case._—The prodromal manifestations are characterized by the results of irritation of the granulomatous tissue upon the nerve fibers and are chiefly neuralgic pains or signs of sensory disturbances as formication, paraesthesias, etc. In particular, are the ulnar, peroneal and facial nerves attacked, the process very rarely extending above the knee or elbow.

Anaesthesia of the region supplied by the ulnar nerve with
contractures of the fourth and fifth fingers may be signs directing
our attention to the true nature of the disease and in those cases
where the appearance of smooth yellowish-brown spots precedes the
neuritis manifestations we may here also find anaesthesia, provided
the eruption has lasted for some time.

In brief the fully developed case of nerve leprosy shows anaesthetic spots, trophic lesions of the skin and bone, together with muscular palsies. The spots often appear singly and may be from ½ to several inches in diameter. They are not raised, have a sunburnt color and do not sweat. Instead of having a preference for the exposed parts they most frequently appear on the covered portion of the body or limbs as trunk, buttocks, scapular region, thighs or arms, although the first appearance of spots may be on the face.

These spots often look like ringworm lesions, as they have an
erythematous border with a paler center, but they are oval in
outline rather than round and there is no scaling. Bullous
eruptions, which are most frequently noted about the knuckles, are
rare manifestations of nerve leprosy. They are often followed by
ulceration.

About this time the nerve trunks begin to enlarge, especially the ulnar at the elbow and the great auricular as it crosses the sterno-mastoid muscle. The characteristic nerve enlargement is spindle-shaped or beaded.

These nerve enlargements are at first tender but later become
painless and we have extensive areas of anaesthesia and trophic
changes of the skin and nails of fingers and toes such as felons,
glazed skin, bullae, which latter on rupturing leave ulcers.

We also have absorption of the bones of the phalanges.

The phalangeal bones may be completely absorbed and a distorted
nail cap the end of the metacarpal bone (_lepra mutilans_). Owing
to the anaesthesia lepers often burn or injure their fingers and
toes. Perforating ulcers are more common in leprosy than tabes.

Muscular palsies, atrophies and contractures are more common in the face and upper extremity than in the lower extremity. We may have changes quite similar to those of progressive muscular atrophy, the thenar and hypothenar, as well as the interossei, undergoing atrophy and resulting in the claw hand. There is extension of the first joint and flexion of the two distal joints of the fingers. Such hands may function quite well. Wrist-drop is not uncommon but foot-drop is rare. Rarely Charcot’s joint condition may be observed.

Of the facial muscles the orbicularis palpebrarum is most apt to
show paralysis. The eyes are affected much less frequently in nerve
leprosy than nodular, 45% as against 85% for nodular leprosy. The
most common changes in nerve leprosy are ectropion of the lower lid
and subsequent corneal ulceration.

=Mixed Leprosy.=—In mixed leprosy we simply have a combination of
the manifestations of the two main types and as a matter of fact
the majority of cases tend eventually to assume a mixed type.

SYMPTOMS IN DETAIL

_Temperature Course._—On the whole leprosy runs an afebrile
course except for the accessions of irregular fever at the time
of the appearance of the successive crops of spots. This leprotic
fever lasts for a few days or a week or so and then the course
becomes afebrile. At such times sweating may be present and suggest
malaria. In the final stages of leprosy the patient may run a high
fever for long periods, associated with profuse sweating and loss
of weight.

_Skin._—The raised spots of nodular leprosy tend to come out in
numbers on lobes of ears, over eyebrows and on cheeks, as well as
backs of hands and forearms and on buttocks and feet. Soles of
feet and palms of hands almost never show spots. In nerve leprosy
the spots are often single and flat and often appear on parts
of body covered by the clothing, as trunk, thighs or arms. The
spots of leprosy are anaesthetic, often showing dissociation of
sensation. The indurated spots of nodular leprosy are succeeded by
tubercle-like growths. The hair falls out of the areas occupied by
the spots.

_Mucous Membranes._—The nasal mucosa is in particular studded with
nodules which later undergo ulceration. An ulcer of the septum is
often the first place from which leprosy bacilli may be obtained.
The pharynx and larynx are also involved early.

