Geoffrey C. Wall
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Recognize major risk factors for developing gout in a given person.
2. Develop a pharmacotherapeutic plan for a patient with acute gouty arthritis or uric acid nephropathy that includes individualized drug selection and monitoring for efficacy and safety.
3. Identify patients in whom maintenance therapy for gout and hyperuricemia is warranted.
4. Select an appropriate drug to reduce serum uric acid (SUA) levels in patients with gout, and outline a plan for monitoring efficacy and toxicity.
5. Educate patients on appropriate lifestyle modifications to help prevent gouty arthritis attacks.
KEY CONCEPTS
Gout results from deposition of uric acid crystals in joint spaces, leading to an inflammatory reaction that causes intense pain, erythema, and joint swelling.
Some drugs can cause hyperuricemia and gout, such as thiazide diuretics, niacin, pyrazinamide, cyclosporine, and occasionally, low-dose aspirin.
Long-term consequences of gout and hyperuricemia include joint destruction, tophi, and nephrolithiasis.
Treatment of gout involves: (a) acute relief of a gouty arthritis attack; and (b) in some patients long-term maintenance treatment to prevent future attacks.
Nonsteroidal anti-inflammatory drugs, colchicine, or corticosteroids are used for acute attacks. Selection depends on several patient factors, especially renal function.
Asymptomatic hyperuricemia usually does not require treatment.
Patients with recurrent gout attacks, evidence of tophi or joint destruction, or uric acid nephrolithiasis are candidates for maintenance therapy with allopurinol or probenecid to lower serum uric acid (SUA) levels.
Tumor lysis syndrome (TLS) is a metabolic disorder caused by rapid cell destruction (usually during chemotherapy treatment for cancer) and is associated with several electrolyte disturbances, notably hyperuricemia.
EPIDEMIOLOGY AND ETIOLOGY
Gout is the most common inflammatory arthritis in the United States and western Europe.1 The annual incidence is approximately 62 cases per 100,000 persons in the United States.2 The incidence increases with age and appears to be rising, probably because of a larger number of patients with risk factors for gout.3
PATHOPHYSIOLOGY
Gout is caused by an abnormality in uric acid metabolism. Uric acid is a waste product of the breakdown of purines contained in the DNA of degraded body cells and dietary protein. Uric acid is water soluble and excreted primarily by the kidneys, although some is broken down by colonic bacteria and excreted via the GI tract.4,5
The solubility of uric acid depends on concentration and temperature. At high serum concentrations, lower body temperature causes the precipitation of monosodium urate (MSU) crystals. Collections of these crystals (called micro-tophi) can form in joint spaces in the distal extremities.
Gout results from deposition of uric acid crystals in joint spaces, leading to an inflammatory reaction that causes intense pain, erythema, and joint swelling. Free urate crystals can activate several proinflammatory mediators, including tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), and IL-8. Activation of these mediators signals chemotactic movement of neutrophils into the joint space that “ingest” MSU crystals via phagocytosis. These neutrophils then are lysed and release proteolytic enzymes that trigger the clinical manifestations of an acute gout attack, such as pain and swelling. These inflammatory mechanisms in gout, especially in untreated disease, can lead to cartilage and joint destruction.
The increased serum uric acid (SUA) involves either the underexcretion of uric acid (80% of patients) or its overproduction. The cause of overproduction or underexcretion of uric acid in most gout patients is unknown; this is referred to as primary gout.2
The reference range for SUA is 3.6 to 8.3 mg/dL (214–494 μmol/L). The risk of gout increases as the SUA concentration increases. Approximately 30% of patients with levels greater than 10 mg/dL (595 μmol/L) develop symptoms of gout within 5 years. However, most patients with hyperuricemia are asymptomatic. Other risk factors for gout include male gender, obesity, ethanol use, hypertension, and dyslipidemia.6,7 Gout is seen frequently in patients with type 2 diabetes mellitus and coronary artery disease, but a causal relationship has not been established.
