- Email: [email protected]
Discussion Following Cases 4 and 5
The American Journal of Medicine (2006) Vol 119 (11A), S16 –S19
Discussion Following Cases 4 and 5 Joseph D. Croft, MD Georgetown University Medical School, Washington, District of Columbia, USA
In many patients, the course of hyperuricemia and gout can be divided into 4 primary segments, including asymptomatic hyperuricemia, acute gout flares, intercritical periods, and advanced gout.1 The duration of each stage is variable and depends on the severity of hyperuricemia. Patient SAS (Case 4)2 and Patient HS (Case 5)3 are good examples of the typical course of gout. Approximately 80% of patients with a first episode of gout will have a recurrent attack within 2 years.4 Untreated attacks of acute gouty arthritis can resolve spontaneously in several hours to approximately 2 weeks. Acute attacks are followed by relatively asymptomatic intercritical segments that may last from months to years. The length of intercritical periods varies: as intercritical phases become shorter and less severe, attacks may become more severe and polyarticular, and may be accompanied by fever.
TREATMENT OPTIONS FOR ACUTE GOUT Standard first-line therapy includes nonsteroidal anti-inflammatory drugs (NSAIDs) or colchicine (Table 1).5 Systemic corticosteroids have also shown significant efficacy in patients with acute gout; intra-articular corticosteroids are frequently used in patients with monarticular gout, particularly in patients who cannot receive oral therapy. Antiinflammatory medications are effective in controlling the symptoms of acute gout but have no effect on the chronic hyperuricemia that may be responsible for chronic gout. Few data from randomized controlled clinical trials are available upon which to make evidence-based recommendations for the treatment of acute gout. Only 1 small trial has examined the natural course of acute gout; in the absence of randomized controlled clinical trial data, this study serves as a benchmark to compare the efficacy of treatments for acute gout.6 This study showed that substantial improvements in pain and swelling are generally seen between 5 and 7 days after onset of symptoms; however, few patients
Requests for reprints should be addressed to Joseph D. Croft, MD, 5530 Wisconsin Avenue, Suite 1150, Chevy Chase, Maryland 20815. E-mail address: [email protected].
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.06.020
experience full resolution of pain after 1 week without treatment.
NSAIDs Generic NSAIDs can provide symptomatic relief within 24 hours of initiation at relatively low cost. These agents are the drugs of choice for the short-term management of acute gout except in patients with underlying contraindications for their use. Comparative clinical trials of NSAIDs indicate that there is little, if any, difference among these agents in terms of efficacy.7–9 A comparative study, conducted in 28 patients with 31 attacks of acute gout, showed that complete subjective relief from pain was obtained after a median of 5 days in patients treated with either indomethacin or phenylbutazone; the results for other outcome measures, including pain, tenderness, heat, erythema, swelling, and recurrences were similar between the 2 treatment groups.10 In a second study, conducted in 59 patients who received ketoprofen 100 mg or indomethacin 50 mg 3 times daily, ⬎90% of patients reported pain relief within 24 hours of initiation of therapy.11 These data, together with the results of additional small clinical trials, suggest that NSAIDs should be a first-line treatment option in patients with acute attacks of gout who do not have contraindications for their use. It is cautioned that these agents are associated with a range of adverse effects that may make them inappropriate in many patients with acute gouty arthritis. Chief among these limitations is the relation between NSAIDs and gastrointestinal adverse events. NSAIDs are also associated with nitrogen retention, reduced creatinine clearance, hyperkalemia, and elevations in liver enzymes. Coadministration of a proton-pump inhibitor should be considered in patients at high risk for gastrointestinal adverse events.
