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2. Krakauer T, Oppenheim JJ, Jasin HE: Human interleukin 1 mediates cartilage matrix degradation. Cell Immunol 91:92-99, 1985 3. Jasin HE: Bacterial lipopolysaccharides (LPS) induce cartilage matrix degradation through chondrocyte activation. J Clin Invest 72:20142019, 1983 4. Von der Mark K, Mollenhauer J , Haffle M, van Menxel M, Muller PK: Role of anchorin CII in the interaction of chondrocytes with extracellular collagen, Articular Cartilage Biochemistry. Edited by K Kuettner, R Schleyerbach, VC Hascall. New York, Raven Press, 1986 5 . Mayne R, Vail MS, Mayne PM, Miller EJ: Changes in the type of collagen synthesized as clones of chick chondrocytes grow and eventually lose division capacity. Proc Natl Acad Sci U S A 73:167&1678, 1976 6. Benya PD, Shaffer JD: Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30:215-224. 1982
Reduce serum uric acid levels before withdrawing antihyperuricemic therapy in patients with tophaceous gout To the Editor: McCarthy and coworkers have described progression of tophi on radiography of 9 patients and progression of tophi on physical examination of 7 patients during antihyperuricemic therapy in a group of 39 patients with gout (McCarthy GM, Barthelemy CR, Veum JA, Wortmann RL: Influence of antihyperuricemic therapy on the clinical and radiographic progression of gout. Arthritis Rheum 34: 14891494, 1991). They found no correlation between radiographic progression and mean serum urate concentration. The results of antihyperuricemic therapy, thus seem disappointing. However, the mean serum urate level in the 9 patients with radiographic progression, as given in Table 5 of their article, is 7.1 mg% ([ 1 x 6.8 + 3 x 6.1 + 5 x 7.81 f 9), and the mean serum urate level in the 7 with clinical progression, as given in Table 4, is 8.2 mg% (0.48 mmoles/ liter), during therapy. During the 10 years of followup, the serum urate concentration was measured only as deemed necessary, e.g., a range of 2-13 and an average of 6 determinations per patient in 10 years (see page 1490). Although all but 2 of the 39 patients had decreased excretion of uric acid, only 9 patients were treated with uricosuric drugs and 30 were treated with allopurinol. There are several causes for the disappointing results. I ) Allopurinol was not the drug of choice for most patients with decreased uric acid excretion. 2) The markedly elevated serum urate level points to poor compliance. 3) The evaluation visits were too fewhot frequent enough. 4) The urate levels were not lowered sufficiently. The authors refer to my reported experience with discontinuation of hyperuricemic agents in 10 patients with tophaceous gout (Cast LF: Withdrawal of longterm antihyperuricemic therapy in tophaceous gout. Clin Rheumatol 6:70-73, 1987; reference 5 in McCarthy’s article). During the therapy in those patients, all tophi had disappeared clinically, osseous tophi had shown radiographic regression, and serum urate levels had reached a mean of 5.6 mg% (0.30 mmolesfiiter), a concentration much lower than reached in McCarthy’s group.
LETTERS My recommendations are that patients with tophaceous gout should be evaluated every 3 months and have their antihyperuricemic therapy adjusted until all tophi have disappeared clinically and the serum urate concentration has become normal. Preferably, a level below 5.6 mg% (0.30 mmoles/liter) should be reached before antihyperuricemic therapy is withdrawn.
L. F. Cast, MD University Hospital Leiden. The Netherlands
To the Editor: Contrary to Dr. Cast’s suggestion, allopurinol therapy was the antihyperuricemic agent of choice in the majority of our patients. Although allopurinol is clearly indicated for use in individuals whose hyperuricemia results from urate overproduction, it is equally effective in lowering serum urate concentrations in those whose hyperuricemia results from underexcretion. In addition, it has the potential advantages of single daily dosage, fewer interactions with other drugs, and less frequent incidents of intolerance. Furthermore, it may be used in patients with impaired renal function ( I ,2). Our study reported the consequences of management of gout in a Veterans Administration Medical Center population managed by several practitioners over a prolonged period of time. It was not a precisely designed therapeutic trial. We agree that the results of antihyperuricemic therapy in this unique population appear disappointing overall, and attribute that to poor compliance. However, we reemphasize the lack of correlation between radiographic progression of gouty lytic lesions or erosions and the mean serum urate concentration. This resulted in radiographic progression in some patients with mean serum urate concentrations within the normal range, whereas others with chronically elevated mean serum urate concentrations did not have radiographic progression of disease. Clearly, more frequent assessment of individual compliance should improve outcome. We have absolute confidence that if serum urate concentrations can be maintained at or below 5.6 mg/dl, tophi will resolve and gout will be “cured.”
