Malik, Schumacher, Dinnella, and Clayburne compared the sensitivity and specificity of the above criteria with synovial-fluid analysis.18 Results showed the following predictive values: Rome, 76.9%; ACR, 65.6%; and New York, 70.0%. There is little variation among the criteria, with sensitivity values ranging from 66.7% to 70.0% and specificity from 78.8% to 88.5%. False positives included 50% of patients with joint aspirates of calcium pyrophosphate dihydrate deposition (CPPD) crystals, which indicates a disease known as pseudogout. Others had rheumatoid arthritis or osteoarthritis. According to Malik et al., “Unilateral first MTP pain or swelling, tophi reported, hyperuricemia, and response to colchicine within 48 hours had positive predictive values greater than 60%.”18 While the criteria aid in diagnosis, positive criteria should not be considered diagnostic without joint-fluid analysis of the affected joint.
Other diagnoses should be ruled out during the initial attack.
Cellulitis. A common disorder often confused with gouty arthritis, cellulitis has an estimated prevalence of 24.6 cases per 1,000 person-years.19 Whereas gout is often abrupt in onset, cellulitis tends to progress from an initial pustule, abscess, ulcer, or patch and gradually expands. Cellulitis may appear similar to gout if the initial location is a joint. However, erythema and swelling may enlarge beyond the joint area and affect multiple digits. Bacterial cultures aid in diagnosis if there is an abscess or ulcer.
CPPD disease (pseudogout). Gouty arthritis and CPPD disease may appear clinically similar. In CPPD, crystals form in cartilage and lead to inflammation. The typical age of onset of pseudogout is later than gouty arthritis, with initial presentation in the sixth decade or beyond. CPPD most commonly involves the wrists and knees. Diagnosis is made through synovial-fluid analysis and x-ray. Synovial-fluid analysis will reveal positively birefringent CPPD crystals.20,21 An sUA level will be within normal limits.2 In gouty arthritis, monosodium urate monohydrate crystals rather than CPPD crystals are found in the joint fluid.22 These can be differentiated during analysis of synovial fluid aspirated from an affected joint. CPPD can also be identified through x-ray of the affected joint. The x-ray will show chondrocalcinosis, which is common in patients with pseudogout. Radiographs are not useful on the initial attack, however.9
Septic arthritis. Like gout, septic arthritis presents with an acute onset of swelling, pain, and heat in a joint. The severity increases over the course of several hours. Fever is common with both gout and septic arthritis. There should be a high index of suspicion for septic arthritis if the patient has had hip- or knee-replacement surgery. The rate of septic arthritis in hip and knee replacements ranges from 0.5% to 2%.23 Unlike gout, septic arthritis occurs frequently in the knee: Infection in the knee occurs in 50% of cases.24 Other areas include the hip, shoulder, wrist, and ankle.2 In cases in which it is difficult to differentiate, septic arthritis should be ruled out through Gram stain and culture of the synovial fluid.9 This is especially important if corticosteroids are being considered for therapy. Synovial fluid will show an elevated leukocyte count exceeding 50,000 cells/mL and an absence of urate crystals.2 Gram stain may reveal staphylococcal or gram-negative bacteria. Hospitalization is indicated if septic arthritis is the working diagnosis.
