PATHOGENESIS AND ETIOLOGY
At the outset it may be stated that there is no longer any reason to
doubt that adult scurvy and infantile scurvy are one and the same
disease, having an identical pathogenesis. For many years, far longer
than the facts warranted, there was discussion whether Barlow's disease
was true scurvy or merely a form or a complication of rickets, or
perhaps a distinct hemorrhagic disease. This question may be relegated
to the past, so that we may proceed to consider the pathogenesis of
scurvy in the infant and in the adult under a common heading.
There is no need of studying all the theories which have been advanced
to account for scurvy. They have been manifold and most of them have
died a natural death. For many years the _potassium deficiency theory_,
suggested by Garrod, gained wide acceptance. That scurvy should be
attributed to a lack of this salt is readily comprehensible in view of
the abundance of potassium in the antiscorbutic foodstuffs, the fruits
and the vegetables. It was not long before it was evident that this was
not the correct solution, as the salts of potassium served neither to
prevent nor to cure scurvy. This theory was accordingly modified to
include only organic potassium. Experiment, however, failed to support
the validity of this hypothesis, and it was gradually abandoned.
Another theory which had a short but popular career was the _citric acid
theory_, which was maintained vigorously by Netter. This explanation
seemed logical in view of the marked potency of the citrous fruits, and
particularly when it was shown that human milk contains a greater
percentage of the salts of citric acid than cow's milk, and that some of
these salts are lost in the course of heating. This hypothesis withstood
neither the practical test nor chemical investigation. It was found that
the various salts of citric acid, either singly or in combination, are
unable to cure scurvy. This treatment has been employed repeatedly on
man and on animals with little or no success; we also have resorted to
it in vain. It was shown, furthermore, that it rested on an insecure
chemical basis, as boiled milk contains but 0.1 g. per litre less citric
acid than raw milk--an amount which is negligible from a therapeutic
point of view.
Before considering what may be termed the prevailing theories, a few
lines must be devoted to the _acidosis theory_ championed by Sir Almroth
Wright. According to this writer scurvy is due primarily to an excess of
acid compared with alkaline food.[5] A theory of this nature was open to
verification, and soon collapsed when put to the test. It was found, in
the first place, that an addition of alkali was unable to cure
experimental scurvy. It may be added that we have found it of no value
in infantile scurvy. Holst and Froelich pointed out that potatoes and
peas, two excellent antiscorbutic vegetables, have an alkaline and not
an acid ash; that adding hydrochloric acid to dandelion juice improves
rather than diminishes its potency; that 1 g. of cabbage, which suffices
to protect a guinea-pig from scurvy, does not contain sufficient alkali
to neutralize an acid state; and, finally, that scurvy is not
encountered in the well-established acidosis of diabetes.
[5] The cases on which Wright based his theory were soldiers who
developed scurvy during the siege of Ladysmith. It is probable that the
men were suffering from starvation, purpura and dysentery. That they did
not have scurvy is proved by the fact that they were cured by giving
lactate and bicarbonate of soda.
Let us turn to some of the current theories of the etiology of scurvy.
For years many have held to the _toxic theory_, believing that poisons
either were consumed in the food or formed in the intestine by means of
bacterial action. At present this view is held by the minority. The
situation in this respect may be compared to that of beriberi, about
which there is also no consensus of opinion, a minority attributing it
to the action of an unknown toxin.
A consideration of the clinical course of scurvy sheds but little light
on this aspect, and can be interpreted as well for as against the action
of a toxin. The nervous system, which is well known to be particularly
vulnerable to toxins, is but slightly affected--the cardiorespiratory
phenomena (indicating an involvement of the pneumogastric nerves), the
occasional changes in the optic disks, and the abnormality of the tendon
reflexes constitute the aggregate. In a general way it may be stated
that the symptoms resemble those brought about by poisons of various
kinds--the cottonseed poisoning in swine, the toxic products of the
wheat embryo, or even mercurial poisoning in man.[6] The nervous
symptoms, especially the irritability of the heart, remind one of the
enterogenous intoxication or enterotoxic polyneuritis described by Von
Noorden. Such analogies are interesting and suggestive, but can be
accorded little weight in deciding the question at issue.
[6] In chronic mercurial poisoning the following suggestive symptoms
occur: anemia, bleeding and spongy gums, loosening of the teeth, a
quickened pulse, ulcers of the extremities. At times mercury attacks the
nervous system, producing palsy. The resemblance is heightened by the
fact that calcium metastases have been found in the muscle in
experimental scurvy (Hart and Lessing) comparable to those
characteristic of mercurial poisoning.
If a toxin is to be regarded as the proximate cause of infantile scurvy,
the question naturally arises as to the nature of the toxin. Is it
exogenous or endogenous? There is sound basis for believing that the
hypothetical poison is not introduced preformed in the food. In the
first place, infantile scurvy frequently develops in babies who receive
milk of the very best grade indeed, in contradistinction to rickets,
this is not preëminently a disease of the poor. Furthermore, there is no
relation between the concentration of the food mixture and its liability
to induce scurvy. For example, if among a large number of infants
receiving pasteurized milk from a common source, some are given the milk
diluted by one-half, others given it diluted by one-third, and still
others whole milk, the last group will show the least tendency to
scurvy, which we should not expect were the poison contained in the
food. Nor is it at all uncommon to encounter scurvy in an infant which
has been fed with a very dilute milk mixture. Another side of this
question should, however, be mentioned--stale pasteurized milk is more
apt to produce scurvy than the freshly pasteurized, but here again the
injury is in inverse ratio rather than in direct ratio to the amount
consumed. There are reports of adult scurvy having been occasioned by
decomposed food, such as Torup's investigation of Nansen's polar
expedition, but the diet had not been faultless in other respects. The
experiments of Jackson and Harley, who produced scurvy in monkeys by
feeding tainted tinned meat, cannot be unreservedly accepted, as they
are substantiated by no pathological examination of the bones, and the
diarrhoea and the blood and mucus in the stools do not suggest simple
scurvy.
Of those who held to the toxic origin of scurvy the majority had in mind
an endogenous toxin, although the conception of the nature of this
poison varied greatly. The minority report of the American Pediatric
Society states that "scurvy appears to be a chronic ptomaine poisoning
due to the absorption of toxins." Neumann considered scurvy a chronic
poisoning, formed probably from the albumin of the milk, and considered
the fact that the infant refused to take the harmful food as weighty
evidence of its toxic nature. Kohlbrugge included scurvy in his group of
"fermentive diseases," due to the overgrowth of harmful bacteria in the
intestine, which are normally restrained by the acid reaction of the
chyme. McCollum and Pitz, on the basis of a study of experimental
scurvy, suggested that as the result of a break in the metabolism it
might be due to the retention of fæces and consequent absorption of
toxins. Still more recently Gerstenberger suggested that as the result
of the break in the metabolism of carbohydrates, a defunctioning
substance, possibly oxalic acid, is produced, which has a strong
affinity for calcium.
It is of no avail to discuss these various hypotheses--the formation of
intestinal toxins--except where they are based on observations which can
be tested and controlled. This is true solely of _the relation of
constipation to scurvy_, and we shall confine ourselves therefore to a
consideration of this aspect of the question.
There can be no question whether retention of fæces of itself can bring
about scurvy; this is excluded by the marked instances of constipation
frequently encountered among thriving babies. The majority of bottle-fed
babies and a large number of the breast-fed suffer from a greater or
less degree of constipation. On looking over our records of infantile
scurvy from this point of view, and comparing them with non-scorbutic
infants, we have not been able to note a characteristic distinction.
