Clinical survey of 354 patients with gout

Full text

Ann.
rheum.
Dis.
(1970),
29,
461
Clinical
survey
of
354
patients
with
gout*
R
GRAHAME*
AND
J.
T.
SCOTT
From
the
Royal
Postgraduate
Medical
School
of
London,
the
Charing
Cross
Group
oJ
Hospitals,
London,
and
the
Kennedy
Institute
of
Rheumatology,
London
Between
the
years
1958
and
1967,
354
patients
with
gout
were
examined
personally
at
Hammersmith
Hospital
(257
cases
seen
between
1958
and
1967),
and
more
recently
at
the
Charing
Cross
and
West
London
Hospitals
(97
cases
seen
during
1966
and
1967).
This
paper
describes
a
retrospective
computer-
assisted
analysis
of
these
patients.
Some
of
them
were
followed
for
considerable
periods
of
time
by
ourselves
or
our
colleagues,
whereas
others
were
seen
on
one
or
two
occasions
only.
The
study
does
not
therefore
trace
the
course
of
the
disorder
over
a
period
of
time
in
individual
patients.
Method
For
the
purpose
of
the
survey
gout
was
defined
as
recurrent
acute
episodes
of
arthritis
in
the
presence
of
hyperuricaemia.
Most
of
the
serum
urate
values
had
been
estimated
with
the
use
of
the
Technicon
Auto-Analyzer;
the
upper
limit
of
normal
for
serum
uric
acid
was
taken
to
be
6
mg./100
ml.
for
males
and
postmenopausal
women
and
5
mg./100
ml.
for
premenopausal
women.
These
figures
had
previously
been
obtained
by
duplicate
sampling
with
sera
from
the
population
survey
of
Popert
and
Hewitt
(1962).
The
presence
of
urate
crystals
in
synovial
fluid
or
of
tophaceous
changes
was
taken
as
confirming
the
Jiag-
nosis
but
these
were
not
necessary
criteria.
The
informa-
tion
for
the
survey
was
abstracted
from
the
patients'
case
notes
and
recorded
on
a
proforma
with
100
slots
which
permitted
65
separate
items
of
data
to
be
assembled
for
each
patient.
These
items
were
punched
and
fed
into
the
Elliott
computer
at
the
Royal
Postgraduate
Medical
School
of
London.
Every
item
was
cross-referenced
with
each
of
the
others,
thus
demonstrating
any
association
between
one
feature
in
relation
to
another.
Results
AGE
AT
ONSETI
Symptoms
were
first
seen
between
the
seco-id
and
ninth
decades
in
both
sexes.
The
distribution
of
the
age
at
onset
is
shown
in
Fig.
1.
The
peak
age
at
onset
in
men
lay
in
the
fifth
decade,
whereas
in
three-quarters
of
the
women
symptoms
commenced
after
the
age
of
50
years.
100
80
*c
60
0.
'0
40
z
20
0
FIG.
1
Age
at
onset
in
354
patients.
DURATION
OF
DISEASE
In
1967
when
the
survey
was
conducted
the
duration
of
disease
was
as
shown
in
Fig.
2.
Approximately
half
the
patients
were
seen
within
10
years
of
onset,
the
remainder
at
a
longer
interval.
90-
80-
70-
60
4'
j50-
o
40G
Z
30-
20
I
0
0
0-
5-
lo-
Is-
20-
25-
30-
35-
40-
45-
50+
4
9
14
19
24
29
34
39
44
49
Duration
of
disease
(years)
FIG.
2
Duration
of
gout
in
354
patients.
Presented
at
a
meeting
of
the
Heberden
Society,
November
1969.
For
discussion,
see
Annals
(1970),
29,
330.
tPresent
address:
Department
of
Physical
Medicine
and
Rheumatology,
Guy's
Hospital,
S.E.I.
Requests
for
reprints
should
be
addressed
to
Dr.kJ.
T.
Scott,
Kennedy
Institute
of
Rheumatology,
Bute
Gardens,
London,
W.6.

462
Annals
of
the
Rheumnlatic
Diseases
RACE
Of
the
354
cases,
22
(6
per
cent.)
were
non-caucasian
subjects;
these
were
all
men,
mostly
Negroes
with
a
few
from
India
and
the
Far
East,
and
they
showed
a
significant
tendency
towards
a
younger
age
at
onset
(P<0-01),
but
this
may
have
been
because
they
belonged
to
a
relatively
young
immigrant
population.
