THE BRITISH
JOURNAL OF DERMATOLOGY.

JULY, 1900.

 

THE VISCERAL LESIONS OF THE ERYTHEMA GROUP.*

BY WILLIAM OSLER, M.D., F.R.S.,

Professor of Medicine, Johns Hopkins University.

In December, 1895,+ I published a series of eleven cases charac-
terised by—

I. Polymorphous skin lesions: (a) acute circumscribed cedema. ;.
(b) urticaria; (c) purpura; and (d) ordinary exudative erythema.

II. Polymorphous visceral lesions : (a) local serous or hemorrhagic
exudate in the walls of stomach or bowels, causing (1) crises of pain
and (2) hemorrhages; (b) acute nephritis; and (c) certain rare
pulmonary and other lesions. ’

Ul. Infiltration of synovial sheaths, peri-articular tissues, and
arthritis.

Tt would have been better, as some of my dermatological friends
suggested, not to have described the cases under the name erythema
exudativum multiforme, the term which has been used to designate
the so-called pure type of polymorphous erythema, but it was really
very difficult to find a name under which to group the cases. Duhring
has suggested that the majority of them should be regarded as
purpura rather than erythema, but in only Cases 6, 7, and 11 was
purpura the sole lesion, while in the remaining cases there was
exudate (either serous or hemorrhagic or both), with swelling,

In the following communication I shall give the subsequent history

* Paper prepared for the Jacobi Festschrift, New York, 1900,
+ American Journal of the Medical Sciences: cf. Brit. Journ. of Dermat.
Vol. VIIL., p. 55. .

VOL. XII. U
228 THE VISCERAL LESIONS OF THE ERYTHEMA GROUP.

of Case 2 of the first series, details of seven additional cases, an
analysis of the symptoms of the whole series, and shall then discuss
briefly the relations of certain members of the erythema group of
skin diseases.

I will first call attention to the extraordinary series of symptoms
presented by Case 2, the condition of which was reported on to the
end of 1895. Briefly summarised: in his tenth year this lad had
severe attacks of colic, a very barking cough, and one attack of
urticaria. In his eleventh year he had colic with an outbreak of
urticaria and purpura; later a well defined localised cedema on the
back of one hand, marked signs at the apex of the right lung, and
an enlarged spleen. In his twelfth year he had one severe attack of
colic, and the pulmonary features became more pronounced. In his
thirteenth and fourteenth years he began to present the picture of
emphysema, and the pulmonary symptoms were dominant. In his
fifteenth year he had pronounced emphysema, dilatation of the heart,
and pericarditis, of which he died. So far as the skin lesions in this
case were concerned, successive physicians in the series of attacks
might have diagnosed urticaria, purpura with urticaria, angio-neurotic
cedema, and well defined exudative erythema.

Case 2 (of Series 1, continued).—W. E. B.* Colic with urticaria in tenth year.
In eleventh year attacks of colic, urticaria with purpura, angto-newrotic edema,
exudative erythema, enlarged spleen, cough with local signs at right apex. In
twelfth year colic, enlarged spleen, cough. In thirteenth year colic, cough. In
fourteenth year pulmonary symptoms dominant, signs of emphysema. In fifteenth
year emphysema well marked, broncho-pneumonia, pericarditis, death,

Good Family History—No rheumatism; healthy, well grown, active and
intelligent; no serious illness; fairly good digestion.

Tenth Year (1898).—Attacks of severe colic, of such intensity that he would roll
on the floor. Several attacks of epistaxis. In the summer of 1893 an attack of
urticaria. In the latter part of the summer a very barking cough, suspected to
be whooping-cough.

Eleventh Year (1894).—First seen by me, March 10th, Well nourished boy, a
little pale; no skin lesions. The spleen was enlarged and extended in the para-
sternal line nearly to the level of the navel. There was moderate anemia,
4,000,000 red blood corpuscles, hemoglobin about 80 per cent. The urine was
normal. At the right apex and in the right upper axillary region there were
medium sized moist rales ; no change in the percussion note. When I first saw
the case I was completely puzzled. The enlarged spleen, with a slight anemia,

raised the suspicions of some primary blood affection, but the cough, which had
been an important feature, and the localised signs at the right apex, suggested with

* The early history of this case is given fully (Case 2) im the paper referred to.
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP. 229

the anemia, the onset of tuberculosis. The sputum (which was muco-purulent)
was examined carefully, but no bacilli were found. In the middle of April the
cough became much aggravated. Throughout May he improved very much. In
the middle of the month he had slight pains about the knees, and on the 18th
there were one or two bluish stains of fading purpura. On May 22nd, when I
saw him, he was in the midst of an attack of urticaria and purpura. This, with
the colic, gave me a clue to the possible nature of the case. Early in June he had
an oedematous swelling, without redness, on the back of the left hand, like the
ordinary lesion of angio-newrotic edema. On June 6th both ankles were swollen,
and the skin of the legs presented the remains of purpura with urticaria. On the
back of one hand there were patches of erythema with exudation. The spleen
was smaller. The patient had a good summer. I saw him October 30th, and he
looked very well. The rales had disappeared at the right apex.

Twelfth Year (1895).—March 9th. He had been at school and very well through
the winter. Last night he had a very severe attack of colic. He had a good deal
of cough, and there were numerous piping rales at the apex of the right lung.
The edge of the spleen could be felt. There were no skin lesions. Early in June
the cough became very much more troublesome, with severe paroxysms at night.
Over the apex of the right lung in front and behind the percussion note was of
higher pitch. There were numerous moist rales over the whole infra-clavicular,
mammary, upper axiliary, and suprascapular regions. The breath sounds were
harsh, not tubular. The spleen could be felt a full hand’s breadth below the costal
margin. Throughout the summer he remained very well. On October 21st the
spleen was only just palpable. The cough, which had almost disappeared, had
recently returned. The right apex had become much clearer; there were a few
rales in the right lower axillary region, and also in the left lower mammary region.
He had not been a mouth-breather and the nostrils were wide and normal.

Tharteenth Year (1896).—This was marked by only one attack of severe colic in
April, of great intensity, requiring morphia for its control. He went north for tha
summer. In October he had a recurrence of the cough, more severely perhaps
than ever before. It was chiefly nocturnal, though sometimes of such severity in
the morning that he would vomit his breakfast.