Some of the infants had normal stools, others suffered from
constipation, while the records of a great number showed occasional
loose stools. Furthermore, in cases of latent or subacute infantile
scurvy, it was of no moment whether a laxative was given or whether
constipation was induced by means of opium. The report of the American
Pediatric Society shows that the majority have had a similar experience;
the bowels were regular in seventy-four instances, irregular in fifteen,
constipated in one hundred and twenty-six, and diarrhoeal in
seventy-seven. In this connection, it may be pointed out that the
preparation termed "malt soup," the diet which in our experience has
been most frequently associated with scurvy, is essentially laxative,
and, on the other hand, that one of the most potent antiscorbutics is
potato, which has no definite laxative property. It may be added, as
noted elsewhere, that scurvy developed in infants in spite of their
receiving cod liver oil or olive oil for long periods. It is evident,
therefore, that the retention of fæces is not the essential factor in
the etiology of scurvy. Its secondary rôle, especially after scurvy has
developed, will be considered later in this chapter.
In order to elucidate this question Torrey and Hess made a study of the
relation of the intestinal flora to the scurvy of guinea-pigs and of
infants. In guinea-pigs they found in the intestinal tract merely such
bacteria as are encountered on the oats and hay fed these animals. The
bacteria were few in number and hardly any were actively proteolytic.
Furthermore, there was no change in the flora on adding antiscorbutic
food, although the scorbutic symptoms disappeared. Recently Givens and
Hoffman, as the result of a similar study, have come to the same
conclusion. The investigation of infants led to similar results, and is
illustrated in Table 1. It will be seen that the infants were all on a
high carbohydrate diet, and that in two instances the flora was
compared, not only during the active scorbutic process, but after orange
juice had been given for a week or more. The bacteria were such as one
should expect on a diet rich in carbohydrates; putrefactive organisms
were present only in small numbers; and in the case in which they were
most numerous (S), they had disappeared upon the subsequent examination,
although the scurvy had become more marked. It is evident, therefore,
that in the scurvy of infants as well as of guinea-pigs there is no
overgrowth of putrefactive bacteria in the intestinal tract, and
therefore no basis for the hypothesis of ptomaine or similar
intoxication. Other poisons may, however, be absorbed from the intestine
as the result of a prolonged deprivation of an essential vitamine.
TABLE 1
FECAL FLORA OF SCORBUTIC INFANTS
=======================================================================
| | | | M | |
I | | | |S a | |
n | | | |o t | |
f | Diet. | Date. |Scorbutic |u o e | Types | Remarks.
a | | |condition.|r f r | of |
n | | | |c i |bacteria.|
t | | | |e a | |
| | | | l.| |
--+-------------+-------+----------+------+---------+------------------
M.|Malt soup and|Dec. 1|Subacute |Rectum|B. |{Normal infant's
| cereal | | | | acidoph.|{ flora.
| | | | |B. |{Gram + bac.
| | | | | bifidus |{ predominant.
| | | | |M. |{No spore-bearing
| | | | | ovalis |{ or putrefactive
| | | | | |{ types.
| | | | |B. coli |{B. acidoph. about
| | | | | |{ 40% viable bact.
| Do. |Dec. 4| Do. | Do. | Do. | Do.
|Same, also |Dec. 11|Sub- | Do. | Do. |{Relatively more
| 20 c.c. | |periosteal| | |{ B. coli.
| liquid | |hemorrhage| | |{Many B. bifidus
| petrolatum, | | | | |{No putrefactive
| one week | | | | |{ bact.
|Same diet, |Dec. 21|Markedly | Do. | Do. | Normal infants'
| oil stopped,| |improved | | | flora.
| _orange | | | | | Bacteria as
| juice_ | | | | | above.
| 10 days | | | | |
K.|Malt soup and|Dec. 11|Sub- |Rectum|Strepto- |{Gram - bacteria
| cereal | |periosteal| | cocci |{ predominant.
| | |hemorrhage| |B. coli |{B. coli gram +
| | | | |M. ovalis|{ diploc. numerous
| | | | | |{B. acidoph. few.
| | | | | |{B. bifidus few.
|Do. + |Dec. 21|Markedly | Do. |B. |{Gram + bact.
| _orange | |improved | | bifidus |{ predominant.
| juice_ | | | |B. coli |{Many B. bifidus.
| (60 c.c.), | | | |Strepto- |{Streptoc.
| 8 days | | | | cocci |{ unchanged.
| | | | | |
S.|Formula: |Dec. 21|Mild |Rectum|B. lact. |{Gram + and -
| Cream, | |scurvy | | aerog. |{ bact. about
| water, | | | |B. coli |{ equal. Many
| flour, | | | |M. ovalis|{ lact. aerog.
| sugar, | | | |B. |{Putrefactive
| also cereal | | | | bifidus |{ bact. in
| | | | |B. |{ minority.
| | | | | welchii |
|Malt soup and|Feb. 11|More | Do. |B. lact. |{Gram + bact. in
| cereal | |marked | | aerog. |{ great majority
| | | | |M. ovalis|{ (B. bifidus).
| | | | |B. |{Spore bearers
| | | | | bifidus |{ very few.
| | | | |Dipher- |{Flora not at all
| | | | | oids |{ putrefactive.
-----------------------------------------------------------------------
There are those who believe that scurvy is of _bacterial origin_, some
going so far as to regard it as a communicable disease. This viewpoint
was maintained by the famous Boerhaave and supported with all the weight
of his authority by Villemin in the seventeenth century. It is a view
held by many, if not by the majority, of physicians in Russia to-day,
and recently has been advanced by European army surgeons. This question
illustrates in an interesting manner how the trend of the day influences
medical thought--it has been suggested lately by Much and Baumbach that
the scurvy microörganism may be carried by means of lice. But clinical
experience points absolutely against the infectious nature of scurvy.
Indeed, the only episode which lends any support to this opinion is its
widespread and seemingly epidemic character; the fallacy of such
deductions has been well illustrated in regard to beriberi, which for
many years was regarded as an infectious and communicable disease. The
fact that whenever scurvy occurs among a body of troops the officers are
spared, constitutes convincing evidence against its communicability.
This peculiarity of incidence was noted by Hoerschelman and others in
the recent World War, and is referred to in the Report of the War of the
Rebellion. Many of the earlier writers, in discussing the occurrence of
ship scurvy, drew attention to the paucity of cases among the officers.
When we turn to bacteriological studies we find that some years ago
Ausset claimed to have isolated "a pasteurella type of organism" from a
case of infantile scurvy, and suggested it as the causative agent of
this disorder. On the other hand, Hart, Rehn, Hirschsprung, von Starck,
Schmorl, and recently Boerich, have failed to find bacteria in the
blood, although the total number of cultures must be admitted to have
been small. Czerny and Keller report negative bacterial growth from
fluid aspirated from affected joints.
The only articles considering this important question from the
experimental side are those of Jackson and Moody, and of Moore, who
conclude tentatively that scurvy may be a bacterial infection. Jackson
and Moody cultivated a diplococcus from the tissues of scorbutic animals
after death, reproduced hemorrhages by inoculating cultures of these
microörganisms into the circulation, and recovered the bacteria from the
tissues some weeks later. Their results are open to the criticism that
bacteria were found only after death, and that all blood cultures
during life proved negative. An article by Moore, however, which has
just appeared from this same laboratory, states that "an organism of the
streptococcus viridans type was isolated from the blood" in a case of
adult scurvy. In one instance we recovered an organism of this type from
the blood of an infant suffering from scurvy. It is highly important
that more blood cultures should be carried out in the course of human or
animal scurvy, and that particular note should be made of the stage of
the disorder when they are taken.