Uric acid excretion is reduced in patients with chronic kidney disease, putting them at risk for hyperuricemia. In patients with persistently acidic urine and hyperuricemia, uric acid nephrolithiasis can occur in up to 25% of patients; in severe cases, uric acid stones can cause nephropathy and renal failure.8 Extreme hyperuricemia can occur because of rapid tumor cell destruction in patients undergoing chemotherapy for certain types of cancer. This phenomenon is known as tumor lysis syndrome (TLS).
Some drugs can cause hyperuricemia and gout, such as thiazide diuretics, niacin, pyrazinamide, cyclosporine, and occasionally, low-dose aspirin. In most cases, these drugs block uric acid secretion in the kidney. Longterm consequences of gout and hyperuricemia include joint destruction, tophi, and nephrolithiasis.
CLINICAL PRESENTATION AND DIAGNOSIS
Aspiration of affected joint fluid is essential for a definitive diagnosis. Joint fluid containing negatively birefringent MSU crystals confirms the diagnosis. Joint fluid has an elevated WBC count with neutrophils predominating (Fig. 59–1).9
Although rarely performed, a 24-hour urine collection can be obtained to determine if the patient is an overproducer or an underexcretor of uric acid. Individuals who excrete more than 800 mg of uric acid in this collection are considered overproducers. Patients with hyperuricemia who excrete less than 600 mg/day are classified as underexcretors of uric acid.
Radiographs of affected joints may have characteristic appearances of gout, including cystic changes, punched-out lytic lesions with overhanging bony edges, and soft-tissue calcified masses. These signs may appear in other arthropathies as well.10
Clinical Presentation and Diagnosis of Acute Gouty Arthritis
General
Patients are usually in acute distress.
Symptoms
• Severe pain, swelling, and warmth in the affected joint(s).
• The attack is usually monoarticular; the most common sites are the metatarsophalangeal and knee joints.
• In elderly patients, gouty attacks may be atypical with insidious and polyarticular onset, often involving hand or wrist joints.
Signs
• Affected joint(s) are warm, erythematous, and swollen.
• Mild fever may be present.
• Tophi (usually on hands, wrists, elbows, or knees) may be present in chronic, severe disease.
Laboratory Tests
• The peripheral WBC count may be only mildly elevated.
• The serum uric acid level often is elevated but may be normal during an acute attack.
• Other laboratory markers of inflammation (e.g., increased erythrocyte sedimentation rate) are often present.
FIGURE 59–1. Synovial fluid containing extracellular and intracellular monosodium urate crystals. (From Schumacher HR, Chen LX. Gout and other crystal arthropathies. In: Fauci AS, Braunwald E, Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine, 17th ed. New York: McGraw-Hill; 2008, Fig. 327–1, page 2166, with permission.)
TREATMENT
Treatment of gout involves: (a) acute relief of a gouty arthritis attack; and (b) in some patients long-term maintenance treatment to prevent future attacks.
Desired Outcomes
The goals of therapy of an acute attack are: (a) achieving rapid and effective pain relief; (b) maintaining joint function; (c) preventing disease complications; (d) avoiding treatment-related adverse effects; (e) providing cost-effective therapy; and (f) improving quality of life.11 Infrequent gouty arthritis is a self-limited disease, and treatment usually focuses on symptom relief.
Nonpharmacologic Therapy
Nondrug modalities play an adjunctive role and usually are not effective when used alone. Immobilization of the affected extremity speeds resolution of the attack. Applying ice packs to the joint also decreases pain and swelling, but heat application may be detrimental.12
Pharmacologic Therapy
Nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids are used for acute attacks. Selection depends on several patient factors, especially renal function (Fig. 59–2). Each drug class has a unique safety and efficacy profile in gout that should be considered carefully before choosing a specific agent (Table 59–1). Generally, the earlier in the course of the arthritic attack these agents are employed, the better the outcome.
