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Clinical Diagnosis of Nodular Syphilis: A Review, Lecture notes of Medicine

The clinical features of nodular syphilis, a form of syphilis characterized by the presence of nodules or gummata on the skin. The author emphasizes the importance of accurate clinical diagnosis, as some nodular lesions may be wassermann negative or weakly positive. The document also describes a method for quantitatively estimating albumin in urine using sodium chloride as a diluent.

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CALIFORNIA
AND
WESTERN
MEDICINE
THE
LATE
NODULAR
SYPHILIDE
By
DOUGLASS
W.
MONTGOMERY,
M.
D.
DISCUSSION
by
Harry
E.
Alderson,
San
Francisco;
Anstruther
Davidson,
Los
Angeles;
Thomas
J.
Clark,
Oakland.
S
tigma
monumenti
revocans
in
memoriam
iniqui-
tatem,
a
memorial
stigma
bringing
iniquity
to
remembrance.
The
efficiency
of
the
Wassermann
reaction
in
detecting
the
presence
of
syphilis,
and
the
success
of
arsphenamine
in
clearing
up
luetic
lesions
of
the
skin
and
mucous
membranes
is
so
marked
that
the
im-
portance
of
the
clinical
diagnosis
of
these
interesting
manifestations
would
seem
to
be
diminished.
Nu-
merically
this
is
so,
as
between
80
and
90
per
cent
of
those
afflicted
with
late
lesions
of
the
skin
give
a
positive
reaction.
The
very
success
of
the
Wasser-
mann
reaction,
however,
makes
it
all
the
more
desir-
able
to
be
able
to
make
the
diagnosis
clinically
when
it
fails.
In
practice
we
find
it
more
and
more
fre-
quent
for
both
the
physician
and
the
patient
to
rely
unqualifiedly
on
the
laboratory
diagnosis,
which
is
a
great
evil.
Not
long
ago
we
had
a
patient
with
late
active
lues
in
the
nose,
in
the
roof
of
the
mouth,
and
in
a
toe,
and
yet
her
serum
reaction
was
negative.
As
practicing
physicians
we
all
are
aware
of
the
moral
value
of
a
positive,
unshakable
diagnosis
as
a
support
in
carrying
out
an
efficient,
continuous
line
of
treat-
ment,
and
this
support
may
be
obtained
equally
well
from
the
clinical
manifestations
as
from
the
labo-
ratory
findings.
Then
there
are
cases
in
which
the
patient
mav
suffer
from
two
different
lesions,
and
it
becomes
eminently
desirable
to
be
able
to
say
that
one
of
th--.
will
heal
expeditiously
under
the
treatment,
while
the
other
will
not
do
so.
iiere
is
still
another
weighty
reason
for
rehears-
ing
the
clinical
features
of
the
late
syphilides
at
every
convenient
opportunity.
The
success
of
ars-
phenamine
in
clearing
up
the
lesions
of
the
skin
and
mucous
membranes,
or
in
preventing
their
appear-
ance,
is
so
great
that
the
occasions
for
seeing
them
have
become
quite infrequent.
Even
in
large
clinics
teachers
complain
of
the
paucity
of
material
for
demonstration.
It
is
therefore
desirable
to
make
the
best
use
of
the
few
chances
available,
and
one
can
only
do
so
by
being
prepared
for
the
event.
The
late
nodular
syphilide
used
to
be
called
the
tubercular
syphilide
because
it
was
usually
larger
than
the
early
papule
and
more
sluggish
in
its
course,
but
since
so
many
nodular
cutaneous
affections
have
been
recognized
as
appertaining
to
tuberculosis,
the
epithet
"tubercular"
has
been
dropped
from
the
spirochetal
affections
entirely,
as
leading
to
confusion.
The
late
syphilitic
papule,
or
nodule,
both
anatomically
and
etiologically,
is
the
same
as
the
early
papule
of
the
widespread
papular
or
papulo-
pustular
rash.
I
well
remember
how
surprised
I
was
in
sectioning
a
papule
from
a
patient
with
a
rare
early
miliary
syphilide
in
the
old
Polyclinic
to
find
that
anatomically
it
was
a
minute
gumma,
even
to
the
presence
of
giant
cells,
and
a
gumma
is
nothing