There
were
no
other
remarkable
features
about
their
gout.
SEX
INCIDENCE
Of
the
354
cases,
43
(9-
7
per
cent.)
were
women,
and
their
gout
differed
from
that
seen
in
men
in
two
important
ways:
the
mean
age
at
onset
was
higher
(Fig.
1),
and
there
was
a
higher
incidence
of
renal
involvement
(see
below).
SOCIAL
STATUS
All
male
hospital
patients
were
classified
by
occupa-
tion
or
profession
according
to
the
Registrar
General's
Classification
of
Occupations
(1951).
For
purposes
of
comparison
a
random
selection
of
200
non-gouty
male
controls
attending
the
out-
patient
department
were
taken
from
the
Medical
Records
of
the
Hammersmith
Hospital
and
classified
in
the
same
manner.
The
result
(Fig.
3)
shows
a
significant
preponderance
of
gouty
subjects
in
the
higher
social
classes
(P<0
002).
The
22
non-
Caucasian
subjects
were
of
a
significantly
higher
social
class
than
whole
series,
because
they
included
12
subjects
in
Grade
I
from
overseas,
e.g.
a
cabinet
minister
from
an
African
country
and
a
maharajah.
80
M
male
qouty
subjects
E3
hospital
controls
=60
MM
040,
20'
ei
201L
I
II
mII
IV
v
Social
class
FIG.
3
Social
class
oJ
maile
gouty
subjects
compared
with
200
hospital
controls
(Registrar-General's
Classifica-
tion).
Note
the
excess
of
gouty
subjects
in
the
higher
classes
(P<0
002).
FAMILY
HISTORY
127
patients
(36
per
cent.)
knew
of
at
least
one
other
member
of
their
family
who
was
said
to
have
had
gout.
OBESITY
169
patients
(48
per
cent.)
were
more
than
15
per
cent.
above
the
ideal
weight
for
their
age
and
height
(Society
of
Actuaries,
1959).
There
were
no
other
differences
between
these
obese
subjects
and
the
remainder,
except
with
regard
to
mild
hypertension
and
alcohol
ingestion
(see
below).
ALCOHOL
A
patient
consuming
a
minimum
average
daily
intake
of
two
pints
of
beer
or
two
double
whiskies
was
classified
as
a
regular
drinker.
130
patients
out
of
the
total
series
(37
per
cent.)
qualified
for
this
grouping.
Only
15
per
cent.
of
the
34
women
were
drinkers
and
this
sex
difference
was
significant
(P<0-01).
There
were
77
regular
drinkers
among
169
obese
subjects
(as
defined
above),
compared
with
only
53
among
185
non-obese
subjects,
a
significant
difference
(P
<
0
*
01).
JOINT
INVOLVEMENT
AND
TOPHUS
FORMATION
The
incidence
of
past
or
present
individual
joint
involvement
was
as
follows
(the
individual
categories
not
of
course
being
mutually
exclusive):
Joint
Patients
Wit/l
individual
joint
involvemwent
No.
Per
cent.
Great
toe
Ankle/foot
Knee
Finger
Elbow
Wrist
Other
Extra-articular
gout
(i.e.
bursae,
etc.)
More
than
one
joint
affected
simultaneously
Permanent
joint
damage
268
178
114
87
35
34
14
10
76
50
32
25
10
10
4
3
37
11
60
17
Joint
x
rays
were
carried
out
in
almost
all
cases
and
radiological
evidence
of
tophi
in
juxta-articular
areas
was
found
in
127
(36
per
cent.).
Subcutaneous
tophi
were
clinically
evident
in
75
cases
(21
per
cent.).
Certain
differences
were
observed
in
the
individual
pattern
of
joint
involvement
(see
below)
in
relation
to
disease
duration.
Involvement
of
the
great
toe,
ankle,
fingers,
and
knees
occurred
irrespective
of
disease
duration,
but
the
incidence
of
wrist
(P
<
0
05)
and
elbow
(P<005)
involvement
was
higher
in
patients
with
a
longer
duration.
Furthermore,
patients
with
elbow
involvement
tended
to
have
an
earlier
age
at
onset
(P
<0
01).
Duration
of
disease
and
permanent
joint
damage
were
also
related
(P
<
0
01).
Of
the
75
patients
with
clinical
tophi,
there
were
33
(44
per
cent.)
with
permanent
joint
damage,
15

Gout
463
(20 per
cent.)
with
either
elbow
or
wrist
involvement,
27
(35
per
cent.)
with
renal
impairment,
21
(36
per
cent.)
with
severe
hypertension,
and
19
(37
per
cent.)
with
coronary
artery
disease
(see
below).