Nonsteroidal Anti-inflammatory Drugs
The NSAIDs largely have supplanted colchicine as the treatment of choice, and many NSAIDs have been used successfully. These agents are most effective when given within the first 24 hours of the onset of pain. Most studies have shown similar results among agents, and all NSAIDs are considered to be effective. Doses at the higher end of the therapeutic range are often needed.13
Indomethacin was used traditionally, but its relative cyclooxygenase-1 (COX-1) selectivity theoretically increases its gastropathy risk. Thus other generic NSAIDs may be preferred. Adverse effects of NSAIDs include gastropathy (primarily peptic ulcers), renal dysfunction, and fluid retention.14 NSAIDs generally should be avoided in patients at risk for peptic ulcers, those taking warfarin, and those with renal insufficiency or uncontrolled hypertension or heart failure.
Cyclooxygenase-2 (COX-2)-selective inhibitors produce results comparable with those of traditional NSAIDs. However, cardiovascular safety concerns and the high cost of COX-2 inhibitors argue against their use for this disorder. NSAIDs are usually continued until 24 hours after symptoms subside.
FIGURE 59–2. Treatment algorithm for gout and hyperuricemia. Renal insufficiency is defined as an estimated creatinine clearance (CrCl) of less than 30 mL/min. (IA, intra-articular; NSAID, nonsteroidal anti-inflammatory drug.)
Colchicine
Colchicine has a long history of successful use and was the treatment of choice for many years. It is used infrequently today because of its low therapeutic index. Colchicine is thought to exert its anti-inflammatory effects by interfering with the function of mitotic spindles in neutrophils by binding of tubulin dimers; this inhibits phagocytic activity.15
Oral colchicine is absorbed rapidly from the GI tract and metabolized extensively in the liver. About two-thirds of patients with acute gout respond favorably if it is given within the first 24 hours of symptom onset. Unfortunately, more than 80% of patients experience adverse effects. GI effects (e.g., nausea, vomiting, diarrhea, and abdominal pain) are most common and are considered a forerunner of more serious systemic toxicity, including myopathy and bone marrow suppression (usually neutropenia). Some clinicians still use the strategy of continuous dosing until either pain relief or GI side effects occur. However, systemic toxicity can occur with oral colchicine without prior GI effects, especially in patients with renal insufficiency.16,17 Because of these problems, oral colchicine should be reserved for patients who are at risk for NSAID-induced gastropathy or who have failed NSAID therapy. IV colchicine was removed from the U.S. market due to an increased risk of serious and potentially fatal systemic effects when administered by this route.18
Table 59–1 Dosage Regimens for Acute Gout and Antihyperuricemic Treatment
In July 2009, the FDA approved Colcrys, a single-ingredient colchicine product for treatment of acute gout attacks. As part of the approval process, a dosing study showed that one dose initially and a single additional dose after 1 hour was just as effective and less toxic than continued hourly colchicine dosing. As a result, the approved dosage regimen is 1.2 mg (two 0.6-mg tablets) at the onset of an acute flare, followed by 0.6 mg 1 hour later.
Corticosteroids
When only one or two joints are affected, intra-articular corticosteroid injection can provide rapid relief with a relatively low incidence of side effects. Joint fluid obtained by arthrocentesis should be examined for evidence of joint space infection and crystal identification. If uric acid crystals are present and there is no infection, intra-articular injection can proceed.