more
than
a
large,
deeply
situated,
solitary
nodule.
The
greatest
incidence
of
the
late
nodular
syphilide
is
about
the
third
year
of
the
disease,
but
it
may
occur
even
in
the
first
year,
and
it
has
been
known
to
appear
as
late
as
fifty-five
years
after
the
primary
lesion
(Fournier).
The
nodule
of
syphilis
is
a
little
tumor,
and
this
should
always
be
borne
in
mind
in
considering
a
diagnosis.
It
is
generally
about
the
size
of
a
small
pea,
and
it
has
the
substantiality
of
a
tumor,
both
to
the
eye
and
to
the
finger.
It
looks
to
be,
and
really
is,
well
set
in
the
true
skin,
and
may
extend
below
it
into
the
subcutaneous
tissue.
Its
surface
may
be
intact,
rounded
and
smooth,
and
its
characteristic
color
is
deep
red
or
that
of
raw
ham,
but
it
may
be
bright
red.
If
it
occurs
as
one
sole
lump
or
nodule,
or a
few
such
widely
scattered,
I
do
not
know
how
to
make
the
diagnosis
clinically,
but
it
seldom
so
occurs,
except
as
a
very
large
node,
when
it
tends
to
central
liquefaction
and
on
opening
discharges
a
glairy
pus,
and
is
called
a
gumma.
Even
here
the
resemblance
between
a
syphilitic
gumma
and
a
tuber-
cular
gumma
may
be
too
close
to
differentiate.
The
course
of
the
tubercular
lesion
is
usually
slower
than
that
of
syphilis,
and
the
infiltration
is
usually
softer.
We
have
such
a
case
under
observation
at
present.
The
late
nodular
syphilide
usually
occurs
as
one
of
a
group,
and
then
its
characteristics
may
be
so
dis-
tinctive
that
any
well-trained
physician
may
make
the
diagnosis.
Like
everything
organic
the
luetic
nodule
grows
to
a
size
limited
by
its
nature
and
then
recedes.
The
nodules
of
any
group
are
all
of
different
ages
and
therefore
of
different
sizes,
and
their
general
appearance
also
differs
with
their
age.
An
individual
nodule
may
pass
through
its
whole
life
cycle
in
or
under
a
superficially
intact
skin,
or
possibly
only
give
rise
to
some
desquamation
as
an
evidence
of
its
inflammatory
nature,
and
may
disappear,
leaving
no
surface
evidence
of
its
previous
existence,
or
it
may
cause
a
scar.
The
presence
of
these
scars
in
a
nodular
patch
is
of
great
diagnostic
value.
Individual
nodules
will
almost
certainly
liquefy
in
the
center,
and
in
opening
on
the
surface
give
rise
to
small
steep-edged
ulcers
with
a
dirty
grey
base.
Instead
of
appearing
as
individual
papules
the
late
nodular
syphilide
may
develop
as
a
solid,
con-
tinuous
infiltration
with
a
smooth,
even
surface
and
a
definite
border,
just
as
tuberculosis
may
develop
as
an
infiltration
instead
of
separate
tubercles.
This
type
is
rare,
however.
THE
ARRANGEMENT
OF
THE
PAPULES
Notation
of
the
arrangement
of
the
papules
is
often
most
important,
as
on
it
may
depend
the
diagnosis.
In
contrast
to
the
early
papular
eruption,
which
is
bilateral
as
becomes
a
disease
scattered
universally
by
the
blood
current,
the
late
nodular
eruption
often
shows
decided
bilateral
asymmetry.
We
have
before
spoken
of
grouping
as
another
peculiarity
of
diagnostic
value,
but
the
papules
in
the
bunch
may
be
numerous
and
well
set
apart,
and
may
exhibit
no
arrangement
whatever,
constituting
what
may
be
called
a
"buckshot
group."
Many
of
the
papules
may
break
down
into
small
circular
steep-edged
ulcers,
some
of
which
may
be
covered
either
with
a
yellow
or
with
a
black
tightly
adherent
crust,
while
others
will
have
healed,
leaving
white
or
Vol.
XXV,
No.
3
3s56
pf3
pf4

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CALIFORNIA AND WESTERN MEDICINE

THE LATE NODULAR SYPHILIDE By DOUGLASS W.^ MONTGOMERY,^ M. D. DISCUSSION by Harry E. Alderson, San Francisco; Anstruther Davidson, Los Angeles; Thomas J. Clark, Oakland.