Fourteenth Year (1897).—January 22nd. He looked well and had grown. I
had not seen him for nearly eight months, and I was much impressed with the
change in the shape of his thorax, which had become more rounded, looked like a
typical emphysematous chest, and the neck muscles stood out prominently. The
resonance was impaired on and below the right clavicle. There were a great many
coarse, mucous rales in front and behind at right apex, and the breath sounds were
harsh, and had lost the breezy quality. Expiration everywhere was somewhat
prolonged. The left lung was clear, He had had no fever. For the first time
since I had seen him the edge of the spleen could not be felt. I was impressed
with the condition of the lung, as the local signs at the apex seemed so pro-
nounced. Dr. Futcher reported that the sputum, which was muco-purulent,
contained no tubercle bacilli. The urine showed no change. He spent February
and March in North Carolina, with great benefit. The cough disappeared entirely,
and he came back looking very well. He had grown and thriven in every way
Though he was free from cough, there were very well defined signs in the lungs,
numerous crackling rales at both apices, most extensive on the right side. In the

uv 2
930 THE, VISCERAL LESIONS OF THE ERYTHEMA GROUP.

right axillary region there was a friction sound. The summer was spent at
Martha’s Vineyard. He had no cough, gained in weight, had a good colour, and
a good appetite. In October, November, and December the condition of
emphysema progressively increased. I saw him again December 18th. There
was elevation of the chest during inspiration and the neck muscles stood out
prominently. Expiration was everywhere prolonged at the right apex. There
were numerous bubbling rales, very similar indeed to those heard on the occasion
when I first examined him. There were piping rales on expiration at the left apex.
At the bases of the lungs the breath sounds were clear and breezy.

Fifteenth Year (1898).—During February I attended the patient with Dr.
Lockwood for two weeks in a severe attack of diffuse bronchitis with areas of
broncho-pneumonia. The temperature ranged from 101° to 104°5°, and for two
days he was very ill. The heart was not affected. The fever gradually subsided,
and he convalesced very slowly. The attack left him with a very weak, feebly-
acting heart. In April he was able to go to Pinehurst, where he remained for a
month, and returned in much better condition. In May, shortly after his return,
he became very short of breath. There were signs of advanced emphysema ; the
percussion note was very low on the right side, the heart dulness was obliterated
and there were loud, piping rales with inspiration and expiration. He passed very
restless nights, and would frequently have to sit up in bed for hours at a time.
During the last week in May dropsy began—swelling of the feet and legs, which
gradually increased, and in the first week in June ascites. The pulse was very
rapid and feeble, and there was a- systolic murmur at the apex. The urine was
scanty, but contained neither albumin nor tube casts. On June 16th Dr. Lockwood
detected an acute pericarditis. On the following night he was very restless, and
could only breathe comfortably with the head held far forward. On the following
day when I saw him there was a very loud pericardial friction over the whole
cardiac region. He was much cyanosed. The pulse was extremely rapid and
irregular, and he died that night.

Srconp SERIES.

Case 12.—Neurasthenia; dilatation of the stomach; cole for two years at
intervals; exudative erythema ; leucocytosis.

Berta L., aged 24 (Hospital No. 18,151), admitted December 19, 1896, com-
plaining of pain and soreness in the abdomen. She had been a very nervous girl,
‘and had had a good deal of uterine trouble. For four years she had had dilatation
of the stomach, for which she had used the stomach tube. She had lost much in
weight. . : .

The patient was extremely neurotic, and impressed us as a case of very severe
neurasthenia with dilated and depressed stomach. She was thin and sallow, the
face pigmented. On admission she had a most extreme grade of dermatographia.
The slightest scratch was followed by. intense erythema and sometimes urticaria.
Two days after admission, on the morning of the 22nd, she had an extensive ery-
thematous rash over the face, arms, and thighs. Upon the skin of the thighs and
arms there were large raised red areas in places diffuse, in others isolated, like big
wheals. In the afternoon she had a violent attack of abdominal colic without
nausea or vomiting, which lasted for about half an hour. The temperature on
admission was 102°, and for four days ranged from 99° to 102°. She had no chills.
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP. 231

There was considerable increase in the area of splenic dulness. The leucocytes
were 13,450, There was no albumin in the urine ; no tube casts. On questioning
the patient, she says that for two years she had been liable to these attacks of colic,
which came on with great suddenness. This was the first one in which it had
been associated with any skin lesions. The erythema persisted for about two days
and then disappeared. It did not extend to the face or hands,

Casu 18.—Attacks of colic every week or ten days for six months ; on admis-
ston typical lesions of erythema exudativum multiforme ; high fever ; tmprove-
ment ; recurrence ; pains in the joints ; arthritis in one joint of finger.

Ruberta F, B., aged 49 (Hospital No. 19,718), admitted June 14, 1897, com-
plaining of pains in the hands and a skin rash. There was no rheumatism in the
family. .

Personal History.—She had had the ordinary diseases of childhood and once
urticaria. No rheumatism. When twenty-six years old she had severe diarrhwa
with bloody stools; was ill five weeks. She has had six children. In November,
1896, she was operated upon successfully for an ovarian tumour,

Present Iliness.—One week after the operation she had an attack of severe
abdominal pain, limited to the epigastrium, which came on very suddenly. While
in hospital she had three attacks, all requiring morphia. Since dismissal she has
had an attack every week or ten days. Twice she has had two attacks in a week.
She has bad no vomiting, but she is always slightly nauseated. The intensity of
the pain is such that she cries out at the top of her voice. She always has fever
with the attacks, The pain comes on, she says, “as suddenly as one could blow
out a light,” and leaves her just as quickly. .

On June 8rd she hada slight chill, and has not been well since. On the morning
of June 12th she noticed a few small red papules on the left hand. About 2 p.m,
she had a slight chill, followed by fever, with sudden pains about the joints, and
an eruption appeared in many regions of the body. Her eyes became red and
painful. On the 13th the eruption became more raised and confluent. She had
considerable pain at the onset, no vomiting, but some nausea, no diarrhoea.