There is no doubt that invasion of the blood-stream does occur readily
in the course of scurvy, but this takes place generally after the
disease has developed and must be regarded as a secondary phenomenon and
therefore unessential from an etiologic standpoint. Indeed one of the
striking and important symptoms of scurvy is the marked susceptibility
to infection (furunculosis, nasal diphtheria, "grippe," etc.), which
comes about as the result of the nutritional disturbance. An excellent
example of this interrelationship is the "epidemic" of hemorrhagic
scurvy described in the chapter on symptomatology. Hemorrhages coming
about in this way should be regarded as focal complications rather than
as truly scorbutic. It should be realized that, at the present time, it
is not possible to distinguish between local symptoms which are truly
nutritional or scorbutic in nature, and those which are bacterial and of
secondary origin.
The newest theory, and the one at present most widely accepted, is the
_vitamine_ (_accessory factor_) _theory_. It was evident to Lind in the
seventeenth century that scurvy could be prevented and cured by means of
fruits or vegetables, a fact which became increasingly clear to
succeeding generations. Until the latter part of the nineteenth
century, however, this miraculous virtue of plants stimulated little
inquiry and no research. As far back as 1841 Budd realized that "the
explanation depended on the study of organic chemistry, and the
experiments of physiologists," but until recently it was not perceived
that the solution of the problem involved the introduction of a new
chemical factor. This view suddenly took shape after Eijkman in 1897
showed the nature of polyneuritis in fowl, and Hopkins in 1906, going a
step farther, demonstrated the necessity of one or more unidentified
food factors for the normal nutrition of the rat. The work which
established this novel theory on a scientific basis in relation to
scurvy was the classic investigation of Holst and Froelich, referred to
so frequently in connection with experimental scurvy. These
investigators showed that the mere drying of vegetables was sufficient
to deprive them of their antiscorbutic power, although from a chemical
standpoint they seemed unaltered; that high degrees of heat had
generally the same effect; that under certain conditions these foods
withstood prolonged heating, demonstrating that the antiscorbutic factor
was not a ferment; that acids and alkalies played no essential rôle in
the etiology; that fats, proteins and carbohydrates were not significant
factors; that as little as 1.0 g. of cabbage suffices to afford
protection to a guinea-pig. In other words, by a process of exclusion
they showed that it is a disorder due to the lack of an unidentified
food factor.
Subsequent studies, carried out within the past few years, have served
only to strengthen this viewpoint. For example, an "artificial orange
juice" composed of the various salts, citric acid, and sucrose in the
proportions in which they are found in the natural juice, failed,
in the experience of Hess and Unger, to protect or to cure
guinea-pigs--demonstrating that this preparation did not contain the
essential factor. In the same way, Harden and Zilva were able to protect
animals from scurvy with a preparation of lemon juice which had been
almost entirely deprived of its salts. It is needless to multiply these
examples. It is sufficient to state that there has been no investigation
during the last years of intensive study of scurvy, which has tended to
weaken the vitamine hypothesis. It may be stated, therefore, that
experiments have demonstrated that scurvy is due essentially to the lack
of a specific vitamine. It is unwise to proceed farther and place it in
the group of so-called "deficiency diseases," including beriberi,
pellagra, etc., unless the reservation is made that these several
diseases may present marked differences. It is quite possible that one
may be what might be termed a simple deficiency disease, whereas another
may have important additional etiologic factors. At any rate, unless it
is realized that there has been no proof that all are due to similar
deficiencies, we may, by stamping them all alike and by grouping them
together, be misled into taking their close relationship for granted. In
regard to scurvy, there may well be other etiologic factors, but they
are of a secondary character. Bacterial invasion has been referred to in
this connection, and it is possible that toxins are absorbed from the
intestine after nutrition has been disturbed. Diarrhoea and digestive
disturbances may play a rôle. Whether the total intake of food or the
correlation of its constituents--protein, carbohydrate, fat and
salts--affects the action of the vitamine, is one which has not been
well studied clinically or experimentally. In regard to beriberi, it is
claimed that there is a direct ratio between the quantity of
carbohydrate ingested and the amount of vitamine required. No such
interrelationship exists in regard to scurvy. This was evident a few
years ago (1917) when some infants receiving pasteurized milk, prepared
with the addition of 3 per cent. flour, did not tend to develop scurvy
more readily than others receiving simple pasteurized milk. A
consideration of the antiscorbutic vitamine will be postponed for a
subsequent chapter.
=Etiology.=--In considering infantile scurvy we are concerned almost
entirely with the artificially-fed baby. It is true that in the
literature we meet with scattered reports of _scurvy in breast-fed
babies_ and that these cases seem to constitute a noteworthy group; in
point of fact, they are comparatively few. The collective investigation
of the American Pediatric Society includes ten infants who had been
given breast milk exclusively, and Concetti adds another ten in his
compilation of 682 cases.[7] In spite of their paucity these cases
require separate consideration because they represent an important
aspect from an etiologic standpoint. How are we to explain the fact that
human milk may lead to rather than protect against this disorder? On
investigating more closely it is found that these cases differ in
several important respects from the group which has been artificially
fed. They are of a different age; instead of being in the second half
year of life they are generally but a few months old. Furthermore, the
signs are not the same. The hemorrhages involve the upper extremities
fully as frequently as the lower extremities, and often appear at
unusual sites--for example, on the scalp or as large subcutaneous
effusions at various parts of the body. In many instances it has been
noted that the nursing mothers were suffering from some debilitating
disease such as tuberculosis or syphilis, or had an insufficient supply
of milk, or that there had been some other unusual factor, as Freund has
shown in an article devoted to this particular aspect. It is not
necessary, however, to fall back on these attendant circumstances to
exclude from consideration many of the cases. For example, Crandall's
case of "scurvy in an infant of six weeks" should be invalidated, not
because, as Freund suggests, the mother had rheumatism and insufficient
milk, but because of the age of the infant, and the course of the
disease; first one arm was involved, then the other, then hemorrhages
appeared on the skin, and finally it was cured by giving a teaspoonful
of fresh cream before each nursing. Had the baby really suffered from
scurvy it could not have been cured by this means. Southgate's case must
also be rejected, not because the mother was tuberculous but in view of
the symptoms--the arms and legs were pseudoparetic, "the legs, feet and
hands were double their normal size," and moderately large hemorrhages
were present on the back and chest. It seems hardly necessary to discuss
in detail the score of cases which comprise this group, as, in general,
the same criticism applies to all. Some evidently were congenital
syphilis, still more must be regarded as sepsis, and others as unknown
toxic conditions. Apart from these cases the question must be considered
whether scurvy can occur in a breast-fed infant. Personally, we have
never met with a case of this kind, and, as Finkelstein aptly remarks,
there has been "no necropsy of a breast-fed case or conclusive X-ray
picture." It seems possible only if an infant, for a period of months,
has obtained a scanty supply of milk, or when the milk has been
exceedingly deficient in the antiscorbutic vitamine. Even under such
conditions it does not seem possible for scurvy to become manifest in
six weeks (Crandall's case), or in four weeks, as in a case reported by
the American Pediatric Society, unless we believe that the infant
suffered also from a certain degree of intrapartum or congenital scurvy.
In view of the fact that an infant requires about one pint of milk to
furnish it with an adequate daily quota of the antiscorbutic factor, it
is theoretically possible, under extreme conditions, for it to become
scorbutic, in spite of being nursed at the breast. Such an occurrence
must be regarded as exceedingly rare, far more so than the current
statistics illustrate, for considerably less than a pint of milk a day
will prevent the appearance of manifest scurvy for a period of several
months. Some of the reported cases may have been latent scurvy, rendered
acute by a complicating bacterial infection.
