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the primitive cardiac muscle. If we recall that Keith, in one
of his latest papers which he read upon the anatomical side of
this question before the Medical Society of London in 1909,
stated his conviction that cardiac nerve and cardiac muscle
come into such close relation that they may fairly be said to
merge in the primitive muscular fibre of the cardiac tube, it
becomes at once apparent that these focal lesions of rheumatic
carditis must have an important bearing upon this aspect of
cardiac disease.

Since Aschoff published his observations they have attracted
considerable attention in this country not because of their
bearing upon the aetiology of rheumatism, but because they are
concerned with the ever fascinating problem of the heart-beat.

Next we will take the second type of evidence supplied by
others who are opposed to our explanations, but who in spite
of this have given us indirect support.

To us there are few more curious points in the history of
cardiac pathology than the attitude held by many toward
rheumatic endocarditis. They admit it is infective ; the
evidence, indeed, in its favour is overwhelming, but they
hesitate to admit that this endocarditis may become malignant.
When, however, we analyse the meaning of this malignancy as
applied to endocarditis, we find it expresses an inability on
the part of the damaged tissues to overcome the local infection.
There may be partial, and exceptionally even complete, success,
but the rule is failure. This malignancy is, then, no new
mysterious change in the tissues, and as its antecedent we find
the most frequent is previous rheumatic endocarditis.

Now come the curious conclusions we are asked to accept :



THE PATHOLOGY OF RHEUMATIC FEVER 269

firstly, that an infection in the endocardium of rheumatic
origin is always simple — that is,, is always capable of healing ;
and, secondly, that malignant endocarditis after rheumatism
is always caused by a secondary infection of valves scarred by
previous disease.

The first conclusion is strange, because infections of the
rheumatic type are not likely to be always " simple " ; they
clearly vary in virulence as do all other infections of the same
group. The second conclusion that bacteria prefer scarred
valves is, in our opinion, a false one. There is no evidence
that bacteria prefer scar tissue ; in fact, all evidence is against
it. If the so-called scarred valves of rheumatism are examined
it will be found that the vegetations are not really scar tissue,
but are masses of unhealthy necrotic material which the scar
formation has not invaded. We hold that in this necrotic
tissue the rheumatic infection that caused the original endo-
carditis often lurks quiescent but not destroyed. The forma-
tion of scar tissue makes it difficult for leucocytosis to deal
with bacteria in these isolated necrotic patches, which, border-
ing as they do on the general circulation, are as much a source
of danger, as a necrotic gland close to the circulation is in
tuberculosis.

The recent vegetations of rheumatism are, in our opinion,
often much more chronic than is generally believed, and those
who investigate them from this point of view will find in
them areas of necrotic tissue shut off by scar tissue — that is,
they will find imperfect healing. We believe that in cases of
malignant endocarditis of rheumatic, origin the disease has been
slightly active long before symptoms call attention to the
serious nature of the disease. This link in the chain of evidence
is difficult to get, but doubtless it will be obtained by clinicians
who keep a constant watch on their patients who leave hospital
with rheumatic heart disease. When in these cases the
malignant type arises it is not necessarily because some added
infection has attacked scar or sclerotic tissue, but because some
agency lowering the general health has aroused the lurking
micrococci of a previous infection which are lying in the
necrotic areas bordering on the general blood stream.

In our original paper u we could not hazard how many
cases of malignant endocarditis were rheumatic, but we
thought future experience would show that a very considerable



270 FURTHER INVESTIGATIONS UPON

percentage would prove to be of this type. We are thus
interested to find a writer discovering that the type of strep-
tococcus most often found in infective endocarditis is not the
highly pathogenic streptococcus of suppurative processes, but
what he terms " one or other of three types of streptococci that
are more closely allied to the ' saprophytic ' streptococci of the
alimentary canal." In an analysis of ioo cases of infective
endocarditis we also note that he finds a streptococcus was
present in 62. We hold that all complete evidence goes to
show that the streptococcus which causes acute rheumatism
is a cause also of malignant endocarditis, and that the further
evidence in this condition of the frequent occurrence of
" streptococci," which for want of a better description from
others we may call peculiar, is an additional support to this view.
We would add that since our first contribution to this
question we have seen further cases in adults and children
which confirm our original examples and entirely support
the view that rheumatism may be a cause of malignant
endocarditis.