On ‘admission she was a well nourished, stout woman; conjunctive deeply
injected; temperature, 104°5°; tongue coated. The skin presented most extensive
lesions of erythema multiforme. Face and neck presented many raised, red, infil-
trated areas, some of which were surmounted by small vesicles. On the legs and
thighs there were deep red blotches, the smallest about lem. in diameter, the
largest about 2.cm., raised and in places looking like erythema nodosum. On the
hands and forearms the rash was infiltrated, the spots less red than those on the
legs and face, and surmounted by large, clear vesicles. On the hands there were
large, confluent, indurated, deep red areas, which were capped in places with
hemorrhagic vesicles. The first phalanx of the right forefinger was swollen, deeply
cyanotic, and surmounted by many vesicles. The skin of the thumb of the right
hand presented a few hemorrhages. The fingers were excessively tender. It was
noted as an interesting point that with the extensive lesions on the hands there
was no tenderness or swelling of the epitrochlear glands or of those in the axille.

During the first two days the temperature ranged from 102° to 108°. The rash
persisted; many of the infiltrated areas on the hands and arms became capped
with small blebs, the contents of which in places became purulent. The hands
and fingers were greatly swollen. The legs showed fresh outbreaks of erythema ;
232, THE VISCERAL LESIONS OF THE ERYTHEMA GROUP.

no vesicles. The edge of the spleen was palpable. There was no involvement of
the heart. The temperature fell on the 19th. Fresh crops appeared on the 17th
and 18th, and on the former date she complained of much soreness in the joints.
Unfortunately the urine chart was mislaid.

Case 14.—Man aged 57; from twentieth year every few months attacks
of nausea, vomiting, and abdominal pain associated with outbreaks of urticaria ;
no hemorrhages from the mucous membranes; final attack with purpura and
urticaria ; much vomiting and profuse and fatal hemorrhage from the stomach,
with blood in the urine and the passage of blood from the bowels,

This very remarkable case in a physician, aged 57, I saw on May 8lst, 1898,
with Dr. Wilkins. He had been a temperate man, of good family history. He
had worked hard, and had been singularly free from diseases, except the one to be
described. He had never had rheumatic fever,

From his twentieth year he had had attacks of urticaria of the greatest
intensity. Asa young man they occurred at long intervals, but during the past
five years he has rarely passed three months without an attack. Hach one was
associated with nausea, vomiting, and great pain and tenderness in the epigastric
region. The eruption usually appeared in broad patches, and-covered almost the
entire surface of the body. It persisted from the outset to the close of the attack,
which lasted usually from a week to ten days, or even two weeks. After the out-
break the vomiting and pain would subside, but the urticaria would persist.
Subcutaneous or mucous hemorrhages did not occur until the last attack. No
microscopical examination of the urine was made until the summer of 1897. For
the past two or three years the attacks have been associated with great depression
of the circulation. The temperature rarely rose above normal. In July, 1897,
Dr. Wilkins found albumin and tube casts in the urine, and detected marked
sclerosis of the peripheral arteries.

Dr, Wilkins, who attended him for years, said that it was impossible to
appreciate the intensity of the attacks without seeing them. The nausea,
vomiting, and abdominal distress, the itching of the skin, and the persistence of the
attacks for a week or ten days, made his life wretched; yet he bore up bravely and
attended to a large practice.

The final attack began April 25th, and followed the usual course until May Ist,
when it was complicated with a bronchitis. On May 20th he went to Atlantic
City, and while there, May 26th, for the first time he vomited blood. He returned
home May 80th, and at 1 a.m. on the 31st he had a profuse hemorrhage from the
stomach.

I saw him on the morning of the 31st with Dr. Wilkins. He was well nourished,
but looked pale and sallow. On the left ear there was a small tophus. The
tongue was clean, but presented on the right margin two spots of hemorrhage, one
of which had broken and was oozing blood. Beneath the skin of the arms, trunk,
and legs, were many bluish-black subeutaneous hamorrhages. On the back there
were at least a dozen, ranging from 2 to 5 or 6 mm. in diameter. On the outer
surface of the right thigh there was a localized solid infiltration of both skin and
subcutaneous tissues, forming a hemorrhagic nodule the size of a walnut. On the
radial side of the left arm there was a very extensive fading ecchymosis. On
different parts of the body there were small petecnie. The apex beat was outside
the nipple line. There were marked hemie murmurs. The urine showed a
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP. 233

moderate amount of albumin and a few tube casts. The radials. were sclerotic ;
pulse a little rapid. ~ ;

On Wednesday, June 1st, he became very much worse. He had epistaxis; the
purpurie spots increased ; he had vomiting of blood, hemorrhage from the bowels,
and blood appeared in the urine. He became very feeble, and died early on the
morning of June 2nd. There was no autopsy.

Case 15.—When a lad one attack of hemiplegia with aphasia lasting for a
week; within a year five or sia attacks of transient hemiplegia; history of
migraine in 1896, and a mild atiack of rheumatism; angio-neurctic edema of the
upper lip; outbreaks of urticaria; in 1897, attack of abdominal colic, with pains
an the legs and an outbreak of purpura and urticaria; in 1898, hematuria and
albuminuria.

- C. A. R., physician, aged 29, a large, robust man, weighing above two hrnudred
pounds, consulted me February 10,1898, and gave a long history of himself, of
which I give an abstract.

From childhood, indigestion. When 12 or 18 years old, after a hearty break-
fast, he had right hemiplegia and aphasia, which lasted for a weék or ten days.
Within the year he had five or six attacks of hemiplegia, each successive one less
severe, and not accompanied by aphasia. From that time until the present he
occasionally feels a numb, tingling sensation in the side. In 1893 he had lumbago
of a severe type. In 1895 a severe attack of grippe. At this time he began to
suffer badly with attacks of migraine, which he has had at intervals for some
years. In 1896 he had a mild attack of rheumatism, confined to bed only two or
three days. In February, 1897, while in New Orleans, he had a sudden attack of
swelling and pain in the feet. About the same time he began to suffer with sore-
ness at the ends of the fingers. The upper lip would frequently swell, and he
would have outbreaks of urticaria, associated with darting pains in the legs of
very great intensity. In May, 1897, after exposure to a draught when heated, he
had an attack of great soreness in the right iliac fossa, supposed to be appendicitis,
temperature 102°, with some colic. While convalescent from this he had another
remarkable attack of pain in the calves of the legs. They became so sore and
tender that he could only walk with a cane, and was afraid that abscesses were
beginning to form. Associated with it, however, there were large wheals of
extravasated red blood. On May 26th he had another attack of nettle-rash.

