typhoid fever but at times it may be so marked as to equal that of
malaria or even kala-azar.
The presence of rose spots as well as the marked apathetic state
and the tendency to diarrhoea should aid in differentiating
typhoid. Unfortunately for diagnosis the leucopenia and polynuclear
percentage reduction is similar in the two diseases.
In kala-azar the double temperature rise in 24 hours with the
_Leishmania_ bodies in spleen puncture material, instead of _M.
melitensis_, are differentiating.
The short course and more sudden onset of influenza and the more
marked pulmonary symptoms of phthisis should prove diagnostic aids.
Liver abscess and empyema with their tendency to anaemia and
sweating may prove confusing, but the history, leucocytosis and
location of pain should differentiate. Then too the joint and nerve
manifestations of Malta fever are absent.
=Laboratory Diagnosis.=—Eyre obtained cultures from blood from the
2d to 300th day of the disease. He recommended the taking of at
least 5 cc. from a vein and that this be done at a time when the
fever is at its maximum point—the days when the fever is at its
maximum and in the evening of that day. By taking 20 to 30 cc. in an
equal amount of citrated salt solution, as described in chapter on
blood examination, one should have as great success as had Eyre—158
positives in 235 cases or 65.4 per cent.
It must be remembered that the colonies only appear about the
fourth day, becoming quite distinct by the tenth day.
Bassett-Smith takes about 10 cc. of blood in the afternoon during
pyrexial waves and distributes this blood in several tubes of
broth. He makes plates from these tubes every day. He also
recommends the taking of 1 cc. of blood which he allows to clot and
subsequently removes the serum and adds bouillon (clot culture).
Agglutination is the chief reliance in diagnosis. As result of two
infections in his laboratory Widal uses emulsions killed by ¾% of
formalin. He uses the microscopic method in the test with dilutions
not exceeding 1 to 200. Such emulsions keep for at least a year.
In connection with agglutination tests Nicolle recommends that the
serum be separated at once and removed from the clot and Nègre
has shown that by heating the serum to 56°C., for thirty minutes,
reactions are not obtained with nonspecific sera.
Some workers prefer the macroscopic agglutination.
Complement fixation methods are of value but the application of
such tests is confined to large laboratories.
PROGNOSIS
The mortality is usually reported as 2% but there have been epidemics
where the mortality, owing to the frequency of the very fatal
malignant type, has exceeded 10%. It must be remembered however
that the invaliding connected with the long course of the disease
and protracted convalescence makes Malta fever a serious affection.
Neurasthenia, susceptibility to neuralgias, cardiac weakness and
formation of morphine habit may result from the disease.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—The danger from carriers seems slight but should be
considered.
Disinfection of excreta, in particular urine, is important.
Boiling of goat’s milk or killing of infected goats is a prime
consideration.
A rapid method of detecting infected goats is by carrying out a
macroscopic agglutination of _M. melitensis_ with the milk obtained
from goats. The lacto-reaction should be confirmed by a serum one.
=Treatment.=—There is no specific treatment generally recognized as
efficient. Recently, an anti-melitensis serum, from animals injected
with the nucleo-proteid material from the organisms, has been used
with some success.
A serum prepared by injecting horses intravenously with the
specific organism has been recommended by Sergent in doses of 50 cc.
Bassett-Smith recommends an autogenous vaccine, during the afebrile
period, in doses of from 50 to 200 millions. He thinks that the
best results are obtained with sensitized vaccines. During acute
phases the vaccine treatment is detrimental—it is only in chronic
cases that such treatment is of value. Some prefer to give doses of
10 million or so at short intervals. He also thinks yeast in 2-dram
doses to be of value. Phenacetin or aspirin may be given, but the
heart weakness makes extensive use of these analgesics dangerous.
The diet should be that for any acute disease but the protracted
course makes it necessary to have regard to an adequate food value.
Care should be taken to avoid chilling or fatigue.
Some recommend moderate use of alcoholic stimulation but this
treatment is questionable.
Cold sponging and local applications to joint or nerve involvements
are indicated.
Morphine should be employed with great caution.
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.
[Illustration: FIG. 76.—Geographical distribution of leprosy.]
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.
[Illustration: FIG. 77.—Section of spleen showing lepra cells and
lepra bacilli. × 800. By permission from Manson’s Tropical Diseases.]
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.
[Illustration: FIG. 78.—Nodular leprosy. Advanced stage with
ulceration. Leontiasis. (Van Harlingen.)]
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.
[Illustration: FIG. 79.—Nerve leprosy. Perforating ulcer of the
foot. (U. S. Naval Medical Bulletin.)]
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.
[Illustration: FIG. 80.—Nerve leprosy, showing deformities,
perforating ulcer, etc. (From U. S. Naval Medical Bulletin.)]
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.
[Illustration: FIG. 81.—Nerve or maculo-anaesthetic leprosy showing
anaesthetic spots on back (U. S. Naval Medical Bulletin.)]
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.
SECTION III
FOOD DEFICIENCY DISEASES
CHAPTER XVIII
BERIBERI
DEFINITION AND SYNONYMS
=Definition.=—Beriberi is a food deficiency disease due to the
absence from the dietary of a neuritis-preventing vitamine. It is
particularly important among the people of the Orient whose diet
is preponderatingly one of rice. In milling the grain the outer
vitamine-containing layers are rubbed off and this polished rice,
when the chief constituent of a dietary, is capable of causing, after
a period of two or three months, a peripheral neuritis.
This neuritis not only involves the nerves of the extremities but,
as well, the pneumogastric, and it is the manifestation of cardiac
disturbances which best differentiate this form of neuritis from
those due to alcohol or arsenic.
The disease is usually described under two types: (1) a wet or
dropsical beriberi, in which the vasomotor nerves are affected with
resultant general oedema and (2) a dry atrophic or paraplegic type,
in which muscular palsies and atrophies are the leading features.
Pathologically, we have a Wallerian degeneration of the peripheral
nerves with possibly axonal degeneration of the cells of the neuron
involved.
=Synonyms.=—Neuritis Multiplex Endemica, Polyneuritis Endemica,
Hydrops Asthmaticus. Japanese: Kakke.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—While modern knowledge of beriberi may be said to
date from the writings of Bontius, in 1642, yet the disease is
distinctly described by Chinese writers of the seventh century and
treated in writings of the second century and possibly referred
to in writings as ancient as B. C. 2697. It is probable that the
disease described by Strabo as occurring in a Roman army while
invading Arabia, in 24 B. C., was beriberi. While mention of the
disease may be found in Japanese writings of the ninth century it
is thought by Scheube that this relates to the disease in China and
that beriberi first appeared in Japan about the eighteenth century.
Bontius described the atrophic form of the disease, Rogers, in
1808, the serous effusions, and Marshall, in 1812, noted two types,
barbiers, when the paralysis predominated, and beriberi, when the
dyspnoea and oedema were leading features.
In 1835 Malcolmson noted that cases of beriberi assumed the type of
barbiers and vice versa, from this time the view has obtained that
the two affections belong to one disease.
The disease seems to have first made its appearance in Brazil in
1866.
[Illustration: FIG. 82.—Geographical distribution of Beriberi.]
=Geographical Distribution.=—Reference to the chart will show
3 markedly endemic centers for beriberi, one embracing Japan, a
second the Dutch East Indies (Java, Borneo, Sumatra), and a third,
involving the Eastern coast of Brazil. In somewhat less degree the
disease prevails in India, Indo-China, Malay Peninsula, Eastern
China, and the Philippine Islands. It is also found in the regions
of the East and West Coasts of Africa, and was devastating to the
laborers on the Congo railway. It has been reported from many parts
of the world among coolies from Asiatic countries. A disease of
similar nature has been noted in asylums in England and America.