Cyclooxygenase-2 Inhibitors The cyclooxygenase (COX)-2 inhibitors— of which only celecoxib remains on the market at the time of this writing—are effective for treating acute gouty arthritis and may be associated with fewer gastrointestinal adverse effects compared with traditional NSAIDs during
Croft
Discussion Following Cases 4 and 5
Table 1
S17
Recommended treatment options for acute gouty arthritis
Drug Class
Major Considerations
Example Regimens
NSAIDs
● May be cost-saving relative to other treatments of acute attacks ● Should be avoided in patients with renal or hepatic failure and in patients at risk for clinically significant GI events ● Consider coadministration of PPI in patients at risk for clinically significant GI events
Naproxen: 750 –1,000 mg/day orally for 3 days followed by 500 –750 mg/day orally for 4 –7 days Sulindac: 300 – 400 mg/day orally for 7–10 days Indomethacin: 150 –200 mg/day orally for 3 days followed by 100 mg/day orally daily for 4 –7 days
COX-2 inhibitors
● May provide better GI tolerability than NSAIDs ● GI-protective effect lost in patients taking concomitant aspirin ● Potential risk for cardiovascular adverse events, including hypertension
Celecoxib: 400 mg orally on first day, then 200 mg/day (in 2 divided doses) for 6–10 days
Systemic corticosteroids
● Avoid use if joint sepsis not excluded ● Avoid in patients subject to hyperglycemia
Prednisone: 40 – 60 mg/day for 3 days, then decrease by 10 –15 mg/day every 3 days until discontinuation Methylprednisolone: 100 –150 mg/day for 1–2 days Triamcinolone acetonide: 60 mg intramuscularly once
Intra-articular corticosteroids
● Only useful in patients with 1 or a few affected joints ● Avoid use if joint sepsis is not excluded
Triamcinolone acetonide: 10 mg in knees and 8 mg in small joints intra-articularly
ACTH
● Not universally available ● Less effective in patients receiving longterm oral corticosteroid therapy ● Risk of corticotropin hypersensitivity (less frequent with synthetic formulation)
ACTH: 25 USP units intramuscularly for acute smalljoint monoarticular gout; 40 USP units intramuscularly or intravenously for larger joints or polyarticular gout
Colchicine (oral)
● Avoid or reduce dose in elderly or frail patients or in those with renal or hepatic dysfunction ● All patients who receive therapeutic dosages of colchicine will develop toxic effects ● Potential drug interactions with erythromycin, simvastatin, and cyclosporine; may increase risk of colchicine-induced toxic effects ● Avoid intravenous colchicine
For acute episodes within the first 24 hr in patients not already on prophylactic low-dose colchicine: 0.6 mg initially followed by additional doses of 0.6 mg/hr (typically for a total of 3–4 doses, maximum of 8 doses; more prolonged dosing often causes significant diarrhea, which can be accompanied by nausea and vomiting and may be severe enough to promote dehydration). This regimen can be used as an adjunct to other modalities and is typically followed by a daily low-dose oral colchicine regimen to prevent rebound.
ACTH ⫽ adrenocorticotropic hormone (corticotropin); GI ⫽ gastrointestinal; NSAID ⫽ nonsteroidal anti-inflammatory drug; PPI ⫽ proton-pump inhibitor; USP ⫽ US Pharmacopoiea. Adapted from N Engl J Med.5
short-term treatment.12 Recently, concerns have been raised regarding the relation between COX-2 inhibitors and cardiovascular adverse events; these concerns may limit the use of these agents in patients at risk for cardiovascular disease. Moreover, the gastroprotective effect of the COX-2 inhibitors is lost in patients taking aspirin.
Colchicine Colchicine has been used to treat inflammatory diseases for nearly 3,000 years.13 Colchicine is a toxic drug that can result in fatal complications; in fact, 1 authority noted that colchicine has the smallest benefit-to-toxicity ratio of any drug that is effective for treating gout.14
Colchicine is frequently administered as an oral 1-mg dose, followed by 0.5 mg at hourly intervals until gastrointestinal side effects occur or a total dose of 8 mg has been administered. In most patients, substantial relief is observed within 18 hours.13 Adverse effects may occur even with low doses of colchicine (⬍2 mg) in patients with hepatobiliary obstruction or renal insufficiency, and/or in elderly patients. Colchicine must be used with caution in these individuals.5 The use of intravenous colchicine has fallen into disfavor as a result of substantial systemic toxicities and reports of deaths.15 Oral colchicine has been studied in 1 placebo-controlled trial. In this study, patients received placebo or colchicine 1
S18
The American Journal of Medicine, Vol 119 (11A), November 2006
mg followed by 0.5 mg every 2 hours until complete response was achieved or evidence of toxicity was seen.16 Two thirds of patients treated with colchicine improved after 48 hours, compared with one third of patients in the placebo group. All patients who received colchicine developed diarrhea after approximately 1 day of treatment or after a mean dose of 6.7 mg. Moreover, gastrointestinal side effects occurred before the relief of pain in the majority of patients.
