Given the increased prevalence of gout and how gout affects the lower extremity, the author discusses current concepts in diagnosis and treatment, and provides an
illuminating case study.
Gout is an inflammatory arthritis that results from hyperuricemia, from either the body’s overproduction or underexcretion of uric acid. It typically presents with acute onset, can be recurrent and the vast majority is monoarticular in presentation. The first metatarsophalangeal joint (MPJ) is involved in 90 percent of individuals with gout. Gout can result in joint deterioration and destruction.
For the last two years, gout has been much more recognizable to the public in print, TV and other forms of media. The painful condition of gout is now more appreciated as the number of gout medications, formulations and reformulations has changed the landscape for the public and patient base, and thus changed the management by physicians.
The formation of crystals that accumulate within a joint triggers gout. It is well known that just because patients have hyperuricemia, it does not mean they have gout. The actual number of true gout cases is likely underestimated. Many times, patients and physicians treat this with OTC analgesics or anti-inflammatories without the proper diagnosis and workup for gout.Hyperuricemia is the cause of gout. According to Chen and Schumacher, there is an increasing prevalence with significant comorbidities including cardiovascular disease, hypertension, renal insufficiency and metabolic syndrome.1
At a recent Podiatry Institute meeting in August of 2011, researchers stated that gout affects approximately 5 to 6 million people in the United States with prevalence on the rise.2 Gout reportedly occurs more in men than women, affecting 2 percent of men older than 30 years of age. Risk factors for gout have been well documented in the medical literature. Risk factors include being male, postmenopausal, a strong family history, kidney disease, organ transplants, excessive alcohol use, a diet high in purines (red meat and seafood), metabolic syndrome, obesity, dehydration and exercise.
Studies have shown that heavy alcohol use in general, particularly beer, increased the incidence of gout whereas moderate use of red wine did not.3 The growing public awareness and public presentation of gout in the last 10 years — with a two- to threefold increase in the incidence of gout — parallels the increases in obesity and metabolic syndrome.4
Gout can be divided into three stages: acute gout, intercritical gout and chronic gout.
Acute gout can occur as a primary non-systemic episode or can be secondary to other systemic issues including kidney failure, myocardial infarction or cerebrovascular accident.
Intercritical gout is typically the asymptomatic period between acute attacks of gouty inflammation. The disease may progress even though it is clinically silent. During this period, tophi may develop as the body stores of uric acid accumulate. Generally, acute gout attacks are infrequent and intercritical periods are long in duration. However, when the disease progresses, acute flare-ups may increase in frequency and intercritical periods may actually shorten.
Chronic gout is characterized by the chronic deterioration and destruction of joints, which include bony erosions and the development of tophi. It is at this stage that acute gout may become polyarticular, occur more proximal than the foot and ankle, and are significantly more painful. These attacks usually last longer and are more severe in nature. They include the carpal tunnel and tarsal tunnel regions, spine, eye involvement, pancreatic involvement, solitary breast nodules or may be cardiac in nature with endocarditis.
Obtaining a comprehensive patient history, comorbidities, concomitant medication use, physical exam and family history is absolutely critical for the optimum treatment and management of gout.5 Janssens and colleagues generated a diagnostic scoring system that can be helpful in detecting gout.6 The variables in their system included male sex, previous patient arthritis attack, onset within one day, joint redness, MPJ involvement and serum uric acid level exceeding 5.8 mg/dL. Additional variables are hypertension or one or more cardiovascular diseases (angina pectoris, myocardial infarction, heart failure, cerebrovascular accident, transient ischemic attack, vascular disease), hospitalization, surgery and diuretic use.
The system by Janssens and colleagues was based on a scale of 0-13.6 From a diagnostic view, a score of 4 or less ruled out gout in 100 percent of patients. For patients with a score of 8 or higher, the diagnosis of gout was confirmed in more than 80 percent of these patients. One must also consider other diagnoses such as rheumatoid arthritis, sepsis, pseudogout, psoriatic arthritis and reactive arthritis in the patient’s initial presentation.
It is well noted that the identification of monosodium urate crystals in joint fluid and tophi is considered a gold standard for the diagnosis of gout.7 The majority of outpatient podiatry practices do not routinely practice the identification of crystals, according to a recent survey, and that is true in my practice as well.8 For example, in one study, the search for crystals only occurred in 11 percent of the patients with gout.9 Identifying crystals is more common in the offices of a rheumatologist, orthopedist or medical internist.
