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Table 1. Distribution of the NAT2genotypes in Japanese patients with SLE and in controls* Genotype Rapid acetylators wt/wt wt/M1 wt/M2 wt/M3 Total Slow acetylators Ml/M1 Ml/M2 M1/M3 M2/M2 M2/M3 M3/M3 Total

SLE patients (n = 48)

Control subjects (n = 53)

18 0

19 1 18 6 44

13

10

41

0 0 1 1 5 2 9

0 1 0 2 3 1 7

* SLE = systemic lupus erythematosus; wt = wild-type.

In our Japanese control population, 17% were of the slow acetylator genotype; in the study by Deguchi et al (10), 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. Because the acetylator genotype determines the acetylator phenotype, this interracial difference is reasonable. Procainamide and hydralazine are known as lupusrelated drugs. An aromatic amino group of pro cain amide and a hydrazino group of hydralazine ar~ substrates for t~e polymorphic NAT. They are also considered to be ~ssentlal in order for the two drugs to induce lupus. Hydrazines are present naturally in tobacco smoke, mushrooms, and a Penicillium. They are also found in a variety of compounds used in industry, agriculture, and medicine. Aromatic amines are present in the diet and permanent hair-c~loring solutions (11). Slow acetylators are more susceptible to lupus induced by procainamid~ and. hydralazine th~n a~e rapid acetylators (11). If aromatic arrnnes and hydrazines in the environment are principal inducers of idiopathic SLE, it is reasonable to speculate that populations of patients with idiopathic SLE show a statistically significant preponderance of slow acetylators. However, in Japanese populations, we could not find any evidence of an association between NAT2 genotypes, which determine the acetylation phenotypes, and susceptibility to idiopathic SLE. Our data, together with those from white populations, suggest that patients with idiopathic SLE and those with drug-related lupus have different genetic backgrounds. Satoshi Shiokawa, MD Masayuki Yasuda, MD Masashi Nobunaga, MD Kyushu University Beppu, Japan Weber WW: Acetylationpharmacogenetics: experimental models for human toxicity. Fed Proc 43:2332-2337, 1984 2. Reidenberg MM, Martin JH: Acetylator phenotype of patients with systemic lupus erythematosus. Drug Metab Dispos 2:7173, 1974 I.

3. Reidenberg MM, Levy M, Drayer DE, Zylber-Katz E, Robbins WC: Acety1ator phenotype in idiopathic systemic lupus erythematosus. Arthritis Rheum 23:569-573, 1980 4. Evans DAP: Survey of the human acetylator polymorphism in spontaneous disorders. J Med Genet 21 :243-253, 1984 5. Weber WW, Hein DW: N-acety1ation pharmacogenetics. Pharmacol Rev 37:25-79, 1985 6. Evans DAP: N-acetyltransferase. Pharmacol Ther 42:157-234, 1989 7. BlumM, DemierreA, Grant DM, Heim M, Meyer VA: Molecular mechanism of slowacetylation of drugs and carcinogensin humans. Proc Natl Acad Sci V S A 88:5237-5241, 1991 8. Haqqi TM, Sarkar G, David CS, Sommer SS: Specific amplification with PCR of a refractory segment of genomic DNA. Nucleic Acids Res 16:11844, 1988 9. BlumM, Grant DM, McBride W, Heim M, Meyer VA: Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression. DNA Cell Bioi 9:193203, 1990 10. Deguchi T, Mashimo M, Suzuki T: Correlation between acetylator phenotypes and genotypes of polymorphic arylamine N-acetyltransferase in human liver. J Bioi Chern 265: 1275712760, 1990 11. Reidenberg MM: The chemical induction of systemic lupus erythematosus and lupus-like illnesses. Arthritis Rheum 24: 1004-1009, 1981

Tophaceous gout as a fungating mass Chronic tophaceous gout has been reported to have a prevalence of 20--50% in untreated patients with gouty arthritis (1,2). Tophaceous deposits, large aggregates of monosodium uric acid crystals, are typically found in the subcutaneous tissue overlying the joints, tendons, or cartilage, with the most common locations being the fingers, first metatarsophalangeal (MTP) joints, knees, olecranon bursae, Achilles tendons, and helices of the ear (3). There have been multiple reports of tophi presenting prior to the first attac~ of gout or in unusual locations, such as the eyes, eyehds, larynx, heart valves, bronchi, pleura, pericardium, meninges, corpus cavernosum, intestine, tongue, nasal septum, buttocks, and finger pads (4,5). Inadequately treated tophi can increase to a size which causes mechanical pressure on the overlying skin, leading to sinus formation and d.rainage of fluid which contains sodium urate crystals (3). This swollen, erythematous, and warm tissue can b~ .confuse~ with ~,!"d must be differentiated from severe cellulitis or septic arthritis. Recently, we treated a patient with a long history of polyarticular gout who had a tophus that presented as a recurring, fungating mass. The patient, a 42-y~ar-old man with a history of alcohol abuse and hypertension (treated with a thiazide diuretic), began experiencing periodic episodes of acute monarthritis of the joints, knees, and ankles in 1984. Serum uric acid levels ranged from 410 ILmoles/liter to 710 ILmoles/iiter (6.9-12.0 mg/dl) and a 24-hour urine collection while on a regular diet contained 5 mmoles (831 mg) of uric acid. The attacks were successfully treated with indomethacin, phenylbutazone, or colchicine, and allopurinol therapy was begun to correct the elevated urate levels. In 1986 a tophus was surgically removed from the subcutaneous tissue overlying the left posterior calcaneus. Subsequently, he had 3 episodes of acute MTP arthritis, accompanied by desquamation of the skin overlying the distal portion of the right first and second toes. These

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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 desquamation, 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 extracellular 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 indomethacin (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 previously, 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 , MeGraw -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

Tophaceous gout as a fungating mass.

1399 CONCISE COMMUNICATIONS Table 1. Distribution of the NAT2genotypes in Japanese patients with SLE and in controls* Genotype Rapid acetylators wt/...
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