Systemic corticosteroids are a useful option in patients with contraindications to NSAIDs or colchicine (primarily renal impairment) or polyarticular attacks, especially in elderly patients. A single intramuscular injection of a long-acting corticosteroid such as triamcinolone hexacetonide may be used. Oral agents may be needed, especially for severe attacks. Prednisone 40 to 60 mg (or an equivalent dose of another agent) is given daily, with a gradual taper over 2 weeks. A recent study found that oral methylprednisolone and naproxen are equivalent in treating acute gout attacks.19,20
Patient Encounter 1, Part 1
A 48-year-old man with a history of hypertension, peptic ulcer disease (gastric ulcer 1 year ago), and morbid obesity presents to the emergency department complaining of excruciating pain in his left big toe and both ankles. This is similar to a painful episode he had with his left toe and ankle 6 months ago. On examination, his left great toe and both ankles are red, swollen, and warm to the touch. He describes the pain as throbbing and rates it as a 10/10 (where 10 is the worst pain he has ever experienced). He admits to drinking a six pack of beer on weekends. He weighs 150 kg (330 lb) and is 5 ft, 9 in. (175 cm) tall. Medications include chlorthalidone 25 mg/day and pantoprazole 40 mg/day. Serum creatinine is 1.0 mg/dL (88 μmol/L).
What information suggests gout as the cause of his symptoms?
What risk factors for gout does he have?
If the diagnosis is an acute attack of gouty arthritis, what treatment plan would you recommend for this patient?
Too rapid tapering of corticosteroids can cause a rebound gouty flare. To prevent this flare, low-dose colchicine (0.6 mg orally daily) sometimes is added to systemic corticosteroid regimens. This is probably unnecessary if an adequate taper is prescribed.
Short-term adverse effects from corticosteroids include fluid retention, hyperglycemia, CNS stimulation, weight gain, and increased risk of infection. Patients with diabetes should have blood glucose levels monitored carefully during the corticosteroid course.
Corticotrophin (adrenocorticotropic hormone [ACTH]) has been used for acute gouty flares. Worldwide supply problems and the possible superiority of traditional corticosteroids have resulted in decreased use.21
ANTIHYPERURICEMIC GOUT PROPHYLAXIS
Gout is an episodic disease, and the number of attacks varies widely from patient to patient. Thus, the benefit of long-term prophylaxis against acute gout flares must be weighed against the cost and potential toxicity of therapy that may not be necessary in all patients.
Asymptomatic hyperuricemia usually does not require treatment.
Nonpharmacologic Therapy
Lifestyle modifications alone usually are insufficient for lowering SUA levels in gout patients. Patients should be advised to lose weight if obese and to discontinue ethanol consumption. Low-purine diets are not well tolerated; instead, dietary recommendations should focus on general nutrition principles. Drugs that may cause or aggravate hyperuricemia should be discontinued if possible. Few patients adhere to lifestyle modifications long term, and pharmacologic therapy usually is needed to treat hyperuricemia adequately.22
Pharmacologic Therapy
Patients with recurrent attacks, evidence of tophi or joint destruction, or uric acid nephrolithiasis are candidates for maintenance therapy with allopurinol, febuxostat, or probenecid to lower SUA levels. Because hyperuricemia is the strongest modifiable risk factor for acute gout, prophylactic therapy involves either decreasing uric acid production or increasing its excretion (Table 59–1). The goal of therapy is to decrease SUA levels significantly, leaving less uric acid available for conversion to MSU crystals.11
Ideally, the selection of long-term prophylactic therapy involves determining the cause of hyperuricemia (primarily by analyzing a 24-hour urine collection for uric acid) and tailoring therapy appropriately. If less than 600 mg of uric acid is found in the 24-hour sample, the patient is considered an underexcretor. However, this approach is not used commonly for several reasons. The urine collection is inconvenient for patients and clinicians and does not identify patients who may be both overproducers and underexcretors of uric acid. Also, drugs used to increase uric acid excretion (uricosurics) generally are not as well tolerated as drugs that decrease production, and uricosurics increase the risk of uric acid nephrolithiasis.23
Because allopurinol (which reduces uric acid production) is effective in both overproducers and underexcretors and is generally well tolerated, many clinicians forego the 24-hour urine collection and treat patients empirically with it.