contraindications, urate-lowering therapy could be continued with an alternative xanthine oxidase inhibitor (e.g., oxypurinol) or the patient could be switched to a uricosuric agent such as probenecid if not contraindicated. Finally, Patient HS also serves to illustrate the universal problem of compliance with pharmacologic therapy. Studies suggest that the majority of patients—regardless of disease state or severity—are insufficiently adherent to therapy. Regular follow-up and monitoring should be conducted to ensure adherence to treatment.
Corticosteroids Systemic corticosteroids have been used for acute gout since 1952. Although systematic studies of the efficacy of corticosteroids are lacking, small studies suggest that shortterm systemic corticosteroid therapy is associated with good response and few important side effects. Intra-articular corticosteroids may be useful in patients with symptoms limited to 1 or few joints. Patients with persistent synovitis may benefit from intra-articular treatment of joints.17 Several studies have examined the impact of systemic corticosteroids on acute gout symptoms. In 1 study, 9 patients received oral prednisone at dosages ranging from 20 to 50 mg/day, with a tapering schedule over a mean of 10.5 days; 3 patients with more complicated conditions received intravenous therapy with prednisolone over 17 days.18 All but 1 patient noted improvement within 48 hours, with complete resolution of symptoms within 7 to 10 days. A second study compared indomethacin 50 mg 3 times daily with intramuscular triamcinolone acetonide 60 mg.19 Symptom resolution was observed in a mean of 7 and 8 days among patients who received triamcinolone acetonide and indomethacin, respectively. Side effects of systemic corticosteroid therapy include osteoporosis, myopathy, peptic ulcer disease, psychiatric complications, predisposition to infections, ocular complications, and edema.18 However, these complications generally are not observed with short-duration therapy.
TEACHING POINTS
ADDITIONAL CONSIDERATIONS
●
All patients presenting with symptoms consistent with gout should be thoroughly evaluated to exclude other potential diagnoses. Although the patients in Cases 4 and 5 have many of the secondary criteria for gout—including pain in the first metatarsophalangeal joint and hyperuricemia, a definitive diagnosis of gout would require aspiration of the joint and inspection of the synovial fluid and identification of monosodium urate crystals under a polarizing light microscope. In both of these cases, however, administration of NSAIDs or colchicine was successful in controlling acute symptoms. Expert consensus suggests that urate-lowering therapies should not be initiated during acute attacks of gouty arthritis because of the potential for intensifying and prolonging the attack and because these agents are associated with significant drug interactions and side effects. In this case, allopurinol was associated with a significant elevation in liver enzyme levels and was subsequently discontinued. In the absence of direct
●
● ●
● ● ●
●
● ● ●
Hyperuricemia is defined by serum uric acid levels: — Asymptomatic hyperuricemia (serum uric acid levels ⬎6.8 mg/dL [⬎0.41 mmol/L]) — Acute gout flares may resolve spontaneously in hours to 2 weeks — Intercritical phases of varying duration may occur — Advanced gout, which is characterized by severe polyarticular arthritis, can occur The primary first-line treatment options for gout include NSAIDs, COX-2 inhibitors, or colchicine NSAIDs provide symptomatic relief in 24 hours but may be contraindicated in certain patient populations, such as those at high risk for gastrointestinal adverse