Geraldine M. McCarthy, MB, MRCPI Robert L. Wortmann, MD Medical College of Wisconsin Milwaukee, WI 1. Wortmann RL: Management of hyperuricemia, Arthritis and
Allied Conditions. Eleventh edition. Edited by DJ McCarty. Philadelphia, Lea & Febiger, 1989 2. Kelley WN, Fox IH, Palella TD: Gout and related disorders of purine metabolism, Textbook of Rheumatology. Third edition. Edited by WN Kelley, E D Harris Jr, S Ruddy, CB Sledge. Philadelphia, WB Saunders, 1989
2. Krakauer T, Oppenheim JJ, Jasin HE: Human interleukin 1 mediates cartilage matrix degradation. Cell Immunol 91:92-99, 1985 3. Jasin HE: Bacterial lipopolysaccharides (LPS) induce cartilage matrix degradation through chondrocyte activation. J Clin Invest 72:20142019, 1983 4. Von der Mark K, Mollenhauer J , Haffle M, van Menxel M, Muller PK: Role of anchorin CII in the interaction of chondrocytes with extracellular collagen, Articular Cartilage Biochemistry. Edited by K Kuettner, R Schleyerbach, VC Hascall. New York, Raven Press, 1986 5 . Mayne R, Vail MS, Mayne PM, Miller EJ: Changes in the type of collagen synthesized as clones of chick chondrocytes grow and eventually lose division capacity. Proc Natl Acad Sci U S A 73:167&1678, 1976 6. Benya PD, Shaffer JD: Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30:215-224. 1982
Reduce serum uric acid levels before withdrawing antihyperuricemic therapy in patients with tophaceous gout To the Editor: McCarthy and coworkers have described progression of tophi on radiography of 9 patients and progression of tophi on physical examination of 7 patients during antihyperuricemic therapy in a group of 39 patients with gout (McCarthy GM, Barthelemy CR, Veum JA, Wortmann RL: Influence of antihyperuricemic therapy on the clinical and radiographic progression of gout. Arthritis Rheum 34: 14891494, 1991). They found no correlation between radiographic progression and mean serum urate concentration. The results of antihyperuricemic therapy, thus seem disappointing. However, the mean serum urate level in the 9 patients with radiographic progression, as given in Table 5 of their article, is 7.1 mg% ([ 1 x 6.8 + 3 x 6.1 + 5 x 7.81 f 9), and the mean serum urate level in the 7 with clinical progression, as given in Table 4, is 8.2 mg% (0.48 mmoles/ liter), during therapy. During the 10 years of followup, the serum urate concentration was measured only as deemed necessary, e.g., a range of 2-13 and an average of 6 determinations per patient in 10 years (see page 1490). Although all but 2 of the 39 patients had decreased excretion of uric acid, only 9 patients were treated with uricosuric drugs and 30 were treated with allopurinol. There are several causes for the disappointing results. I ) Allopurinol was not the drug of choice for most patients with decreased uric acid excretion. 2) The markedly elevated serum urate level points to poor compliance. 3) The evaluation visits were too fewhot frequent enough. 4) The urate levels were not lowered sufficiently. The authors refer to my reported experience with discontinuation of hyperuricemic agents in 10 patients with tophaceous gout (Cast LF: Withdrawal of longterm antihyperuricemic therapy in tophaceous gout. Clin Rheumatol 6:70-73, 1987; reference 5 in McCarthy’s article). During the therapy in those patients, all tophi had disappeared clinically, osseous tophi had shown radiographic regression, and serum urate levels had reached a mean of 5.6 mg% (0.30 mmolesfiiter), a concentration much lower than reached in McCarthy’s group.
LETTERS My recommendations are that patients with tophaceous gout should be evaluated every 3 months and have their antihyperuricemic therapy adjusted until all tophi have disappeared clinically and the serum urate concentration has become normal. Preferably, a level below 5.6 mg% (0.30 mmoles/liter) should be reached before antihyperuricemic therapy is withdrawn.
L. F. Cast, MD University Hospital Leiden. The Netherlands
To the Editor: Contrary to Dr. Cast’s suggestion, allopurinol therapy was the antihyperuricemic agent of choice in the majority of our patients. Although allopurinol is clearly indicated for use in individuals whose hyperuricemia results from urate overproduction, it is equally effective in lowering serum urate concentrations in those whose hyperuricemia results from underexcretion. In addition, it has the potential advantages of single daily dosage, fewer interactions with other drugs, and less frequent incidents of intolerance. Furthermore, it may be used in patients with impaired renal function ( I ,2). Our study reported the consequences of management of gout in a Veterans Administration Medical Center population managed by several practitioners over a prolonged period of time. It was not a precisely designed therapeutic trial. We agree that the results of antihyperuricemic therapy in this unique population appear disappointing overall, and attribute that to poor compliance. However, we reemphasize the lack of correlation between radiographic progression of gouty lytic lesions or erosions and the mean serum urate concentration. This resulted in radiographic progression in some patients with mean serum urate concentrations within the normal range, whereas others with chronically elevated mean serum urate concentrations did not have radiographic progression of disease. Clearly, more frequent assessment of individual compliance should improve outcome. We have absolute confidence that if serum urate concentrations can be maintained at or below 5.6 mg/dl, tophi will resolve and gout will be “cured.”
Geraldine M. McCarthy, MB, MRCPI Robert L. Wortmann, MD Medical College of Wisconsin Milwaukee, WI 1. Wortmann RL: Management of hyperuricemia, Arthritis and
Allied Conditions. Eleventh edition. Edited by DJ McCarty. Philadelphia, Lea & Febiger, 1989 2. Kelley WN, Fox IH, Palella TD: Gout and related disorders of purine metabolism, Textbook of Rheumatology. Third edition. Edited by WN Kelley, E D Harris Jr, S Ruddy, CB Sledge. Philadelphia, WB Saunders, 1989