Beriberi occurred among the British soldiers in Mesopotamia during
the recent war—more than 300 cases in 1915. It is interesting
to note that scurvy, and not beriberi, occurred among the Indian
troops in Mesopotamia at this time. There was no scurvy in the
British troops.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—There is probably no disease about which there exist so
many views as to etiology as with beriberi. Many of those formerly
advanced are so negatived by recent investigations that it would
seem hardly worth while to mention them. While the cause is still
unsolved attention is at present almost exclusively directed to some
deficiency of a neuritis-preventing substance in the dietary and
such studies have in large part centered about the question of such
deficiencies in certain kinds of rice.
Reserving until the last the discussion of the rice theories we may
briefly dismiss such views as those assigning bacterial or protozoal
causes with the exception of those of Manson and Hamilton Wright.
_Manson’s Theory._—Under conditions of overcrowding, filth,
warmth, moisture and lack of ventilation, as would obtain in the
forecastle of a ship carrying a native crew, the development of a
hypothetical germ is favored. This germ in its growth gives off
emanations which like alcohol act as toxins upon the peripheral
nerves. The germ itself does not infect the patient.
_Wright’s Theory._—According to this view a bacillus which was
given off in the faeces was ingested and locating in the duodenal
mucosa gave off a toxin similar to that of the diphtheria bacillus.
Instead of developing its soluble toxin in the membrane of the
region of the throat this action took place in the upper part of
the small intestines.
Of the bacterial causes may be mentioned: (1) The coccus of
Pekelharing and Winckler. This organism was supposed to be short
lived in the body and repeated infections were necessary to produce
the disease.
(2) Dangerfield held views somewhat similar to those of Pekelharing
and thought a coccus in the alimentary canal the cause.
(3) Isuzuki regarded a coccus isolated from the urine as the cause.
(4) Okata and Kokubo thought a coccus obtained from the blood to be
the infecting agent.
Various bacilli, other than that incriminated by Wright, have been
brought forward as pathogenic agents but it may be stated without
further discussion that the claims of the advocates of bacterial
causes have not been verified and are solely of historical
interest. The same statement will hold for the plasmodium-like
protozoon of Glogner which was found in the splenic blood.
_Of the chemical theories_ may be mentioned; (1) Arsenic poisoning.
In an outbreak of arsenical neuritis in England, from arsenic
contained in the glucose used in making beer, Ross diagnosed the
illness as beriberi. Subsequently, arsenic was found in the hair of
certain patients with beriberi, hence the theory which has never
been substantiated. It may be stated that a careful study of this
epidemic by Reynolds and Bury indicated that the alcoholic factor
was also operative as persons taking an equal amount of arsenic but
without alcohol, did not develop neuritis.
(2) Treutlein’s oxalate theory.—This was based on the fact that
polyneuritis gallinarum could be produced in fowls by feeding them
oxalic acid.
_Of the food deficiency theories_, the most prominent is (1) that
of Takaki, generally designated the _nitrogen deficiency_ theory.
As the result of increasing the proteid constituents of the ration
of the Japanese Navy from 109 to 196 grams, the disease was largely
eliminated (from about 32% incidence to less than 0.5%).
In the old ration the ratio of N to C was as 1 to 17—32, in the
new ration, 1—16. In looking over the constituents of the new
ration the addition of about 100 grams of beans is noted. These are
rich in vitamines.
(2) According to Fales the hypothetical germ of beriberi can only
live in body fluids deficient in potassium carbonate. The high
content of potash in potatoes made him greatly increase the amount
of this vegetable in the dietary he recommended. Fales noted scurvy
as well as beriberi in the Bilibid prisoners on a diet deficient in
potash.
(3) Deficient fat. (4) Deficient phosphorus.—It was Schaumann’s
idea that the phosphorus contained in the outer layers of the rice
grain was essential in the prevention of beriberi. While it is
now known that the beriberi-preventing substance does not contain
phosphorus, yet the idea has proven of practical value as giving an
index of beriberi-producing power of rice.
_P_{2}O_{5} Index of Beriberi-producing Rice._—If a rice contain
under 0.4% of phosphorus pentoxide it is liable to produce beriberi.
Schaumann now considers that the antineuritic substance in rice
polishings acts as an activator in the metabolism of phosphorus.
_Vitamine Deficiency._—Grijns was the first to insist that beriberi
was due to the absence in the diet of some substance essential to
proper metabolism of the peripheral nerves. His views were along the
line of our present _vitamine deficiency ones_. There are undoubtedly
many different vitamines, varying as to nature of protective
power, temperature at which destroyed, solubility, etc. McCollum
emphasizes the importance of a fat soluble A and a water and alcohol
soluble substance B for proper metabolism. This latter, usually
designated “Water soluble B,” is generally considered the same as the
anti-neuritis vitamine but there is recent evidence that this may not
be the case. The antiscorbutic vitamine is water soluble C.
_Food Poisoning as Cause._—There are other theories as to
intestinal parasites causing the disease and in particular views as
to relation of fish eating to the disease, which are (1) that it is
caused by the ingestion of raw fish, or again (2) from the eating
of certain poisonous fish.
Miura, who is the great advocate of a fish intoxication, believes
that this comes about from eating fish belonging to the Scomberidae
family. As proving this, he cites the absence of beriberi in
prisons in Japan, where no fish is allowed. He does not recognize
that it is the diet of barley 6 to rice 4 parts which is the
prophylactic factor. Barley is rich in vitamines.
RICE AND BERIBERI
There are a few points in connection with rice which should be
understood. The larger part of the rice grain is starch and
covering this central starch core we have the rather thin aleurone
layer containing the proteid and fat constituents of the grain.
Externally there is an adherent layer, the pericarp, which varies
in color from red to white according to the kind of rice. The
pericarp contains the salts. The grain is covered by the husk which
is always removed to render the rice suitable for food. Unhusked
rice is called _padi_ in India and _palay_ in the Philippines. In
the process of removing the husk (milling) the pericarp and more or
less of the aleurone layer may be rubbed off the grain. When the
milling process is carried to the extent that but little remains
except the starch the rice is termed _polished_, _highly milled_,
or _white_ rice. A process of parboiling causes the husk to be more
easily detached and the pericarp to adhere more firmly to the grain
and when milled there is less loss of the anti-neuritis principle,
which is contained in the outer layers. Such rice is called
_cured_ rice. The embryo also contains the anti-neuritis vitamine
as well as the fat soluble A one. It is also lost in milling. The
scale-like dust is termed _rice polishings_ and has curative value
for those who have developed beriberi under a diet of polished
rice. When the milling process is less complete the rice so treated
is called _undermilled_ rice or _red_ rice. Polished, highly milled
or white rice contains as a rule less than 0.4% of phosphorus
pentoxide while the beriberi-preventing rices contain more than
0.4% of this compound for which reason legislation has required
rice to have more than 0.4% phosphorus pentoxide.
Siam rice is a polished white rice which contains about 0.25%
phosphorus pentoxide and has more often been associated with severe
outbreaks of beriberi than Rangoon rice, which has about 0.32%,
this latter, however, being a well-recognized beriberi-producing
rice. Unpolished rice contains about 0.55% of phosphorus pentoxide.
Natives generally prefer the polished rice because it is clean and
free from weevils, while the undermilled kind is dirty. Parboiled
rice has a disagreeable odor.