events, renal disease, and hypertension — Coadministration of a proton-pump inhibitor may be considered COX-2 inhibitors (i.e., celecoxib) may be considered in some patients at risk for gastrointestinal adverse events Colchicine has been shown to be effective in patients with acute gout and must be administered with caution Systemic and intra-articular corticosteroids may be effective in acute gout; however, evidence from randomized controlled clinical trials is limited Urate-lowering therapies should not be initiated during acute attacks of gouty arthritis because these agents may also exacerbate acute gout Compliance with treatment must be monitored to ensure optimal outcomes The diagnosis of gout requires the identification of monosodium urate crystals in joint fluid Hyperuricemia and gout may exist with multiple comorbidities There are multiple therapeutic options for the treatment of acute and chronic gout
References 1. Popp JD, Edwards NL. New insights into gouty arthritis. Contemp Intern Med. 1995;7:55– 64. 2. Croft JD. Case 4: chronic synovitis secondary to gout. Am J Med. 2006;119(suppl 11A):S13. 3. Croft JD. Case 5: treatment options for acute gout. Am J Med. 2006; 119(suppl 11A):S14 –S15. 4. Yu TF, Gutman AB. Efficacy of colchicine prophylaxis in gout: prevention of recurrent gouty arthritis over a mean period of five years in 208 gouty subjects. Ann Intern Med. 1961;55:179 –192.
Croft
Discussion Following Cases 4 and 5
5. Terkeltaub RA. Gout [Clinical practice]. N Engl J Med. 2003;349: 1647–1655. 6. Bellamy N, Downie WW, Buchanan WW. Observations on spontaneous improvement in patients with podagra: implications for therapeutic trials of non-steroidal anti-inflammatory drugs. Br J Clin Pharmacol. 1987;24:33–36. 7. Weiner GI, White SR, Weitzner RI, Rubinstein HM. Double-blind study of fenoprofen versus phenylbutazone in acute gouty arthritis. Arthritis Rheum. 1979;22:425– 426. 8. Shrestha M, Morgan DL, Moreden JM, Singh R, Nelson M, Hayes JE. Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis. Ann Emerg Med. 1995;26:682– 686. 9. Maccagno A, Di Giorgio E, Romanowicz A. Effectiveness of etodolac (‘Lodine’) compared with naproxen in patients with acute gout. Curr Med Res Opin. 1991;12:423– 429. 10. Smyth CJ, Percy JS. Comparison of indomethacin and phenylbutazone in acute gout. Ann Rheum Dis. 1973;32:351–353. 11. Altman RD, Honig S, Levin JM, Lightfoot RW. Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. J Rheumatol. 1988;15:1422–1426.
S19 12. Schumacher HR Jr, Boice JA, Daikh DI, et al. Randomised double blind trial of etoricoxib and indomethacin in treatment of acute gouty arthritis. BMJ. 2002;324:1488 –1492. 13. Emmerson BT. The management of gout. N Engl J Med. 1996;334: 445– 451. 14. Roberts WN, Liang MH, Stern SH. Colchicine in acute gout: reassessment of risks and benefits. JAMA. 1987;257:1920 –1922. 15. Bonnel RA, Villalba ML, Karwoski CB, Beitz J. Deaths associated with inappropriate intravenous colchicine administration. J Emerg Med. 2002;22:385–387. 16. Ahern MJ, Reid C, Gordon TP, McCredie M, Brooks PM, Jones M. Does colchicine work? The results of the first controlled study in acute gout. Aust N Z J Med. 1987;17:301–304. 17. Gray RG, Tenenbaum J, Gottlieb NL. Local corticosteroid injection treatment in rheumatic disorders. Semin Arthritis Rheum. 1981;10: 231–254. 18. Groff GD, Franck WA, Raddatz DA. Systemic steroid therapy for acute gout: a clinical trial and review of the literature. Semin Arthritis Rheum. 1990;19:329 –336. 19. Alloway JA, Moriarty MJ, Hoogland YT, Nashel DJ. Comparison of triamcinolone acetonide with indomethacin in the treatment of acute gouty arthritis. J Rheumatol. 1993;20:111–113.
