CONCISE COMMUNICATIONS 1399

Table 1. Distribution of the NAT2genotypes in Japanese patients 3. Reidenberg MM, Levy M, Drayer DE, Zylber-Katz E, Robbins
with SLE and in controls* WC: Acety1ator phenotype in idiopathic systemic lupus erythe-
matosus. Arthritis Rheum 23:569-573, 1980
SLE patients Control subjects 4. Evans DAP: Survey of the human acetylator polymorphism in
Genotype (n = 48) (n = 53) spontaneous disorders. J Med Genet 21 :243-253, 1984
5. Weber WW, Hein DW: N-acety1ation pharmacogenetics. Phar-
Rapid acetylators macol Rev 37:25-79, 1985
wt/wt 18 19 6. Evans DAP: N-acetyltransferase. Pharmacol Ther 42:157-234,
wt/M1 0 1
wt/M2 13 18 1989
wt/M3 10 6 7. BlumM, DemierreA, Grant DM, Heim M, Meyer VA: Molec-
Total 41 44 ular mechanism of slowacetylation of drugs and carcinogensin
Slow acetylators humans. Proc Natl Acad Sci V S A 88:5237-5241, 1991
Ml/M1 0 0 8. Haqqi TM, Sarkar G, David CS, Sommer SS: Specific amplifi-
Ml/M2 1 0 cation with PCR of a refractory segment of genomic DNA.
M1/M3 0 1 Nucleic Acids Res 16:11844, 1988
M2/M2 2 1 9. BlumM, Grant DM, McBride W, Heim M, Meyer VA: Human
M2/M3 3 5 arylamine N-acetyltransferase genes: isolation, chromosomal
M3/M3 1 2 localization, and functional expression. DNA Cell Bioi 9:193-
Total 7 9 203, 1990
10. Deguchi T, Mashimo M, Suzuki T: Correlation between acety-
* SLE = systemic lupus erythematosus; wt = wild-type. lator phenotypes and genotypes of polymorphic arylamine
N-acetyltransferase in human liver. J Bioi Chern 265: 12757-
12760, 1990
11. Reidenberg MM: The chemical induction of systemic lupus
In our Japanese control population, 17% were of the erythematosus and lupus-like illnesses. Arthritis Rheum 24:
slow acetylator genotype; in the study by Deguchi et al (10), 1004-1009, 1981
the value was 9%. On the other hand, 23 of the 44 individuals
(52%) examined by Blum et al (7), most of whom we
presume were Caucasoid, had slow acetylator genotypes. Tophaceous gout as a fungating mass
Because the acetylator genotype determines the acetylator
phenotype, this interracial difference is reasonable. Chronic tophaceous gout has been reported to have a
Procainamide and hydralazine are known as lupus- prevalence of 20--50% in untreated patients with gouty
related drugs. An aromatic amino group of pro cain amide and arthritis (1,2). Tophaceous deposits, large aggregates of
a hydrazino group of hydralazine ar~ substrates for t~e monosodium uric acid crystals, are typically found in the
polymorphic NAT. They are also considered to be ~ssentlal subcutaneous tissue overlying the joints, tendons, or carti-
in order for the two drugs to induce lupus. Hydrazines are lage, with the most common locations being the fingers, first
present naturally in tobacco smoke, mushrooms, and a metatarsophalangeal (MTP) joints, knees, olecranon bursae,
Penicillium. They are also found in a variety of compounds Achilles tendons, and helices of the ear (3). There have been
used in industry, agriculture, and medicine. Aromatic multiple reports of tophi presenting prior to the first attac~ of
amines are present in the diet and permanent hair-c~loring gout or in unusual locations, such as the eyes, eyehds,
solutions (11). Slow acetylators are more susceptible to larynx, heart valves, bronchi, pleura, pericardium, meninges,
lupus induced by procainamid~ and. hydralazine th~n a~e corpus cavernosum, intestine, tongue, nasal septum, but-
rapid acetylators (11). If aromatic arrnnes and hydrazines in tocks, and finger pads (4,5). Inadequately treated tophi can
the environment are principal inducers of idiopathic SLE, it increase to a size which causes mechanical pressure on the
is reasonable to speculate that populations of patients with overlying skin, leading to sinus formation and d.rainage of
idiopathic SLE show a statistically significant preponder- fluid which contains sodium urate crystals (3). This swollen,
ance of slow acetylators. However, in Japanese populations,
erythematous, and warm tissue can b~ .confuse~ with ~,!"d
we could not find any evidence of an association between must be differentiated from severe cellulitis or septic arthritis.