Acute Rheumatism and Rheumatic Fever Faulty Terms

The next point we would emphasise is the retarding influence
that the terms acute rheumatism and rheumatic fever exert
upon the study of rheumatism. If we compare any one other
great infection to rheumatism in its clinical course it would be
tuberculosis. This is but a repetition of a former statement,
but we allude to it now because it is so thoroughly supported
by a recent paper by Dr. R. Miller 12 upon chorea. In this
paper the writer dwells upon the fact that the choreiform
movements are but the developed disease, and that there may
be warnings weeks before these appear. The late Dr. W. B.
Cheadle, Sir Thomas Barlow, and Sir Dyce Duckworth have
called attention to the same point. This premonitory stage is
not peculiar to chorea, for heart disease and arthritis show the
same features. Many cases in childhood which develop obvious
rheumatism may suffer for some weeks from fever, anaemia,
and debility before anyone can foresee the exact meaning of
these symptoms, a point which, we may add, Dr. <G. H. M.
Dunlop has also insisted upon. How can we, in face of these
facts, keep the terms acute rheumatism and rheumatic fever
as indicative of anything but phases of rheumatism ? We have



THE PATHOLOGY OF RHEUMATIC FEVER 271

no doubt that a good deal of the mystery of unexplained heart
disease, and in particular mitral stenosis, is the result of this
imperfect naming of the disease. It is essential that some
more general term such as rheumatism, which implies neither
acuteness nor chronicity, should be used.

Rheumatic Hyperpyrexia

Hyperpyrexia is an event in rheumatism which all would
point to as one which should throw light on the pathology of
the disease. Through the kindness of Dr. Lauriston Shaw and
Dr. A. F. Hertz we have had assistance from Guj^'s Hospital
upon this question. Until this recent opportunity we had
only one case for investigation, and that not a classical
example. It was fully published by us in the Lancet in 1905
(Paper No. 18) 13 and was peculiar in that there was severe
cerebro-spinal meningitis. In the exudation there were great
numbers of strepto-diplococci, and we satisfied ourselves that
it was a rheumatic case. There is no necessity to- recount the
details of that investigation here. Our second from Guy's was
of the classical type, the patient, an adult, dying with a
temperature of 107 ° F., and the post-mortem examination
showing active rheumatism but no meningitis. The following
details give the salient features of this investigation.

The following tubes, among others, were received from
Guy's Hospital on August 13th, 1909 : (1) the turbid peri-
cardial fluid in a sterilised pipette ; (2) the blood ; and
(3) portions of the cerebral cortex. The two latter were
placed in bouillon. The pericardial fluid was incubated over-
night without addition of any medium.

The following results were obtained. A pure growth of
strepto-diplococci was present in the incubated pericardial
fluid. The cerebral cortex gave a growth of diplococci with a
few colonies of staphylococcus aureus. The blood gave a
growth of diplococci and bacillus coli. A film of the cerebro-
spinal fluid showed a few diplococci. A film of the pericardial
fluid showed the diplococci in streptococcal chains and in
considerable number.

On August 15 two intravenous inoculations were made into
rabbits. No. 1 received 30 drops of the pericardial fluid.
No. 2 received 20 drops of the bouillon culture from the
cerebral cortex which contained some colonies of staphyl -



272 FURTHER INVESTIGATIONS UPON

coccus aureus with the diplococcus. The second rabbit died
in 24 hours from acute pericarditis, and the pericardial fluid
from this, incubated overnight, showed a pure growth of
strepto-diplococci. The other organs showed no obvious
change. They were not soft and there were no haemorrhages.
The first rabbit lived a week and during that time it rapidly
wasted and developed pyrexia, endocarditis, and arthritis of
the right knee-joint. The post-mortem examination showed
early endocarditis of the tricuspid valve, a fibrino -plastic
exudation in the right knee-joint, and an infarct in the right
kidney. Cultures from the right knee-joint gave a pure
culture of strepto-diplococci.

A third rabbit was inoculated intravenously with 10 minims
of the incubated pericardial fluid from rabbit No. 1. Three
days later there was arthritis of both shoulder- joints with
wasting and general illness, but during the next week there
was gradual recovery from the arthritis. This animal died
from acute intussesception 12 days after the injection, and the
post-mortem examination showed no cardiac lesion and a
healing arthritis.

A fourth rabbit was inoculated on August 25 with a culture
from the cerebro-spinal fluid. On the 28th the right knee
became swollen and tender and the animal began to waste. No
cardiac lesion was detected.

Examination of fragments of the aortic and mitral valves,
portions of the motor cortex and pia mater of the patient
showed that the valvular lesions were of old standing and
that the brain and pia mater examined only showed a few
diplococci.