When I saw this patient in February, 1898, his general condition was good, he
had no arthritis, and there were no signs of appendicitis.

In May, 1898, the patient had a chill, followed by hematuria and albuminuria,
which had disappeared by June Ist, With this there was a.return of the pain in
the right side. oe

The doctor writes: ‘I am convinced that this attack of nephritis is only a part
of my old trouble.” : :

Case 16.—For three months, attacks of pain in the abdomen, with vomiting ;
swelling of the joints; purpura; recovery. »~

Harry L., aged 11, applied at the Out-Pétient Medical Department March 22rd,
1899, complaining of indigestion, pain %n the stomach, and vomiting.

Family History.—Father and méther living and well; one sister living who

has indigestion; one brother dféd of dysentery. No members of family have
suffered with rheumatism.
234 THE VISCERAL LESIONS OF THE ERYTHEMA GROUP.

Personal History.—He was delicate as a baby. Has had measles, chicken-pox,
and whooping-cough. When 9 years old he had some stomach trouble of doubtful
nature. : . . .

Present Illness —In January, just about two months ago, the patient was taken
ill suddenly with pain in the abdomen and vomiting; the attack was attributed to
the food which he had eaten the night before. The symptoms persisted for nearly
a week, and the patient could only retain diluted milk. The pain came in
paroxysms of great severity. From this time the patient has been ill off and on,
frequently having had to remain in bed with the attacks of pain, and particularly
if he took any extra food. He has been weak and nervous, and has lost in weight.
During the first attack in January an eruption was noticed on the legs, and at this
time one ankle was considerably swollen, and later one knee.

‘When seen March 28rd, he was just recovering from an attack. He looked pale
and weak, and a little anemic. There was nothing of note in the examination of
the chest. Neither the spleen nor the liver was enlarged. The abdomen was not
swollen, nowhere tender on pressure. On both thighs and legs there were recent
purpuric spots, varying in size from a pin-head to a split pea. They were not
raised. The left ankle still looked a little swollen. The right knee was slightly
flexed and still a little stiff. The urine showed no trace of blood or albumin.

The blood coagulation time was three minutes. He was ordered Fowler's
solution, and the mother was given very specific instructions with reference to the
diet of the patient.

April 10th.—The patient has improved very rapidly. He has had no gastro-
intestinal symptoms, the joints are now quite well, and the purpuric spots have
disappeared completely.

Case 17.—Following influenza, in January, attacks of arthritis with cramps
an the abdomen and an outbreak of urticaria; eight attacks between January
and May; during stay in hospital, swelling of wrists and back of hand;
erythema ; urticaria, spontaneous and factitious ; no purpura; recovery.

Geo. K., aged 18, admitted to Ward F, May 17th, 1899, complaining of pains |
in the joints, shortness of breath, and pains in the abdomen.
Family History.—Father died of an accident. Mother is living and well.

There are two sisters and one brother. No similar troubles in the family. No
rheumatism.

Personal History.—Measles and mumps when 7 years old. Never ill again
until last summer, when he had chills and fever, but, on inquiry, there is no history
of any definite chills. In December he had an abscess on the back of the hand.
In January of this year he was ill with influenza. He has worked hard for a year
making confectionery. He does not use alcohol or tobacco. His general health
has been excellent; he has never had rheumatism or chorea,

He has always bled easily, from the nose, and last year, during the very hot
weather, he bled almost every ather day.

Present Iliness.—While in bed in January with what was called the influenza
the patient had swelling and pain in theeet and hands. He has not been able to
work since the middle of January, except fox two weeks. During the first week in
January he noticed on his legs and on the arms “ lumps” like those following the
bites of insects, about the size of a quarter of a dozlar (2°5 cm.) in diameter. They
burned and itched, and gradually disappeared. As Many as a hundred came out

 
  
 
 
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP. 235.

in a crop together. With this there was some swelling of the arms and legs, At
the same time he had attacks of cramps in the abdomen. He has had in all about
eight of these attacks since January. They were usually very severe, causing him |
to ery out, and he was doubled up in them. _ He has noticed that he has been short
of breath for nearly a month. He has had no fever, ,

Condition on Admission.—The patient was a well nourished, healthy-looking
young man. The tongue was clean; pulse regular, 80, of good volume.

The arms looked natural ; no pain or swelling about the shoulders or elbows.
The right wrist was somewhat swollen and painful. Both hands were swollen;
looked a little cyanotic, cold, and were slightly tender on pressure; there were no
urticarial wheals. No swelling over the metacarpal or phalangeal joints. There
was slight tenderness of the right knee; no swelling. There was no purpura.

Heart.-The maximum impulse was in the fifth interspace, outside the nipple
line. There was no thrill. At the apex there was a loud, rough, blowing murmur,
propagated into axilla, and heard distinctly over the whole back of the chest. At
the aortic area there was a rough systolic murmur of less intensity than at the
apex. The spleen was not palpable. There was no fever. The specific gravity of
the urine was 1°107; no albumin, no tube casts.

May 18th.—On the backs of both arms I noted a slight erythema with a few
wheals of urticaria. They were present also on the outer side of the left thigh.
Over the back of the left hand there was a swelling without special redness. The
patient had improved very much.

On May 28rd he complained of pain in the first phalangeal joint of the left ring
finger, which was reddened and swollen, not tender. There were two urticarial
wheals on the right forearm, and one on the left. Factitious urticaria was readily
produced. The blood coagulation time was four minutes fifty seconds.

May 26th.—The patient had a severe attack of colic to-day at 12.30. It passed
off in a few hours. There was no rise in temperature. The abdominal pain
persisted at intervals for a few days.

On June 4th the dermatographia was not so marked. There were still some
urticarial blotches.

June 9th.—The patient had been up and about. The joint pains had subsided.
The urticaria still came out at times about the joints.

June 19th.—Condition very good. Patient discharged. During his illness this
patient had no purpura.