[7] These figures constitute an irrefutable argument against the
statement frequently made that a monotonous diet leads to scurvy. It is
only when the monotonous diet does not contain an adequate quantity of
antiscorbutic vitamine that it is to be feared.
It might be expected that by ascertaining _the occurrence of infantile
scurvy in countries where it is endemic_, we could learn under what
conditions and how frequently breast-fed babies develop this disorder.
Approaching the question from this angle, it is found that the
available data is meagre and not entirely convincing. Peculiarly enough
infantile scurvy has rarely been reported from Russia, where scurvy is,
in many sections, endemic. For example, although Tschudakoff, who
personally examined over 10,000 persons, in connection with the great
scurvy epidemic in Russia (1898-99) found 11.11 per cent. of the people
suffering from this disease, he did not meet with a single case under
the age of five years. Fuerst writes that Filatow, the celebrated
Russian children's specialist, declared that he knew of no instance of
Barlow's disease described in the Russian literature.[8] Shortly after
the recent war scurvy broke out among the wet-nurses in an infant asylum
in Vienna. A very few of the infants nursed by these women developed the
disorder, far fewer than might have been expected (personal
communication). Hopkins recently wrote a communication to the effect
that in the island of Aruba, in the Dutch West Indies, they had been
unable to grow any crops in 1912, 1913, 1914, that 3000 cases of scurvy
had developed there during the year 1915, and that in 1917 it was again
being noted. In answer to a personal inquiry regarding the occurrence of
scurvy among the infants of Aruba, he wrote that "infantile scurvy is
very rare," although "most all of the babies are breast-fed for about a
year."[9]
[8] This is not literally correct, as Doepp described an epidemic of
scurvy in the St. Petersburg Foundling Asylum occurring in 1831.
[9] During 1919 in Aruba there were 293 births and 30 deaths under one
year, most of these deaths being due to intestinal diseases. The mothers
subsist mainly on maize or guinea small corn, with some goat and sheep
meat, and a little fresh fish, but no vegetables or fruit. The water is
brackish.
On the other hand, descriptions of the coincidence of scurvy in mother
and nursling are even more fragmentary; in fact, we have been able to
find but two reports of this kind. The one most frequently cited is that
of Cheadle, which consists merely of the following bald statement: "With
the exception of one or two doubtful cases, of which the details of
breast-feeding and diet are imperfectly given, the only instances of
scurvy arising in sucklings are those when the nursing mother has been
suffering from scurvy at the time." The other report has been gleaned
from a recent editorial in the _British Medical Journal_, which refers
to the above mentioned outbreak of scurvy in Vienna, affecting in some
cases both mothers and breast-fed infants.
It is difficult to pass judgment on this question in view of the paucity
of data. In the near future, probably, when we learn in detail about the
epidemics of scurvy which occurred during and immediately following the
war, we shall be in a better position to weigh its pros and cons. In
view of the above data it does not seem that nursing infants readily
develop scurvy, even though their mothers do not obtain a full quota of
antiscorbutic vitamine in their food. This appears to be the clinical
result, whatever its interpretation may be. It cannot be explained on
the assumption that human milk contains a particularly large quota of
this factor. In a test carried out to elucidate this question it was
found that eight ounces a day of breast milk was insufficient to
alleviate the symptoms in a case of scurvy, and that twelve ounces
barely sufficed. This milk was from a woman who was on a liberal diet
containing an adequate supply of vegetables. It had been previously
demonstrated that sixteen ounces of cow's milk is sufficient to cure
infantile scurvy, so that it is evident that human and cow's milk do not
differ essentially in this respect. There are, however, other factors to
be considered--for example, the incomparable freshness of the milk
suckled from the breast, which may endow it with additional potency, or
the possibility that the lack of vitamine may be compensated for by the
large quantity of milk consumed. It also may not be entirely immaterial
whether the vitamine is supplied in one dose, as, for example a daily
feeding of orange or tomato juice, or whether this factor is furnished
to the infant in frequent small quantities in the mother's milk
throughout the day. In this connection we cannot help contrasting the
relation of beriberi to breast feeding. As is well known, infants which
develop beriberi are almost always nursed and not bottle-fed, and show
signs of this disorder, although the mothers are in apparent health, and
give no clinical evidence of disease.
Turning to a consideration of _the artificially-fed infant_, there
exists a somewhat similar situation in regard to the occurrence of
scurvy on a diet of raw cow's milk. In almost all reports of this kind
the quantitative viewpoint is entirely disregarded, and little or
nothing is stated to indicate how much milk the infant consumed. And yet
this factor is of essential importance in interpreting the cause of the
nutritional failure. It is clear, for example, that if a baby receives
but eight ounces daily of raw milk--one-half the requisite amount--it
may well develop scurvy, notwithstanding the fact that the milk has not
been heated. In addition to the quantity, there are other factors which
play a greater or less rôle in the relation of raw milk to the etiology
of scurvy. It is no doubt of consequence whether the fodder of the cows
was rich or very poor in the antiscorbutic factor, and, accordingly,
whether the baby received what may be termed an "antiscorbutic-rich" or
an "antiscorbutic-poor" milk. Furthermore, the age of the milk must be
borne in mind, for we have found that even raw milk loses some of its
potency on becoming stale.[10]
[10] Moore raises the interesting question as to whether a diseased
condition of the cow may decrease the vitamines of the milk--whether a
certain outbreak of scurvy among guinea-pigs might have been due to
their having been fed on the milk of a cow suffering from experimental
streptococcus mastitis. If such proves to be the case, it would have an
important bearing on the question of scurvy and pseudo-scorbutic
conditions in nursing infants.
One of the mooted questions relative to the etiology of scurvy is the
rôle of heated milk, and more particularly of _pasteurized milk_. In
view of the vogue which pasteurization has acquired in the large
municipalities, especially in the United States, this aspect has assumed
increasing importance, and deserves detailed investigation.
Pasteurization has achieved so much in limiting the infectious diseases,
especially the diarrhoeal disorders of infancy, that it has come to be
looked upon as heresy to deprecate its virtues in any regard.
It has become increasingly evident that in the course of pasteurization
milk loses an important measure of antiscorbutic vitamine. The term
pasteurization, when employed in this connection, is not meant to be
synonymous merely with the heating of milk to 140° to 165° F., but
embraces the entire commercial process--the heating, handling,
subsequent cooling, aging and all other factors involved. There can be
no doubt that milk which has undergone this elaborate treatment has
suffered in its antiscorbutic property. In 1914 Hess and Fish reported
mild cases of scurvy occurring among infants who had received milk
heated to a temperature of 165° F. for thirty minutes. This degree of
heat is claimed by many physicians and hygienists, including the
National Commission on Milk Standards, not to destroy its chemical
constituents. Nevertheless typical cases of scurvy supervened after this
diet had been followed for a period of six to nine months. Subsequent
experience, published by Hess in 1917, with milk heated to only 145° F.,
served to confirm the previous observations. That these cases were true
scurvy was proved by the fact that a cure resulted when raw milk was
substituted. A similar experience in Berlin reported by Neumann and
others was convincing, but was not heeded in this country. In 1901 one
of the largest dairies in that city established a pasteurizing plant
where all milk was raised to a temperature of about 60° C. After an
interval of some months infantile scurvy began to be reported from
various sources throughout the city. Neumann depicts the situation as
follows: "Whereas, Heubner, Cassel and myself had seen only thirty-two
cases of scurvy from 1896 to 1900, the number of cases suddenly rose
from the year 1901, so that the same observers--not to mention a great
many others--treated eighty-three cases in 1901 and 1902." At a spirited
meeting held by the Berlin Medical Society in 1903 to discuss this
subject, Heubner was able to report 65 cases. An investigation was made,
and the pasteurization discontinued. The result was almost immediate,
the cases decreasing just as suddenly as they had increased. These
reports and others demonstrate that unless additional antiscorbutic food
is given, a diet of pasteurized milk will lead to the development of
scurvy. As the antiscorbutic vitamine is not entirely destroyed by
pasteurization, the severity of the disorder will be in inverse ratio to
the amount of milk which is consumed.