All
these
constituted
a
significantly
greater
incidence
than
in
the
total
group
(P
<0
05
in
the
case
of
renal
failure;
P<0
01
in
the
remainder.)
HYPERTENSION
AND
RENAL
DISEASE
184
patients
(52
per
cent.)
showed
a
diastolic
blood
pressure
of
90
mm.
Hg
or
more;
in
31
of
these
it
was
130
mm.
Hg
or
more
(designated
"severe
hypertension");
the
remaining
153
(43
per
cent.)
were
designated
"moderate
hypertension".
Renal
failure
was
said
to
be
present
when
a
blood
urea
of
more
than
45
mg./100
ml.
was
found
on
any
occasion,
and
occurred
in
86
patients
(25
per
cent.).
The
incidence
of
both
moderate
and
severe
hypertension
was
not
related
to
duration
of
disease,
indicating
that
there
does
not
appear
to
be
an
increasing
risk
of
developing
hypertension
with
longer
duration
of
gout
(Fig.
4).
Similarly,
the
inci-
dence
of
renal
failure
showed
no
tendency
to
rise
until
the
disease
had
been
present
for
40
years
or
more
(Fig.
5).
After
this
time
the
incidence
approxi-
mately
doubled,
but
these
final
decades
of
duration
-
moderate
hypertension
600
&40
4
220
0.
IV0
40
-
severe
hypertension
20
20
-
0-
5-
10-
15-
20-
25-
30-
35-
40-
45-
50+
4
9
14
19
24
29
34 39
44
49
Duration
of
disease
(years)
FIG.
4
hicidenee
of
hypertension
r
elated
to
duration
ojf
disease.
@
80
60
-
40-
FIG.
5
Incidence
of
renal
failure
(blood
ul-ea
>45
iug.
per
cent.)
i-elated
to
duration
of
disease.
represent
very
old
people
and
numbers
are
small.
Otherwise
there
appears
to
be
little
if
any
deteriora-
tion
in
renal
function
with
increased
duration
of
disease.
With
respect
to
age
at
onset,
however,
a
different
pattern
was
found.
The
incidence
of
moderate
hyper-
tension
rose
with
increasing
age
at
onset,
but
that
of
severe
hypertension
was
highest
in
the
decade
10
to
19
years
(Fig.
6).
In
this
group
of
12
patients,
3
(25
per
cent.)
had
severe
hypertension.
The
inci-
dence
of
renal
failure
related
to
age
at
onset
showed
a
bimodal
distribution
curve
(Fig.
7).
It
is
apparent
that
there
is
a
progressive
rise
in
the
incidence
of
renal
failure
as
the
age
at
onset
rises
from
the
fourth
decade
onwards;
but
there
also
appears
to
be
a
separate
group
in
which
disease
begins
in
the
second
or
third
decade
and
in
which
there
is
a
high
incidence
of
renal
failure.
100
o
80
60
-C
4,
4,40
I
u.-
Ua
20L
0
l-
severe
hypertension
19
29
39
Aqe
at
onset
(years)
D-
60-
70-
80-
59
69
79
89
FIG.
6
Incidence
of
hypertension
i-elated
to
age
at
onset.
100
L,
80
0
C
c c
,
°'
c40
X
20
u
0
10-
20-
30-
40-
50-
60-
70-
80-
19
29
39
49
59
69
79
89
Age
at
onset
(years)
F
IG.
7
Incidence
of
renal
failure
(blood
urea
>
45
mng.
per
cent.)
related
to
age
at
onset.
The
incidence
of
renal
failure
in
the
group
with
severe
hypertension
was
16
out
of
31,
higher
than
that
in
those
with
moderate
hypertension
(39
out
of
153)
and
normal
tension
(31
out
of
170)
(P
<
0
05).
In
the
group
with
severe
hypertension
there
was
a
significantly
greater
incidence
of
permanent
joint
damage
(P
<0
01),
tophus
formation
(P
<0
01),
and
4
9
14
19
24
29
34
39
44
49
Duration
of
disease
(
years)

464
Annals
of
the
Rheumatic
Diseases
X-ray
changes
(P
<
0
05)
than
in
the
remainder,
but
this
was
not
so
in
the
moderate
group.
An
associ-
ation
was
also
apparent
between
renal
impairment
and
the
presence
of
chronic
tophi
(P
<
0
01).