When identified, monosodium urate crystals appear to be needle-shaped and 2 to 20 μm in length. Under polarized light, they exhibit strong negative birefringence. The crystals appear yellow with a line parallel to the slow vibration of the compensator and appear blue when the line is perpendicular to it. If one suspects a sepsis process, the synovial fluid analysis is absolutely essential. Measuring the increased uric acid levels may be unreliable for diagnosis and can be misleading in either direction.
Serum urate levels may aid in supporting the diagnosis of gout. However, be aware that serum urate levels can be misleading in some cases and unreliable for the diagnosis of gout. For example, a patient with joint pain with elevating serum urate may be inappropriately diagnosed with gout. Someone with a truly gouty attack who has normal serum urate levels may not actually have gout. Laboratory testing is only part of making a diagnosis. One may consider X-rays, ultrasound or magnetic resonance imaging (MRI). More recently, researchers noted that a new therapeutic imaging technique — dual-energy computed tomography (CT) — can identify four times as many areas of involvement than the standard clinical assessment. It may actually replace the gold standard of joint aspiration.10
The clinical presentation of gout is typically acute monoarticular arthritis. It is usually located in a joint of the lower extremity but can occur in joints other than the feet including ankles, elbows, knees, wrists and fingers. With gout, one will typically note a warm, erythematous, swollen, tender joint with painful range of motion. It is also important to note that acute inflammatory gout may occur in adjacent soft tissue or connective tissues, and is not limited to joint involvement itself. Typically, gout attacks last from six to 72 hours of onset, usually subsiding in three to 10 days.
Other clinical symptoms may involve the complaints of headache, fatigue and chills often with the onset of symptoms at night. The presentation may be symmetric or asymmetric, monoarticular or polyarticular. One should check the other body parts including the elbow (olecranon bursa). Tophi may present with a chalky, usually painless irregular substance from the tips of fingers and toes as well as the joints themselves.11 A podiatrist should be well aware of atypical presentations of gout that mimic other disorders such as rheumatoid arthritis, osteoarthritis, septic arthritis, myeloproliferative disorders, and lymphoproliferative disorders.
Also be aware of atypical gout presentations in patients taking cytotoxic drugs, immunocompromised patients with diabetes, those on dialysis, patients who have had an organ transplant and those who have high fructose ingestion. These all may influence the turnover of uric acid.
Hyperuricemia is defined as urate levels greater than 6.8 mg/dL. Levels of uric acid of greater than 6.8 are considered to be above the saturated level, predisposing the patient to crystal formation/deposition. The uric acid levels reflect a balance of dietary factor synthesis and excretion of uric acid. The uric acid concentration is caused either by decreased intravascular volume (dehydration) or truly increased total body uric acid levels. It is critical to remember that increased uric acid levels can result from increased uric acid production, decreased uric acid secretion or drugs that alter uric acid levels.
It is well known that the incidence of gout is higher in people with increased dietary intake of purines, particularly meat and seafood, as well as ingestion of beer and spirits, soft drinks and fructose.12 It is lower in those with increased intake of coffee, dairy products and vitamin C (all lower uric levels). It must be clarified that coffee and tea can also increase uric acid levels and the presentation of gout. Purine-rich fruits, vegetables and foods include oranges and citrus fruits, cranberries, tomatoes, pineapples, pomegranates, peanuts, beans, lentils, peas, spinach and asparagus. All of the aforementioned foods affect the balance between urate reabsorption and secretion, which is critically linked to the net uric acid elimination in the urine.
One should diagnose patients on an acute presentation with aspiration and I strongly advise obtaining an analysis of the synovial fluid.13 The presence of yellow urate crystals, possible moderate amounts of white blood cells and negative cultures is truly the gold standard.
It is also important to use lab tests to assess the overall state of patient. This includes a complete metabolic panel, urinalysis, blood urea nitrogen, serum creatinine, C-reactive protein and erythrocyte sedimentation rate (ESR). With clinical judgment, additional tests may be advised, especially in light of other suspicions for metabolic involvement. Sometimes, even though there is an acute attack, the uric acid levels may not be above 6.8 mg/dL until two weeks after the attack has subsided. Consider obtaining repeat labs two to four weeks after the initial presentation.
The treatment of gout is generally divided into two major phases of management: therapy for acute gouty attacks and chronic therapy for prophylaxis of these episodes.
Treatment for an acute gout attack should begin as soon as possible. The choices of agent, appropriate dosage and duration of therapy are dependent on coexisting illnesses, clinical circumstances and the severity of the gout attack. Some measures include: re-evaluating the patient’s medication profile, especially diuretic use; the discontinuation of alcohol ingestion; and altering the diet and overall proper hydration.