Allopurinol
Most patients in the United States are treated with allopurinol, which usually is effective if the dosage is titrated appropriately. The drug and its primary active metabolite, oxypurinol, reduce SUA concentrations by inhibiting the enzyme xanthine oxidase, thereby blocking the oxidation of hypoxanthine and xanthine to uric acid.11
Allopurinol is well absorbed with a short half-life of 2 to 3 hours. The half-life of oxypurinol approaches 24 hours, allowing allopurinol to be dosed once daily. Oxypurinol is cleared primarily renally and can accumulate in patients with reduced kidney function. Allopurinol should not be started during an acute gout attack because sudden shifts in SUA levels may precipitate or exacerbate gouty arthritis. Rapid shifts in SUA can change the concentration of MSU crystals in synovial fluid, causing more crystals to precipitate. Thus some clinicians advocate a prophylactic dose of colchicine (0.6 mg/day) during initiation of antihyperuricemic therapy. This is continued until uric acid levels return to normal or maximum of 3 to 6 months. Acute episodes should be treated appropriately before maintenance treatment is started.
The initial dose of allopurinol is based on the patient’s renal function. Patients with a creatinine clearance (CrCl) of 50 mL/min or less should receive a starting dose of less than 300 mg/day, although the product literature and other sources list alternative dosing regimens for those with renal insufficiency. The relationship between dose of allopurinol and its most severe side effects is controversial.24 However, the dose can be adjusted upward as needed and tolerated. It is reasonable to reduce the dose temporarily in patients who develop reversible acute renal failure.
SUA levels must be monitored periodically, with the first follow-up level obtained 6 months (or sooner) after starting therapy. The target SUA level is less than 6 mg/dL (357 μmol/L). The dose should be titrated upward (to a maximum of 800 mg/day) or downward as these levels dictate.
Allopurinol generally is well tolerated; nausea and diarrhea occur in a small percentage of patients. A generalized, maculopapular rash occurs in about 2% of patients.25 Although usually mild, this can progress to severe skin reactions such as Stevens-Johnson syndrome. Perhaps the most feared side effect is the allopurinol hypersensitivity syndrome, which may involve severe desquamating skin lesions, high fever (usually greater than 39°C [102.2°F]), hepatic dysfunction, leukocytosis with predominant eosinophilia, and renal failure. Although rare, this severe reaction has a 20% mortality rate.26 Patients with a history of the syndrome should never again receive allopurinol (including desensitization) or oxypurinol (which is available outside the United States). Patients with a mild skin rash who require allopurinol can be desensitized to it using published protocols.27,28
There are several important drug-drug interactions with allopurinol. The effects of both theophylline and warfarin may be potentiated by allopurinol. Azathioprine and 6-mercaptopurine are purines whose metabolism is inhibited by concomitant allopurinol therapy; the dose of these drugs must be reduced by 75% with allopurinol cotherapy. Patient’s taking allopurinol who receive ampicillin are at increased risk of skin rashes.
Febuxostat
In 2009, the FDA approved febuxostat (Uloric), a nonpurine xanthine oxidase inhibitor structurally distinct from allopurinol, for chronic hyperuricemia associated with gout. The initial dose is 40 mg orally once daily. The dose may be increased to 80 mg orally once daily if the SUA does not decrease to 6.0 mg/dL (357 μmol/L) or less after 2 weeks of treatment. No dosage adjustment is necessary in patients with mild or moderate renal impairment. Because of its potency and rapid reduction of SUA levels, prophylactic low-dose colchicine or an NSAID is recommended for 3 to 6 months during initiation of therapy.
Data from phase III trials suggest that febuxostat may be more effective than allopurinol in achieving target SUA levels of 6.0 mg/dL (357 μmol/L) or less and may be more effective in reducing the number of acute gouty flares.29However, fixed allopurinol doses were used rather than titrating the allopurinol dose to reach the target SUA level, which may confound these findings.