In
obese
subjects
the
incidence
of
moderate
hyper-
tension
was
84
out
of
169,
compared
with 69
out
of
185
non-obese
subjects,
a
significant
difference
(P
<0
01).
The
incidence
of
severe
hypertension
(14
out
of
169
obese
subjects)
was
about
the
same
as
that
in
the
non-obese
group
(17
out
of
185).
Proteinuria
was
present
in
77
cases
(22
per
cent.).
There
was
no
correlation
with
permanent
joint
damage,
tophus
formation,
or
duration
of
disease,
but
the
incidence
of
proteinuria
was
significantly
higher
in
patients
with
renal
failure
(P
<0
01).
A
history
of
renal
stones
or
renal
colic
was
obtained
from
32
patients
(11
per
cent.).
Nine
of
these
had
passed
stones
of
known
uric
acid
compo-
sition.
Stone
formation
correlated
with
the
presence
of
renal
impairment,
proteinuria,
and
longer
duration
of
disease.
Moderate
hypertension
was
found
in
18
of
the
34
women
(53
per
cent.)
compared
with
119
of
the
320
men
(37
per
cent.)
(P
<0
01).
Severe
hypertension
was
found
in
S
women
(15
per
cent.)
compared
with
26
men
(8
per
cent.)
(P
<
0
05).
Similarly,
19
of
the
women
34
(56
per
cent.)
showed
renal
impairment,
compared
with
67
of
the
320
men
(21
per
cent.)
(P<0
05).
In
the
whole
series
renal
failure
and
hypertension
were
commoner
in
patients
with
a
higher
mean
age
at
onset,
and
this
may
partially
explain
this
sex
difference.
OTHER
FORMS
OF
VASCULAR
DISEASE
The
incidence
of
coronary
artery
disease,
as
evidenced
by
a
history
of
myocardial
infarction
or
angina,
or
by
suggestive
electrocardiogram
changes,
was
found
in
52
of
the
354
patients
(15
per
cent.).
A
history
indicative
of
cerebrovascular
disease
was
obtained
from
12
patients
(3
per
cent.)
and
7
patients
had
other
evidence
of
severe
atheroma
(e.g.
affecting
limb
vessels).
In
the
coronary
group
there
was
a
high
incidence
of
moderate
(25
subjects)
and
severe
(6
subjects)
hypertension,
and
22
had
renal
failure.
These
figures
are
significantly
greater
than
in
the
rest
of
the
series
only
in
the
case
of
renal
failure
(P<0
01).
There
was
also
a
high
incidence
of
hypertension
and
renal
failure
in
the
very
small
number
with
cerebral
or
peripheral
vascular
disease.
SECONDARY
GOUT
15
of
the
354
cases
(4-
2
per
cent.)
had
a
known
blood
dyscrasia
believed
to
be
the
main
underlying
cause
of
the
hyperuricaemia
and
gout;
these
may
be
classified
as
follows:
Polycythaemia
rubra
vera
10
Polycythaemia
due
to
cyanotic
heart
disease
I
Chronic
myeloid
leukaemia
1
Malignant
lymphoma
1
Myelofibrosis
I
Congenital
haemolytic
anaemia
1
Most
of
these
patients
were
referred
by
colleagues
in
the
radiotherapy
or
haematology
departments.
Secondary
renal
gout
is
often
difficult
to
define
because
of
multiple
aetiological
factors.
There
were
eight
patients
in
whom
thiazide
diuretics
were
con-
sidered
to
be
contributory
to
hyperuricaemia
and
gout,
but
in
none
was
the
serum
uric
acid
level
quite
normal
when
the
drug
was
not
being
taken.
One
patient
developed
gout
for
the
first
time
while
taking
the
antituberculous
drug
pyrazinamide.
Serum
levels
of
uric
acid
were
very
high
but
were
controlled
with
uricosuric
agents
and
he
remained
symptom-free.
He
was
re-assessed
after
pyrazin-
amide
had
been
discontinued
and
the
uric
acid
level
was
found
to
be
normal.
Five
patients
(described
in
detail
elsewhere:
Scott,
Dixon,
and
Bywaters,
1964)
had
severe
hyperuricaemia
and
gout
associated
with
hyper-
parathyroidism.
One
other
man
with
gout
and
myxoedema
has
also
already
been
discussed
(Scott,
1966).
SERUM
URIC
ACID
LEVELS
In
each
case
the
highest
level
recorded
before
treatment
was
taken
for
inclusion
in
the
survey.