Discussion Following Cases 4 and 5 Joseph D. Croft, MD Georgetown University Medical School, Washington, District of Columbia, USA
In many patients, the course of hyperuricemia and gout can be divided into 4 primary segments, including asymptomatic hyperuricemia, acute gout flares, intercritical periods, and advanced gout.1 The duration of each stage is variable and depends on the severity of hyperuricemia. Patient SAS (Case 4)2 and Patient HS (Case 5)3 are good examples of the typical course of gout. Approximately 80% of patients with a first episode of gout will have a recurrent attack within 2 years.4 Untreated attacks of acute gouty arthritis can resolve spontaneously in several hours to approximately 2 weeks. Acute attacks are followed by relatively asymptomatic intercritical segments that may last from months to years. The length of intercritical periods varies: as intercritical phases become shorter and less severe, attacks may become more severe and polyarticular, and may be accompanied by fever.
TREATMENT OPTIONS FOR ACUTE GOUT Standard first-line therapy includes nonsteroidal anti-inflammatory drugs (NSAIDs) or colchicine (Table 1).5 Systemic corticosteroids have also shown significant efficacy in patients with acute gout; intra-articular corticosteroids are frequently used in patients with monarticular gout, particularly in patients who cannot receive oral therapy. Antiinflammatory medications are effective in controlling the symptoms of acute gout but have no effect on the chronic hyperuricemia that may be responsible for chronic gout. Few data from randomized controlled clinical trials are available upon which to make evidence-based recommendations for the treatment of acute gout. Only 1 small trial has examined the natural course of acute gout; in the absence of randomized controlled clinical trial data, this study serves as a benchmark to compare the efficacy of treatments for acute gout.6 This study showed that substantial improvements in pain and swelling are generally seen between 5 and 7 days after onset of symptoms; however, few patients
Requests for reprints should be addressed to Joseph D. Croft, MD, 5530 Wisconsin Avenue, Suite 1150, Chevy Chase, Maryland 20815. E-mail address: [email protected].
0002-9343/$ -see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.06.020
experience full resolution of pain after 1 week without treatment.
NSAIDs Generic NSAIDs can provide symptomatic relief within 24 hours of initiation at relatively low cost. These agents are the drugs of choice for the short-term management of acute gout except in patients with underlying contraindications for their use. Comparative clinical trials of NSAIDs indicate that there is little, if any, difference among these agents in terms of efficacy.7–9 A comparative study, conducted in 28 patients with 31 attacks of acute gout, showed that complete subjective relief from pain was obtained after a median of 5 days in patients treated with either indomethacin or phenylbutazone; the results for other outcome measures, including pain, tenderness, heat, erythema, swelling, and recurrences were similar between the 2 treatment groups.10 In a second study, conducted in 59 patients who received ketoprofen 100 mg or indomethacin 50 mg 3 times daily, ⬎90% of patients reported pain relief within 24 hours of initiation of therapy.11 These data, together with the results of additional small clinical trials, suggest that NSAIDs should be a first-line treatment option in patients with acute attacks of gout who do not have contraindications for their use. It is cautioned that these agents are associated with a range of adverse effects that may make them inappropriate in many patients with acute gouty arthritis. Chief among these limitations is the relation between NSAIDs and gastrointestinal adverse events. NSAIDs are also associated with nitrogen retention, reduced creatinine clearance, hyperkalemia, and elevations in liver enzymes. Coadministration of a proton-pump inhibitor should be considered in patients at high risk for gastrointestinal adverse events.