Voegtlin has recommended a P_{2}O_{5} requirement of 0.5% for corn
products and 1% for wheat ones. Thus whole wheat contained 1.12%
while highly milled flour had only 0.114%. Fowls fed on this flour
developed polyneuritis in twenty to thirty-two days.
Whole corn contains 0.76% P_{2}O_{5}, while highly milled corn
grits has approximately 0.2%, and highly milled corn meal about
0.3%. These highly milled corn products produced polyneuritis
within from thirty to thirty-five days.
With rock ground corn meal, containing 0.7% P_{2}O_{5} the fowls
remained well.
_Experiment of Fraser and Stanton._—While there have been numerous
instances reported to show the connection between polished rice and
beriberi, when such rice was the predominating article of diet, it
will suffice to refer to the experiments of Fraser and Stanton and of
Strong.
In 1909, Fraser and Stanton experimented with 493 Javanese coolies
who were employed in building a road far removed from any village
which might introduce the factor of bacterial etiology into the
problem. They noted that the Javanese prefer white rice, and
reference is made to the fact that many cases of beriberi occurred
among these laborers in 1906, which outbreak ceased upon requiring
them to eat parboiled rice at the suggestion of Doctor Braddon.
They state that they informed the coolies of the danger of white
rice but, notwithstanding, they all expressed a preference for the
white rice over parboiled rice. For the purpose of comparison, only
one-half were allowed the white rice diet. The two parties were
quartered in virgin jungle and were isolated from each other by an
interval of 7 miles. Of 220 individuals on white rice there were 20
cases of beriberi recorded while among 273, who lived on parboiled
rice, no cases occurred.
_Prolonged Continuation of Faulty Diet Necessary._—It appeared that
a considerable period of continuance of white rice diet was necessary
before the appearance of the disease (eighty-seven days). As against
the infectious nature of the disease they note that contact of
persons on a parboiled rice diet with the beriberi cases was without
result. Substitution of parboiled rice for white rice brought about a
cessation of the outbreak.
The Philippine scouts, numbering about 5000 natives, gave 618 cases
of beriberi in 1908 and 550 cases in 1909. In 1910 undermilled rice
was substituted for polished rice and they were required to eat 1-6
oz. beans daily. No other change in their mode of living was made.
By 1913 beriberi had disappeared among them, although the disease
still prevailed among the native population in contact with them.
_Experiment of Strong and Crowell._—Strong and Crowell stated that
the object of their study was to determine whether beriberi, as it
occurs in the Philippines, is an infectious disease or whether it is
one which has its origin in disturbances of metabolism, due chiefly
to the prolonged use of polished rice as a staple article of diet.
The experiments were carried out in Bilibid prison. Prisoners, who
had been condemned to death, were informed of the nature of the
experiment and were told of the diet on which it was proposed to
place them. They were also told that they might contract beriberi.
Twenty-nine volunteered and each signed a statement in his own
dialect that he undertook the experiment voluntarily.
In general, the groups were fed for the greater part of the time
occupied by the experiments as follows: Group (1) “White rice and
extract of rice polishings and special diet.” Group (2) “White rice
and special diet.” Group (3) “Red rice and special diet.” Group (4)
“White rice and special diet.”
Of 6 men on the Group 1 diet, 2 developed beriberi. The symptoms
however, were not marked, being chiefly loss of weight,
tachycardia, slight oedema of legs and tenderness of muscles of
calves. Four of the 6 men of Group 2 developed beriberi and 6 out
of 11, in Group 4, showed symptoms of beriberi. In Group 3, only 2
in 6 developed symptoms and these consisted in case No. 13 only in
tenderness of epigastrium, paraesthesia, cardiac disturbance and
marked diminution of knee jerk. In case No. 18 there was noted only
slight cardiac disturbance and epigastric pulsation. In none of
the cases was the complete picture of beriberi obtained except in
those in which the white polished rice formed the staple article of
diet, but in one case, fed on red rice, the diagnosis of beriberi
was almost definite.
The results of their experiments with the addition of rice polishings
to the diet would indicate that whatever may be the results obtained
with extracts from this material in preventing polyneuritis of fowls
or in curing it after it has developed it is not as efficient in man
as the cheaper and more readily obtainable mongo or katjangidjo bean
or yeast.
Evidently symptoms of beriberi may also sometimes occur in
individuals fed on red rice as a staple article of diet when the
diet is very monotonous, comprising few articles and continued
for long periods of time. From the experiments it is evident that
beriberi may be produced by the prolonged consumption of white rice
as a staple diet. Of 17 individuals fed on such diet 8 developed
beriberi, all with distinct loss of knee jerk, as well as with
other marked symptoms of the disease. Symptoms appeared within 61
to 75 days after the commencement of the diet.
Vedder thinks that the red rice used in these experiments may not
have been sufficiently undermilled, as it was found most difficult
to obtain such a beriberi-preventing rice for the Philippine
scouts. As regards the lack of success with extract of rice
polishings the same author considers that a sufficient amount of
alcohol for the extraction of the vitamines was not used in the
above experiments, as he found it necessary to use 30 litres of
alcohol to 5 kilos of rice polishings. Strong and Crowell used only
14 litres of 95% alcohol to 5 kilos of polishings.
_Braddon’s views._—Prior to the investigations of Fraser and
Stanton the importance of the rice factor in the etiology of
beriberi was insisted upon by Braddon who thought that a poison
was elaborated by some organism which poison was contained in the
beriberi-producing rice. This development was thought to occur
in rice stored in damp places, but Vedder has shown that storing
undermilled rice in a damp place for a year does not cause it to
lose its anti-beriberi-producing properties.
_Endocrine Gland Disturbances and Beriberi._—We owe in particular
to the researches of McCarrison our appreciation of the important
rôle of the endocrine glands in deficiency diseases. With dietaries
deficient in vitamines he noted in birds and other animals
hypertrophy of the adrenals, atrophy of the thyroid, thymus,
testicles and ovary. The pituitary was unaffected. Vitamine
deficiency seems to impair the activity of the thyroid and to thus
favor the action of products of intestinal bacteria. It is now
accepted as important this secondary factor of bacterial infection
in all types of food deficiency pathology. Dietaries rich in fats
and proteins with sufficiency of vitamines bring about thyroid
hyperplasia. In a diet too rich in carbohydrates and deficient in
vitamines marked endocrine disturbances are noted.
The adrenals show hypertrophy on a vitamine-deficient diet and this
hypertrophy is associated with increase of the adrenalin content of
the glands. Oedema seems to be associated with adrenal hypertrophy.
McCarrison believes the oedema to be associated with increased
intracapillary pressure from the effect of adrenalin but others
dispute the explanation. The adrenalin content of the enlarged
adrenals varies; it is in excess with a diet rich in carbohydrates
and deficient in proteins and vitamines, but is below normal when the
diet is scurvy-producing. Butter, probably from its fat soluble A
content, seems to protect against oedema.
_Polyneuritis gallinarum._—The work of Eijkman in showing that
polyneuritis could be produced in fowls by feeding them on polished
rice and prevented when a diet of rice polishings was added to
the neuritis-producing rice opened the way for a vast amount of
experimental work. As regards the nature of the neuritis-preventing
substance in the rice polishings it was soon found that it had no
relation to the phosphorus content. Funk has isolated a substance he
calls _vitamine_, a pyramidine base precipitated by phosphotungstic
acid, which is present in rice polishings and seems to possess
extraordinary curative properties in polyneuritis gallinarum. Heart
muscle, egg yolk and yeast are rich in this anti-neuritis substance,
which is also present in lentils and barley.