The
distribution
pattern
is
shown
in
Fig.
8.
80-
*l60
cL
40
0.
0'
v
20-
cI
0~
(
6-6-9
7-7-9
8-8-9
9-9.9
10109
11-1119
1212-9
143-19
14-19
15
+
Serum
uric
acid
level
FIG.
8
Pre-treatment
serum
uric
acid
levels,
mostly
estimated
by
Technicon
Auto-Analyzer
method.
Upper
limit
of
normal
6
mg.
per
cent.
for
males
and
post-meno-
pausal
women,
and
5
mg.
per
cent.
for
pre-menopausal
women.
(Duplicate
sampling
with
sera
from
Manchester
population
survey
(Popert
and
Hewitt,
1962)
).
Patients
showing
chronic
joint
change
and
also
those
with
gout
secondary
to
a
blood
dyscrasia
gave
significantly
higher
serum
levels
of
uric
acid
than
the
remainder
(P
<0
01
and
P
<0
05
respectively).
Apart
from
this
the
level
of
uric
acid
before
treat-
ment
did
not
correlate
with
any
of
the
other
features
investigated,
e.g.
tophus
formation
or
duration
of
disease.

Gout
465
URIC
ACID
EXCRETION
This
was
measured
over
one
or
more
24-hour
periods
in
89
patients,
who
had
taken
a
low
purine
diet*
for
about
5
days
previously
to
minimize
the
effect
of
dietary
purines.
In
order
to
determine
whether
or
not
the
daily
quantity
of
uric
acid
excreted
was
associated
in
any
way
with
the
clinical
pattern
of
disease,
56
patients
in
whom
the
24-hour
urinary
excretion
exceeded
600
mg.
were
compared
with
the
other
33
in
whom
the
excretion
rate
was
less
than
this.
No
difference
was
found
between
these
two
groups
with
regard
to
any
of
the
features
examined
(except
that
three
patients
with
a
blood
dyscrasia
whose
24-hour
excretion
was
measured
were
all
found
to
excrete
high
quantities
of
urate).
Only
three
of
the
nine
patients
known
to
have
passed
a
uric
acid
stone
had
their
urinary
urate
excretion
measured:
two
of
them
had
high
levels.
One
patient
excreting
a
high
level
of
uric
acid
also
had
epilepsy
and
mental
retardation;
he
was
found
to
have
a
partial
deficiency
of
the
enzyme
hypoxanthine-guanine
phosphoribosyl
transferase,
and
his
case
has
been
presented
in
full
elsewhere
(Bluestone,
1968).
TREATMENT
At
some
time
in
their
previous
history
174
patients
(49
per
cent.)
had
received
probenecid
and
30
(8
per
cent.)
sulphinpyrazone,
while
112
(32
per
cent.)
had
been
treated
with
allopurinol.
Complications-
usually
dyspepsia
or
skin
rashes-were
seen
in
9
patients
on
probenecid,t
5
on
sulphinpyrazone,
and
3
on
allopurinol.
Acute
attacks
of
gout
supervening
within
3
months
of
starting
long-term
therapy
occurred
in
14
patients
on
probenecid,
1
on
sulphinpyrazone,
and
17
on
allopurinol.
The
last
group
showed
a
greater
liability
to
develop
acute
gouty
arthritis
than
the
uricosuric
group
(P
<0
05).
DEATHS
At
the
time
of
the
survey
31
of
the
354
patients
had
died
while
in
hospital,
from
the
following
causes:
Carcinoma
Myocardial
infarction
Malignant
hypertension
and
uraemia
Rheumatic
or
congenital
valvular
heart
disease
Amyloid
Cerebral
haemorrhage
Cirrhosis
Septicaemia
Congenital
haemolytic
anaemia
Nephrotic
syndrome
Chronic
nephritis
Myelosclerosis
Pulmonary
embolus
5
8
4
2
1
I
1
1
1
1
1
*NIH
Bethesda
low
purine
diet,
containing
about
200
mg.
purine
daily.
tThis
also
includes
two
patients
who
developed
nephrotic
syndrome
while
taking
probenecid
(Scott
and
O'Brien,
1968).
Discussion
Several
large
series
of
patients
with
gout
have
been
recorded
during
the
last
150
years
(reviewed
by
Copeman,
1964:
Talbott,
1967).
A
retrospective
study
of
this
type
must
present
certain
unsatisfactory
features.