Cyclooxygenase-2 Inhibitors The cyclooxygenase (COX)-2 inhibitors— of which only celecoxib remains on the market at the time of this writing—are effective for treating acute gouty arthritis and may be associated with fewer gastrointestinal adverse effects compared with traditional NSAIDs during
Croft
Discussion Following Cases 4 and 5
Table 1
S17
Recommended treatment options for acute gouty arthritis
Drug Class
Major Considerations
Example Regimens
NSAIDs
● May be cost-saving relative to other treatments of acute attacks ● Should be avoided in patients with renal or hepatic failure and in patients at risk for clinically significant GI events ● Consider coadministration of PPI in patients at risk for clinically significant GI events
Naproxen: 750 –1,000 mg/day orally for 3 days followed by 500 –750 mg/day orally for 4 –7 days Sulindac: 300 – 400 mg/day orally for 7–10 days Indomethacin: 150 –200 mg/day orally for 3 days followed by 100 mg/day orally daily for 4 –7 days
COX-2 inhibitors
● May provide better GI tolerability than NSAIDs ● GI-protective effect lost in patients taking concomitant aspirin ● Potential risk for cardiovascular adverse events, including hypertension
Celecoxib: 400 mg orally on first day, then 200 mg/day (in 2 divided doses) for 6–10 days
Systemic corticosteroids
● Avoid use if joint sepsis not excluded ● Avoid in patients subject to hyperglycemia
Prednisone: 40 – 60 mg/day for 3 days, then decrease by 10 –15 mg/day every 3 days until discontinuation Methylprednisolone: 100 –150 mg/day for 1–2 days Triamcinolone acetonide: 60 mg intramuscularly once
Intra-articular corticosteroids
● Only useful in patients with 1 or a few affected joints ● Avoid use if joint sepsis is not excluded
Triamcinolone acetonide: 10 mg in knees and 8 mg in small joints intra-articularly
ACTH
● Not universally available ● Less effective in patients receiving longterm oral corticosteroid therapy ● Risk of corticotropin hypersensitivity (less frequent with synthetic formulation)
ACTH: 25 USP units intramuscularly for acute smalljoint monoarticular gout; 40 USP units intramuscularly or intravenously for larger joints or polyarticular gout
Colchicine (oral)
● Avoid or reduce dose in elderly or frail patients or in those with renal or hepatic dysfunction ● All patients who receive therapeutic dosages of colchicine will develop toxic effects ● Potential drug interactions with erythromycin, simvastatin, and cyclosporine; may increase risk of colchicine-induced toxic effects ● Avoid intravenous colchicine
For acute episodes within the first 24 hr in patients not already on prophylactic low-dose colchicine: 0.6 mg initially followed by additional doses of 0.6 mg/hr (typically for a total of 3–4 doses, maximum of 8 doses; more prolonged dosing often causes significant diarrhea, which can be accompanied by nausea and vomiting and may be severe enough to promote dehydration). This regimen can be used as an adjunct to other modalities and is typically followed by a daily low-dose oral colchicine regimen to prevent rebound.
ACTH ⫽ adrenocorticotropic hormone (corticotropin); GI ⫽ gastrointestinal; NSAID ⫽ nonsteroidal anti-inflammatory drug; PPI ⫽ proton-pump inhibitor; USP ⫽ US Pharmacopoiea. Adapted from N Engl J Med.5
short-term treatment.12 Recently, concerns have been raised regarding the relation between COX-2 inhibitors and cardiovascular adverse events; these concerns may limit the use of these agents in patients at risk for cardiovascular disease. Moreover, the gastroprotective effect of the COX-2 inhibitors is lost in patients taking aspirin.
Colchicine Colchicine has been used to treat inflammatory diseases for nearly 3,000 years.13 Colchicine is a toxic drug that can result in fatal complications; in fact, 1 authority noted that colchicine has the smallest benefit-to-toxicity ratio of any drug that is effective for treating gout.14
Colchicine is frequently administered as an oral 1-mg dose, followed by 0.5 mg at hourly intervals until gastrointestinal side effects occur or a total dose of 8 mg has been administered. In most patients, substantial relief is observed within 18 hours.13 Adverse effects may occur even with low doses of colchicine (⬍2 mg) in patients with hepatobiliary obstruction or renal insufficiency, and/or in elderly patients. Colchicine must be used with caution in these individuals.5 The use of intravenous colchicine has fallen into disfavor as a result of substantial systemic toxicities and reports of deaths.15 Oral colchicine has been studied in 1 placebo-controlled trial. In this study, patients received placebo or colchicine 1
S18
The American Journal of Medicine, Vol 119 (11A), November 2006
mg followed by 0.5 mg every 2 hours until complete response was achieved or evidence of toxicity was seen.16 Two thirds of patients treated with colchicine improved after 48 hours, compared with one third of patients in the placebo group. All patients who received colchicine developed diarrhea after approximately 1 day of treatment or after a mean dose of 6.7 mg. Moreover, gastrointestinal side effects occurred before the relief of pain in the majority of patients.