_Various Vitamines._—The anti-neuritis vitamine is soluble in
water and alcohol and is comparatively thermostable (destroyed by
a temperature of 120°C. in two hours). It is affected by alkaline
reaction but is stable in acid solution. The water soluble B vitamine
does not seem to be destroyed by a temperature of 120°C. for two
hours, hence it may be different from the anti-neuritis one. The
antiscorbutic vitamines differ in being thermolabile, these factors
in certain foods being destroyed by a temperature of 60°C. Another
vitamine, fat soluble A, found particularly in butter, seed embryos
and leaves of plants, is a food essential. Its absence from a diet
causes xerophthalmia. Cod-liver oil and glandular organs of animals
contain it.
Schaumann considers malt as richer in the anti-neuritis vitamine
than any other article of diet, rice bran coming next. Many think
that vitamines have not as yet been separated but that they are
intimately combined with some mother substance in the food.
There is, in all probability, a large number of vitamines present
in various animal and vegetable foods, the deficiency of which in a
diet may lead to vague disorders or to well-recognized diseases,
such as scurvy, ship beriberi, beriberi or pellagra.
Schaumann considers the curative principle to be of the nature of
an activator. An increase in the ingestion of carbohydrates and
necessarily in the vitamine as well seems to produce neuritis more
rapidly than where a smaller amount is given, this indicating the
importance of these vitamines in carbohydrate metabolism.
There are those who deny this carbohydrate metabolism function of
vitamines and it is a fact that polyneuritis of fowls will develop on
a diet from which carbohydrates are excluded.
In epidemics of beriberi it has been observed that those who eat
most rice are more often attacked, thus men more frequently than
women. A temperature of 120°C. destroys the vitamine. Owing to the
absence of rice as a constituent of other than slightest importance
in the dietary of Brazilian cases of beriberi, as well as from
numerous reports of the occurrence of the disease in nonrice-eating
persons, the view that is now entertained is that not only polished
rice, but any predominating carbohydrate article of diet, which
is deficient in the neuritis-preventing substance, can produce
beriberi. Wellman and Bass have shown that such articles of diet as
sago, boiled white potatoes, corn grits and macaroni practically
parallel polished rice in the production of polyneuritis in fowls.
=Predisposing Causes.=—There does not seem to be any racial
predisposition other than that associated with the more varied
and the more neuritis-preventing diet of the white race. For the
same reason beriberi is more prevalent among the poor than among
the prosperous classes of countries where the disease exists
extensively.
It is customary to consider as predisposing causes bad hygienic
surroundings, such as occur in jails, camps, etc., as well as
the influence of warmth and dampness of the atmosphere. Beriberi
is more common among men than women and affects most commonly
individuals between 15 and 30 years of age. Physical exhaustion,
excessive grief, digestive derangements, abuse of alcohol and
tobacco are considered to have a bearing in the production of
the beriberi symptoms. Surgical operations may be followed by
manifestations of the disease.
=Epidemiology.=—Inasmuch as the experiments of Strong force us to
the conclusion that the disease is not infectious, the study of the
prevention of the disease would appear to rest almost exclusively in
the question of a neuritis-preventing dietary.
In this connection Heiser, in the Philippines, has reported that
with a diet in which polished rice was contained the monthly death
rate at the leper colony at Culion was approximately 100, the
majority of these deaths being from beriberi. As a result of the
substitution of unpolished rice, about 1909, the monthly death rate
fell to less than 20 and of these none were from beriberi.
Toward the close of 1911 there was a great shortage of the rice
crop and the Philippine government bought quantities of rice in
order to protect the people from extortionate dealers. Much of
this rice was polished rice. The use of this polished rice was
commenced at Culion in November, 1911. In January, 1912, there
were 35 deaths, of which 2 were from beriberi. In February 86
deaths with 36 from beriberi and in March 82 deaths with 60 from
beriberi. In February the use of polished rice was discontinued
and unpolished rice substituted. In April the deaths had fallen to
25 with 3 from beriberi and, subsequent to that month, deaths from
beriberi cases developing at Culion ceased to be reported.
As regards the length of time necessary for the production of
the symptom-complex, Strong’s experiments show that beriberi was
produced in from sixty-one to seventy-five days. In Fraser and
Stanton’s work no case developed under eighty-seven days and many
of the cases did not develop for 120 to 160 days. Hamilton Wright
considered that the incubation period for his toxin-producing
bacillus was ten to thirty days.
PATHOLOGY AND MORBID ANATOMY
In polyneuritis gallinarum, Vedder and Clark are of the opinion
that there may be two vitamines involved, the absence of one from
the dietary causing the neuritis, while that of the other leads to
general prostration and cardiac degeneration, so that there may be
other factors in the production of beriberi than the degeneration of
the peripheral nerves and involvement of the vasomotors.
Furthermore, extract of rice polishings rapidly cures the cardiac
condition as well as the dropsy, but not the paresis; while Funk’s
vitamine base, which will cure the paralysis, will not affect the
cardiac disorder.
The blood of beriberics in the acute stage, has been shown to
contain a substance capable of profoundly influencing the vasomotor
functions, causing venous engorgement and a fall of blood pressure.
In deaths from wet beriberi the tissues are very moist so that
incisions tend to fill with fluid. There are generally present
pleural and in particular pericardial effusions. Serous fluid
in the abdominal cavity may also be present. The lower end of
the stomach and the upper portion of the small intestines, in
particular the duodenum, show marked congestion with more or less
abundant haemorrhagic extravasations. Some authorities do not admit
the existence of this duodenal congestion so insisted upon by
Wright.
The oesophagus is usually congested as may be also the pharynx and
the larynx.
Next to the peripheral nerve degenerations, to be later considered,
the most important lesions are found in connection with the heart.
All chambers of the heart show a dilatation with hypertrophy
as well as dilatation of the right ventricle in cases that
have lasted for some time. The heart muscle has the faded-leaf
appearance indicative of fatty degeneration. Microscopically there
are segmentation and vacuolation of the fibres. The lungs show
congestion and at times present the characteristics of pulmonary
oedema. The kidneys are congested but show only exceptionally
parenchymatous or interstitial changes. As would be expected, the
back pressure in the right heart gives a dilatation of the central
vein of the liver lobules which at times is productive of atrophy
of the adjacent liver cells. The muscles supplied by the affected
peripheral nerves show more or less atrophy according to the
duration of the disease.
Microscopically, the affected fibres show a loss of striation
with a colloid degeneration. These changes are more marked in
beriberic residual paralysis. The key to the disease is in
the changes present in the peripheral nerves. While these may
appear normal yet histological examination shows varying nerve
degenerations from slight medullary degeneration in a few fibres to
complete destruction of the nerve, giving a Wallerian degeneration
(vacuolation and formation of myelin droplets in the medullary
sheath with fragmentation of the axis-cylinder).
While it is usually stated that the central nervous system (brain
and cord), remains uninvolved yet we note axonal degeneration in
the cells of the nuclear centres of the affected peripheral nerves
as shown by convexity of the cell sides, dislocation of the nucleus
and disappearance of the tigroid substance. The striking feature of
the pathology of beriberi is the involvement of the vagus nerve and
there is evidence of degenerative changes in the cells of the vagal
origin in the floor of the fourth ventricle.
Various investigators have shown that in fowls marked peripheral
neuritis can exist long before clinical manifestations appear
and that typical cases of beriberi may show striking improvement
following vitamine administration, notwithstanding the continued
existence of peripheral nerve degeneration. For such reasons Vedder
thinks the more important changes to probably belong to cells of
cord and brain.