Adverse effects of febuxostat include nausea, arthralgias, rash, and transient elevation of hepatic transaminases. Periodic liver function tests are recommended (e.g., at baseline, 2 and 4 months after starting therapy, and then periodically thereafter). Due to structural differences, febuxostat would not be expected to crossreact in patients with a history of allopurinol hypersensitivity syndrome. The place of febuxostat in therapy of hyperuricemia has not been fully determined.
Probenecid
Probenecid is a uricosuric agent that blocks the tubular reabsorption of uric acid, increasing its excretion. Because of its mechanism of action, probenecid is contraindicated in patients with a history of uric acid stones or nephropathy. Probenecid loses its effectiveness as renal function declines and should be avoided when the CrCl is 50 mL/min or less. Its uricosuric effect is counteracted by low aspirin doses, which many patients receive for prophylaxis of coronary heart disease.2,11
Although generally well tolerated, probenecid can cause GI side effects such as nausea and other adverse reactions including fever, rash, and rarely, hepatic toxicity. Patients should be instructed to maintain adequate fluid intake and urine output to decrease the risk of uric acid stone formation. Some experts advocate alkalinizing the urine to decrease this risk.
Patient Encounter 1, Part 2
The patient returns for a follow-up visit at your clinic 6 weeks later. He reports no pain or swelling in the joints affected previously. The emergency department physician had instructed him to stop the chlorthalidone, so he is currently taking only pantoprazole.
PE:
VS: BP 164/84, P 72, RR 15, T 37.2°C (99°F)
Ext: Trace edema in both ankles
Labs: Serum uric acid 11.5 mg/dL (684 μmol/L); serum creatinine 0.9 mg/dL (80 μmol/L); uric acid crystals were identified on arthrocentesis of the ankle 6 weeks ago.
Given this additional information, what is your assessment of the patient’s condition?
Is the patient a candidate for antihyperuricemic therapy? If so, which agent would you choose?
Other Uricosuric Agents
Sulfinpyrazone was used in the past; it is no longer available in the United States. Several other medications have mild uricosuric effects and may be appropriate adjunctive therapy in some patients. Losartan increases both uric acid excretion and urine pH and may be an option in hypertensive patients with gout.30 Fenofibrate is also a uricosuric and may be appropriate in selected dyslipidemic patients with gout.
Tumor Lysis Syndrome
TLS is a metabolic disorder caused by rapid cell destruction (usually during chemotherapy treatment for cancer) and associated with several electrolyte disturbances, notably hyperuricemia.
TLS is most commonly associated with the chemothera-peutic treatment of cancers, such as leukemias and lymphomas. These types of cancers have a large tumor cell burden and are highly sensitive to destruction by chemotherapy. Massive lysis of intracellular contents occurs including the breakdown of nucleotides into hypoxanthine, xanthine and, eventually, uric acid. These large amounts of uric acid overwhelm normal urinary excretion capacities and can undergo crystalline precipitation. This can lead to acute renal failure and a host of electrolyte disturbances including hyperkalemia and hyperphosphatemia.31 If not prevented or treated early, TLS can lead to acute kidney damage and perhaps death; thus TLS is considered an oncologic emergency. The incidence of TLS varies according to definition, tumor type, and patient characteristics but is thought to be approximately 5% in high-risk cancers.
Due to the potential severity of TLS, strategies to prevent this disorder are mandatory in susceptible patients. Aggressive hydration (usually with isotonic fluids such as 0.9% saline) and diuresis are the cornerstones of TLS prevention. This strategy promotes the excretion of uric acid before crystallization occurs. Some authors also recommend alkalinization of the urine, which increases the solubility of uric acid. However, investigations of this modality have failed to show a clear benefit, and recent practice guidelines do not recommend its routine use.32
Allopurinol has a crucial role in the prevention of TLS. The IV formulation reduces uric acid levels in high-risk patients by as much as 57% and can prevent hyperuricemia in up to 90% of patients treated.33Unfortunately, allopurinol does not reduce levels of uric acid formed before treatment, and the IV formulation can cause adverse effects similar to the oral form.