Case 18.—During first year swelling of knees; from second to seventh years
frequently recurring attacks of pain in the abdomen with vomiting and with
swelling of the knees, but no skin rash; following vaccinatio., attack of great
severity with extensive lesions of erythema, purpura, and urticaria; melena ;
recovery ; recurrence of the skin lesions; enlargement of the spleen.

Barbara P., aged 7, admitted to Ward G, March 28th, 1899, complaining of pain
in the abdomen and high fever.

Family History —The parents are living and well, There are three brothers
and three sisters. No history of rheumatism ; no siinilar cases have occurred. It
seems in all respects to be an exceptiomally healthy family.

Personal History.—The child kas had measles, mumps, chicken- -pox, and
whooping cough. When three wonths old she had swelling of the knees, which
the doctor called acute inflammatory rheumatism, and which lasted on and off for
236 THE VISCERAL LESIONS OF THE ERYTHEMA GROUP.

five months. No other joints were affected. The condition has recurred occasion-
ally. She never had any breaking out upon the body; never had bleeding from
any mucous membranes. Since her second year she has had at intervals of a week
or two gastro-intestinal attacks, characterised by vomiting and severe cramp-like
pain about the navel, which would cause her to ery out. The attacks lasted for
one or two days. At times during these attacks the legs would become swollen to
the ankles, and the knees were tender, the left always worse than the right. They
were never reddened. The mother, who seems an intelligent woman, was
questioned very carefully as to these attacks, and gave always the same account.
She was positive that not a month had passed since the child’s second year without
an attack of this cramp colic and vomiting. She has never noticed any blotches or
redness of the skin.

Present Attack.—Three weeks ago the patient was vaccinated, and two days
later was unable to go to school on account of loss of appetite and pains in the
limbs, which lasted for two or three days, and have recurred at intervals. She had
no cramps, no vomiting. The present attack dates from four days ago, when she
began to have fever and vomited a good deal, chiefly the food she had eaten.
With this there was much pain in the abdomen. ‘he left leg became swollen
from the knee down, and a dark eruption appeared upon the skin of the legs in the
form of dark brown spots about the size of a quarter of a dollar (2°5 cm.) in
diameter, raised and capped with small blisters. The spots were painful, The
next day the eruption had faded, but other red spots came out about the knees, and
yesterday they appeared on the back and elbows. The pain has persisted during
the past four days, and she has vomited at intervals. The mother says it is the
same sort of painful attacks that she has had so frequently.

Present Condition.—Dr, Futcher dictated the following note: The child is fairly
well nourished. Lips and mucous membranes are of a good colour. The teeth are
discoloured, but not decayed. The tongue is coated with a slight brownish fur.
Pupils equal and of normal size, react to light and on accommodation. Pulse, 108,
of fairly good volume and tension, regular in force and rhythm. Vessel wall not
felt. Temperature on last admission at 10.80 last night was 99°5°, since when it
has not been higher.

On left upper arm is a very large scab, the result of vaccination sixteen days
ago. The skin is slightly reddened and infiltrated about the crust. The glands in
the axilla slightly enlarged. Over the right elbow are a number of slightly
elevated papules which are somewhat hemorrhagic in character. The redness
does not disappear on pressure. There is one small hemorrhagic papule on
the left elbow-joint. Over the right knee-joint are a number of purpuric spots.
Some of these are about three-quarters of a cm. in diameter. A few pin-head
purpuric spots over left knee-joint. There are no urticarial wheals on the body.
Vaso-motor skin reflex active, but no factitious urticaria. None of the joints are
swollen, nor are any of them psinful this morning; no stiffness of the cervical
muscles. Post-cervical glands slightiy enlarged: left epitrochlear gland distinctly
enlarged and easily palpable: inguinals very slightly enlarged.

Thorax.—Well formed and symmeical. - Lungs clear over fronts and backs on
auscultation. .

Aeart.—Point of maximum impulse visible and palpable in fourth interspace,
4 em. from mid-sternal line. Impulse forcible; no thrill. Cardiac dulness not
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP. 237

imereased. Auscultation—first sound very loud and booming at apex; both are
clear at aorticand pulmonary areas, and of normal relative intensity. No murmur
in vessels of neck. ,

Liver,—Is not enlarged.

Abdomen.—Looks natural, symmetrical. Respiratory movements present.
General abdominal tenderness. The pain is most severe in the umbilical region ;
no localizing symptoms in region of appendix. Patient says it is a little more
tender in the right than left iliac fossa. There is no muscular spasm. Spleen not
palpable. .

March 30th.—Her temperature is normal. There-is a diffuse erythematous
rash over the right cheek and the lower jaw, and a few discrete erythematous
raised patches on the neck: The redness does not entirely disappear on pressure.
On the upper. and lower lips are small patches of a cherry-red colour, which
partially disappear on pressure. No.pain or swelling of the joints. Blood cultures
made by the usual method negative. The urine has a specific gravity of 1:027,
no albumin, no tube casts.

March 81st.—There are a few new purpurie spots over the left knee-joint.
Those on thé right knee and right elbow are gradually clearing. She still com-
plains of pain in the region of the navel. On examination there is a little blood
in the stools to-day.

April 1st——Tongue still very heavily coated. Over the left elbow there is a
fading crop of purpura. On the right elbow there is patch of erythematous
infiltrated nodules of a deep red colour, capped with dried vesicles. On the
right knee I noted that there were several infiltrated patches looking like purpura
urticans.

April 2nd.—Patient cries if the abdomen is touched. There are a few fresh
raised purpuric spots on both elbows,

April 8rd.—Fresh purpuric spots in both gluteal regions, many of them slightly
elevated.

April 4th.—Fresh spots on knees, elbows, and buttocks. Yesterday the child
complained much of pain. She still vomited occasionally after taking food. A
few flecks of blood in the stools.

April 5th.— Fine small purpuric spots appeared since yesterday on the left
elbow. Noabdominal pain to-day. The heart sounds are quite clear. ’

April 6th.—Yesterday the child began to pass more blood in the stools. During
the night she had several evacuations of bloody mucus and of a thin bloody fiuid.
She had slight pain in the abdomen. She has had about a dozen small stools this
morning, all with blood and mucus.