contraindications, urate-lowering therapy could be continued with an alternative xanthine oxidase inhibitor (e.g., oxypurinol) or the patient could be switched to a uricosuric agent such as probenecid if not contraindicated. Finally, Patient HS also serves to illustrate the universal problem of compliance with pharmacologic therapy. Studies suggest that the majority of patients—regardless of disease state or severity—are insufficiently adherent to therapy. Regular follow-up and monitoring should be conducted to ensure adherence to treatment.
Corticosteroids Systemic corticosteroids have been used for acute gout since 1952. Although systematic studies of the efficacy of corticosteroids are lacking, small studies suggest that shortterm systemic corticosteroid therapy is associated with good response and few important side effects. Intra-articular corticosteroids may be useful in patients with symptoms limited to 1 or few joints. Patients with persistent synovitis may benefit from intra-articular treatment of joints.17 Several studies have examined the impact of systemic corticosteroids on acute gout symptoms. In 1 study, 9 patients received oral prednisone at dosages ranging from 20 to 50 mg/day, with a tapering schedule over a mean of 10.5 days; 3 patients with more complicated conditions received intravenous therapy with prednisolone over 17 days.18 All but 1 patient noted improvement within 48 hours, with complete resolution of symptoms within 7 to 10 days. A second study compared indomethacin 50 mg 3 times daily with intramuscular triamcinolone acetonide 60 mg.19 Symptom resolution was observed in a mean of 7 and 8 days among patients who received triamcinolone acetonide and indomethacin, respectively. Side effects of systemic corticosteroid therapy include osteoporosis, myopathy, peptic ulcer disease, psychiatric complications, predisposition to infections, ocular complications, and edema.18 However, these complications generally are not observed with short-duration therapy.
TEACHING POINTS
ADDITIONAL CONSIDERATIONS
●
All patients presenting with symptoms consistent with gout should be thoroughly evaluated to exclude other potential diagnoses. Although the patients in Cases 4 and 5 have many of the secondary criteria for gout—including pain in the first metatarsophalangeal joint and hyperuricemia, a definitive diagnosis of gout would require aspiration of the joint and inspection of the synovial fluid and identification of monosodium urate crystals under a polarizing light microscope. In both of these cases, however, administration of NSAIDs or colchicine was successful in controlling acute symptoms. Expert consensus suggests that urate-lowering therapies should not be initiated during acute attacks of gouty arthritis because of the potential for intensifying and prolonging the attack and because these agents are associated with significant drug interactions and side effects. In this case, allopurinol was associated with a significant elevation in liver enzyme levels and was subsequently discontinued. In the absence of direct
●
● ●
● ● ●
●
● ● ●
Hyperuricemia is defined by serum uric acid levels: — Asymptomatic hyperuricemia (serum uric acid levels ⬎6.8 mg/dL [⬎0.41 mmol/L]) — Acute gout flares may resolve spontaneously in hours to 2 weeks — Intercritical phases of varying duration may occur — Advanced gout, which is characterized by severe polyarticular arthritis, can occur The primary first-line treatment options for gout include NSAIDs, COX-2 inhibitors, or colchicine NSAIDs provide symptomatic relief in 24 hours but may be contraindicated in certain patient populations, such as those at high risk for gastrointestinal adverse