It has been our experience that milk pasteurized in the home or
institution did not lead to scurvy to the same extent as that which was
commercially pasteurized. Babies fed on home-pasteurized milk did not
develop manifest scurvy. The difference in the two processes consists
mainly in the amount of handling during the process of heating and the
subsequent aging which the milk undergoes. An interval of forty-eight
hours usually elapses between commercial pasteurization and the delivery
of the milk to the consumer. In New York city most of the better-grade
milk is pasteurized at the farm, so that it is subjected to a longer
period of aging than the poorer grade, which is not pasteurized until it
reaches the city. Although our results indicated the effect of freshness
or staleness on milk which had been heated, they showed also that other
factors must be involved, for home-pasteurized milk which is forty-eight
hours old is superior to the commercial product of the same age. This
difference we believe is due to the handling which the milk undergoes,
to the mechanical processes involved in commercial pasteurization.
In considering this aspect of the development of infantile scurvy on a
diet of heated milk, it is of interest to refer to the experience of
Switzerland and of France. In 1907 Bernheim-Karrer reported nine cases
of scurvy which occurred on "homogenized" milk. This milk is forced
between rapidly-rotating surfaces at a temperature of 55° to 65° C. at a
pressure of 150 atmospheres. This process had been introduced the year
previous by a large dairy which was well known for its excellent grade
of milk. Before this innovation, milk usually had been boiled for a long
while before being fed to infants. In France a similar epidemic of
scurvy followed the introduction of the use of homogenized milk (lait
fixé). Lecornu gives an interesting account of this episode, remarking
on the large number of cases of scurvy occurring on this milk compared
with sterilized milk, which was employed so much more extensively. These
experiences furnish excellent examples of _the harmful effect of
industrial methods on milk_, especially on its antiscorbutic vitamine.
Lecornu also emphasized the scorbutic influence of "lait maternisé,"
which is similar to the German Gaertner milk, and is subjected to
dilution, centrifugation, and sterilization.[11] He states that before
this preparation was introduced scurvy was practically unknown in
France. Lecornu attributes the deleterious effect of the "lait
maternisé" and the "lait fixé" to bacterial contamination, as does
Bernheim-Karrer. We believe, rather, that its loss of potency is due to
the mechanical processes to which it has been subjected.
[11] In the case of the "lait maternisé," which is a milk of high fat
content, the dilution of the preparation also must have been a factor.
Ounce for ounce, cream is poorer in antiscorbutic vitamine than an equal
quantity of milk. It is also possible that the mere dilution of
milk--quite apart from the absolute amount consumed--is not immaterial
in affecting this highly sensitive vitamine.
Boiled and, more particularly, sterilized milk, is regarded as a common
cause of infantile scurvy and figures prominently among the foods held
accountable for this disorder. It has been pointed out, however, that
thousands of infants, especially in Europe, receive milk of this kind,
and do not develop scurvy. Statistics such as those of Variot, who has
distributed in his out-patient department, during a period of twelve
years, 400,000 quarts of sterilized milk (heated in half-litre bottles
and hermetically sealed at the farm) without observing a case of scurvy,
must be accorded weight in this connection.[12] Escherich, some years
previously, stated that he did not meet with scurvy in Graz, although he
was accustomed to feed babies on sterilized milk. Budin, the celebrated
French children's specialist, writes: "As for the so-called infantile
scurvy which is alleged to follow the use of sterilized milk, I have
heard a very great deal about it during the last few years, but I am
still looking for my first case." Evidence from such sources cannot be
summarily cast aside, but must be given due consideration. It is evident
that the mere heating or sterilization of milk, although it reduces the
antiscorbutic vitamine, does not do so to a degree sufficient to lead to
the production of clinical scurvy. Our experience accords with that of
the above observers. Some years ago we fed infants with milk which had
been boiled for five minutes, and, at another time, made use of
home-made evaporated milk which had been heated for a period of
seventeen hours, until it had been reduced to one-eighth its volume.
This evaporated milk was well borne for months, although slightly
caramelized in the course of heating, and did not lead to any signs of
scurvy. Clearly there are other factors involved in this question
besides the mere subjection to heat. We believe that every step in the
process is important--the freshness of the milk, whether or not it is
agitated and exposed to the air, whether it is sealed carefully and used
soon after sterilization,[13] and, finally, whether the baby receives a
sufficient quantity. If this milk, which has certainly lost some of its
vitamine content, is given in small amount, it will not supply an
adequate amount of the antiscorbutic factor.
[12] It is to be noted, however, that Variot remarks that these infants
frequently develop anemia unless additional diet is given, so that it
must be considered open to question whether some of these babies did not
have latent scurvy. Of course, unless it is certain that these infants
were receiving only sterilized milk, and absolutely no other food, for a
period of at least six months, they cannot be considered apposite to the
question.
[13] Carel reports an interesting case which points to the importance of
staleness. A baby was taken to the country with a supply of sterilized
milk sufficient to last for some weeks. At the end of this time it did
not thrive, but regained its health when a fresh supply of milk was
used. When this second supply became stale the infant again developed
the same signs, and the condition was diagnosed as scurvy.
Neumann, Czerny, and others state that they have even cured infantile
scurvy by giving boiled milk obtained from a different source. In the
Berlin epidemic, Neumann laid particular emphasis on the fact that the
milk which induced scurvy had been doubly heated, having been
pasteurized commercially and later boiled in the home before it was fed
to the baby. Plantenga has also laid stress on the influence of
_two-fold heating_, citing an interesting experience with scurvy in his
clinic. When the milk was pasteurized one day and boiled for five
minutes on the subsequent morning, 23 cases of infantile scurvy
developed among the 200 infants attending his dispensary. The following
year when the procedure was altered so that the milk was merely
pasteurized, no case of this disorder developed. There can be no doubt
that milk which has been heated twice must have lost more of its
antiscorbutic properties than milk which has been heated but once, and
that aging also must contribute to this loss. Whether there is what may
be termed a peculiar sensitization of milk following pasteurization, has
not been definitely shown.
Up to the present time _dried milk_ has played an insignificant rôle in
the etiology of infantile scurvy. One of the factors which has hindered
the general acceptance of dried milk by physicians and laymen has been
the fear that its use might lead to the development of Barlow's disease.