The result of this investigation may be thus summarised :
From a case of rheumatic fever with carditis, arthritis, and
hyperpyrexia a strepto-diplococcus was obtained in pure
culture direct from the pericardial fluid incubated overnight.
This strepto-diplococcus produced, on intravenous inoculation
into rabbits, non-suppurative multiple arthritis, pericarditis,
endocarditis, and infarction, and the micro-organism was again
isolated from the lesions in pure culture. The same micro-
organism was present in the cerebro-spinal fluid, motor cortex,
and blood of the patient.

It would be a mistake to infer too much from a single case,
but we believe this investigation supports the general opinion
















'VB






FIG. 84

Incubated human pericardial tiuid (x 600) from a case of rheumatic pericarditis

and fatal hyperpyrexia. The diplococcus growing- in streptococcal chains



/i-




fig. 85

Incubated pericardial fluid of a rabbit dead from pericarditis resulting from intravenous
inoculation with the diplococcus isolatedfrom the case of rheumatic hyperpyrexia. ( x 1000.)



THE PATHOLOGY OF RHEUMATIC FEVER 273

among physicians that rheumatic hyperpyrexia is a peculiar
toxsemic process rather than an intense bacterial invasion, for
although the micrococci were both isolated and demonstrated,
they were not present in the tissues or blood in any extra-
ordinary numbers.

Investigations upon the Tonsils in the Rheumatic

Two other lines of investigation have occupied our attention
in the last five years : the first is another step in the study of
the tonsils suggested to us by Mr. George Waugh ; the second
is an experimental study of arthritis, with a view to ascertain-
ing whether more than one form of arthritis may result from
intravenous inoculation of the same micro-organism. The
object of this second investigation is to widen the field of study
of rheumatoid affections, reversing, as it were, the usual method
of inquiry. The clinician seeks among this heterogeneous
group to find some one clear path. We have started along
one clear path (the study of the diplococcus) and endeavoured to
find our way some little distance into this heterogeneous group.

Taking first the tonsils in rheumatic fever we need only
mention the great frequency of tonsillitis in this disease, and
the demonstration by Dr. William Hill 14 some twenty years ago
of deep-seated foci of disease in enlarged tonsils removed from
the rheumatic. In 1900 we showed that a micrococcus found
in rheumatic lesions could be isolated from acute rheumatic
angina, and be demonstrated in the tonsils, and further would
produce similar lesions. In the next year Fritz Meyer published
an extensive paper upon the same subject, and we have
returned to the question again to work out Mr. Waugh 's
suggestion. Mr. Waugh advocates enucleation of the large
unhealthy tonsils that are so often present in rheumatic
children, and in some carefully chosen cases has done this for
us between the rheumatic attacks. These tonsils were seared
on removal, cultures were taken from their depths, and the
histological appearances of them investigated. One example
will suffice to show the kind of case investigated, six of which
have been examined up to the present date.

The patient, a male aged 10 years and 5 months, came to
the Hospital for Sick Children, Great Ormond Street, in
February 1908, suffering from slight chorea and rheumatic
pains. In 1906 he had an attack of rheumatic fever, since

18



274 FURTHER INVESTIGATIONS UPON

which he had never quite recovered his usual health, and had
always had shortness of breath on exertion. The heart was
obviously affected. There was considerable mitral regurgita-
tion, with hypertrophy and dilatation. In addition he had
two very large tonsils and was subject to sore-throats. The
cervical glands showed a moderate enlargement. In April,
when quite recovered from his active rheumatism, Mr. Waugh
enucleated both tonsils. Immediately after removal the
surface was seared, and cultures were taken from the centre of
one gland. Histological examination by section and films of
the other tonsil showed the presence of streptococci in the deep
part of the gland. The culture gave an almost pure growth
of strepto-diplococci, from which it was easy to isolate this
organism in pure culture. Five minims of this culture injected
intravenously into a rabbit produced no result. Two cubic
centimetres produced arthritis and fatal aortic endocaraitis.
One cubic centimetre in another experiment produced arthritis
of the left knee, which slowly recovered. Subsequently smaller
doses produced arthritis of the right knee-joint and fatal
endocarditis.

We have here but a repetition of the results obtained in our
original case in 1899, and independently confirmed by Fritz
Meyer 15 in 1901. The particular point of interest lies in the
fact that here we are dealing with tonsils in the rheumatic
when they are not in the stage of acute inflammation, during
an attack of acute rheumatism, but in the latent period after
previous attacks of the disease.