_Nervous System._—Besides the characteristic anaesthesia we have
various manifestations of neuritis, especially involving the ulnar,
facial and peroneal nerves. The affected nerves show a fusiform
enlargement and are tender. Later we have trophic changes in
skin, bone and nails of the fingers and toes. Absorption of bones
and perforating ulcers are common. Muscle palsies and atrophies,
especially the main-en-griffe, are common. The orbicularis
palpebrarum is not infrequently paralyzed. The olfactory, optic
and auditory nerves are rarely if ever involved. The reflexes are
slightly exaggerated.

Patients often complain of a sensation of cold. Some authorities
have called attention to the frequency of a mental and moral apathy
in lepers.

_The Circulatory System._—Honeij considers a high pulse rate,
especially in the morning, as characteristic of progressive stages
of leprosy.

_The Eye._—In nodular leprosy eye lesions, chiefly leprotic
nodules in conjunctivae or iris, with subsequent ulceration, are
met with at some time in the course of the disease in almost 90%
of cases. In nerve leprosy, corneal ulcerations, chiefly resulting
from paralyses of the facial muscles, with ectropion, give eye
symptoms in about 45% of cases.

_Genito-urinary Symptoms._—Atrophy of the testicles with increase
of connective tissue often result in males but data would indicate
that the procreative power of the female is but little diminished.
Lepers often die of renal complications, the kidney lesions being
rather those of amyloid change. Bacilli may be eliminated in the
urine during accessions of fever.

_The Lymphatic Glands._—These tend to enlarge and show bacilli,
but rarely suppurate.

The inguinal and cervical glands are most often enlarged.

_The Blood._—The changes, other than those of a secondary anaemia
as the disease progresses, are not characteristic. Bacilli are
present in the blood of cases of nodular leprosy quite constantly
but less so in that of cases of nerve leprosy. The bacilli are more
apt to be found in the blood at the time of febrile accessions.

DIAGNOSIS

=Clinical Diagnosis.=—It must be remembered that leprosy is very slow in development, so that for months or even years there may be but slight indications of the disease, as an anaesthetic spot or the palsy of an orbicularis palpebrarum. One should always run over the lobes of the ears or region of the eyebrows to feel for shot-like nodules.

In the making of a diagnosis the information as to possible exposure to the disease is of first importance.

The leprous spots are at first rather oily from increased action
of the sebaceous glands but subsequently become dry. In ancient
times the hypersecretion of sebaceous material about the facial
spots of nodular leprosy served as the basis of a test for leprosy,
the suspected eruption being dashed with water. If the surface was
not wetted it was a point in favor of leprosy. Of prime importance
however is the pin prick for anaesthesia, which is the most
important distinguishing characteristic, next to the finding of
the bacilli, for a leprous spot. The anaesthesia is more marked
in the center of the spot and may show dissociation of sensation.
It is very important to examine for enlargement of the ulnar or
great auricular and the earliest signs of a nerve leprosy may be
anaesthesia and a slight contraction of the ring and little finger.

Of the general diseases, which may be confused with leprosy, we have the circumscribed form of scleroderma. Such spots however are dead white in color and are not anaesthetic. The prodromal manifestations with fever and sweatings simulate malaria. Elephantiasis and Madura foot have been confused with leprosy but the marked tendency to limitation to the lower extremities and absence of anaesthesia should differentiate. Probably the most difficult disease to differentiate from leprosy is syringomyelia. Morvan’s disease is only a form of syringomyelia in which the neuralgic pains, anaesthesia of the skin and painless whitlows, with tissue loss, are features. In fact Zambaco has advanced the idea that Morvan’s disease is leprosy.

In syringomyelia the dissociation of sensation is marked, as
with leprosy. In syringomyelia, however, the upper extremities
are, as a rule, alone affected and the muscular atrophy is more
of the scapulohumeral type, with involvement of trunk muscles
causing scoliosis, than of the thenar and hypothenar eminences, so
that while the fingers may be more contracted and rigid than in
leprosy we do not get the main-en-griffe. The anaesthetic areas
of syringomyelia continue to sweat, and we may also get spastic
symptoms and speech defects in syringomyelia.

Raynaud’s disease has also been confused with leprosy.