S tigma^ monumenti^ revocans^ in memoriam^ iniqui- tatem, a memorial stigma bringing iniquity to remembrance. The (^) efficiency of the Wassermann reaction in detecting the presence of syphilis, and the success of arsphenamine in clearing up luetic lesions of the skin and mucous membranes is so marked that the im- portance of the clinical diagnosis of these interesting manifestations would seem to be diminished. Nu- merically this is so, as between 80 and 90 per cent of those afflicted with late (^) lesions of the skin give a positive reaction. The very success of the Wasser- mann reaction, however, makes it all the more desir- able to be able to make the diagnosis clinically when it fails. In practice we find it more and more fre- quent for both the physician and the patient to rely unqualifiedly on the laboratory diagnosis, which is a great evil. Not long ago we had a patient with late active lues in the nose, in the roof of the mouth, and in a toe, and yet her serum reaction was negative. As practicing physicians we all are aware of the moral value of a positive, unshakable diagnosis as a support in carrying out an efficient, continuous line of treat- ment, and this^ support may be obtained^ equally well from the clinical manifestations as from the labo- ratory findings. Then there are cases in which the patient mav suffer from two different lesions, and^ it becomes eminently desirable to be able^ to^ say that^ one^ of th--. will heal expeditiously under the^ treatment, while the other will not do so. iiere (^) is still another weighty reason for rehears- ing the clinical features of the late syphilides at every convenient opportunity. The success of ars- phenamine in clearing up the lesions of the skin and mucous membranes, or in preventing their appear- ance, is so great that the (^) occasions for seeing them have become quite infrequent. Even in large clinics teachers complain of the paucity of material for demonstration. (^) It is therefore desirable to make the best use of the few chances available, and one can only do so by being prepared for the event. The late (^) nodular syphilide used to be called the tubercular syphilide because it was usually larger than the (^) early papule and more sluggish in its course, but since so (^) many nodular cutaneous affections have been (^) recognized as appertaining to tuberculosis, the epithet "tubercular" has been dropped from the spirochetal affections entirely, as leading to confusion. The late (^) syphilitic papule, or nodule, both anatomically and^ etiologically, is the^ same as the early papule of the widespread papular or papulo- pustular rash. I well remember how surprised I was in sectioning a papule from a patient with a rare early miliary syphilide in the old (^) Polyclinic to find that (^) anatomically it was a minute gumma, even to the presence of (^) giant cells, and a (^) gumma is nothing more than a large, deeply situated, solitary nodule. The greatest incidence of the late nodular syphilide is about the third year of the disease, but it may

occur even in the first year, and it has been known

to appear as late as fifty-five years after the primary lesion (Fournier). The nodule of syphilis is a little tumor, and this should always be borne in mind in considering a diagnosis. It is generally about the size of a small pea, and it has the substantiality of a tumor, both to the eye and to the finger. It looks to be, and really is, well set in the true skin, and may extend below it into the subcutaneous tissue. Its surface may be intact, rounded and^ smooth, and^ its characteristic color is deep red or that of raw (^) ham, but it (^) may be bright red. If it occurs as one sole (^) lump or (^) nodule, or a few such widely scattered, I do not know how to make the diagnosis (^) clinically, but it seldom (^) so occurs, except as a very large node, when it tends to central (^) liquefaction and on opening discharges a glairy pus, and is called a gumma. Even here the resemblance between a (^) syphilitic gumma and a (^) tuber- cular gumma may be too close to differentiate. The course of the tubercular lesion is usually slower than that of (^) syphilis, and the infiltration is (^) usually softer. We have such a case under observation at present.

