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The Journal of Rheumatology
Volume 36, no. 1
Acute Gouty Arthritis After Taking Sildenafil: An Old Disease with a NewEtiology
WEI-LIANG CHEN, HONG-I CHEN and CHING-HUI LOH
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is a monthly international serial edited by Earl D.
The Journal of Rheumatology
Silverman featuring research articles on clinical subjects from scientists working in rheumatology and related fields.
Acute Gouty Arthritis After Taking Sildenafil: An Old
examination was unremarkable and his uric acid level was 4.6 mg/dl with-
Disease with a New Etiology
It is tempting to speculate that sildenafil induced gout episodes in this
case because this has not been documented in any report. In addition, gout
Sildenafil citrate (Viagra), a selective inhibitor of cyclic guanosine
flares are often observed when urate-lowering therapy has been started or
monophosphate (cGMP)-specific phosphodiesterase type 5, is an effective
stopped. The temporal sequences in this case do not absolutely preclude
treatment for male erectile dysfunction. By enhancement of the effect of
this as an explanation of the gout flares. However, the temporal association
nitric oxide and cGMP, it leads to smooth-muscle relaxation and inflow of
between administration of sildenafil and episodes of acute gouty arthritis
blood to the corpus cavernosum1. Sildenafil has suitable pharmacodynam-
implies a causal relation. The recurrence of acute arthritis after taking
ic and pharmacokinetic properties for use as an oral therapeutic drug for
sildenafil (rechallenge test) also suggests a causal relation. Gouty arthritis
erectile dysfunction2. Numerous adverse reactions to sildenafil have been
is listed as one of many side effects (Viagara package insert; Pfizer Inc.),
reported, including headache, facial flush, dyspepsia, nasal stuffiness, and
so it must have been detected during the phase III clinical trial. In addition,
conjunctival suffusion. However, there have been no reports that sildenafil
an unpublished safety surveillance and reporting from Pfizer Inc. describes
is associated with acute gout. We describe a 41-year-old man who devel-
7 adverse events with gout attacks during use of sildenafil5.
oped gouty arthritis after taking sildenafil. There was a temporal relation
Sildenafil has been widely prescribed; in the absence of evidence from
between the attacks of gouty arthritis and administration of sildenafil.
reports in the literature it is imperative to be aware of this problem. We con-
Symptoms then subsided after the withdrawal of sildenafil. The symptoms
clude that sildenafil can induce acute gouty arthritis, and any physician
did recur when he took sildenafil again (positive rechallenge test).
encountering a case with acute arthritis of primary gout will need to sus-
Recognizing the possible association and prompt management will prevent
pect the possibility of this etiology. The lack of this awareness may result
in delay recognizing the etiology and providing prompt management.
A previously healthy 41-year-old man with no significant medical his-
tory presented to our outpatient department (first visit) with sudden onset
WEI-LIANG CHEN, MD, Department of Family Medicine and
of severe exquisite pain and swelling at the metatarsophalangeal (MTP)
Community Health; HONG-I CHEN, MD, PhD, Division of Urology;
joint of the right hallux. He had had 6 or 7 similar attacks in the past 5
CHING-HUI LOH, MD, PhD, Department of Family Medicine and
months. He had visited 3 primary care physicians, who prescribed “pain
Community Health, Tri-Service General Hospital, National Defense
killers” for his acute symptoms. He specifically denied illicit drug use.
Medical Center, Number 325, Section 2, Cheng-Kung Road, Neihu 114,
There was no contributory family history or drug and food allergy history.
Taipei, Taiwan. Address reprint requests to Dr. Loh;
Examination showed tenderness, swelling, and redness over the MTP joint.
Laboratory data revealed normal findings except his serum level of uricacid was 9.0 mg/dl (reference value < 7.0). Based on the diagnostic crite-
ria of the American Rheumatism Association3, he was diagnosed as having
1. Boolell M, Gepi-Attee S, Gingell J, Allen M. Sildenafil, a novel
acute gouty arthritis at second visit. By taking sulindac and colchicine, fol-
effective treatment for male erectile dysfunction. Br J Urol
lowed by uric acid-lowering agents (benzbromarone), he had been able to
have 2–3 weeks symptom-free. Then he presented (third visit) at the out-
2. Boolell M, Allen MJ, Ballard SA, et al. Sildenafil: an orally active
patient department and asked to see the attending physician (CHL) pri-
type 5 cyclic GMP-specific phosphodiesterase inhibitor for the
vately. He stated he had had another attack of acute arthritis, which he
treatment of penile erectile dysfunction. Int J Impot Res 1996;
believed was because he had taken 50 mg sildenafil one night before. He
also recalled that there had been a temporal relation between the use of
3. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF.
sildenafil and the previous episodes of attacks. He was advised not to take
Preliminary criteria for the classification of the acute arthritis of
sildenafil until we consulted other specialists.
primary gout. Arthritis Rheum 1977;20:895-900.
An extensive literature review failed to find any report relating silde-
4. Loh CH, Cang YW, Liou SH, Chang JH, Chen HI. Case report:
nafil use and gouty arthritis. Confirmation of acute arthritis of gout related
hexachloroethane smoke inhalation: a rare cause of severe hepatic
to sildenafil by rechallenge test would be reliable but unjustifiable4. Three
injuries. Environ Health Perspect 2006;114:763-5.
weeks later (fourth visit), he again developed painful swelling at the same
5. D’Amato S, Hassett J. Summary bridging report: Sildenafil, safety
location one day after taking sildenafil 50 mg. Synovial fluid analysis con-
surveillance and reporting. New York: Pfizer Inc.; 2006.
firmed the presence of monosodium urate crystals. After treatment, he hasbeen symptom-free with discontinuation of sildenafil for more than 2
J Rheumatol 2009;36:1; doi:10.3899/jrheum.080572
months since that episode. In December 2007 (fifth visit), a followup
Personal noTogy Copyright 2009. Al rights reserved.
The Journal of Rheumatology 2009; 36:1
1. HANDELSNAME: Amin-Polymer-Grundreiniger Ing.G.Linker GmbH, Chemische Fabrik, Am Leveloh 20, D-45549 Sprockhövel Tel.: +49/(0)2324/9798-0, Fax: +49/(0)2324/9798-98, (Notfall: 0177-6610066) Verwendung des Stoffes siehe 3. Beschreibung. Notrufnummer Seite 2 Punkt 16 MÖGLICHE GEFAHREN Besondere Gefahren für Mensch und Umwelt Risikohinweise für Mensch
CLINIQUE DE LA DHUYS 1 Rue Pierre Curie 93170 BAGNOLET Standard : 01.49.97.50.50 TITRES DOCTEUR GILBERT ZERAH ANCIEN EXTERNE DES HOPITAUX DE PARIS : 1961-1968 ANCIEN ATTACHE DES HOPITAUX DE PARIS : 1968-1976 MEMBRE DE LA SOCIETE FRANCAISE DE CARDIOLOGIE : 1970 (North American Society of Pacing and Electrophysiology) CHEF DE SERVICE HOSPITALIER : 1981-2004 cardiologue DIRECTE