Therapeutic options for the management of acute gout include: nonsteroidal anti-inflammatory drugs (NSAIDs); low-dose colchicine; glucocorticoids; intraarticular or oral steroids; corticotropins; and interleukin-1 (IL-1) inhibitors.5,12,14
In November 2011, Regeneron Pharmaceuticals announced the FDA accepted for review the company’s supplemental biologic licensing application for rilonacept (Arcalyst). Rilonacept is a subcutaneous injection for the prevention of gout flares in patients during the initial months of therapy. The drug would be used in combination with the standard of care for uric acid lowering therapies. Rilonacept is a biologic/monoclonal antibody and an IL-1 inhibitor.
Oral colchicines and/or NSAIDs are first-line agents for systemic treatment of acute gout in the absence of contraindications.12,15 There have been no high quality, randomized, placebo-controlled trials for acute gouty arthritis performed to date on the effectiveness of interventions for the treatment of gout and prevention of gout with NSAIDs.
Commonly used medications include: naproxen 500 mg two to three times daily with food; celecoxib (Celebrex, Pfizer) 200 mg BID; ketorolac 10 mg TID; or indomethacin 50 mg TID for five days. One may use a Medrol dose pak for six days or possibly prednisone 10 mg tapering of 10 mg BID for five days, 10 mg qd for five days and 5 mg for five days. Local application of diclofenac 1% gel (Voltaren, Novartis) or diclofenac 3% (Solaraze, PharmaDerm) are other options. It is generally recommended that NSAID dosages continue for five to seven days after an acute attack but gradually taper off.
Colchicine is highly effective when patients take it within the first 12 to 36 hours of the attack. It acts as an anti-inflammatory but not an analgesic. This drug has been utilized for decades in acute gout. The FDA removed intravenous colchicine for acute gout from the market in the U.S. in 2008 due to inappropriate use and multiple deaths were reported. High doses of colchicine may potentially lead to side effects, particularly troublesome diarrhea.
Subsequently, it was reformulated as an oral agent and approved by the FDA in July of 2009 and is now marketed as Colcrys (URL Pharma). Colcrys is currently the only single-agent colchicine with FDA approval. Other FDA-approved colchicine formulations contain probenecid (Benemid).
Low doses of colchicine (0.6 mg) three times a day may be sufficient for the management of patients with acute gout.12 Specifically, one should give 1.2 mg of colchicine for the treatment of acute gout at the first sign of flare-up. This would be followed by a second dose of 0.6 mg in one hour. The recommended prophylactic use for acute gout is 0.6 mg once or twice daily.5
Colchicine is a tricyclic alkaloid.15 The mechanism of colchicine involves microtubular polymerization, an important process in neutrophil functioning.
When the use of NSAIDs or colchicines is contraindicated, not properly tolerated or inappropriate for the patient, then one can give glucocorticoids or corticotropins orally or parenterally for acute gouty inflammation depending on the clinical presentation. For single joint involvement, intraarticular aspiration followed by subsequent injection of a corticosteroid into the joint can be effective. This usually involves the use of a short tapering, oral, low-dose systemic corticosteroid such as prednisone or methylprednisolone, typically p.o. but one can also administer it via IV.
For the purpose of comprehensiveness, one can conceivably use IL-1 antagonist/inhibitors. These include anakinra, canakinumab and rilonacept.16-18 For intercritical and chronic gout, it is critical to prevent further crystal accumulation and recurrent gouty flare-up episodes.
Therapy should begin immediately after the acute attack. Many suggest giving patients the option of initiating the next course of therapy because if they do not, they may risk another episode of an acute flare-up. As mentioned previously, one should redo lab work two to four weeks after the acute episode.
It is generally accepted that in patients with tophi or with two or more attacks in one year, one should initiate therapy for chronic gout. The key in the urate lowering therapy is the reduction and maintenance of a serum uric acid level of less than 6.0 mg/dL. At this level, there is a decreased number of flares, less uric crystal accumulation in joints and dissolved tophi.
