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Studies with allopurinol HPP in patients with tophaceous gout.

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Studies with Allopurinol (HPP) in Patients
with Tophaceous Gout
By CHARLEY
J. SMYTH, M.D.
University of Colorado School of Medicine
We elected to use HPP in four of our most stubborn patients and studied
them on a metabolic ward. The pattern of the experiment is illustrated in
Figure 131.
The patients all had advanced tophaceous disease. Each of these patients
was removed from all his previous urate diuretic therapy during a control
period and was then given HPP in a dose of 800 mg. per day. Following
another control period each patient was given both HPP and Anturane
together.
The serum urate levels have followed the patterns that others have described and this needs no repetition. The amount of urinary output in this
patient remained remarkably unchanged. An acute attack of gout occurred
while receiving HPP. We also have found that acute attacks of gout are
very frequent and in each of the four patients that we have studied there
has been an acute exacerbation of acute gouty arthritis either during HPP
therapy or immediately after it. Our interest was to follow the serum urate
concentration upon withdrawal of HPP and upon resumption of the drug.
The urate levels rose to the pretreatment level and when exhibiting the
drug again, the serum urate immediately came down. When we gave the
patient a combination of Zyloprim and Anturane, a very satisfactory
and sustained urinary excretion of urate occurred, and a sustained suppression of the serum urate below normal level was attained. The patient is
now on about the 130th day of the study and is receiving both drugs as an
outpatient with very satisfactory control and without any further acute
attacks (Fig. 131).
The second patient exhibited a little different response as far as the
urinary excretion of uric acid is concerned. There was a very significant drop
in the amount of urinary uric acid output. When the HPP was stopped, the
amount of urinary uric acid in the urine returned to the pretreatment level.
The serum urate returned toward normal and when the drug was again exhibited it came down again. When the two drugs, HPP and Anturane, were
given together, the urinary uric acid excretion increased. An acute attack
occurred which was treated with Butazolidin and a very satisfactory result
was observed. As others have observed, a rash occurred. Because of this we
reduced the amount of HPP from 800 mg. per day to 400 mg. per day. The
rash did not recur. It would appear that 200 mg. HPP was not adequate to
bring the serum urate to 6 mg. per cent or below (Fig, 132).
The third patient is one who had six years of therapy with sulfinpyrazone.
The finger which was normal six years before had gone on to this destructive
907
hTHRITIS AND
RHEUMATISM,VOL. 8,
NO. 5-PART
1 (OCTOBER), 1965
908
GOUT AKD PUfiINE METABOLISM
PATIENT H A UNIV
COtO. HOSP r 2 1 2 9 8 4
/
NORM 4 L
SFRUM URIC ACID
mgm
2
m g m x
do"
4
8
6
10
12
14
I6
I8
PO
22
24
2e
el
30
32
-
36
3B
40
HOSPIlLI DAIS
34
47
61
81
102
--OUlPLTlENl
CLINIC
42
llB
137
DAIS
Fig. 131.
PATIENT E.G. UNIV. COLO. H O P #217007
109 8-
7-
-6
5 -
32-
I
I
4
6
8
10
I2
I4
I6
I8
10
22
24
26
28
HOSllIAL DAYS
-30
32
Fig. 132.
40 4 7
54
61
68
OUr?AlIENT C L I N K DAYS
75
82
96
I24
145
167
169
HPP I N P A T E N T S WITH TOPHACEOUS GOUT
909
Fig. 133.-(Left): Left index finger patient, F. D. (Case 111) at the beginning
of allopurinol therapy ( 8/11/64) showing draining and infected tophus overlying
distal interphalangeal joint. (Right) : Same finger 41/2 months later (1/6/65) with
marked reduction in the size of the finger and healing of the ulcerated tophus.
stage of the disease, with the development of ulcerated tophi as shown in
Figure 133. This patient showed a different pattern of urinary excretion with
HPP although the serum urate pattern is identical with that of the three previous patients. The serum urate came down and stayed down. When the drugs
were discontinued, it came up again, and when the combination of HPP
and Anturane was given the serum urate came down. This patient is now on
about the 50th day of the study. The urinary uric acid excretion swings
widely and I think he illustrates another type of urinary excretion pattern
(Fig. 134).
In these three patients with advanced tophaceous disease and with renal
disease, there has been a different urinary pattern excretion and the urinary
uric acid excretion will probably vary from those who do not have advanced
tophaceous disease.
We think that this new drug, HPP, has a n exciting potential for therapy.
There is no interference with urate diuretic therapy and we can attack the
overproduction of uric acid with the xanthine oxidase inhibitor, HPP, and increase the urinary output wtih the currently available drugs. With this dual
attack we may be able to improve the management of the difficult cases of
gout which we all encounter.
910
GOUT AND PURINE METABOLISM
PATIENT F.D. UNIV. COLO. HOSP. #220257
F
U R I N A R Y URIC A C I D m g r n / 2 4 H r r
-
~~
~
2
-~&=
4
6
8
10
12
14
16
18
20
22
24
26
28
HOSPITAL
30
32
34
DAYS --OUTPATIENT
36
38
42
56
70
91
CLINIC DAYS
Fig. 134.
I turn the meeting back to Dr. Gutman and say for our participants that
we deeply appreciate your efforts.
DR. GUTMAN:This Conference has been a most inspirational experience, I
think, for all of us. The credit does not go to me but to Dr. Lamont-Havers
and his staff. I want to express to them our appreciation of their wonderful
arrangements for the meeting, and also our thanks to the supporting agencies.
I want to thank the participants again for their interest and .indulgence.
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patients, gout, allopurinol, studies, tophaceous, hpp
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