707

ALILOPURINOL HYPERSENSITIVITY CHRONIC, TOPHACEOUS GOUT

ELLA WEBSTER and RICHARD S. PANUSH

We report our experience managing a patient with severe, chronic, tophaceous gout and allopurinol hypersensitivity. Our patient was successfully desen- sitized to allopurinol and also benefited from extensive removal of tophi as well as amputation of tophaceous digits. We are aware of 2 previous case reports of desensitization to allopurinol in patients with associat- ed hypersensitivity (1,2). This experience illustrates possible approaches to an unusual and seemingly hopeless clinical situation.

Case report. The patient, a 61-year-old white man, has a history of gout dating back to 1944. Within 5 years of that time he developed tophi over his ankles, knees, wrists, elbows, and shoulders. Despite therapy with allopurinol, probenecid. colchicine, and occa- sionally prednisone, he had acute attacks every 2-3 months and in 1973 was forced to retire from his job as a postal carrier.

While being treated with allopurinol, the patient

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From the Division of Clinical Immunology, Department of Medicine, College of Medicine, University of Florida and the Clinical Immunology Section, Medical and Research Services, Veterans Administration Medical Center, Gainesville, Florida.

Supported by grants from the Veterans Administration and the Florida Chapter of the Arthritis Foundation.

Ella Webster, MD: Postdoctoral Fellow, Division of Clini- cal Immunology, Department of Medicine, College of Medicine, University of Florida; Richard S. Panush, MD: Associate Professor of Medicine and Immunology and Medical Microbiology, Chief, Division of Clinical Immunology, Department of Medicine, College of Medicine, University of Florida, and Chief, Clinical Immunology Section, Veterans Administration Medical Center, Gainesville.

Address reprint requests to Richard S. Panush, MD, Divi- sion of Clinical Immunology, Department of Medicine, Box 5-277, JHMIIC, University of Florida, Gainesville, FL 32610.

Submitted for publication August 27, 1984; accepted in revised form January 17, 1985.

IN A PATIENT WITH SEVERE,

developed a pruritic, erythematous, maculopapular rash of the face, trunk, and extremities; the allopurinol was discontinued with apparent resolution of the rash. The rash recurred following re-challenge with allopuri- nol. Biopsies were not performed. He was then treated with colchicine, probenecid (1.5-2 gm/day), and indo- methacin. His serum uric acid level ranged from 10.0- 10.9 mg/dl. In May 1980, with poorly controlled, re- current episodes of gouty arthritis superimposed on chronic, draining tophi, the patient was admitted for desensitization and retrial of allopurinol under close observation, and for surgical drainage and debride- ment of tophi.

Physical examination results were notable for a confluent, erythematous, maculopapular rash with some scaling and excoriation, diffuse swelling of both wrists, elbows, knees, ankles, and multiple metacar- pophalangeal and proximal interphalangeal joints, and ulcerated, draining tophi over the elbows, hands, wrists, knees, and ankles (Figures 1 and 2). Labora- tory findings included blood urea nitrogen (BUN) 18 mg/dl, serum creatinine 1.2 mg/dl, serum uric acid 11.5 mg/dl, erythrocyte sedimentation rate 12 mm/hour, normal SMAC profile and complete blood count with differential, 24-hour urinary uric acid 304 mg, and creatinine clearance 44 cchinute.

He was initially treated with sulfinpyrazone (400 mg/day) and indomethacin (150 mg/day), but his BUN rose to 28 mg/dl and serum creatinine to 1.7 mg/ dl, while serum uric acid was 9.7 mg/dl. Indomethacin dosage was then decreased to 25 mg twice a day, sulfinpyrazone was discontinued, bicarbonate was be- gun, and fluid intake increased. His creatinine clear- ance improved to 77 cdminute, and 24-hour urinary uric acid level rose to 1,008 mg.

Arthritis and Rheumatism, Vol. 28, No. 6 (June 1985)

708 BRIEF REPORTS

Figure 1. Gouty involvement of the patient’s right arm.

On June 24, 1980, allopurinol desensitization was initiated as shown in Table 1. The patient tolerat- ed desensitization without complication, receiving gradually increasing doses of oral solution and then tablets of allopurinol. There was an initial increase in his serum creatinine; this improved with continued hydration and alkalinization of his urine. Serum uric acid decreased from a peak of 1 1.5 mg/dl while he was in the hospital to 8.5 rng/dl at discharge.

The patient was subsequently transferred to the orthopedic surgery service where he underwent resec-

tion of ulcerating tophi on both index fingers and excision of tophi from the right elbow, right prepatellar bursa, left great toe, left ankle, and left Achilles tendon. He had an uneventful recovery and continued on a regimen of allopurinol300 mg/day, colchicine 0.6 mg twice a day, and indomethacin.

Discussion. Allopurinol is now commonly used for treatment of certain patients with hyperuricemia and gout. Adverse reactions include fever, pruritis, gastrointestinal distress, diarrhea (3,4), toxic epider- mal necrolysis, interstitial nephritis, renal insufficien- cy (3, granulomatous hepatitis (6), and vasculitis (7). Reports estimate that up to 10% of patients given allopurinol will have minor adverse reactions (3,4), particularly cutaneous reactions (8,9) which could limit use of this drug.

Allopurinol is particularly important for therapy of patients with tophaceous gout and/or gouty nephri- tis. Drug hypersensitivity, as occurred in our patient, would seriously limit the ability to manage such pa- tients. Our patient had severe, debilitating, topha- ceous gout which benefited from amputation of digits and excision of ulcerated, draining lesions. He may have also had some underlying renal insufficiency,

Table 1. Allopurinol desensitization regimen

Day Dosage of allopurinol (mg)

1 2 3 4 5 6 7 8 9

10 1 1 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

0.008 0.016 0.024 0.032 0.040 0.048 0.056 0.064 0.072 0.080 0.160 0.320 0.480 0.640 0.800 0.960 1.120 1.280 1.600 2.000 2.560 5.120

10.240 20.000 50.000 75.000

100.000 150.000 200.000 300.000

BRIEF REPORTS 709

Figure 2. Gouty involvement of the patient's feet.

possibly related to his tophaceous gout. He did well with both desensitization and operative procedures and is now managed in a conventional manner with adequate control of joint discomfort and serum urate level.

Our experience, which supports that of others, indicates that cautious desensitization of patients with cutaneous hypersensitivity to allopurinol is both feasi- ble and clinically useful.

Acknowledgments. The authors appreciate the assist- ance of Barbara Gibbs in preparing the manuscript and the helpful advice of Drs. Selden Longley and N. Lawrence Edwards.

1.

2.

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Jarzofski J, Ferry J, Wombolt D, Fitch DM, Fegan JD: Vasculitis with allopurinol therapy. Am Heart J 79: 116- 121, 1970 Frisch JM, Lovatt GE, Sproit ARM, Turmer R: The adverse reaction profile of allopurinol, Frontiers of Inter- nal Medicine, 1974. Edited by SH Blondheim. Basel, Karger, 1975, pp 412-419 Boston Collaborative Drug Surveillance Program, Boston University Medical Center: Excess ampicillin rashes as- sociated with allopurinol or hyperuricemia. N Engl J Med 286:505-507, 1972

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