The late nodular syphilide usually occurs as one of

a group, and then its characteristics may be so dis-

tinctive that any well-trained physician may make

the diagnosis. Like everything organic the luetic

nodule grows to a size limited by its nature and

then recedes. The nodules of any group are all of different ages and therefore of different sizes, and their general appearance also differs with their age. An individual

nodule may pass through its whole life cycle in^ or

under a^ superficially intact^ skin, or possibly only give

rise to some desquamation as an evidence of its

inflammatory nature, and may disappear, leaving no

surface evidence of its previous existence, or it may

cause a scar. The presence of these scars in a

nodular patch is of great diagnostic value. Individual

nodules will almost certainly liquefy in the center,

and in opening on the surface give rise to small steep-edged ulcers with a dirty grey base.

Instead of appearing as individual papules the

late nodular syphilide may develop as a solid, con-

tinuous infiltration with a smooth, even surface and

a definite border, just as tuberculosis may develop

as an infiltration instead of separate tubercles. This

type is rare, however.

THE ARRANGEMENT OF THE PAPULES

Notation of the arrangement of the papules is

often most important, as on it may depend the

diagnosis.

In contrast to the early papular eruption, which is

bilateral as becomes a disease scattered universally

by the blood current, the late nodular eruption often

shows decided bilateral asymmetry.

We have before spoken of grouping as another

peculiarity of^ diagnostic value, but the papules in

the bunch (^) may be numerous and well set apart, and

may exhibit no arrangement whatever, constituting

what may be called a "buckshot group." Many of

the papules may break down into small circular

steep-edged ulcers, some of which may be covered

either with a yellow or with a black tightly adherent

crust, while others will have healed, leaving white or

3s56 Vol. (^) XXV, No. 3

CALIFORNIA AND WESTERN^ MEDICINE

Circular ulcer^ of^ late^ syphilis. A^ band of^ epithelialization may be seen extendint, from about 5^ o'clock^ on^ the^ circle toward the central nub, which will presently transform the circular ulcer into a kidney-shaped one.

reddish brown scars. The variegated appearance of the field may be imagined. A nodular syphilide may begin as a single nodule, and then others may arise immediately around it, so spreading out continuously from the original center. The spread, however, does not usually take place in an even circle; only a segment remains active, form- ing an advancing wall, invading the normal skin. Ulceration follows the wall, so that a crescentic lesion is formed with an advancing bow-shaped in- durated wall, within which there is a crescent-shaped ulcer, in the hollow of which there is scar tissue. This is the typical syphilitic horseshoe-shaped ulcer with the indurated border of raw ham^ color. This is the lesion so often mistaken for either lupus or epithelioma, but which is so much more rapid in its course than either of them. In the development of such a patch quite a variety of grotesque figures may be formed. For instance, Gougerot recently showed a photograph in which

two bows joined, forming the letter "S," as^ if^ the

disease were trying to write its own signature, and recently I saw a crescentic ulcer in^ which^ the^ two horns of the crescent had met, forming^ a^ circular ulcer with a nub of sound skin in^ the center.^ Subse- quently the healing began at^ one point on^ the^ edge and extended toward the central nub, as may be seen in the photograph. This circular ulcer will presently, therefore, again become a crescent-shaped one, THE (^) SITUATION OF THE LATE NODULAR SYPHILIDE These (^) syphilides have their favorite situations, and in their order of (^) frequency they occur on the face,

especially on^ the^ wings^ of^ the^ nose,^ about^ the^ mouth, and on the forehead. On the forehead they may occur along the hair line, causing the corona veneris of the tertiary period. Next^ in^ frequency^ of location comes the palmar^ and^ plantar^ surfaces,^ the^ thighs, nape of the neck, posterior surface^ of the^ forearms, and the scapular and lumbar regions of the back.

They may^ occur^ on^ any^ part^ of^ the^ cutaneous^ sur-

face, but it is apparent from the above that the

trained observer will pay particular attention to any

destructive lesion about the nares, mouth or fore- head, to see if by chance any additional signs of syphilis may be discovered.