Of the skin diseases the most important confusing lesions are
the cutaneous manifestations of tuberculosis and syphilis. In
lupus the tubercles are very much smaller, show the apple jelly
appearance, the lesion spreads peripherally, is rather purplish and
is not anaesthetic. Syphilitic ulcerations are more punched out,
do not affect the same sites and respond to syphilitic treatment
immediately. You do not find nerve enlargements in syphilis.

There is great lack of agreement as to the frequency of the Wassermann reaction in leprosy, some reporting a positive test as common in nodular leprosy while others have reported negative findings where there was not ground for suspecting syphilis. Nerve leprosy does not often give a positive test.

Fletcher obtained 22% positives in 100 cases of leprosy—28% in
nodular and 17% in nerve cases. One-third of the cases gave a
history of syphilis.

Sutherland and Mitra obtained 17 positive Wassermann reactions
in 34 nodular cases, 16 positives in 52 anaesthetic cases and 8
positives in 14 cases of mixed leprosy. The sera of 12 children of
leprous parents were negative.

The luetin reaction is negative in leprosy.

Mycosis fungoides has not the characteristic location about the
face and itches markedly and does not show anaesthesia.

Vitiligo shows an abrupt margin and is not anaesthetic.

=Laboratory Diagnosis.=—The usual procedure is to scrape a spot or nodule with a scalpel until the epidermis has been gone through and then smear out the serous exudate on a slide and stain by the Ziehl-Neelsen acid-fast method or by Gram’s stain. Twenty per cent. sulphuric acid is less apt to decolorize than the 3% acid alcohol, the leprosy bacilli being less resistant to acid alcohol decolorization than to aqueous acid solutions. There is a great variation in the resistance to decolorization of leprosy bacilli, a preparation from one case holding its color almost as well as tubercle bacilli, while material from another case may decolorize very easily.

I am partial to Tschernogabow’s technique. In this, one punctures
the subepithelial granulomatous tissue with a capillary pipette,
the end of which has been broken off by tapping the point in order
to give a cutting point, and the serum which exudes is smeared out
and stained.

Some prefer emulsifying a piece of the tissue and centrifuging and
staining the sediment. Quite recently the antiformin method of
treating leprous tissue, as for tuberculous tissue, has been used.

Many insist that the best method is to cut out small sections of
the lesion, going well into normal tissue, and putting through
paraffin and cutting thin sections and staining. Gram’s method,
counterstaining with bismarck brown, gives beautiful preparations.
For acid-fast staining first stain with haematoxylin to obtain
a histological background and then steam with carbol fuchsin,
decolorize very briefly with acid alcohol, then through absolute
alcohol and xylol.

Of the greatest diagnostic value is the staining of the nasal mucus or scrapings from ulcerations on nasal septum for leprosy bacilli. These are often found in the characteristic cigar package bundles or engulfed in lepra cells. A standard procedure is to give 60 grains of iodide of potash to cause a drug coryza, in the secretions of which leprosy bacilli may be found. However, one will have better success if the nasal secretion be obtained at a time when a natural coryza exists.

Thibault examined the nasal mucus, gland juice and blood of 30
lepers. He obtained leprosy bacilli in the nasal mucus of 20, in
the gland puncture juice of 18, and in the blood of 7.

Hollman detected leprosy bacilli in the nasal mucus of 90% of 58
nodular cases, of 67% of 6 mixed leprosy and of 45% of anaesthetic
cases, after making 329 examinations.

Leprosy bacilli are apt to be found in the blood of nodular cases,
especially at the time of the febrile accessions. The blood is
best taken in 5 or 10 cc. quantities into 1% sodium citrate in
distilled water. After centrifuging, the sediment is treated with
10% antiformin, at 37°C. for one hour. Again centrifuging, and
washing, the sediment is smeared out on a slide and stained. The
bacilli are not apt to be found in the blood of cases of nerve
leprosy.

Smith and Rivas add 10 vols. of 2% acetic acid to 1 vol. blood,
centrifuge and make smears.

Gland puncture has recently been considered as an important
diagnostic procedure in leprosy.

It must not be forgotten that while the finding of leprosy bacilli is usually very easy in the nodules of nodular leprosy it is a painstaking and discouraging procedure with the spots of nerve leprosy. Even the affected nerves, at autopsy, often fail to show bacilli. For nerve leprosy the examination of nasal mucus is of prime importance.