It is therefore important to consider this aspect of the subject,
especially as dried milk seems destined to be used to an increasing
extent. A recent report to the Local Government Board by Coutts states
that "Millard and Naisch in England confirmed the testimony of Miele in
Belgium, and Gautier and Genevoix in France, that scurvy is not to be
feared" from this foodstuff. This coincides with our experience, namely,
that _dried milk not only does not lead to scurvy, but may contain
sufficient antiscorbutic vitamine to cure this disorder_. Recently a
scorbutic baby was fed with milk which had been dried by the so-called
Just-Hatmaker process--whereby it is subjected on a drum for a few
seconds to about 230° F.--with the result that the hemorrhages of the
gums began to be absorbed in about three days, and all symptoms to
disappear shortly thereafter. This infant received dried milk to the
equivalent of 24 ounces of fresh milk, and this preparation had been
dried and canned somewhat over three months before it was used. Recently
two infants, suffering from marked scurvy, were treated with milk which
had been dried six months previously. The one received only sixteen
ounces a day and the other a quart; both recovered within a few days
after this food had been substituted for malt soup. Not long ago, as
reported elsewhere in a paper by Unger and myself, after curing a baby
of scurvy by means of this milk, it was maintained in health for a
subsequent period of three months on a diet which contained no
additional source of antiscorbutic vitamine. These results are
emphasized as illustrating the peculiar relationship of drying and of
the application of heat to the antiscorbutic vitamine, and because
recently several reports have appeared, for example, that of Barnes and
Hume in England, and of Hart, Steenbock and Smith in this country, to
the effect that dried milk is devoid of antiscorbutic value. The
difference of opinion is due to the assumption that dried milk is a
uniform product and has identical antiscorbutic properties. For milk to
retain its antiscorbutic value, notwithstanding drying, it must have
been rich in vitamine before desiccation, it must have been dried
quickly, and packed within the shortest possible interval in air-tight,
preferably hermetically sealed, containers. As in relation to the
heating of milk, so in regard to its drying, it is not the degree of
heat to which it is subjected which is all important, but rather the
associated conditions. The merits of each process will have to be tested
individually and perhaps even each particular brand of milk.[14]
[14] In making tests of dried milk particular attention should be paid
to the age of the milk before it is desiccated. Investigators should
also be certain that the milk has not undergone heating previous to the
drying process. Some well-known brands of dry milk have been not only
pasteurized, but subsequently evaporated before drying.
In the foregoing, the dictum has been accepted without comment that
fresh milk may be either rich or poor in antiscorbutic vitamine. This
point of view has recently gained general acceptance, on the assumption
that the milk of the stall-fed cow is markedly deficient in this factor.
Recent work by Hart, Steenbock and Ellis gives evidence that "summer
pasture milk is much richer in this nutritive factor than dry feed milk
or winter produced milk, involving the use in the ration of corn silage
or sugar mangels." In some experiments (unpublished) we have found that
dried milk shows similar variations, being a much more potent
antiscorbutic when obtained from cows fed on fresh fodder than a similar
milk from the same cows on fodder containing a minimum amount of
antiscorbutic vitamine. The supposition of a direct quantitative ratio
between the antiscorbutic intake in the food and output in the milk
needs confirmation, especially as it does not quite coincide with the
experience among human beings in countries where adult scurvy is
endemic. In such countries--for example, Russia--nursing infants do not
develop scurvy to the extent that would be expected, and it is possible
that this exemption is due in part to a selective secretion of
antiscorbutic vitamine into the milk.
As is well known, a diet of _condensed milk_ leads to scurvy. This is
not surprising, considering the prolonged heating to which this milk has
been subjected. It is probable that many cases of mild scurvy developing
on this food and characterized by beading of the ribs (rosary) and other
indefinite manifestations, have been erroneously diagnosed as rickets.
It is hardly necessary to discuss separately the various kinds of milk
which have led to scurvy in the course of infant feeding.[15] The
principles laid down in the preceding discussion hold good for milk of
all kinds. Heat will destroy a certain amount of vitamine, and, if the
heating is followed by aging, still more will be lost. If an interval
elapses and a second heating ensues, there will be further loss of
vitamine. It should never be forgotten in considering foods in their
relation to the causation of scurvy, that _the amount of food_ given
must not be overlooked. For example, a pint of ordinary pasteurized milk
will lead to scurvy, whereas a quart in most cases will be sufficient to
tide the baby over until the period of mixed feeding. No general rule
can be laid down, however, as may be judged from the fact that dried
milk which has been subjected to almost all the influences which are
deleterious to the antiscorbutic vitamine--heating, drying, aging, all
carried out in a neutral medium--nevertheless retains its specific
potency.
[15] Ausset reports a definite case of scurvy developing in a baby nine
months old, which had received buttermilk almost since birth. At the
time of admission to the hospital it was getting 900 c.c. a day. This
case is interesting on account of the acid nature of the food.
Infantile scurvy has always been far more prevalent in England and in
America than in Europe, notwithstanding the fact that on the continent
practically all milk for babies is boiled or sterilized. This has been
ascribed, and probably rightly so, to the widespread usage of
_proprietary foods_ in the English-speaking countries. Among the cases
reported by the American Pediatric Society about 60 per cent. had been
given foods of this description. How is this relationship to be
explained? These preparations in general may be stated to consist of
cereals, sugar, with occasionally a small amount of dried milk; they are
mixed with varying proportions of water and milk and then cooked. It is
evident that two important causative factors of scurvy are thus
furnished, namely, a small and inadequate quota of milk and the
application of heat. In most instances not more than sixteen to twenty
ounces of milk are used to make up the day's feeding, and frequently
this has been previously pasteurized. But there is an additional factor
which comes into play in this connection, one to which we have recently
drawn attention in treating of "The Deleterious Effect of the
Alkalization of Infants' Food." It has been shown that the antiscorbutic
vitamine is peculiarly sensitive to the faintest alkaline reaction, in
which medium it rapidly undergoes deterioration, and even total
destruction if heat is applied. Proprietary foods, with but few
exceptions, are alkaline, having been rendered so by the addition of
potassium carbonate or bicarbonate, in order to prevent acid
fermentation of the fat and to counterbalance the relative poverty of
potassium in cow's milk. Little or no regard has been paid to this
reaction; the textbooks on children's diseases give this point no
consideration whatsoever, expressing the salt content merely in terms of
total ash. By this means ideal conditions are furnished for the
destruction of a large part of the vitamine, and if this factor is not
present in excess, scurvy will readily develop. It is to these various
circumstances--the deficiency of milk, the alkalinity and the
heating--that the scorbutic quality of proprietary foods is to be
ascribed.
The most flagrant example of an infant's food leading to scurvy is "malt
soup"--an alkaline preparation of malt, which is prepared with flour and
a small amount of milk.[16] This food brings about scurvy almost
invariably unless an antiscorbutic is added to the dietary. That this
effect is due to the alkaline potassium carbonate was shown by a recent
test which is illustrated in chart. (Fig. 2). Here we see that in a case
of scurvy, when the food was altered and prepared with the same amount
of milk and alkali, the disorder did not abate (although the
carbohydrate had been discontinued), but when the potassium carbonate
was omitted a gain in weight ensued, and, we may add, the symptoms
disappeared.
[16] Malt soup is prepared by dissolving the alkaline malt soup extract
in water, and mixing wheat flour with milk. These two mixtures are then
boiled together for about three minutes. According to some directions,
11 ounces of milk are used; in our formula 16 ounces were employed.
[Illustration: FIG. 2.--Human scurvy: weight curve of a baby that
developed scurvy on a diet of malt soup (period 1). During period 2 the
flour and malt soup were omitted from the diet, the same amount of milk
and potassium carbonate being continued. The disorder did not abate. The
only change in period 3 was a discontinuation of the potassium
carbonate. This brought about a gain in weight and cure, showing the
destructive effect of the alkali on the vitamine.]