There can be very little doubt, we believe, that these large
unhealthy tonsils are a constant menace to the rheumatic,
and that these investigations originated by Mr. George Waugh
show decisively that there abound in the depths of these dis-
ordered tissues strepto-diplococci which will produce with
much constancy in appropriate dosage endocarditis, peri-
carditis, and arthritis on intravenous injection into rabbits.
We believe they may well explain some rheumatic relapses.
The relation of acute rheumatism and tonsillitis to the
diplococcal infection is now so well defined by clinical observa-
tion, histological investigation, and experimental research that
it constitutes one of the most satisfactory advances in the
study of the disease. We have only to contrast the explanation
it gives us with the older nervous and lactic acid theories to



276 FURTHER INVESTIGATIONS UPON

recorded example of experimental osteo-arthritis by intra-
venous inoculation. Since that date we have produced osteo-
arthritis ana peri-articular arthritis with the diplococcus
rheumaticus, and at the present time we have a very striking
specimen of an arthritis resulting from this infection. This
occurred in a rabbit which had developed inflammation first
of one knee-joint and then of the other, from which it gradually
recovered, but eighteen months later, though in good health, it
limped to some extent upon the hind limbs. This specimen
showed that there was a clear fluid in both articulations, but
the right patella was dislocated and had formed for itself a
new facet on the inner side of the internal femoral condyle and
the original facet had lost much of its cartilage, and the bones
had been eroded. The left joint showed erosion of cartilage.
This specimen is in the museum of the Royal College of
Surgeons. The occurrence of dislocations of joint surfaces in
human " rheumatoid arthritis " is well recognised, and the
production of such a deformity is strictly analogous to the
condition in the specimen just described, in that there are in
both a stretching and damaging of the capsules of the articula-
tions by a non-suppurative process, a damage to the articulating
surfaces themselves, and a faulty pull of tendons connected
with the joints. At the British Medical Association meeting
at Manchester we also demonstrated convincing examples of
the " guttering " of osteo-arthritis, and published illustrations
of these changes in a paper in the Medical Press and Circular} 1
In this paper we also showed that perivascular fibrosis occurred
in the capsules of articulations, the subject of experimental
and pathological chronic arthritis, explaining thereby the
" withering " of joints in rheumatoid affections. We have
also produced that rarefying osteitis of bone ends in the neigh-
bourhood of joints affected by chronic disease which is well
recognised in " rheumatoid arthritis."

In conclusion, we would repeat that no explanation of
acute rheumatism can, we believe, compare with that which
attributes it to an infection with a diplococcus of the strepto-
coccal group ; and that although during the last ten years
this view has gained but little headway in this country the
Chelsea Clinical Society in 1900 marked a forward step in
London when they opened a discussion on " Acute Infective
Rheumatism."



THE PATHOLOGY OF RHEUMATIC FEVER 277



REFERENCES

1 Lancet, September 22 and 29, 1900.

2 Ainley Walker, Practitioner , 1903.

3 Vernon Shaw, Journal of Pathology and Bacteriology, 1903.

4 Beattie, Brit. Med. Jour., December 1904 ; Journal of Experimental
Medicine, vol. ix, No. 2, 1907.

5 Transactions of the Pathological Society of London, 1901. Lancet,
May 4, 1 90 1.

6 La Tribune Medicate, February 26, 1910, p. 134.

7 Poynton, Transactions of the Royal Medical and Chirurgical Society,
vol. lxxxii, 1899.

8 Transactions of the Pathological Society of London, 1901 ; Inter-
national Clinics, vol. iii, Series 13.

9 Brit. Med. Jour., 1906, vol. ii, p. 1103.

10 Quarterly Journal of Medicine, vol. ii, No. 5.

11 Transactions of the Royal Medical and Chirurgical Society, vol.
lxxxv, 1903.

12 Lancet, December 18, 1909, p. 1808.

13 Lancet, December 16, 1905, p. 1761.

14 " Tonsillitis in Rheumatic States," 1889.