events, renal disease, and hypertension — Coadministration of a proton-pump inhibitor may be considered COX-2 inhibitors (i.e., celecoxib) may be considered in some patients at risk for gastrointestinal adverse events Colchicine has been shown to be effective in patients with acute gout and must be administered with caution Systemic and intra-articular corticosteroids may be effective in acute gout; however, evidence from randomized controlled clinical trials is limited Urate-lowering therapies should not be initiated during acute attacks of gouty arthritis because these agents may also exacerbate acute gout Compliance with treatment must be monitored to ensure optimal outcomes The diagnosis of gout requires the identification of monosodium urate crystals in joint fluid Hyperuricemia and gout may exist with multiple comorbidities There are multiple therapeutic options for the treatment of acute and chronic gout
References 1. Popp JD, Edwards NL. New insights into gouty arthritis. Contemp Intern Med. 1995;7:55– 64. 2. Croft JD. Case 4: chronic synovitis secondary to gout. Am J Med. 2006;119(suppl 11A):S13. 3. Croft JD. Case 5: treatment options for acute gout. Am J Med. 2006; 119(suppl 11A):S14 –S15. 4. Yu TF, Gutman AB. Efficacy of colchicine prophylaxis in gout: prevention of recurrent gouty arthritis over a mean period of five years in 208 gouty subjects. Ann Intern Med. 1961;55:179 –192.
Croft
Discussion Following Cases 4 and 5
5. Terkeltaub RA. Gout [Clinical practice]. N Engl J Med. 2003;349: 1647–1655. 6. Bellamy N, Downie WW, Buchanan WW. Observations on spontaneous improvement in patients with podagra: implications for therapeutic trials of non-steroidal anti-inflammatory drugs. Br J Clin Pharmacol. 1987;24:33–36. 7. Weiner GI, White SR, Weitzner RI, Rubinstein HM. Double-blind study of fenoprofen versus phenylbutazone in acute gouty arthritis. Arthritis Rheum. 1979;22:425– 426. 8. Shrestha M, Morgan DL, Moreden JM, Singh R, Nelson M, Hayes JE. Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis. Ann Emerg Med. 1995;26:682– 686. 9. Maccagno A, Di Giorgio E, Romanowicz A. Effectiveness of etodolac (‘Lodine’) compared with naproxen in patients with acute gout. Curr Med Res Opin. 1991;12:423– 429. 10. Smyth CJ, Percy JS. Comparison of indomethacin and phenylbutazone in acute gout. Ann Rheum Dis. 1973;32:351–353. 11. Altman RD, Honig S, Levin JM, Lightfoot RW. Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study. J Rheumatol. 1988;15:1422–1426.
S19 12. Schumacher HR Jr, Boice JA, Daikh DI, et al. Randomised double blind trial of etoricoxib and indomethacin in treatment of acute gouty arthritis. BMJ. 2002;324:1488 –1492. 13. Emmerson BT. The management of gout. N Engl J Med. 1996;334: 445– 451. 14. Roberts WN, Liang MH, Stern SH. Colchicine in acute gout: reassessment of risks and benefits. JAMA. 1987;257:1920 –1922. 15. Bonnel RA, Villalba ML, Karwoski CB, Beitz J. Deaths associated with inappropriate intravenous colchicine administration. J Emerg Med. 2002;22:385–387. 16. Ahern MJ, Reid C, Gordon TP, McCredie M, Brooks PM, Jones M. Does colchicine work? The results of the first controlled study in acute gout. Aust N Z J Med. 1987;17:301–304. 17. Gray RG, Tenenbaum J, Gottlieb NL. Local corticosteroid injection treatment in rheumatic disorders. Semin Arthritis Rheum. 1981;10: 231–254. 18. Groff GD, Franck WA, Raddatz DA. Systemic steroid therapy for acute gout: a clinical trial and review of the literature. Semin Arthritis Rheum. 1990;19:329 –336. 19. Alloway JA, Moriarty MJ, Hoogland YT, Nashel DJ. Comparison of triamcinolone acetonide with indomethacin in the treatment of acute gouty arthritis. J Rheumatol. 1993;20:111–113.