NAT2 genotypes, which determine the acetylation pheno- Recently, we treated a patient with a long history of
types, and susceptibility to idiopathic SLE. Our data, to- polyarticular gout who had a tophus that presented as a
gether with those from white populations, suggest that recurring, fungating mass. The patient, a 42-y~ar-old man
patients with idiopathic SLE and those with drug-related with a history of alcohol abuse and hypertension (treated
lupus have different genetic backgrounds. with a thiazide diuretic), began experiencing periodic epi-
sodes of acute monarthritis of the joints, knees, and ankles in
Satoshi Shiokawa, MD 1984. Serum uric acid levels ranged from 410 ILmoles/liter to
Masayuki Yasuda, MD 710 ILmoles/iiter (6.9-12.0 mg/dl) and a 24-hour urine collec-
Masashi Nobunaga, MD tion while on a regular diet contained 5 mmoles (831 mg) of
Kyushu University uric acid. The attacks were successfully treated with indo-
Beppu, Japan methacin, phenylbutazone, or colchicine, and allopurinol
therapy was begun to correct the elevated urate levels.
I. Weber WW: Acetylationpharmacogenetics: experimental mod- In 1986 a tophus was surgically removed from the
els for human toxicity. Fed Proc 43:2332-2337, 1984 subcutaneous tissue overlying the left posterior calcaneus.
2. Reidenberg MM, Martin JH: Acetylator phenotype of patients Subsequently, he had 3 episodes of acute MTP arthritis,
with systemic lupus erythematosus. Drug Metab Dispos 2:71- accompanied by desquamation of the skin overlying the
73, 1974 distal portion of the right first and second toes. These
1400
episodes were treated symptomatically with indomethacin
and local wound care, with subsequent resolution of the
gouty arthritis flares.
In July 1988 he was referred to us for a recurrent
t-ern fungating ulcer with serous drainage on the right
second toe. There was surrounding swelling, skin desqua-
mation, erythema, and tenderness (Figure I). Findings on
radiographs were unremarkable. Scrapings of the lesion and
a slide preparation with potassium hydroxide failed to reveal
fungal elements. Results of staining for acid-fast bacilli were
similarly negative, as were bacterial and fungal cultures.
However, the serous drainage did contain numerous extra-
cellular monosodium urate crystals seen under polarized
light microscopy. His serum uric acid level was 280 p,moles/
liter (4.7 mg/dl). Aggressive treatment for tophaceous gout
was begun, with long-term colchicine (0.65 mg orally, 3 times/
day), allopurinol (300 mg orally, each day), and indometh-
acin (50 mg orally, 3 times/day). This management of the
tophaceous gout was successful in achieving ulcer healing
Figure 1. Photograph of the patient's right forefoot, showing the
fungating mass on his second toe . A complete evaluation revealed
only extracellular monosodium urate crystals.
CONCISE COMMUNICATIONS
and in preventing a recurrence of arthritis or desquamation
during 2 years of followup .
The appearance of tophi at sites of trauma and in the
finger pads has been described (4-6). A tophus presenting as
a recurring, fungating mass has not been reported previ-
ously, and in our patient, suggested the possibility of an
infectious or malignant etiology. These were effectively
ruled out with the appropriate stains and cultures and the
favorable response to therapy with antihyperuricemic
agents . Fungating ulcer of the toe pads should be added to
the list of possible dermatologic manifestations of gout.
The views expressed herein are those of the authors
and do not reflect the official policy or position of the
Department of the Army, the Department ofDefense, or the
US Government.
Lewis L. Low, MD
Walter Reed Army Medical Center
Washington, DC
Aida G. Cervantes, MD
Kaiser Permanente Medical Group
Walnut Creek, CA
William L. Melcher, MD
Tripler Army Medical Center
Honolulu, HI
I. Grahame R, Scott JT: Clinical survey of 354 patients with gout.
Ann Rheum Dis 29:461-468, 1970
2. Gutman AB: The past four decades of progress in the knowledge
of gout, with an assessment of the present status . Arthritis
Rheum 16:431-445, 1973
3. Seegmiller JE: Skin manifestations of gout , Dermatology in
General Medicine. Edited by TB Fitzpatrick. New York , Me-
Graw -Hill, 1979
4. Talbott JH, Yu TF: Gout and Uric Acid Metabolism. New York ,
Stratton Intercontinental Medical Book Corporation , 1976
5. Schmerling RH , Stern SH , Gravallese EM, Kantrowitz FG :
Tophaceous deposition in the finger pads without gouty arthritis .
Arch Intern Med 148:1830-1832, 1988
6. Kraines JL, Ellman MH: Plasterer's tophi (letter). Arthritis
Rheum 25:472-473, 1982