Two classes of drugs for long-term therapy/maintenance of the reduction of serum uric acid include xanthine oxidase inhibitors and uricosurics. Allopurinol (Zyloprim) is a xanthine oxidase inhibitor and is most commonly used to reduce hyperuricemia regardless of its etiology. The dosing of allopurinol is individually based. Typically, the initial dose of allopurinol is 100 mg but again, depending on the severity, 100 mg 1 to 3 tabs p.o. can be a starting dose. Hypersensitivity syndrome and refractoriness to the drug (2 percent of patients on allopurinol have hypersensitivity syndrome or refractoriness) could create an erythematous rash, hepatitis, eosinophilia, fever, declining renal function or even fatality.19
Febuxostat (Uloric, Takeda) has been approved as a non-purine selective inhibitor of both oxidized and reduced forms of xanthine oxidase.20,21 Febuxostat has not been recommended for the treatment of asymptomatic hyperuricemia. Liver enzymes may elevate the use of this drug. Clinical trials have shown a higher rate of cardiovascular thromboembolic events with febuxostat in comparison to patients tested with allopurinol. Low-dose NSAIDs and colchicines can be used as prophylaxis with the concomitant use of a urate lowering agent until the serum uric acid level is stable at less than 6.0 mg/dL.21
Seven clinical trials showed that febuxostat 40 mg/dL was inferior to allopurinol 300 mg/dL in lowering the serum level to less than 6.0 mg/dL.21 The febuxostat dosage of 80 mg/dL was superior when researchers tested it against allopurinol. Although febuxostat 40 mg/dL and 80 mg/dL were well tolerated, liver enzyme elevations, nausea, arthralgias and rash may occur. Multiple studies show that febuxostat 80 mg/dL has more effectively lowered and maintained serum uric acid levels to a level less than 6.0 mg/dL, typically within two to four weeks, in comparison to allopurinol 300 mg/dL.20
If patients do not tolerate xanthine oxidase inhibitors, then probenecid can be the first drug of choice. Concurrent use of aspirin will block the effect of probenecid. The use of probenecid can block the excretion of penicillin, increase the serum concentration of generic furosemide and may extend heparin metabolism.
Once the patient has become asymptomatic and the intercritical phase has begun, the use of chronic therapy and follow-up visits are important especially in the very beginning following the acute phase. Until a second acute episode occurs, many patients do not want to modify their lifestyle even after receiving education about the joint destruction effects of gout. The effects of gout are even more critically important because of the greater occurrence of metabolic syndrome, cardiovascular disease, obesity and stress in America.
The podiatrist’s role in healthcare today is now more critical than ever with the increasing emphasis on comprehensive, collaborative and correlated care among other healthcare professionals. One should consider referral to a rheumatologist or to the primary care physician as part of the treatment course.
Statistics regarding referral to a rheumatologist and the rheumatologist’s treatment course parallels my experience when referring to a rheumatologist. Patients evaluated by a rheumatologist are: 21.9 percent more likely to have gout diagnosed by synovial fluid analysis; 25.7 percent more likely to have had a culture and sensitivity in the workup; and 18.3 percent more likely to have documented serum urate levels.22 Patients with acute gout who were treated by a rheumatologist were 30.3 percent less likely to need NSAIDs and higher doses of colchicine. Interarticular cortisone injections were 32.4 percent more likely to occur when a rheumatologist treated patients.
Rheumatologists recommended prophylaxis with allopurinol in 31.1 percent more patients.22 Similar to my personal treatment course, once one obtains target serum urate concentration level of 6.0 mg/dL, one can titrate allopurinol down to lower doses.
A 75-year-old retired Air Force colonel presents to the office on an emergency basis. I have known him for 13 years. He has a history of midsubstance plantar fasciitis treated by custom orthotics and painful radiculopathy of vertebrae L-4 and L-5 with difficulty walking.
He recently returned from the Caribbean with progressive swelling of both legs and feet in the last six days. Twenty-four hours after returning home from the Caribbean, he presented to a local hospital emergency room for the progressive swelling of both legs and feet but was discharged. He received no diagnosis except for possible prostatitis. The patient had an extensive workup and doctors told him to take an additional diuretic, hydrochlorothiazide. He did have a urologic consult, which resulted in a catheter implantation and got instructions to follow up with a urologist.
Six days later, he called the office and came in during our normal evening hours. He presented with a painful ingrown toenail in the left hallux. The patient also had increased difficulty walking (which led him to use a cane), shortness of breath, difficulty urinating, more redness to his feet and ankles, painful fingertips with dischargeof tophi, and painful Achilles tendons with a lack of propulsion. He had no recent history of injury on his trip to the Caribbean.
The patient regularly sees a number of professionals including a vascular surgeon, an internal medicine physician, a cardiologist and an orthopedist both locally and in the city nearby.
His past medical history includes: atrial fibrillation and ventricular tachycardia, L-5 spine radiculopathy with moderate stenosis at vertebrae L4-5; a positive electromyography of mild motor sensory polyneuropathy; elevated cholesterol; elevated blood pressure; gastroesophageal reflux disease; glaucoma; and multiple joint degenerative joint disease.