At the bend of the left elbow there appeared since yesterday subcutaneous
hemorrhages from 5 em. to 2°5 x 1:5 cm. in diameter. They are tender to the
touch and resemble recent bruises. A number of smaller patches are scattered along
the extensor surfaces of the forearm. Fresh purpura about the left elbow.

April Tth.—Patient does not look so well this morning. Complains of severe
pain in the abdomen. She looks a little anwmic from the intestinal bleedings,
which continued throughout yesterday and last night, but are less frequent to-day.

April 9th.—She had seven stools in the past twenty-four hours; fluid, greenish-
black, with a small amount of thin fluid blood. Very little abdominal pain.

April 10th.—Fresh hemorrhages on both surfaces of the forearms, a few on the
238 THE VISCERAL LESIONS OF THE ERYTHEMA GROUP.

right hand. -Bruise-like ecchymoses on the palm of the right hand, and a large
one on. the left.

From the 12th the patient improved. There were afew fresh purpurie spots on
the 14th and on the 16th, on which date too there were noticed several small ulcers
over the tongue and inner surface of the right cheek.

April 22nd.—The patient has been doing remarkably well. On the 29th she was
discharged.

Blood.—A very careful study of the blood in this case was made: ‘by Dr. Gwyn,
of which the following is a summary :—

Red Blood Corpuscles.—On admission they were nearly 6,000,000 per c.mm.
After the hemorrhages from the bowels they were reduced, but did not fall
below about 4, 800,000.

_ Hemoglobin.—Eighty per cent. on admission, falling after the hemorrhages,
and was only 60 per cent. on April 24th. .

Leweocytes.—There was pronounced leucocytosis from the onset: on March 29th,
18,800; ori March 31st, 87,000; on April 2nd, 45,000. Then they gradually fell
and were normal on April 27th. The differential count at the height of the
leucocytosis (500) gave polynuclears 86 per cent., small mononuclears 6° 2, large
mononuclears 2°6, transitionals 2°8, eosinophiles -4, nucleated red blood cor-
puscles 1.

Coagulation Time, April 7th, from 1 minute 80 seconds to 1 minute 55 seconds;
April 28rd, 2 minutes to 2 minutes 15 seconds.

Blood Platelets, April 13th, 122,000 per c.mm.; April 23rd, 230,000 per ¢c.mm.

Blood Cultures, made twice, were negative.

The temperature range was between 99° and 100°5°; even when she was quite
convalescent her temperature was between 99° and 100°.

May 8th.—The patient returned to-day complaining of a breaking out of spots
on the legs, which came the day after her discharge. She looked a little pale, and
she had numerous purpuric spots over the ankles, legs, knees and lower thighs,
Over each elbow on the olecranon there was an erythematous spot about 2 em. in
diameter, pale red, raised, with a tendency to clear in the centre. An identical
spot almost completely surrounded the tip of the little finger of the right hand.
The edge of the spleen was distinctly felt. There were no urticarial wheals, and
no abdominal tenderness.

ANALYSIS OF THE SympProms.
I.—- THE VISCERAL MANIFESTATIONS.

(a) The Gastro-Intestinal Crises.—This special feature in the entire
group of cases presents the most distressing, though not the most
dangerous, of the visceral complications. The attacks may be
characterized by colic alone, more frequently colic and vomiting,
colic with vomiting and diarrhea, and lastly colie with vomiting of
blood, or the passage of blood in the stools. As a rule, with the
gastro-intestinal crises there are cutaneous manifestations,- but not
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP, 239

invariably. In Case 2 there were severe attacks of the most
agonizing colic without any other symptoms. Cases 1 and 18 are
particularly interesting as illustrating the nature of certain obscure
forms of gastro-intestinal colic, particularly in children. Case 1
consulted me for remarkable attacks, which recurred every two
months, lasting for from six to ten hours, accompanied with fever
and remarkable delirium. These had recurred for nearly eight years,
For the first six years, with the attack he had an outbreak of what
he called big liver-spots. For two years there had been no skin
complications. In Case 18, for five years the child had been plagued
with attacks of colic and vomiting, for which the mother had
consulted many physicians. When she came under my observation
the nature of the trouble was made evident by the concurrent out-
break of an exudative erythema. These crises are identical with
those which occur in the angio-rieurotic edema. Several members
of the family with this disease which I have described* had had
urticaria, and the patient who came under my care lad coin-
cidentally with the angio-neurotic oedema characteristic urticarial
wheals on the chest and thighs.

Case “14 “illustrates the remarkable relationship which exists
between urticaria and the gastro-intestinal crises. The association
of digestive disturbance. and hives is common enough, but these cases
are, I think, somewhat different, and it is reasonable to suppose that
the lesions causing the pain in the abdomen are associated with the
formation of wheals and swelling in the mucous membrane of the
stomach and intestines. F. A. Packardt has recently considered the
question of urticaria of the mucous membranes in an exhaustive
paper, in which many references are given to the formation of wheals
in the throat and mouth. Though writers speak of involvement of
the stomach and intestines, I know of no instance in which the
lesions have been actually seen in these parts. Coleott Fox, in his
article on “ Urticaria,” in Allbutt’s System, states that wheals have
been seen in the stomach of a rabbit and dog and cat. In Case 14
the patient had for yeats recurring attacks of severe pain in the
stomach, with coincident urticaria, the skin lesions lasting for a
much longer period’ than the abdominal symptoms. Packard refers to

* American Journal of the Medical Sciences, Aptil, 1888.
{ Archives of Pediatrics, October, 1899.
240 THE VISCERAL LESIONS OF THE ERYTHEMA GROUP.

a case of Lemonnier, in which there had been giant urticaria and an
attack of. vomiting of blood, which was attributed to urticaria of the
stomach. Both Pringle* and Chittenden} have reported cases of
recurring attacks of hematemesis with urticaria. It is interesting to
note that in Case 14 the patient had hemorrhage from the stomach
as a terminal symptom. In the series of eighteen cases, urticaria
was present at some time or other in eight cases, not including the
three cases in which acute circumscribed cedema was present.