Rheumatoid arthritis. Gout in advanced stages may become difficult to discern from rheumatoid arthritis (RA). As the disease progresses, periods between flare-ups become shorter.2 Periods in between attacks are painful, and joints may remain swollen.6 Chronic gouty arthritis or chronic tophaceous gout may occur if treatment is inadequate.2,6 If a patient’s age of onset is younger than 50 years, it is more likely that he or she will have a more progressive and advanced state of gout after an extended period of time. Prior to this, the two diseases may be differentiated based on the waxing and waning nature of gouty arthritis compared with RA, which is a slowly progressing disease. RA typically affects multiple joints simultaneously whereas gout is typically monoarticular. However, crystal deposition and inflammation may occur in multiple joints during RA flares. Unlike RA, gouty arthritis usually does not present in the hips and shoulders. Tophi appear similar to rheumatoid nodules and are not useful in diagnosis without further histologic studies. Positive anti-cyclic citrullinated peptide antibodies and rheumatoid factor confirm the diagnosis of RA.2 Positive x-ray findings for RA include juxta-articular osteoporosis, joint erosions, and joint-space narrowing.2
Charcot neuro-osteoarthropathy. Although rare, it is important to include Charcot neuro-osteoarthropathy (CNO) in the differential diagnosis in diabetic patients presenting with a hot, swollen, and red joint. While there is only a 0.3% incidence rate, treatment regimen requires immobilization of the foot.25 The patient will develop a foot deformity if prolonged delay of treatment occurs.26 Also, correct diagnosis would prevent placing these patients through the side-effect profile of pharmacologic therapy for gout. Often, long-term diabetic patients have peripheral neuropathy that reduces pain sensation. Therefore, it may be difficult to determine between gouty arthritis and CNO. CNO patients will report a history of trauma, surgery, or prior infection.26 Helpful indicators of CNO include an abnormal x-ray, bone scan, and MRI.27 However, a normal radiograph does not rule out CNO.27
According to the Arthritis Foundation, treatment goals include stopping acute attacks; providing rapid relief of pain and inflammation; averting future attacks; and preventing the development of tophi, kidney stones, and renal disease.6
The specific treatment for patients with gouty arthritis depends on the stage of the illness (i.e., asymptomatic hyperuricemia, acute attack, and intercritical periods). Treatment is not necessary for those who have asymptomatic hyperuricemia.2 Therapy is indicated for an acute attack, however.
Several treatments are available for patients during an acute attack, including NSAIDs, colchicine, and corticosteroids. Also, resting the joint will help with recovery.6 NSAID therapy is the treatment of choice for acute gout.2 Contraindications include impaired renal function, current peptic ulcer disease, and allergies to NSAIDs.2 Oral indomethacin 25-50 mg every eight hours is recommended.2
Colchicine is recommended as an alternative to NSAID therapy if not contraindicated.6 Ideally, this treatment is used within hours of an attack and typically provides pain relief within 48 hours of onset.6 Side effects include severe nausea, vomiting, and diarrhea.6 The patient must stop treatment if side effects develop.1 Traditional high-dose therapy (i.e., 1.2 mg followed by 0.6 mg every hour up to a maximum of 5.0-6.0 mg) has proven effective.2 Side effects are common, however. Low-dose oral colchicine (i.e., 1.2 mg followed by 0.6 mg one hour after initial dosage) has been proven as effective as high-dose therapy in treatment of acute flares with fewer adverse effects.28 Contraindications to colchicine include severe hepatic or renal impairment as well as simultaneous use of protease inhibitors, CYP3A4 inhibitors, and P-glycoprotein.29,30
Corticosteroids are another alternative to NSAIDs and are effective in most attacks.2 However, coexisting septic arthritis must be ruled out prior to use. Urate-lowering drugs are no longer indicated, as these may worsen the attack.6 Gout is highly painful, and narcotics may be recommended in severe cases.31
Patients in the intercritical phase should focus on preventing future flares. A strategy currently recommended is to lower sUA <6.0 mg/dL.32 Urate-lowering therapy is necessary in cases in which lifestyle modification alone is insufficient. Current urate-lowering medications include xanthine oxidase (XO) inhibitors and uricosuric agents.
Two XO inhibitors commonly used are allopurinol (Lopurin, Zyloprim) and febuxostat (Uloric). Allopurinol is frequently given as a 300-mg tablet once daily. Another tactic includes beginning at 100 mg and escalating the dose by 100 mg every two weeks until sUA is <6.0 mg/dL. Maximum daily dosage is 800 mg. Hepatic function, renal function, and sUA level should be assessed prior to starting therapy. During therapy initiation, sUA levels should be redrawn every two weeks until the therapeutic goal is reached. Afterward, levels should be checked every six months or yearly. Monitor hepatic and renal function for signs of toxicity.33
Approved for use in 2009, febuxostat is a newer XO inhibitor.34 Dosing is either 40 or 80 mg/day in patients with normal renal function or mild-to-moderate renal impairment. A recent trial compared the efficacy of febuxostat 40 mg, 80 mg, and allopurinol on lowering sUA over the course of six months.35 At the conclusion of the trial, febuxostat was the most effective. Overall, febuxostat 40 mg is equivalent to allopurinol 300 mg. Febuxostat was also found to have improved results in patients with low renal function.Rates of side effects were similar across the treatment groups.Liver function tests are recommended on initiation of therapy as well as at two- and four-month points. Periodic hepatic testing is recommended afterward.34