In
the
first
place
it
must
be
remembered
that,
although
some
of
the
patients
in
the
survey
have
been
the
subject
of
various
published
studies,
many
were
seen
on
a
consultative
service
basis
only.
Investigation
was
therefore
often
minimal.
Secondly,
it
is
now
well
recognized
that
many
factors
may
cause
or
contribute
to
hyperuricaemia
(Scott,
1969)
and
thus
to
gout,
which
cannot
therefore
be
regarded
as
an
aetiological
entity.
Nevertheless
the
many
points
of
similarity
demonstrated
in
this
study
between
gouty
subjects
excreting
more
or
less
than
600
mg.
uric
acid
daily
emphasize
the
general
clinical
homogeneity
of
the
condition
as
it
presents
itself
to
the
physician.
Obvious
exceptions
to
this
include
overproducers
of
uric
acid
who
form
renal
calculi,
cases
of
gout
complicating
myeloproliferative
dis-
orders
or
advanced
renal
failure,
and
subjects
with
the
Lesch-Nyhan
syndrome
(Lesch
and
Nyhan,
1964).
Our
finding
that
in
males
the
peak
age
at
onset
lies
in
the
fifth
decade
is
in
conformity
with
most
other
surveys
conducted
during
the
20th
century
(Futcher,
1915;
Brochner-Mortensen,
1941;
Barcel6,
Sans-Sold,
Santamaria,
and
Obach
Benach,
1967).
By
contrast,
in
19th
century
studies,
the
peak
in
males
was
one
decade
earlier
(Scudamore,
1823;
Strandgaard,
1899).
The
reason
for
this
discrepancy
is
not
certain
but
could
be
explained
on
the
basis
of
an
increasing
life-expectancy
over
the
past
150
years.
In
women
the
peak
age
at
onset
lies
in
the
sixth
decade,
and
this
no
doubt
reflects
the
physiological
rise
in
the
level
of
serum
urate
that
occurs
in
women
after
the
menopause
(Mikkelsen,
Dodge,
and
Valkenburg,
1965).
The
percentage
of
women
in
the
present
study
is
higher
than
in
almost
all
other
surveys
in
which
the
incidence
ranged
from
2
7
per
cent.
(Barcelo
and
others,
1967)
to
7'
9
per
cent.
(Schnitker
and
Richter,
1936).
The
finding
of
a
female
incidence
of
26
per
cent.
-by
Kuzell,
Schaffarzick,
Naugler,
Koets,
Mankle,
Brown,
and
Champlin
(1955)
is
exceptionally
high
and
certainly
does
not
conform
to
common
experience.
It
has been
a
distinct
clinical
impression
since
the
time
of
Sydenham
(1717)
that
gout
affects
the
rich
more
than
the
poor.
Popert
and
Hewitt
(1962)
showed
that
there
was
an
excess
of
individuals
in
the
Registrar
General's
Social
Classes
I
and
II
among
gouty
patients
compared
with
patients
attending
a
general
rheumatology
clinic.
The
present
study

466
Annals
of
the
Rheumatic
Diseases
confirms
this
finding.
Though
gout
clearly
occurs
in
all
socio-economic
classes
there
was
a
significant
bias
towards
the
higher
classes
among
the
gouty
men.
This
is
compatible
with
the
finding
of
higher
serum
uric
acid
levels
in
business
executives
than
in
craftsmen
(Dunn,
Brooks,
Mausner,
Rodnan,
and
Cobb,
1963;
Montoye,
Faulkner,
Dodge,
Mikkelsen,
Willis,
and
Block
1967).
The
familial
tendency
of
gout
has
been
known
since
classical
times
from
the
writings
of
Galen
and
Seneca.
Our
finding
that
36
per
cent.
of
our
gouty
patients
knew
of
at
least
one
other
member
of
their
family
similarly
affected
is
in
general
accord
with
previous
series
in
which
the
incidence
ranged
from
10
per
cent.
(Br0chner-Mortensen,
1941)
to
89
per
cent.
(Barcelo
and
others,
1967).
Similarly,
the
association
between
gout
and
obesity
has
previously
been
well-documented
(Williamson,
1920;
Brochner-
Mortensen,
1941).
Defining
obesity
as
any
weight
in
excess
of
15
per
cent.
above
the
Ideal
Weight,
we
find
that
the
incidence
among
our
gouty
patients
is
48
per
cent.