McCarrison has noted striking changes in the endocrine glands in
avian polyneuritis, particularly hypertrophy of the adrenals and
atrophy of the other glands of internal secretion. He attributes
the oedema to increase in adrenalin content. Shimbo has reported
adrenal hypertrophy in 14 human cases of beriberi.
SYMPTOMATOLOGY
It is well to remember that beriberi is but a form of multiple
neuritis which in many cases shows only motor and sensory
disturbances of the lower portions of the upper and lower extremities.
In fact an extensive epidemic of arsenical neuritis, or, to be more
exact, a neuritis in which both alcoholic and arsenical factors
were operative, was regarded by eminent authorities as beriberi.
The key to beriberi, however, is the peculiar and striking selection
of the vagus nerve in the degenerative processes as well as those of
the peripheral nerves of the extremities. It is vagal involvement,
giving disturbances of heart particularly and lungs in less degree,
which chiefly differentiates beriberi from other forms of multiple
neuritis.
Another peculiarity of beriberi is the tendency to vasomotor
involvement as shown in the patchy areas of oedema.
_Epidemic Dropsy._—Beriberi is typically a nonfebrile disease.
There is, however, a disease with fever, called epidemic dropsy,
which seems to have a similar etiology to beriberi. It also shows
the symptoms of a peripheral neuritis plus cardiac disturbances. In
fact Pearse has maintained the identity of the two diseases. Greig
considers epidemic dropsy as resembling ship beriberi.
The first record of epidemic dropsy was during a famine in Southern
India in 1877. Outbreaks again occurred in 1902 and 1907. The fact
that it is a disease which often shows a house infection has caused
the advancing of a theory that the bedbug transmits the disease.
While greatly resembling beriberi clinically the following points
of difference are usually noted by those who hold that it is a
distinct disease entity.
1. The presence of fever, which rarely exceeds 102°F. and is
usually only about 99° to 100°F.
2. An erythematous rash upon the oedematous portions of the
extremities.
3. The frequent generalized oedema, which suggested the designation
dropsy for the disease, cannot be differentiated from wet beriberi.
4. The neuritis manifestations are slight or absent. There may
be formication of the feet but anaesthesia is wanting. The vagal
involvement gives cardiac disturbances. There is anaemia.
_Infantile Beriberi._—There is also a condition in nursing infants
which would be difficult to recognize if unaware of the existence of
this type of beriberi. It is called _infantile beriberi_.
In 1898 Hirota first noted the existence of a condition in infants
nourished by beriberi mothers which has more recently been
carefully studied by McLaughlin and Andrews and to which the name
infantile beriberi is now generally given. In the Philippines it is
called “taon.” Clinically there is restlessness, vomiting, altered
voice, increased heart action, oedema and cyanosis. After death
there is found a marked hypertrophy and dilatation of the right
side of the heart with no change of the left side. The peripheral
nerves also show the lesions of beriberi of adults but of less
intensity.
The disease most often shows itself in an acute form, the child
rather suddenly being seized with great pain, crying constantly and
soon becoming cyanosed. Death, which may occur in a few minutes or
hours, is often thought to be due to meningitis, although there is
no fever or true convulsions. There is only rigidity of the body.
Less frequently the disease appears in a chronic form in which
vomiting and constipation are most marked. There is often a history
of the loss by the mother, who herself may have only a rudimentary
beriberi, of several children from this disease.
The infants improve rapidly when other infant feeding is
substituted for the mother’s milk. An extract of rice polishings
gives striking results in these cases.
_Asylum Beriberi._—The beriberi outbreaks which have frequently
been reported from European and American camps, prisons and
asylums do not differ from the cases one may see in the
classical distribution of the disease among the rice-eating
populations of the Orient. The cause is the same, a deficiency
in beriberi-preventing vitamines, and the symptoms are similar.
These vitamines may be deficient in the rice or other cereal or
proteid food supplied. Again they may have originally been present
in sufficient quantity but later destroyed by too great heat or
otherwise.
=Types of Beriberi.=—The ordinary clinical division of beriberi
is into (1) _wet or dropsical beriberi_ and (2) _dry or atrophic
beriberi_. At the same time, in a typical case, we find such
a combination of the vasomotor disturbances which lead to the
oedematous or dropsical manifestations of wet beriberi, and likewise
of those of peripheral nerve involvement causing more or less
development of muscular palsies or atrophies, as seen more strikingly
in dry or atrophic beriberi, that it does not seem advisable to
employ such a division.
In fact typical cases of wet or dropsical beriberi after a profuse
diuresis may change in a short time, as Manson has so aptly stated,
from a bloated carcass to little more than skin and bones and
assume all the appearance of a case of dry or atrophic beriberi.
Even Vedder, who states that from a theoretical standpoint wet and
dry beriberi may be considered separate pathological processes
(deficiency in the anti-cardiac degeneration vitamine rather than
the anti-neuritis one), is inclined to believe it inadvisable, from
a clinical standpoint, to consider the one type apart from the
other.
One sees cases which combine the features of dry and wet beriberi
which can best be designated _typical beriberi_. Again we see cases
where the vagal and vasomotor involvement is so marked that the
patient resembles a man with acute nephritis plus all the evidence
of extreme cardiac decompensation. Such cases may be designated
_fulminating_, _pernicious_ or better _cardiac_.
Again we observe cases which from the start show little if any
oedema and very slight cardiac involvement, but with marked motor
disturbances as shown by muscular atrophies and palsies. The
sensory changes are not so marked as the motor ones. Complete
anaesthesia is rarely present, it is rather paraesthesia and
blunting of sensation which characterize the sensory phenomena.
This is usually designated the _atrophic_ or _paraplegic_ type.
_Rudimentary or Larval Beriberi._—Scheube recognizes a rudimentary
type and it must have been the experience of every one in the tropics
that these indefinite types of beriberi are quite common.
In such cases there may be nothing more than some weakness of the
legs with vague manifestations of blunting of the sensation or
variation of the reflexes. At times there may be marked anaesthesia
in the region over the shin bones.
Many of these cases show cardiac palpitation on exertion and at
times we may note slight evidences of oedema about the lower part
of shin bone or dorsum of the foot. It is the frequency of such
cases that causes physicians in the tropics to consider almost
any affection showing neurological manifestations as of beriberi
nature. A careful study of the neurological features of cases in
the tropics will show that many of these cases are not beriberi but
rather the common cosmopolitan diseases of the nervous system.
=A Typical Case of Beriberi.=—The patient first complains of
weakness and heaviness of the legs, particularly after fatiguing
work. There is also noted a sense of fullness and tenderness in
the epigastric region. The slightest exercise brings about cardiac
palpitation and more or less dyspnoea.
As the symptoms of peripheral neuritis become more prominent we
have hyperaesthesia of the calf muscles so that squeezing these
muscles gives rise to rather marked pain. The thenar muscles or
those of the forearm may also be more or less hyperaesthetic.
Attention has been called to a circumoral anaesthesia.
An examination at this time will probably show an active patellar
reflex, some oedema over the shin and malleoli, possibly extending to
the dorsum of the foot, with partial anaesthesia in the oedematous
areas. It is a blunting of sensation as though a layer of cotton
were interposed between the skin and the examining instrument. Other
favorite sites for the oedema are the sacral and sternal regions.
Occasionally sharply defined oedematous patches may be observed,
particularly on the arms.
The exercise attendant upon the physical examination will probably
cause a rather marked cardiac palpitation. The pulse is usually rapid
and its rate is markedly affected by the slightest exertion. The
systolic pressure is low.