A test of this kind once more raises the question whether carbohydrates
lead to the development of scurvy. As previously stated, there are many
who believe that the carbohydrates, especially starch, have this harmful
effect by requiring a large amount of the various vitamines for their
metabolism. This relationship was first brought forward by Bradden and
Cooper in regard to beriberi. It is a suggestion which cannot be
disregarded in view of the great amount of scurvy which comes about on
diets rich in carbohydrates, especially those containing malt sugar. We
do not believe, however, that the harmful effect which this foodstuff
exerts can be explained on the above hypothesis, as experience has shown
that infants may receive for many months equally large amounts of
carbohydrates--cane sugar, flour, or a combination of both--and
nevertheless not manifest a similar tendency to develop scurvy.
=Age Incidence.=--Scurvy may occur at any age if the diet does not
furnish sufficient antiscorbutic factors. As a matter of fact, it is
encountered most often among infants and adults, not because these two
age-groups are particularly susceptible, but because there are peculiar
attendant circumstances. In the case of the infant, it is due to the
fact that for almost the entire first year of its life it is dependent
entirely upon milk, a foodstuff poor in antiscorbutic vitamine, and
containing, under favorable conditions, barely enough to meet its
requirement. If, therefore, the potency of the milk is weakened, or if
an insufficient quantity is fed, and more particularly when both of
these factors are involved, a scorbutic condition will ensue. The reason
why older children, those over one and a half or two years of age, do
not develop scurvy is largely due to their varied and liberal diet,
which is amply provided by the mother or guardian, so that even in times
of want they receive more than their due share of the available food
supply.[17]
[17] It would seem, however, that the growing infant requires relatively
more antiscorbutic vitamine than does the adult. We know that its
caloric requirement is fully a quarter to a third greater. In regard to
vitamine, judgment cannot be based on experimental evidence, but on
comparative figures. For example, unless we take this viewpoint, we must
believe that, as an infant of six months weighing 15 pounds requires 15
c.c. of orange juice daily to furnish its antiscorbutic quota, an adult
weighing 160 pounds requires 180 c.c. daily--the juice of three
good-sized oranges. On this basis the adult would require six quarts
(6000 c.c.) of fresh milk daily, twelve times the minimum requirement
for an infant, which is one pint (500 c.c.) a day. These figures are
manifestly too high.
From a clinical standpoint scurvy may be said to occur in infants during
the second half year of their lives. There is general agreement on this
point; it is borne out by the investigation of the American Pediatric
Society and by the statistics of various individuals. On the basis of a
large experience, Still states that nearly eighty per cent. of the cases
appear between the ages of six and ten months, and that in no case did
the disorder occur before the age of five months. It is of importance
from both the etiologic and the therapeutic standpoint to distinguish
clearly between the age when infantile scurvy is commonly diagnosed, and
the earlier stage when it appears as a general nutritional disorder. We
must remember that scurvy generally takes from six to nine months to
become manifest, this developmental period varying mainly in proportion
to the degree of the dietary deficiency. It is evident, therefore, that
there must be a prolonged period of nutritional failure which precedes
the diagnosis. This stage consists of two early phases, the first months
where the faulty diet causes no apparent change and seems to have no
deleterious effect on the infant, and the second, of latent and subacute
scurvy. The "latent" condition is one merely of unsatisfactory nutrition
and retarded growth, which it is not possible to interpret; "subacute
scurvy," which develops subsequently, is distinguished by characteristic
signs and symptoms. We shall not review their symptomatology, as it is
given in the chapter devoted to this topic. The subject is brought
forward in this connection to emphasize the fact that the scorbutic
condition occurs far earlier than is generally realized, and
furthermore, that if the earlier and more subtle symptoms of scurvy were
comprehended, the age incidence would fall earlier than the current
figures indicate. The earliest instance of this disorder which we have
seen occurred in a baby four and a half months of age.
Age does not seem to play a definite rôle in regard to the incidence
among adults. Scurvy frequently has been encountered among old men, and
is of common occurrence among the most vigorous of the nation, the young
soldiers and sailors. Some have stated that it takes place less often
among soldiers in the twenties than among those in the thirties, but
this has not been demonstrated. The fewest cases have been reported
among children over two years of age. It was due to the apparent
immunity of this age-group that, until very recently, German writers
doubted the identity of infantile and adult scurvy. The exclusion of
children of this age is merely fortuitous and, moreover, is by no means
absolute. One of the earliest cases of scurvy in children, reported by
Montfalcon, occurred in a child six years old. Bateman in America
described a case in a child of about this age. Barlow, in one of his
first articles, reported scurvy in a small group of older children. The
case so frequently quoted by German authors in this connection is that
of Fraenkel, who described both clinically and pathologically a case of
scurvy in a boy eight years of age. These cases by no means exhaust the
number which are reported. Recently, Tobler has given us an account of
scurvy, occurring during the war, in a Viennese foundling asylum which
harbored children between the ages of two and fourteen.
=Season and Climate.=--Many of the older writers laid great stress on
the influence of season on the occurrence of scurvy, which they believed
broke out particularly in the cold and damp months of the fall, winter
and early spring. It is true that most of the epidemics have occurred at
these seasons of the year. This is merely what should be expected,
considering that the disease depends mainly upon the supply of fresh
fruits and vegetables. Where conditions are abnormal, as in war, there
have been notable exceptions to this seasonal incidence. In the "Report
of the War of the Rebellion" there is an instructive graph illustrating
the occurrence of scurvy in our Civil War and in the Crimean War, which
shows that this disease prevailed to the greatest extent during the
winter months in the former, whereas in Crimea, the season of greatest
frequency was the summer time. One of the severest outbreaks of scurvy
on record is that which occurred at the siege of Thorn in Germany in the
year 1703. During the months of July and August, when the weather was
excessively hot, scurvy ravaged the besieged army. There are,
furthermore, many reports of scurvy in the tropics during the dry
season. In the island of Aruba, in the Dutch West Indies, which has been
visited by scurvy year after year, and which is referred to elsewhere,
the disease is endemic during the dry, hot season. Formerly it broke out
on the men-of-war and vessels of the mercantile marine while they were
in southern waters. As regards infantile scurvy, it has always seemed to
us that season played a slight rôle; that cases which occurred in the
summer tended to be less severe and to be characterized by periods of
intermission rarely observed in the winter time.
The effect of _climate_ has been accorded a variable place in the
etiology of scurvy. Lind believed that a damp, cold climate, such as
that of the Low Countries, was conducive to scurvy. On the other hand,
since it is realized that diet is the essential element, all other
factors have been regarded as of no moment whatsoever. It is difficult
to pass judgment on this question, since scurvy is now endemic in such a
limited area of the world. It seems quite possible that a damp, cold
climate, which depresses the various functions of the body, may exert an
influence where the quota of antiscorbutic foodstuff is not quite
adequate. Exposure to infection is also greater under such climatic
conditions.
Economic status has to be considered in connection with infantile
scurvy. Numerous writers have drawn attention to the fact that scurvy is
seen relatively more frequently among the infants of the well-to-do and
the rich than among those of the poor. This curious and paradoxical
situation is due to the zealous care which the former receive--the
extreme precautions in sterilizing the milk, the addition to the
formulas of expensive proprietary foods, the watchfulness to avoid the
child's obtaining a chance bit of fruit or vegetable. Since the
popularization of commercially-pasteurized milk in the larger
municipalities, and the advertising propaganda for the sale of "baby
foods" which has extended their use among the masses, this distinction
in the social status has been largely obliterated.