Many
patients
with
gout
are
regular
drinkers
(37
per
cent.
in
the
present
series),
and
this
association
too
has
been
noted
in
the
past
(William-
son,
1920;
Brochner-Mortensen,
1941).
It
has
been
established
that
acute
alcoholic
intoxication
pro-
vokes
hyperuricaemia
by
means
of
lactic
acidaemia
(Lieber,
Jones,
LoSowsky,
and
Davidson,
1962),
but
the
relationship
between
this
phenomenon
and
hyper-
uricaemia
in
habitual
chronic
alcohol
ingestion
is
not
clear.
The
various
factors
which
govern
the
association
of
hyperuricaemia,
gout,
renal
disease,
and
hyper-
tension
are
as
yet
ill-defined
and
causal
relationships
are
difficult
to
establish.
It
has
been
stated
that
renal
failure
is
the
most
frequent
cause
of
death
in
patients
with
gout
(Talbott
and
Terplan,
1960).
This
has
to
be
reconciled
with
the
finding
of
Talbott
and
Lilien-
feld
(1959)
that
life
expectancy
is
not
materially
reduced
in
patients
with
gout;
of
the
31
patients
who
died
in
the
present
series,
8
died
of
myocardial
infarction
and
this
was
the
most
common
single
cause
of
death.
It
is
true
that
we
have
information
concerning
only
those
patients
who
died
while
in
hospital,
and
a
number
of
others
have
probably
died
elsewhere
of
causes
unknown
to
us.
However,
the
available
figures
do
not
indicate
a
preponderance
of
renal
causes
for
death.
The
occurrence
of
renal
disease
in
primary
gout
has
been
studied
in
recent
years
by
Gonick,
Rubini,
Gleason,
and
Sommers
(1965)
and
by
Barlow
and
Beilin
(1968);
the
latter
authors
examined
53
gouty
patients
and
confirmed
the
frequent
occurrence
of
hypertension,
renal
insufficiency,
urolithiasis,
and
obesity.
There
are
also
several
reports
indicating
that
the
serum
uric
acid
level
tends
to
be
raised
in
patients
with
essential
hypertension.
Thus
Brecken-
ridge
(1966)
found
an
incidence
of 27
per
cent.;
in
these
subjects
the
filtered
load
of
uric
acid
was
higher
than
in
normouricaemic
patients,
but
urate
clearance
was
lower,
indicating
a
tubular
defect
of
uric
acid
excretion.
A
high
incidence
of
hypertension
and
renal
failure
was
found
in
the
subjects
of
the
present
study.
It
is
of
interest
that
no
correlation
could
be
found
be-
tween
hypertension
and
duration
of
disease
until
gout
had
been
present
for
40
years
or
more,
when
the
increased
incidence
referred
to
a
small
number
of
very
old
people.
It
may
therefore
be
inferred
that
there
is
in
general
little
deterioration
in
renal
function
with
increased
duration
of
disease;
the
possibility
remains,
however,
that
a
process
of
selection
was
operating,
in
that
the
patients
with
disease
of
long
duration
were
those
with
a
benign
prognosis
in
whom
blood
pressure
and
renal
function
had
not
deteriorated
and
who
had
therefore
survived.
This
question
could
be
finally
settled
only
by
a
prospective
study
in
which
the
progress
of
untreated
gouty
patients
was
compared
with
that
of
a
control
group,
a
situation
unlikely
ever
to
occur.
This
situation
may
be
contrasted
with
the
relation
to
age
at
onset.
The
incidence
of
moderate
hyper-
tension
rose
with
increasing
age
at
onset,
but
severe
hypertension
was
relatively
commoner
in
the
young.
Again,
although
there
was
a
progressive
rise
in
the
incidence
of
renal
failure
with
rising
age
at
onset
after
the
fourth
decade,
there
was
a
relatively
high
incidence
in
the
second
and
third
decades.
These
findings
emphasize
the
heterogeneity
of
our
popula-
tion
and
indicate
the
existence
of
a
separate
group
of
young
subjects
with
gout
and
severe
hypertension
and/or
renal
failure.
It
may
be
pointed
out,
however,
that
these
patients
presented,
in
the
first
instance,
with
the
symptoms
of
gout,
and
not
with
those
of
renal
or
vascular
disease;
although
these
soon
followed.
The
existence
of
these
two
groups
is
in
conformity
with
a
previous
analysis
of
some
of
these
patients
(Hall,
1966)
and
is
consistent
with
the
good
prognosis
found
in
most
patients
by
Talbott
and
Lilienfeld
(1959).