The _Roentgen ray_ has been utilized in the recognition of the very
early, trophic changes in bone, showing the commencing absorption
of phalanges. Neve has reported a case in which there were no
satisfactory indications of leprosy other than slight deformity of
toes and fingers but showing marked changes in the phalanges, even
to disappearance of terminal phalanx of some toes when examined
with X-ray.

PROGNOSIS

The progress of the disease is so slow that it is difficult to estimate improvement or cure. At present the possibility of a cure, with the new methods of treatment, is encouraging. There is no doubt but that many of the reported cures have simply been instances of remissions in the course of the disease for periods covering months or even three or four years. It would seem that the earlier treatment is instituted the greater the possibility of cure. There were 38 cases officially reported as cured, in Norway, from 1881 to 1885.

Nodular leprosy runs its course much more quickly than does nerve
leprosy. It is in nodular leprosy particularly that intercurrent
affections carry off the patients. Tuberculosis carries off about
23% of cases and nephritis almost 30%, while a combination of
tuberculosis and renal disease about 10%. In the remainder, the
cachexia or accidents of leprosy itself are responsible for a
large portion of the deaths. Cases of nodular leprosy are more
often carried off by kidney disease than those with nerve or mixed
leprosy.

It must not be forgotten that lepers, especially those with the
nerve form, may live for twenty to forty years.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—As was noted under epidemiology there seems to be little evidence to show that insects play any part in the transmission of leprosy. Nevertheless it would seem advisable to prevent flies from becoming contaminated with the discharges from leprous ulcerations which so often teem with leprosy bacilli. This possible method of transmission would seem more deserving of attention than the question of the taking up of bacilli from the blood by mosquitoes, bedbugs or biting flies, as the leprosy bacilli are found in the blood of nodular leprosy chiefly during the febrile accessions and very rarely in the blood of cases of nerve leprosy. In all of the ordinary insects the bacilli seem to disappear in a very short time, with the exception of the cockroach, for which reason it would seem advisable to destroy these pests, which can be easily done by sprinkling around a little sodium fluoride.

There is some evidence that scabies favours infection so that this
disease should be looked for and actively treated in endemic areas.

Leprosy tends to spread where there is marked personal
uncleanliness and close contact with lepers in overcrowded
quarters. Many authorities consider the free use of soap and water
the most important means of avoiding infection. While segregation
is generally considered the one proven prophylactic measure there
are those who question its value. There does not seem to have been
any very marked influence on the spread of leprosy among the native
Hawaiians through the enforcement of isolation of such cases.
Partial segregation at their homes has given very satisfactory
results. Where a leper is not excreting bacilli, or where acid-fast
organisms cannot be found after careful search there is no danger.
Such patients, however, should report for examination every few
months. Evidence as to contact indicates that all young children
are particularly liable to the infection, as has been noted for
children of lepers and brothers and sisters. Even if segregation
of lepers is not carried out as regards adults, it should be the
rule for children, so that infants and young children should be
separated from their leper parents or parent. A very remarkable
feature in connection with leprosy is the hysterical dread that
many communities have of a leper, when they must know or could
easily learn, that the contagiousness of the affection is so
slight, that notwithstanding our efforts, we can scarcely point to
a single instance to prove undoubted transmission of the disease
from one person to another. At any rate knowing that immense
numbers of the bacilli are given off from ulcerations and the nose,
we should guard against the dissemination of leprosy bacilli from
such sources.

=Treatment.=—Many so-called specific products, whether of the nature of extractives, as leprolin or nastin, or of bacterial vaccines, have been tried with results which have not tended to gain the confidence of conservative men. The product which has been given most general trial is nastin. This is a neutral fat, extracted from a streptothrix growth, obtained by Deycke from leprous nodules. It is combined with benzoyl chloride and is contained in ampoules containing from one-half to one-fifth of a milligram.

Wise and Minett treated 244 cases with nastin for periods of from
one to two years, the treatment having been at first supervised by
Deycke himself. It was stated that nodular cases did not seem to be
improved and that anaesthetic leprosy was not apparently influenced.