The anaesthesia noted in the lower extremities soon tends to show
itself about the back of the hands and the finger tips, so that it
may be difficult for the patient to button his coat. There is also
weakness of the grip. The temperature is normal and the mind is
entirely clear. The results from a blood examination are practically
negative, although later on there is the blood picture of a secondary
anaemia.
In cases where the oedema is more marked and generalized and when
pericardial or other effusions are developing we find a diminution
in the amount of urine, but with an absence of albuminuria.
Later the case may show a dropsical condition more or less resembling
nephritis, but with only slight scrotal oedema. At the same time
there will be found a dilatation of the right heart with blowing
systolic murmurs and equal spacing of the heart sounds. There may be
marked pulsation of the veins of the neck. At this time the patellar
reflex may be diminished and the anaesthetic areas more extensive.
This condition of wet, dropsical or oedematous beriberi may be
fairly rapidly succeeded by a disappearance of the oedema with, as
a result, the making more striking of the muscular atrophy incident
to the neuritis of the peripheral nerves. In this, the atrophic,
dry or paralytic beriberi, the _jongkok test_ is of value. With the
hands over the head the patient squats down on the calves of his
legs and attempts to rise—something impossible for the beriberic.
At this time the patellar reflex probably cannot be elicited and
later on there will be found foot and wrist-drop with atrophy of
muscles. With complete foot-drop, the reactions of degeneration
will be found.
A combination of the dry and wet types of beriberi is often described
as the mixed type.
It must always be remembered that the course of the ordinary case
of beriberi is essentially chronic, running over months or years.
=Acute Pernicious Beriberi.=—This is the fulminating type of
beriberi in which the marked involvement of the vagus overshadows
the other but less manifest phenomena of the disease. In some cases
the signs of peripheral neuritis may be quite prominent before the
fulminating onset of the cardiac manifestations, there being almost
a total lack of disturbance of the vasomotor system. Again we may
have slight if at all demonstrable motor or sensory disturbances but
with marked oedema. It should be borne in mind that this development
of cardiac disturbance with its fatal tendency may develop even
in a case of rudimentary beriberi. It is a common experience that
cases considered as mild types may, in a few hours, show cardiac
involvement and terminate fatally with striking suddenness.
There is apt to be marked epigastric tenderness or even distress
coming on with the onset of the acute cardiac involvement. It may
be so extreme that the patient dreads the slightest palpation of
his epigastrium. From a marked palpitation and praecordial distress
evidences of the dilatation of the right heart become prominent.
Indications of tricuspid insufficiency are seen in the pulsating
jugulars and cyanosis. The cardiac dullness is greatly increased
to the right and various abnormalities of sounds and rhythm may be
observed. There is also dyspnoea and a sensation of constriction
of the chest (beriberic corset). These are the cases which give
as horrible a picture of death as one ever sees. In the final
struggle for breath and praecordial agony of the last stages of
decompensation in old heart lesions we have a more gradual course
in a more asthenic patient. Acute pernicious beriberi may run its
course in a strong, vigorous patient in a few hours. In some cases
we have paralysis of the diaphragm.
=Paraplegic and Rudimentary Types.=—The rudimentary type has
already been considered and it would be impossible to draw a line
between slightly developed paraplegic cases and rudimentary ones.
The paraplegic cases show the weakness of feet and hands going on
to wrist and foot-drop. There is also marked blunting of sensation
of feet and hands which gives one the impression of ataxia when the
patient tries to button his coat.
[Illustration: FIG. 83.—_A_, Mixed Beriberi. _B_, Wet Beriberi. _C_,
Dry Beriberi. (From Jackson’s Tropical Medicine.)]
There is atrophy of muscles so that the grip of the patient
is enfeebled. This partial anaesthesia also accounts for the
pseudoataxic gait in which the element of muscular weakness is
prominent as opposed to the vigorous heel stamping gait of the
ataxic tabetic. The patient drags the toes and leans forward on a
cane when walking, thus suggesting the tripod.
It is the typical steppage gait of degeneration of the lower motor
neurones. It is a flaccid, atrophic paralysis of the muscles.
There is no involvement of the sphincter.
_Beriberic Residual Paralysis._—Hamilton Wright has used the term
beriberic residual paralysis to indicate cases which, in the course
of convalescence and favorable regeneration of axis-cylinders and
more or less return to a normal condition, become subject to some
factor lowering the vital forces and body resistance and experience
a return of the beriberi manifestations. To use a common expression
the patient has a set-back and the favorable progress to complete
recovery is temporarily in abeyance.
Symptoms in Detail
_Nervous Symptoms._—The most common symptoms are those connected
with degenerations involving the peripheral nerves of the
extremities. The motor nerves are more involved than the sensory
ones, there being rarely complete anaesthesia, but rather a
blunting of sensation as though a piece of cloth were interposed
between the examining instrument and the skin. At first there is
weakening of the muscle power as shown by the grip of the hand
or weakness of foot muscles. In more advanced cases we may have
foot and wrist-drop. Hyperaesthesia of the muscles is prominent,
especially that of the calf muscles. The unsteadiness of gait is
not true ataxia as the patient does not clearly show the Romberg
sign. It is muscular weakness rather than incoördination.
The Argyll-Robertson pupil is absent. The gait is the steppage
one of peripheral neuritis, the patient walking as if extracting
one foot after the other from clinging mud. Later on, when other
muscles than the foot extensors are involved, the gait becomes a
shuffling one. The mind is entirely clear. The vasomotor phenomena
are often marked as shown by patchy or most extensive development
of oedema and serous exudates. The knee-jerk is usually absent.
Fibrillary twitchings may be observed in beriberi as well as in
progressive muscular atrophy. The extensors of arms and legs are
more markedly affected than the flexors. The cardiac symptoms are
really connected with vagal involvement.
_The Cardio-respiratory Symptoms._—Owing to involvement of
the vagus the inhibitory apparatus is deranged so that we have
palpitation and rapid pulse rate both of which are markedly
increased by the slightest exertion.
The blood pressure is below normal. Shortness of breath is the
earliest feature of respiratory trouble. This may go on to marked
thoracic oppression and dyspnoea.
Aphonia may be present in acute pernicious beriberi and probably
indicates laryngeal palsies. Such cases are usually fatal.
Pulmonary congestion and oedema always accompany the terminal right
side dilatation of the heart which is responsible for the cyanosis,
pulsating jugulars and various murmurs. The pulmonic second sound
is accentuated and may be reduplicated. The rhythm of the heart
sounds is replaced by the equal spacing of embryo-cardia. The
diaphragm may be paralyzed as may also happen to the intercostal
muscles.
_Digestive and Urinary Symptoms._—Those who considered beriberi
as an acute infectious disease were disposed to note frequently
evidences of toxaemia as manifested by nausea, vomiting and
epigastric distress. As a matter of fact these symptoms only become
very prominent in pernicious beriberi and may well be connected
with the cardiac decompensation. However caused vomiting is of
unfavorable prognostic import.
The amount of urine is markedly decreased when oedema is advancing
but is succeeded by a polyuria when this diminishes. If albumin
should be present it is not connected with beriberi but some other
condition.
_Other Features._—There is nothing characteristic about the blood
other than a slowly developing anaemia.
Oedema is the most striking feature of wet beriberi. When slight
this oedema may only involve the pretibial-region or sternum.
Circumscribed areas of oedema may be present on the upper parts of
the body as neck and trunk.
Hydropericardium is the most frequent of the exudates into serous
cavities. Fever is almost always absent except in epidemic dropsy.