15 A paper read before the Congress of Internal Medicin, Berlin, 1901:.

16 Transactions of the Pathological Society of London, 1902.

17 Medical Press and Circular, April 5, 1907.



PART II

SUB-GROUP E

THE THREE PAPERS IN THIS SUB-GROUP ARE IN THE
MAIN CLINICAL IN CHARACTER, THE FIRST TWO
DEALING RESPECTIVELY WITH RHEUMATISM IN
VERY EARLY LIFE AND WITH THE ASSOCIATION
OF SCARLET FEVER AND RHEUMATISM. THE THIRD
PAPER TREATS IN PARTICULAR OF RHEUMATIC
HEART DISEASE AS AN EVENT IN THE HISTORY
OF AN INFECTIVE PROCESS RATHER THAN AS A
PARTICULAR FORM OF CARDIAC AFFECTION

XXL A CONTRIBUTION TO THE SUBJECT OF RHEUMA-
TISM BASED UPON THE STUDY OF FIFTY -TWO
CASES IN CHILDREN UNDER FIVE YEARS OF AGE,
AND AN ANALYSIS OF ONE HUNDRED CASES OF
SUPPURATIVE PERICARDITIS IN CHILDHOOD

XXII. A CONTRIBUTION TO THE STUDY OF RHEUMATISM,
WITH NOTES ON THE AFTER-HISTORY OF TWENTY-
FIVE CASES OF " SCARLATINAL RHEUMATISM "

XXIII. A RESEARCH UPON COMBINED MITRAL AND AORTIC
DISEASE OF RHEUMATIC ORIGIN. A CONTRIBUTION
TO THE STUDY OF MALIGNANT RHEUMATIC ENDO-
CARDITIS



$79



PAPER NO. XXI

A CONTRIBUTION TO THE SUBJECT OF RHEU-
MATISM BASED UPON A STUDY OF FIFTY-
TWO CASES IN CHILDREN UNDER FIVE
YEARS OF AGE, AND AN ANALYSIS OF
ONE HUNDRED CASES OF FATAL SUP-
PURATIVE PERICARDITIS IN CHILDHOOD

(Reprinted from the Quarterly Journal of Medicine, April 1908)

This short clinical paper demonstrates that acute rheumatism is not
infrequent at five years and even under that age. The suggestion that
there is any peculiarity in the age incidence of this disease which
militates against the theory of its infective origin is thus disposed of,
and its identity at this age with the condition in later life established.
Finally, a study of pneumococcic pericarditis gives a striking proof of
the great differences in the effects of the pneumococcic and rheumatic
infections upon the heart, and shows that, though the diplococcus of
rheumatism in vitro would appear to be, in some respects, closely akin
to the pneumococcus, yet in their pathogenic properties in the human
tissues these micrococci are essentially different.

There has been a good deal of difference of opinion expressed
by writers as to the frequency of acute rheumatism in children
under five years of age. Some have maintained that it is an
exceedingly rare occurrence, while others have doubted this.
The question is one of theoretical and practical import-
ance, and this is the excuse for putting on record here our
own experience as a contribution to the subject of acute
rheumatism.

The theoretical interest lies mainly in our conception of the
cause of acute rheumatism, or, as we would prefer to call it,
rheumatism. If, as one is now almost compelled to admit,
there is an infective agent, or, in the opinion of many, more
than one, which determines the active disease, it is difficult to

2S1



282 ACUTE RHEUMATISM IN THE VERY YOUNG

understand why, during the first five years of life, the occur-
rence of the infection should be very unusual. It may be
reasonably admitted that prior to school life there is less
exposure to the infection, but even then, one can hardly help
believing that a sufficient number of cases must be met with
to enable us to recognise that rheumatism does not make a
mysterious appearance at any particular age, but is
throughout life a menace to some constitutions. If this
should prove to be the case, it will help us to bring the
rheumatic infection into line with such other great infections
as the pneumococcic and tubercular.

In a symposium upon rheumatic fever in childhood, the
result of a recent Congress in America, we find one writer has
the hardihood to suggest that in England a disease in children
has been manufactured which we call rheumatism, by fitting
together all manner of divers symptoms. This procedure,
according to him, has been adopted to account for the disease
up to the age of twelve years ! No one in this country has
any qualms as to the reality of the disease from five to twelve
years, and this unguarded writing can only be a warning to
those who live in a different country and attempt to criticise
the clinical acumen of physicians who have special advantages
in any particular line of investigation.

In rheumatism at this early age there are several points of
practical interest. The question of diagnosis is one, for under
five years of age such widely different disorders as scurvy,
anterior poliomyelitis, spinal caries, congenital syphilis, gono-
coccic and meningococcic arthritis, congenital heart disease,
influenzal and pneumococcic septicaemia come into the field of
discussion. This particular aspect of the question we shall
not consider here, for it is dealt with in many books.



Online LibraryF. J. (Frederic John) PoyntonResearches on rheumatism → online text (page 25 of 42)