Minett mentions the efficiency of a 2½% solution of benzoyl
chloride as a nasal spray and as an application to leprous ulcers,
this treatment causing the bacilli rapidly to disappear from the
discharges of nose or ulcers. On the other hand Scott, in Assam,
reports practically 50% of cures, or cases greatly improved, in
patients treated with nastin for a year or more. He gave nastin B1
injected intramuscularly at two weeks intervals.

Salvarsan does not seem to have been of any value in leprosy.

The standard treatment for leprosy is chaulmoogra oil given internally, in capsules, in doses of 5 to 10 minims increased gradually, according to stomach tolerance, to 40 to 60 minims.

For hypodermic use Heiser makes a mixture of 60 cc. each of
chaulmoogra oil and camphorated oil with 4 grams resorcin.
Injections are made weekly, commencing with 1 cc. This dose is
increased steadily according to tolerance, but in some patients
marked reaction in the lesions, with fever, occurs after a dose of
only a few cubic centimeters has been reached.

Rogers has for some time been giving subcutaneous injections of
sodium gynocardate, the sodium salt of the lower melting-point
fatty acids of chaulmoogra oil. Finding that large doses of sodium
gynocardate could be administered to animals with safety he has
recently given intravenous injections and has substituted this
method for the subcutaneous one. For use in the treatment of
leprosy he prepares a 2 or 3% solution in distilled water and,
after sterilization in an autoclave, adds ½ per cent. carbolic
acid. The solution should be quite clear. He starts with one-tenth
of a grain and increases the dosage by one-tenth with each
successive injection up to four-fifths of a grain. He states that
this method has as great superiority over the subcutaneous one
as that has over the administration of chaulmoogra oil by mouth.
Rogers now uses a solution of 3% sod. gynocardate with 1% phenol
and 1% sod. citrate. At first the intravenous injection is with 0.5
cc. thrice weekly, which dose is gradually increased up to as much
as 5 cc.

It is possible that sodium morrhuate (cod-liver oil) may be as
efficacious as the gynocardate salt. Rogers has used _Hydnocarpus_
instead of the true chaulmoogra oil and thought he obtained better
results. One explanation of the uncertainty of success with
chaulmoogra oil is the difficulty of securing oil obtained from
proper sources. The standard treatment of leprosy in Honolulu, as
reported by McDonald, is the weekly injection of the ethyl esters
of the entire fatty acids of the whole chaulmoogra oil, with 2% by
weight of iodine, chemically combined. The treatment begins with 1
cc. injected intramuscularly, increased by 1 cc. at every second
or third injection, until a dose of from 2 to 6 cc. is reached,
according to age and weight of patient.

For internal use the mixed fatty acids, carrying 2½% iodine,
chemically combined, are given in capsule. The dose by mouth is
0.25 grams per 100 lbs. weight, three times daily, an hour or two
after meals. This is gradually increased every two weeks until a
maximum dose of 1 gm. per 100 lbs. weight is reached.

Dyer combines hydrotherapy with the administration of chaulmoogra
oil. He gives a daily bath as hot as can be borne, and, in addition
to the specific treatment, gives 1/60th grain of strychnine three
times daily.

Antileprol, a preparation of chaulmoogra oil, which is more satisfactory than oil, may be given in doses approximating 120 grains by mouth daily or 60 grains subcutaneously. Such drugs as arsenic salicylate of soda and bichloride of mercury have been used.

Thyroid extract has seemed to benefit cases of anaesthetic leprosy
in rare instances. The high frequency current with the needle
applied to the nodular lesions has been recommended by Unna. Radium
and X-rays have also been employed. There have been reports as to
the value of the antimony treatment in leprosy.

Leprosy is a disease in which improvement often occurs when the patient is placed under more favorable conditions as to food, climate, etc. Again, there is at times a tendency for the disease to abort or ameliorate without relation to treatment or environment.

Surgical treatment is frequently of use, as nerve stretching for
the leprous neuralgias. Various eye operations are necessitated
by the ectropion or leprotic iritis. The amputations of the area
involved in perforating ulcer is recommended. Tracheotomy is often
demanded for the laryngeal stenosis.

McCoy has combined carbon dioxide snow local treatment with
chaulmoogra oil. The lesions showed decrease in size but remained
bacteriologically positive.