DIAGNOSIS
When the case is one of mixed type with the oedema, cardiac
involvement and signs of peripheral neuritis the diagnosis is
readily made. A diagnosis of nephritis is often given the wet type
of beriberi and locomotor ataxia the dry form, by those who have not
in mind the possibility of the disease existing in an oriental crew
after a long voyage.
The urine in beriberi is as a rule normal and there are no
peripheral nerve disorders in nephritis. Chagas has noted that a
quartan form of malaria gives rise to oedema about the ankles and
is often mistaken for beriberi by the physicians of the Amazon
region.
The cardiac manifestations of beriberi differ from those of
valvular disease in that the murmurs are muffled and there does not
exist the definite areas for the location of the murmurs of the
various valvular lesions. The rapid development of a pericardial
effusion is also against valvular heart disease.
The absence of lancinating pains, typical Romberg sign and
Argyll-Robertson pupil should differentiate from tabes.
The tripod gait of beriberi takes its name from the wide separation
of feet and use, with the hands, of a cane in front. It is a steppage
gait instead of the ataxic one of tabes. On account of the lack of
power to raise the toes in walking, the beriberic lifts the hip and
swings to one side in order to avoid scraping his toes.
In progressive muscular atrophy the palsy attacks the hand first
and in a more advanced case showing the main-en-griffe there would
also be deltoid involvement. Of course beriberi may show the
main-en-griffe characteristic but the greater involvement of the
feet with vagal phenomena differentiates.
_Ship Beriberi._—A disease of importance on Scandinavian sailing
ships to which the designation “ship beriberi” has been given
resembles beriberi in that we have oedema particularly of the lower
extremities and at times generalized so that a case would appear to
be one of wet beriberi.
More or less dyspnoea and cardiac palpitation are features of
the disease as of beriberi. In fact death often is the result of
acute cardiac paralysis. The striking point of difference is the
generally reported absence of manifestations of neuritis and Nocht
in an autopsy of a case failed to find evidence of degeneration of
the peripheral nerves.
Another point of distinction is that once the ship arrives in port
and a diet of fresh meat and vegetables is substituted for the one
of sterilized canned meats and desiccated and preserved vegetables,
the patient recovers rapidly so that in one or two weeks there is
no sign of the disease remaining. Beriberics improve at once when
put on a curative diet but the damage done the peripheral nerves
makes complete recovery a matter of weeks or months. Nocht is of
the opinion that ship beriberi is closely related to scurvy as he
found sore gums and haemorrhages into muscles in some of his cases.
He also notes that even in true scurvy there may be cases of dropsy
without the spongy gums and haemorrhages. Dropsy plus sore gums is
not infrequently noted in the beriberi-like affection of the men of
the French fishing fleet off the Newfoundland banks.
Schaumann believes that ship beriberi is due to an acute deficiency
in phosphorus, a chronic deficiency causing beriberi. It is
probable that this disease is caused by a deficiency in certain
vitamines, these being destroyed in the sterilization of canned
meats or by drying vegetables.
_Scurvy._—It will be remembered that in scurvy, which is the classic
food deficiency disease, we have spongy, swollen gums, loose teeth,
oedema about ankles and, in particular, haemorrhages into skin at
site of hair follicles and tumor-like haemorrhages into subcutaneous
and muscular tissues. Haemorrhages into the mucous membranes are not
uncommon. The heart shows marked palpitation and weakness.
The scurvy vitamine is much less stable than the beriberi one. It
is contained in fresh foods only, drying destroying it.
In connection with the question of multiplicity of vitamines
monkeys fed on rice will develop beriberi while if fed on a bread
deficiency diet they develop scurvy.
In Mesopotamia the Indian troops suffered greatly from scurvy
but not from beriberi while the British troops had many cases
of beriberi. From July to December there were 11,445 cases of
scurvy among the Indian forces and 104 cases of beriberi among the
British. During this period the British ate white biscuits, tinned
meats and horse flesh. This latter protected them from scurvy but
the Indian troops would not eat the fresh meat but ate barley flour
instead. The antiscorbutic vitamines are sometimes designated as
water soluble C vitamines.
_Rand Scurvy._—In investigating the endemic scurvy on the Rand,
in South Africa, Darling noted hypertrophy and dilatation of right
heart. Such cases often showed vagal degeneration. Pathologically,
these cases were closely related to beriberi, but clinically, they
showed spongy gums, and haemorrhages elsewhere. The knee-jerks were
always exaggerated.
_Infantile Scurvy._—As differing from infantile beriberi, we have
in infantile scurvy, which is attributed to the use of sterilized
milk instead of fresh milk, a tendency to separation of the
epiphyses from the shafts of the bones and extreme sensitiveness
to any movement particularly of the legs. A markedly anaemic and
asthenic condition is also characteristic. The chief lesion is a
subperiosteal blood extravasation.
Milk contains several vitamines some of which, as the growth
vitamine, are, destroyed in boiling; others, however, are not
destroyed until subjected to a temperature of about 120°C.
_War Oedema._—In those areas of Europe where famine conditions
were approached during the great war a condition of weakness and
oedema was noted by many observers and to this symptom-complex
various designations were applied such as war dropsy, war oedema,
etc. The oedema was more marked than would be true in ordinary
cases of starvation so that such factors as consumption of large
amounts of water and salt in the thin soups so prominent in the
dietary, plus hard work, must have been additional causes.
The oedema was most common in the feet and legs, at times extending
to the thighs and trunk, and in about one-half the cases involving
the face. Marked muscular weakness and alimentary disturbances
were common. There was dyspnoea on slight exertion with a slow
pulse, but cardiac disturbances were not features of the disease.
The urine was pale, of low specific gravity and free of albumin.
There was reduction of red cells and a tendency to leukopenia.
These cases showed marked emaciation upon the disappearance of
the dropsy. As is well known the deficiency in fats was marked
in Central Europe so that it was to be expected that ocular
manifestations should be frequently noted, deficiency of fat
soluble A being the exciting cause of xerophthalmia. The cases
tended to recovery under proper diet and hospital care.
Probably the most important conditions to consider in differentiation
of beriberi are the peripheral nerve involvements caused by alcohol
and arsenic.
In alcoholic neuritis there is the history of alcoholic excesses,
long-standing digestive disorders and tremors of hands, lips and
tongue. Chiefly characteristic, however, is the mental involvement,
such cases almost always showing loss of memory and defective
mental concentration.
Mental symptoms and tremors are practically absent in beriberi and
we have here the marked feature of vagal involvement plus vasomotor
phenomena.
In arsenical neuritis we have an early puffiness under the eyelids
and pigmentation of the skin which first shows itself in areas
normally pigmented. A dysenteric syndrome may also be present.
There would be less chance of confusing lead palsy as this chiefly
involves the upper extremity. Punctate basophilia, lead colic and
the blue line on the gums should differentiate.
In diphtheritic palsies the muscles of the soft palate are involved
in more than 75% of cases. Ocular palsies are also not infrequent.
In lathyrism we have a history of the eating of the chick-pea
(Lathyrus sativus) or other vetches, as may occur in times of famine.
Pain in the back, weakness of the legs and symptoms of spastic
paraplegia appear. The spasticity differentiates. The heart is not
affected.
It may be stated that there is no laboratory diagnosis for beriberi.
PROGNOSIS
There is no disease in which one should be more conservative in
making a favorable prognosis than in beriberi. A case which seems
to be progressing toward recovery may suddenly develop cardiac
disturbances and die in a very short time.
We now know that a change to a beriberi-preventing diet is
practically curative.
The mortality rate varies in different countries and in different
epidemics, so that we have death rates varying from less than 2 per
cent. to those exceeding 50 per cent. In acute pernicious beriberi
the prognosis is almost surely fatal.