SUPERINFECTION AND CRUSTING

The tissue of a late syphilitic nodule is diseased

and of low resistance, and it is situated near the

surface, and therefore^ is^ readily^ attacked^ by^ pyogenic

bacteria. Under these conditions desquamation,

ulceration and crusting are natural consequences.

THE ULCER RESULTING FROM^ THE SOLITARY NODULE

The solitary nodule may break^ down^ into^ an^ ulcer

with a definite indurated border, on^ the^ surface^ of

which the pus tends to dry, forming a crust.^ The

spirochete is strongly inclined^ to^ attack the blood

vessels, and I suppose it is because of this^ that^ the^ pus

is so frequently mixed with blood. The admixture of

blood makes the crust dark brown or^ black, and

very tough. It is also very adherent and fits within

the border of the ulcer like a watch crystal in^ its

setting. As the ulcer extends the crust becomes larger, and at the same time rises above its base, and

so takes on a roughly pyramidal shape, resembling

an oyster shell. The indurated border and the black

tightly adherent, accurately fitting, thick, rough

pyramidal crust^ form^ a^ striking^ and^ characteristic

picture.

THE DESQUAMATION AND CRUSTING OF THE GROUPED NODULAR SYPHILIDE

The nodules, as before remarked, may be^ grouped,

but irregularly scattered. They^ may,^ however,^ be

closely agglomerated so as to form a continuous

desquamating surface, in which case the diagnosis

may be impossible to make. I remember well^ an

incident in the old Toland Clinic^ at^ North^ Beach

that made a great impression upon me. A woman had what appeared to be an indurated eczema on the

side of the nose near the eye, for which I prescribed

ammoniated mercury ointment.^ At the^ next^ visit,^ a

week later, the lesion had so cleared up as to show

plainly its nodular character, and then I^ discovered

several other stigmata of lues that had^ previously

escaped my^ notice.^ It^ was a^ good^ illustration^ of^ the

clinic axiom that one finds what one^ looks^ for.

The crusting may be impetiginous, and so thick

as to completely hide the subjacent definite luetic

symptoms, and so give rise to an^ erroneous^ diagnosis

of impetiginous eczema, or^ of^ impetigo. In^ any

doubtful case nodules and scars should be sought for.

One must also remember that it is impossible to

tell beforehand how much real loss of substance has

taken place under a^ crusted^ syphilide, and^ it^ is^ often

September, 1926 357

September, 1926 CALIFORNIA AND^ WESTERN MEDICINE^359

tertiary lesions the percentage of^ positive^ blood^ findings drops sharply, so it is very important to recognize the disease by its clinical characteristics. Doctor Montgomery's broadminded attitude of using these cases of tertiary syphilis to educate the younger medical men is commendable.

QUANTITATIVE ESTIMATION OF ALBUMIN

IN URINE

By A. M. MOODY AND^ LOUISE STOCKING (From the Laboratory of St. Francis Hospital, San (^) Francisco) T (^) HIS paper relates the details of an accurate and rapid method for the quantitative^ estimation of

albumin in urine. The discussion is limited, first, to

a brief review of the inaccuracy and delays en-

countered in using the ordinary textbook procedures

and, second, to the technical aspect of the test, with- out any consideration of the pathological significance of albuminuria.

In February, 1925, a patient in whom we were

especially interested developed an albuminuria of

such a high degree that^ it was^ impossible^ to^ obtain

a (^) reading on the Esbach tube without diluting the

original specimen. This^ was^ done^ with^ water,

although most^ textbooks simply^ state^ "to^ dilute,"

but do not specify the diluent. Our readings seemed

somewhat large, so we set up a series of dilutions

and found that as the dilution increased we obtained

greater estimations of albumin. The results when

compared with gravimetric determination on the same specimens proved the inaccuracy of diluting urine with water. Those interested in laboratory

analyses are aware of the fact that the Esbach deter-

mination of albumin in urine gives only an approxi- mate estimation, requires twenty-four hours' time, and is influenced by many factors, yet it is probably the most widely used method.