Sex seems to play no part in the etiology of scurvy. Several writers
have claimed, however, that there is a certain degree of racial
immunity. For example, Sheppard reports that the Zhob Kakai seldom
develops scurvy, although he naturally excludes vegetables from his
diet, and Boerich noted among the prisoners of war that the Slavs,
especially the White Russians, were more susceptible.[18] Of course a
lack of susceptibility of this nature can be merely relative. Such a
racial distinction may seem far-fetched, but if we admit that
disposition and habits of life can play a rôle, it is quite possible for
races to vary in their predisposition to this disorder. Moreover, we
shall see that individuals differ markedly in this respect. Lind and
others repeatedly emphasize the fact that the indolent and slothful
sailor was stricken with scurvy far oftener than the one who was active,
and claimed that physical exercise even tended to bring about a
cure.[19] Those who have had a large experience with scurvy in adults
are almost unanimous in believing that a _psychic element_ enters into
its etiology. In this way, in a measure, they account for the frequency
of scurvy among defeated troops, in besieged armies, and among men
depressed by homesickness, fatigue, and discouragement. This point of
view cannot be lightly disregarded, bearing in mind that depressed
mental states alter the functions of the organs and markedly affect
secretion. The many cases and epidemics in institutions for the insane
cannot, however, be attributed to this cause, but are probably almost
entirely due to a want of supervision of the dietary. Among infants, the
question of the influence of race and of the mental state needs but
little consideration.[20] For some time we have carefully observed the
course of scurvy among happy and contented infants compared with those
of an unhappy and fretful disposition; in some instances the former,
although the diet was similar, seemed to develop scurvy less readily
than the latter.
[18] It would be of interest to know whether the negro infant is more
susceptible than the white baby, in view of its markedly heightened
susceptibility to rickets. There are, however, no reports or statistics
to enlighten us on this point.
[19] "Where the indisposition is but beginning, and even when the gums
have been pretty much tainted, there have been numerous instances of a
perfect _recovery without having the benefit of fresh vegetables_;
provided the patient is able to use due exercise.... When it is advanced
to what I have called the second stage it is hardly to be cured without
their (fruits and vegetables) assistance." (Lind.)
[20] Caillé has described a case of scurvy in an infant suffering from
Mongolian idiocy, and we have also seen a similar case.
There can be no doubt that there is _predisposition_ to scurvy, as there
is, probably, to every nutritional disorder. Among soldiers and sailors
a certain number develop scurvy on the same ration which does not harm
others. Some years ago when scurvy developed among a group of infants
fed on pasteurized milk, this idiosyncrasy was noted. The distinction,
however, is rarely sharply defined. Careful clinical investigation will
generally show that the infants which seem to be spared are not
thriving quite normally; they are somewhat pale, and do not gain in
weight as they should, and their appetite is poor. The most interesting
experience of this kind is the following which is frequently cited: In a
family where the first child developed scurvy, Finkelstein took the
precaution, in the case of the second child, to have the milk boiled for
as short a time as possible, and to begin mixed feeding early. In spite
of these precautions this boy also developed scurvy. Finkelstein states
that once before he had met with a similar mishap. An experience which
he relates, regarding a foster-mother, an excellent nurse, who had three
infants in succession develop scurvy in spite of preventive measures, is
also of interest in this connection. The latter occurrence evidently
cannot be attributed to hereditary or family predisposition, and serves
to emphasize the inherent difficulties of the subject. v. Starck's
report of an instance where twins were fed on similar milk mixtures and
one developed scurvy, whereas the other thrived satisfactorily, is a
striking illustration of the rôle of idiosyncrasy. This case, as well as
many others, fails to be absolutely convincing in view of the fact that
the daily intake of milk is not recorded.
A predisposition to scurvy cannot be ascribed to a condition of general
malnutrition. For example, among infants it has never seemed that those
suffering from marasmus or atrophy were particularly prone to develop
scurvy. Whether syphilis, tuberculosis or malaria tends to precipitate
the onset of this disorder cannot be stated.[21] In view of the fact
that prematurity is such an important factor in the pathogenesis of
rickets, it would be of interest to know whether a similar relationship
exists between infantile scurvy and prematurity. The only clinical
condition which we have found predisposing to scurvy is the "exudative
diathesis" of Czerny, a term which implies a tendency to develop
exudations of the skin or of the mucous membranes. Probably it is not
without significance that in this diathesis the blood-vessels may evince
a decided weakness, an increased permeability, as demonstrated by the
"capillary resistance test." (See Symptomatology.)
[21] Many of the older authors believed that mercurial drugs were
especially prejudicial in cases of scurvy.
Nothing whatsoever is known regarding the possible influence of the fat,
protein, carbohydrate and salt content of the diet on the development of
scurvy. Is it entirely immaterial whether one or another food element
largely predominates, or is the antiscorbutic factor to some extent
modified by other components of the food? Influences of this kind, which
at most are secondary, cannot be ascertained by the biologic test which
at present has to be relied on to measure the development of scurvy and
the potency of antiscorbutics. It is quite possible that the course of
scurvy may be affected by the character of gastric and intestinal
digestion, by the activity of the glands which pour their secretions
into these organs, by the destruction or elimination of the
antiscorbutic factor in the food. The frequent association of dysentery
and scurvy noted during the recent war and referred to by many previous
writers, shows the effect of intestinal disorders. These hypotheses are
tentatively advanced because it is evident that some factor exists,
apart from the mere antiscorbutic value of the diet, which at times
exerts a potent influence on the development of scurvy. Cases developing
in spite of a moderate amount of antiscorbutic food, and others not
responding to the addition of vegetables or fruit to the diet--although
not numerous--have occurred too frequently and have been reported by too
experienced observers to be brusquely disregarded. For example, Neumann,
one of the keenest clinical students of scurvy, stated that he had met
with four instances of this nature. Hess and Fish reported two similar
experiences.
The secondary etiologic factors are mainly predisposing; a few words,
however, must be added concerning what may be termed _exciting factors_.
Infection is the most important condition which may suddenly and
precipitously induce scurvy. This fact was brought to our attention in
1912 in connection with the outbreak of scurvy among infants receiving
pasteurized milk. Its explanation was not clear at the time, but was
elucidated by subsequent experience, and was described in 1917 as
follows: "Latent scurvy was prematurely changed to florid scurvy by the
presence of a ward infection; an epidemic of 'grippe' precipitated an
epidemic of scurvy exceptional in its hemorrhagic tendency." The
association of scurvy and infection has been recently emphasized by
McCarrison and others, and seems to hold good for the other so-called
deficiency diseases. In this connection one other exciting cause of
scurvy may be mentioned, namely, trauma. The older writers noticed that
following a fall or an accident, a sailor frequently developed scurvy,
and Barlow in 1894 remarked on the influence of trauma in connection
with infantile scurvy. As might be inferred, its effect is mainly to
induce premature rupture of the weakened blood-vessels; in infants we
have seen this occasioned by pressure exerted on the lower end of the
thigh to ascertain the presence of tenderness. Viewing the situation
broadly, it must be acknowledged that except for the realization that
scurvy is due to a new food factor--a vitamine--our fundamental
understanding of its pathogenesis has advanced but little, in spite of
the employment of experimental methods and the availability of modern
technic.
It is doubtful whether mere clinical studies will contribute in a large
measure to the solution of the pathogenesis of scurvy. Much may,
however, be learned by investigations of the metabolism in human
scurvy--an aspect of the problem which, as will be brought out in a
subsequent chapter, hardly has been explored. By this means may be
acquired a clearer understanding of the effect of an antiscorbutic
deficiency on the tissues and on cellular activity. Much may be expected
from physiologic and pharmacologic studies of the specific vitamine,
although it is not yet available in a pure state. Finally, it is
probable that the solution of similar questions relating to the
pathogenesis of cognate disorders--a study which is engaging the best
efforts of so many workers throughout the world--will shed light on this
particular disease.