The epidemic of beriberi which prevailed at Manila in 1882 seems to
have been attended by a great mortality, this having been as high
as 60% during the early part of the outbreak.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—It must be remembered that not only is rice, from
which the neuritis-preventing vitamine has been removed by excessive
milling, productive of beriberi but that the same applies to other
cereals which have been similarly deprived of their vitamines.
The same result may be obtained by the employment of excessive
sterilization for canning.
Fresh meat is as valuable as fresh vegetables in prophylaxis but if
either kind of food be subjected to excessive heat, as is the case
with tinned meats, etc., they not only do not prevent beriberi but in
a negative way are beriberi-producing.
While boiled beef is heated throughout, with more or less complete
destruction of vitamines, roast beef does not sustain a temperature
above 70°C. in its interior, hence the greater portion of the
vitamine content is present in such meat.
It is possible that moulds may deprive cereals of their vitamines
so that spoiled cereals may be beriberi-producing. There have been
many reports both from asylums and prisons which would indicate
that the employed and the patients or prisoners lived on the same
ration yet the guards or nurses failed to develop beriberi, which
disease was prevalent among the inmates. Such statements rarely
stand the test of investigation. The same is true of pellagra.
Many of the reported outbreaks of beriberi among those who were
enjoying an abundant ration have been found to be connected with the
almost exclusive consumption of expensive canned meats and vegetables.
As the beriberi vitamine is apparently important in carbohydrate
metabolism, a greater ingestion of carbohydrates demands more
vitamine, hence an increase in carbohydrates, without corresponding
increase in vitamine-containing foods, may bring on beriberi where,
before the increase in carbohydrates, there was an absence of
beriberi.
In connection with the development of beriberi it must always
be kept in mind that debilitating conditions such as unhygienic
quarters and overexertion, as well as disease conditions (malaria,
ancylostomiasis, etc.) are factors of importance. In military forces
excessive drills should be stopped. The fatigue factor is to be kept
in mind in this as in other food deficiency diseases.
A combination of barley, which is rich in vitamines, with the rice
is important in oriental countries, thus a diet containing 6 parts
barley to 4 parts rice and used in Japanese prisons, on account of
its cheapness, not only prevented beriberi but cured the disease in
beriberics entering prison.
There is no doubt but that legislation against rice which contains
less than 0.4% of P_{2}O_{5} is a valuable measure of prophylaxis.
Polished rice has lost in P_{2}O_{5} as well as in vitamines.
Heiser has proposed that an excessive tax be placed on polished
rice with free entry for the unpolished article. The following
suggestions of Vedder in connection with prophylaxis would seem to
be worthy of consideration in pellagra as well as in beriberi.
1. In any institution where bread is the staple article of diet, it
should be made from whole wheat flour.
2. When rice is used in any quantity, the brown, undermilled, or
so-called _hygienic rice_ should be furnished.
3. Beans, peas, or other legume, known to prevent beriberi, should
be served at least once a week. Canned beans or peas should not be
used.
4. Some fresh vegetable or fruit should be issued at least once a
week and preferably at least twice a week.
5. Barley, a known preventive of beriberi, should be used in all
soups.
6. If corn meal is the staple of diet it should be yellow meal or
water-ground meal, i.e., made from the whole grain.
7. White potatoes and fresh meat, known preventives of beriberi,
should be served at least once a week, and preferably once daily.
8. The too exclusive use of canned food must be carefully avoided.
McCarrison has noted the value of onions even in a diet in which
protein and vitamine constituents are sufficient. The onions seem
to inhibit the growth of putrefactive bacteria.
=Treatment.=—The most important treatment is that of the
substitution of a diet containing the essential vitamines for the
beriberi-producing one. In carrying this out regard must be had
for the customs and tastes of the race concerned. Thus fresh beef
may be excellent for some people but objectionable to others.
Eggs, particularly the yolk, are very valuable as is also true of
unsterilized milk. Extract of rice polishings has given splendid
results in infantile beriberi but does not seem to have been as
efficacious in the disease in adults. Yeast has great curative value.
An extract of yeast known as _marmite_ has achieved reputation
when given in doses of 20 grains daily. Seidell has recently used
an autolyzed brewers’ bottom yeast. By treating this material with
Lloyds’ reagent he has extracted the vitamines so that instead of
having to give 200 cc., a dose of 10 grams of the concentrated
product suffices.
Malt extract is very rich in vitamines and liver seems to have a
higher content than beef muscle. Fat soluble A vitamine is abundant
in glandular organs but scarcely present in the beef of our
markets—this is probably true of water soluble B. Heart muscle is
about on a par with liver. Germinating wheat and beans seem to have
special value in treatment as well as prophylaxis.
In the treatment of a case care must be had not to allow a patient
with any cardiac involvement to sit up in bed as this may cause
sudden death. Braddon considers atropine hypodermically as of value
in cardiac types of cases.
Amyl nitrite inhalations or injections of 1% solution of
nitroglycerine are indicated when there is evidence of extreme
cardiac dilatation. Venesection is also to be kept in mind. Cardiac
tonics are of less value than rest, diet and venesection.
In the feeding of such patients only small amounts should be given
at a time to avoid epigastric distress. Again carbohydrates should
be restricted as there is evidence that excess of carbohydrates as
well as vitamine deficiency may be concerned in the disease. The
bowels should be kept open with salines. Mineral oil tends to keep
down intestinal putrefaction which is a factor of importance.
Strychnine is usually given as a routine treatment in the less
acute cases. With muscular atrophy massage is of prime importance.
Electrical stimulation is also usually employed. With the palsies
there is great danger of contractures so that even the bed clothing
should not rest upon the paralyzed feet. Even splints may be
necessitated.
CHAPTER XIX
PELLAGRA
DEFINITION AND SYNONYMS
=Definition.=—For a time it seemed as if the old idea that pellagra
was connected with a dietary defect, chiefly as regarded some factor
in a preponderating diet of maize, had been replaced by one assigning
as cause some infectious process, probably protozoal, possibly
bacterial.
The important advances recently made in the study of beriberi have
tended once more to swing the pendulum to the food deficiency
etiology. The latest views assign to food deficiency the basic
etiology, but regard some other factor, possibly an infectious one,
as secondarily operative.
The disease is essentially chronic with periodic exacerbations but
may run a rather acute course with a rapidly fatal termination. The
trend of symptoms consists of (1) mild neurasthenic manifestations
in the winter to be followed in the spring by (2) disturbances of
the alimentary tract, consisting of stomatitis, burning sensations
going up the oesophagus, gastric eructations and recurring
diarrhoeas. (3) In addition to the neurological and alimentary
tract symptoms we have the third and diagnostically the most
important group, those of the cutaneous system. The pellagrous
eruption is characterized by strikingly symmetrical, sharply
delimited patches of erythema, resembling sunburn. The sites of
preference are backs of hands, extending up the forearms, bridge of
nose or neck. The neurasthenia tends to pass into a toxic psychosis
or even a confusional insanity.
=Synonyms.=—Maidismus, Alpine Scurvy, Asturian Leprosy, Mal de la
Rosa, Mal del Sole.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Strambio considers some of the references of
Hippocrates to refer to pellagra but Castellani and Chalmers state
that after searching the writings of Hippocrates they have been
unable to find any references to a disease showing a resemblance to
pellagra.
The first definite description of the disease is generally credited
to Casal who, in 1735, described the disease as it existed in the
Asturias.
In his writings he notes that the peasants lived chiefly on corn
and that they rarely had fresh meat.