Since we now know that diluting urine with water

increased the inaccuracy of albumin determinations

by the Esbach test, and since we did not think that

the gravimetric or other known accurate quantita-

tive methods were practical as routine procedures,

we set out to find something which could be relied

on to dilute urine without disproportionately altering

the albumin content.

Many fluids were tried, including the^ following:

Albumin free urine, Tsuchya's reagent, 2 per cent

acetic acid, various strengths of alcohol, sodium

chloride solutions (2 per cent to .85 per cent), and

others. In brief, all the above^ solutions as diluting

fluids were found to yield inaccurate results.

Tsuchya's reagent or alcohol used as diluting fluids

decreased disproportionately the albumin estimation.

Beginning with 2 per cent sodium chloride and

decreasing to a concentration of .85 per cent, in-

accurate results were obtained similar to those when

water was used as diluent. We noted, however, that

2 per cent sodium chloride yielded results which

were more promising.

At this point in our work we discovered that

Doctor Wykoff of Stanford University Hospital was

working independently on the same problem, and

that he began at 2 per cent sodium chloride and,

working with increasing concentrations, found that

2.5 per cent sodium chloride was the desired strength to be used. He was also working with a standard

control of egg albumin, using a modified Purdy

technique for the test.

With these facts we now felt that our difficulties

were about over, but believed that a standard made

from human blood serum would perhaps be more

nearly ideal, since urinary albumin so closely re-

sembles the coagulable proteins in the blood serum.

Then, too, Folin, in his laboratory manual, gives the

details of a test, using a standard made with hemo- globin free sheep's blood serum, so you see the idea

is not new. Sheep's blood serum is not as readily

obtained in our laboratory as is human serum, so

it seemed quite logical to use the latter as a standard.

It was found that 5 mls. of pooled human serums

diluted to 100 mls. with 2.5 per cent sodium chloride

solution yielded by gravimetric determination an

average albumin content of 6 grams per liter. With this standard solution we then proceeded to shorten

the time element from twenty-four hours^ to^ fifteen

minutes by adopting a modified Purdy test instead

of the Esbach.

The procedure as now used is as follows: Place in a 15 mls. capacity graduated centrifuge tube 10 mis. of urine to be tested, and in another similar tube 10 mls. of standard serum solution; thenaddtoeach tube 5 mls. of Tsuchya's reagent (phosphotungstic acid 15 gms. hydrochloric acid 50 mls., and make up to 1000 mls. with alcohol 95 per cent); mix thor- oughly by inverting back and forth, and let stand for ten minutes; then place the tubes in the centrifuge and centrifugalize for three to five minutes. Record the amount of precipitate in each tube and calculate the result.* The standard tube reading equals 6 gms. albumin per liter.

We have made over one thousand determinations,

using the^ above^ technique as^ routine, with^ frequent

checks by the gravimetric method. The average

difference was 3 per cent higher by the centrifugc

method. In many determinations identical results

were obtained, figuring to one decimal. No attempt

has been made to estimate closer with one decigram.

Slight errors^ may readily occur in reading amounts

between the graduations on the centrifuge tube, and also in the (^) gravimetric method, if the sediment is not properly dried to a constant weight.

When using the above method it must be remem-

bered that the standard is set up at the same time

as the unknown, and that all solutions are kept under

the same temperature conditions at all times until the

final reading is made. In this way only is one justi-

fied in comparing results. If it is necessary to dilute

the unknown, do so with 2.5 per cent sodium

chloride solution, a stock bottle of which is kept

under the same temperature conditions as the

standard and unknown. In this laboratory it has

been practical to keep our standard solutions at room

temperature.

The standard solution is made fresh each week,

oftener only when the stock has been used. A small

amount of preservative (chloroform 1 to 1.5 mls.

per 100 mls. of serum solution) can be added to

prevent bacterial growth or other determination. In

  • (^) The supernatant fluid should be water clear after centrifuging. If there is the slightest turbidity then the concentration of^ albumin is too great for complete precipitation, and the original specimen must be diluted. This necessitates repeating the entire pro- cedure.