(0) Hematuria and Nephritis—Acute nephritis occurred in eases
3, 4, 5, 6, 8 and 15. Chronic nephritis occurred in Case 14, and
hematuria at the close. In a case referred to in my previous paper,
reported by Dr.. Prentiss, of Washington, a chronic nephritis of
several years’ duration followed an attack of arthritis, with purpura
and gastro-intestinal crises.

To two of the instances of nephritis I may call particular attention,
as death directly occurred from this complication. In Case 8, a boy
of six years, the onset was with pains in the ankles, colic and urti-
caria. The colic recurred with great severity. It was not until the
fifth week of his illness that the urine became scanty and albuminous,
and showed red blood corpuscles and many tube casts. He died with
dropsical symptoms in three months. In Case 8 the disease set in
with pain in one ankle and urticarial rash. Within a month the
child had anasarca, with albuminuria and tube casts in the urine.
The patient died in uremic coma.

(c) Hemorrhages from the Mucous Surfaces.—These occurred in six
cases; from the bowels in Cases 3, 6, 11, 14 and 18; from the nose
and gums in Case 10; from the stomach in Cases 11 and 14; from
the kidneys in Cases 11 (not associated with nephritis) and 14.
Several of the cases of acute nephritis had a few red blood corpuscles
in the urine.

(d) Cerebral Symptoms.—In two cases in the series there were
remarkable symptoms pointing to involvement of the brain. In
Case 1, a man aged 27, who. during six years had recurring
attacks of gastro-intestinal crises, with the onset of the symptoms he
had fever and became delirious and talked nonsense. In Case 15 it
seems highly probable that the recurring attacks of hemiplegia, five

* Clinical Soctety’s Transactions, Vol. XVIII.
+ British Journal of Dermatology, 1898.
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP. 241

or six within a year, were associated with changes in the brain of
essentially the same nature as those which subsequently occurred on
the lip and in skin. They remind one somewhat of the attacks of
recurring aphasia with paralysis in cases of Raynaud’s disease.

(ec) Pulmonary Complications.—Only one case of the series (2)
presented marked pulmonary symptoms, to which I have referred in
the supplementary history of the case.

In erythema nodosum and in urticaria, asthmatic attacks have
been described, due, it is thought, to changes in the mucous mem-
branes of the bronchi of a nature analogous to those in the skin.

Packard, in the paper already referred to, reports cases of the
coincidence of asthmatic attacks with urticaria, and gives a very full
consideration of tne literature. The two conditions have occurred
coincidently, or an outbreak of urticaria may replace an asthmatic
attack. In Case 2, without positive asthmatic attacks, there were
constant signs of bronchial trouble, but it was not until the
emphysema was well established that there were bouts of nocturnal
dyspnoea.

It is interesting to note that in not one of the series of eighteen
cases was there acute endocarditis, a not very infrequent lesion in
certain forms of polymorphous erythema.

Il.—-SKIN LESIONS.

An analysis of the lesions of the skin in this series is of interest.
In four (Caseg 6, 8, 11 and 16) purpura alone was noted. In the
remaining fourteen cases the lesions were characterized by erythema
with exudation, either urticaria or urticaria with purpura, acute
circumscribed cedema, or the lesions of a typical erythema multi-

forme. Acute circumscribed cedema occurred in Cases 2, 7, and
15, all in association with other exudative lesions. It is interesting
to note that the skin lesions may be absent for a protracted period as
in Case 1 for two years with recurring crises of great severity, or in
Case 8, severe attacks for five years before any skin lesions appeared.

One of the most interesting features in these cases is the incon-
stancy of the character of the skin lesions; thus in Case 2 the lad
had urticaria in his first outbreak, subsequently urticaria and
purpura, and later an area of angio-neurotic edema of the most
249, THE VISCERAL LESIONS OF THE ERYTHEMA GROUP.

characteristic form, and still later, on one hand; very typical lesions
of an exudative erythema.

Case 14 illustrates an “extraordinary recurrence of urticarial attacks
for m=ny years. No cutaneous Hemorrhages™ appéared until his ‘final
and fatal illness, in which there were hemorrhages into the skin and
from the-mucous surfaces. In some cases urticaria has existed with
the purpura, and in some, simple purpura in one place and purpura
urticans in another. I have not seen the co-existence of urticaria
with angio-neurotic cedema, which has been referred to recently by
Oppenheimer (Lancet, 1898, Vol. I. p. 570), but in one case of the
hereditary form, which I described some years ago, urticaria had
preceded the outbreaks of cedema.

This great variability in the character of the skin lesions is of
considerable moment, and it is quite possible that within a year in
an individual case the diagnosis might be given of simple purpura,
peliosis rheumatica, angio- -neurotic oedema, exudative erythema, and
simple urticaria.

III.— ARTHRITIS.

“Swelling of the joints: or of the synovial sheaths or peri-articular
tissues occurred in ten of the cases in the series. The joint trouble
may be transient, and, as in Case 2, may occur but once in a
prolonged illness. There may be .a polyarthritis of great intensity
simulating acute rheumatic fever, as occurred in Case 4. Infiltration .
of the peri-articular tissues and of the subcutaneous structures over
the joints may simulate a genuine arthritis. In some of the cases
’ the swelling was chiefly along the tendons, as on the backs of the
hands.: In one case (5) there were swelling and pain in the left
biceps muscle. In other instances, as in Cases 7 and 18, there may
be swelling of the foot and ankle joint and of the leg, due to extensive
infiltration, edematous or hemorrhagic. In Case 18, the attacks of
swelling of the knees and legs, without any skin rash and in connec-
tion with the recurring cramp-colic, were due, in all probability, to
infiltration about the joints. I have not seen subcutaneous fibroid
nodules in any of the cases.

And lastly a few remarks on. the mutual relations of the members of
the erythema g group.