It
has
been
shown
that
there
is
a
correlation
be-
tween
urinary
urate
excretion
and
uric
acid
turnover
rate
(Scott,
Holloway,
Glass,
and
Arnot,
1969),
so
that
a
high
excretion
is
an
index
of
overproduction.
It
has
been
demonstrated
that,
on
a
purine-free
diet,
21
to
28
per
cent.
of
gouty
patients
excrete
more
than
600
mg.
uric
acid
per
24
hrs.
(Gutman,
Yu,
and
Berger,
1959;
Seegmiller,
Grayzel,
Laster,
and
Liddle,
1961).
The
much
higher
incidence
in
this
series
(63
per
cent.
of
89
patients
tested)
is
no
doubt
to
be
explained
by
the
more
generous
allowance
of
purine
in
the
diet
used.
No
difference
could
be
found
between
the
subjects
producing
large
amounts
of

Gout
467
uric
acid
and
the
others;
it
is
known
that
urinary
urate
excretion
tends
to
be
high
in
patients
with
uric
acid
calculi
(Gutman
and
Yu,
1968),
but
the
number
of
such
patients
in
the
present
study
was
too
small
to
analyse.
In
only
4c
5
per
cent.
of
the
gouty
patients
was
there
an
underlying
myeloproliferative
disorder.
Many
of
these
patients
were
referred
by
Departments
of
Radiotherapy
and
Haematology
specializing
in
the
treatment
of
these
disorders,
so
that
the
true
incidence
is
almost
certainly
lower.
In
the
series
reported
by
Yu
(1965),
it
was
3
7
per
cent.
The
present
study
did
not
attempt
to
assess
the
effect
of
long-term
therapy
aimed
at
lowering
the
level
of
serum
urate.
It
was,
however,
established
that
the
occurrence
of
acute
gout
within
3
months
of
the
institution
of
such
therapy
was
significantly
higher
in
those
receiving
allopurinol
than
in
those
receiving
the
uricosuric
drugs.
Summary
A
computer-assisted
analysis
has
been
carried
out
on
354
patients
with
gout,
all
seen
personally
between
1958
and
1967.
The
peak
age
at
onset
lay
in
the
fifth
decade
in
men
and
in
the
sixth
decade
in
women.
The
series
included
34
women
(9
7
per
cent.).
There
were
significantly
more
members
of
the
higher
social
classes
than
in
a
control
group
of
out-patient
attenders.
127
patients
(36
per
cent.)
gave
a
family
history
of
gout.
169
patients
(48
per
cent.)
had
body
weights
which
lay
more
than
15
per
cent.
above
their
ideal
weight
and
130
(37
per
cent.)
of
the
patients
were
classified
as
regular
alcohol
drinkers.
The
pattern
of
joint
involvement
was
analysed.
Subcutaneous
tophi
were
present
in
75
patients
(21
per
cent.).
184
patients
(52
per
cent.)
had
a
diastolic
blood
pressure
of
90
mm.
Hg
or
more;
31
(9
per
cent.)
of
these
had
severe
hypertension
with
a
blood
pressure
of
130
mm.
Hg
or
more,
the
remaining
153
(43
per
cent.)
being
designated
as
cases
of
moderate
hypertension.
A
blood
urea
of
more
than
45
mg./100
ml.
was
observed
in
86
patients
(25
per
cent.).
The
incidence
of
both
mild
and
severe
hyper-
tension
was
not
related
to
duration
of
disease.
Similarly,
the
incidence
of
renal
failure
did
not
rise
until
the
disease
had
been
present
for
over
40
years.
In
contrast,
although
the
incidence
of
moderate
hypertension
rose
with
increasing
age
at
onset,
severe
hypertension
and
renal
failure
were
relatively
common
in
a
group
of
young
subjects.
In
15
patients
(4W
2
per
cent.)
gout
was
believed
to
be
secondary
to
a
known
blood
dyscrasia.
No
difference
in
the
clinical
pattern
of
gout
could
be
observed
between
subjects
excreting
large
or
small
amounts
of
urinary
uric
acid,
although
the
number
of
patients
with
uric
acid
calculi
was
too
small
for
analysis
in
this
respect.
We
should
like
to
express
our
gratitude
to
the
staff
of
the
Computer
Centre,
Royal
Postgraduate
Medical
School,
and
to
the
Records
Department
of
Hammersmith,
West
London,
and
Charing
Cross
Hospitals,
for
their
inval-
uable
assistance.
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