Rasburicase is a recombinant form of urate oxidase indicated for the prevention and treatment of TLS in pediatric patients. This enzyme converts uric acid to the more soluble compound allantoin. This potent agent can dramatically reduce uric acid levels in patients at high risk.34 Rasburicase is well tolerated; mild cutaneous hypersensitivity reactions are the most common adverse effect. It can also cause hemolysis, especially in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Rasburicase has a higher acquisition cost than IV allopurinol, and some investigators have studied lower doses of the drug or use it preferentially in patients with existing renal insufficiency or uric acid levels greater than 10 mg/dL (590 μmol/L).
OUTCOME EVALUATION
Acute Gout
• Monitor the patient for pain relief and decreased swelling of the affected joints. Both parameters should be improved significantly within 48 hours of starting acute gout therapy.
• Assess the patient’s subjective complaints and objective information for adverse effects. For NSAID therapy, be alert for new-onset epigastric pain, dark or tarry stools, blood in vomitus, dizziness or lightheadedness, development of edema, decreased urine output by more than 50% over a 24-hour period, or shortness of breath. For colchicine, monitor for nausea or vomiting, diarrhea, easy bruising, cold or flulike symptoms, lightheadedness, muscle weakness, or pain. Counsel the patient to inform you of any new medications started or stopped while taking colchicine.
• Monitor patients receiving intra-articular corticosteroid injections for increased swelling or pain at the injection site.
Patient Care and Monitoring
1. Assess the patient’s symptoms to determine the time of attack onset, which joints are affected, the level of pain, and other symptoms.
2. Review the patient history for contributing lifestyle factors and other disease states that may help guide therapy.
3. Obtain a thorough medication history for prescription drug, nonprescription drug, and dietary supplement use. Determine if any of these products may be contributing to hyperuricemia.
4. Educate the patient on lifestyle modifications that will improve symptoms, including weight loss, if appropriate, and avoidance of ethanol.
5. If the diagnosis of gout has not been confirmed previously, consider aspiration of an affected joint to identify uric acid crystals.
6. Initiate therapy to treat the acute gout attack without delay. Develop a plan to assess this therapy after 24 and 48 hours.
7. Select therapy based on comorbidities and potential for adverse effects. In patients with no other disease states, NSAIDs are the preferred drug class.
8. Assess the need for continuous antihyperuricemic therapy. Use patient factors such as comorbidities to select an agent. Allopurinol is the standard prophylactic agent used in the United States.
9. Do not start antihyperuricemic therapy within 4 weeks of an acute attack.
10. Evaluate the patient for the presence of adverse drug reactions, drug allergies, and drug interactions.
11. Stress the importance of adherence with the therapeutic regimen, including lifestyle modifications, to prevent future gout attacks and long-term complications.
12. Provide patient education about the disease state, lifestyle modifications, and drug therapy.
• Assess patients receiving systemic corticosteroids for mental status changes, fluid retention, increased blood glucose, muscle weakness, or development of new infections.
Antihyperuricemic Therapy
• Assess for new gouty arthritis attacks or the development of tophi. If neither one develops, continue antihyperuricemic therapy as prescribed.
• Obtain the first follow-up SUA level within 6 months of starting therapy. Then monitor levels at least every 6 to 12 months, and adjust the dose to achieve a target SUA level of less than 6 mg/dL (357 μmol/L).
• Evaluate patients taking allopurinol for development of rash, nausea, or new fever. These symptoms usually appear within the first 3 months of therapy but can occur anytime.
• Assess patients receiving probenecid for fever, nausea, or skin rash. Reevaluate therapy if a significant decrease in urine output occurs (greater than 50% in a 24-hour period).
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
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