- That there is a close affinity between exudative erythema, Henoch’s
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP. 243,

purpura, peliosig rheumatica, urticaria, and angio-neurotic oedema,
is shown by, first, the similarity of conditions under which they
occur; secondly, the identity of the visceral manifestations; thirdly,
the substitution of these affections for each other in one and the
same patient at different times. The student is, however, at the
outset confronted by this interesting feature. On the one hand,
similarity of lesions may result from a variety of causes. The
mm —4¢ rash of iodism, of endocarditis, of scurvy, and of small-pox
‘uce“identical. The wheals of urticaria from nettles, of an acute
gastric toxemia, and from the poison of the malarial parasites are
indistinguishable. A typical acute exudative erythema may result
from several causes. On the other hand, unity of cause may be
associated with a variety of lesions. In one and the same person
within a few months, presumably under the same. etiological condi-
tions, there may be a multiplicity of skin lesions ; and, as in several
of the cases here described, four. or five separate diagnoses would be
required to cover the cutaneous lesions at different periods. We
cannot say why in one case there is exudate of red blood corpuscles
without erythema (purpura), in another a serous exudate with
hyperemia (urticaria), in a third serous exudate with hyperemia
and hemorrhage in varying degrees (erythema exudativum multi-
forme), in a fourth serous exudate alone (localized cedema). Two or
three of these lesions may co-exist or may rapidly succeed each other
during the same attack, or in succeeding attacks the skin lesions
may vary, urticaria in one, purpura in another, and so on.
ABtiologically the cases here reported are very difficult to group.
Cases 1 and 15 are peculiarly obscure, and suggest a relationship with
migraine. In Case 12, associated with a dilated stomach, the cause
could be looked for in all probability in the products of gastric fermen-
ation. Case 14 belongs to that remarkable group, comprising many —
-cases of localised cedema (as well as ordinary urticaria), in which we
must suppose that during long periods of years, in association with a
‘special vulnerability, inherited or acquired, of the vaso-motor system,
here is manufactured some poison, either endogenous or exogenous
astro-intestinal). Case 5 followed an acute infection (gonorrhea),
and comes in the category of the acute infectious erythemas, of which
two forms may be recognised, a specific independent malady, which
has been met with in epidemic form, and a variety which may occur

   
  
 
   
244 THE--VISCERAL LESIONS OF THE ERYTHEMA GROUP.

in any of the acute infectious diseases. It is quite possible that some
of the cases were of rheumatic origin, though I hold with those who
do not look upon the arthritis, so commonly present, as necessarily
indicating the presence of a rheumatic poison.

A point of special interest is the relationship of certain forms of
purpura to the erythemas. Schénlein’s peliosis rheumatica may be
regarded as a hemorrhagic type of an exudative erythema, and
Henoch’s purpura, which is characterised specially by the occurrence
of gastro-intestinal crises, belongs to the same group.

Several interesting communications have of late dealt with this
question. The case reported by Dr. J. Fayrer* illustrates the sequence
of arthritis, oedema, erythema exudativum purpuricum, and finally
sloughing of the affected areas. The illustration suggests peliosis
rheumatica. A very important paper ‘On the Relationship of
Purpura Rheumatica to Erythema Exudativam Multiforme,” + after
describing several interesting cases of purpura rheumatica and giving
an analysis of those under his care, forty-two in number, Mackenzie
says: ‘I now come to the nosological position of purpura rheumatica.
The prevailing view is that purpura rheumatica is a variety of
erythema multiforme, and Schénlein’s original description of the
disease certainly is in accordance with this conclusion. With this
view I do not altogether agree. I admit its very close alliance, and
that the various forms of erythema are almost as closely associated
with rheumatism as is the form of purpura, to which I should restrict
the term purpura rheumatica. But in e. multiforme the hemorrhage
is only incidental, whilst in purpura it is primary and essential, and
in the majority there is no co-existing erythema. Still in a small
minority we find some form of erythema co-existing. In erythema
nodosum we see precisely the same thing. In the majority of cases
we find the eruption limited to the nodose form, though more rarely
we have other forms of erythema associated with it. Thus, admitting
that e. nodosum is a variety of polymorphic erythema, we recognize
it as a distinct type. Some would go so far as to call it a distinct
disease, but in this I donot concur. Similarly I claim p. rheumatica,
such as I have sketched, as a distinct clinical type which deserves
recognition, and I have endeavoured to indicate the class of cases to
which I think the term should be restricted.” He very correctly

* British Journal of Dermatology, Vol. VII. + Ibid.
THE VISCERAL LESIONS OF THE ERYTHEMA GROUP. 245

concludes that it is undesirable to consider all cases of purpura to be
essentially of the nature of polymorphic erythema.

Certain French writers, as Thibierge, in the recently issued second
edition of the Traité de Médecine (Vol. JII.), group under the
e' ythemas both the purpuras and the urticarias, describing only three
Principal types of the. former—the rheumatic and infectious purpura,
and the purpura hemorrhagica of Werlhof.

The relation of the go-called angio-neurotic cedema to the other
members of the erythema group is, I think, less doubtful. That it is
essentially of the same nature as urticaria, and should be groy th
it, shown by their simultaneous outbreak, by their substitution one
for éhe other, by the identity of the visceral complications, and by the
peculiar local limitation occasionally seen in both, as to the face or
hands. . I do not know if the simple urticaria has ever been described
in members of the same family through a series of generations, but, as
I have already mentioned, a patient under my eare with the hereditary
form also had urticaria. A very interesting paper on this affection
has recently been published by Schliesinger, under the name of
“‘ Hydrops hypostrophos” (Miinchener med. Woch., August 29th, 1899).
He groups together the various manifestations of angio-neurotic
cedema—the acute recurring oedema of the eyelids or of the lips, the
acute recurring -exophthalmos, certain forms of nervous coryza, the
hydrops articulorum intermittens, the acute edema of the tongue, of

- the pharynx, and of the larynx, certain forms of nervous asthma, the
acute cedematous swelling in the stomach and the intestines (causing
' recurring attacks of colic and the intermittent vomiting of Leyden),
intermittent forms of nervous diarrhea, and, lastly, certain affections
of the kidneys causing polyuria or hemoglobinuria. There is really no
warrant for separating too sharply angio-neurotic oedema and urticaria ;
Oppenheimer has seen them occur together, and many observers have
noticed the interchange of urticaria with acute localised odema.

- What is needed, in truth, is a dermatological Linnezus, to bring
order out of the chaos at present existing in the group of erythemas.
While I feel that in bringing together a somewhat motley series of
eases I may only have contributed to make the “ confusion worse
confounded,” on the other hand there is, I think, a positive advantage
in recognizing the affinities and the strong points of similarity in
affections usually grouped as separate diseases,

x 2