The patient is allergic to warfarin (Coumadin, Bristol-Myers Squibb) and has a history of purple toe syndrome from warfarin. His medications include simvastatin (Zocor), generic omeprazole, tamsulosin (Flomax, Boehringer-Ingelheim), alprazolam (Xanax), candesartan (Atacand), hydrochlorothiazide, metoprolol (Lopressor), Tylenol prn, aspirin 325 mg, bimatoprost (Lumigan, Allergan) timolol and Azopt eye drops.
In regard to the examination, the patient presented with local redness, tenderness and hypertrophy to the left great toe border. He had increased heat and redness of the right first MPJ, ankles and across both midfoot regions. Edema was +3 of the calf and feet, and there was palpable tenderness to both midfoot regions/ankles.
I contacted the ER physician and asked the doctor why the patient was discharged at the time of his visit six days prior. The ER doctor said there was no reason for him to be admitted. After much discussion with the ER doctor, he stated that there was no reason even that night to admit the patient with his progressive symptoms. Lab testing results obtained from the ER visit six days prior showed a urinalysis with 30 to 50 white blood cells in the urine, negative glucose/ketones and +1 occult blood. Other lab testing results showed a red blood cell count of 7.3, a white blood cell count of 4.10, potassium 4.1 mmol/L, sodium 138 mmol/L, sugar 128 mg/dL, and a uric acid level of 8.2 mg/dL with no HgA1c completed.
The EKG showed ventricular tachycardia. X-rays upon examination show significant midfoot degenerative joint disease and soft tissue swelling. His dorsalis pedis pulse was 1+/4 and his posterior tibial pulse was 0/4 B/L.
Working diagnoses include hyperglycemia, hyperuricemia, possible prostatitis, ventricular tachycardia, acute kidney failure and other organ shut down, and L-5 spine stenosis with radiculopathy.
During this office visit, I contacted his internal medicine physician and he agreed with me to send him to the nearest ER. We were both concerned about the progressive symptoms. I again contacted the ER doctor and after much pressure, he decided to reconsider the patient coming back to the ER for possible hospitalization with working diagnosis discussed.
The patient was admitted to the local hospital through the ER and a hospitalist, urologist, vascular surgeon and rheumatologist saw him.
The final diagnoses include acute prostatitis, acute gout, kidney failure and ventricular tachycardia. Treatment included medical management for hyperuricemia secondary to prostatitis. Once the patient was stable, the patient underwent successful prostate surgery. Within 10 days, the patient was medically stable with significant improvement in swelling with both local and systemic symptoms essentially resolved. All lab testing results returned to near normal values.
This case demonstrates the important role of the podiatrist for the comprehensive care, collaboration and correlation with other professionals of the healthcare team for the treatment of local and systemic medical issues. This case has become an excellent practice builder. This single case alone has created multiple new patient referrals for both conservative care and surgical intervention.
Gout is a relatively common inflammatory arthritis that occurs in all age groups. It can be a particularly debilitating disease, causing limitation of activity and lowering the quality of life. It is now associated with the comorbidity of other systemic diseases.
With the onset of the baby boomers getting older, the further scope of podiatric medicine integrated with the changes in the healthcare system of more comprehensive, collaborative, correlated care, podiatrists must be well educated on the options for the acute management and chronic treatment of hyperuricemia. It is crucial to rule out sepsis because symptoms of acute gout can mimic an infectious process.
The patient population must have the knowledge of all phases of the disease in order to manage their hyperuricemia and gout effectively. Typically, physicians must manage the intercritical phase well in order to decrease the incidence of acute attacks and limit the further risk of joint destruction.
By treating the underlying epidemic of metabolic syndrome and other disease states in concert with other members of the healthcare team, we will hopefully see a decreased prevalence of gout. Along with multidisciplinary collaboration, we will hopefully see more patient education on how to minimize known risk factors and prevent hyperuricemia.
Dr. Romansky is a Fellow of the American College of Foot and Ankle Surgeons. He is in private practice at Healthmark Foot and Ankle Associates in Media and Phoenixville, Pa.
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2. Podiatry Institute Seminar, Portland, OR, Aug. 11-14, 2011.
3. Choi HK, Atkinson K, Karlson EW, et al. Alcohol intake and risk of incident gout in men: a prospective study. Lancet. 2004; 363(9417):1277-81.
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5. Doghramji PP. Managing your patient with gout: A review of treatment options. Postgraduate Medicine. 2011; 123(3):56-71.
6. Janssens HJ, Fransen J, van de Lisdonk EH, et al. A diagnostic rule for acute gouty arthritis in primary care without joint fluid analysis. Arch Intern Med. 2010; 170(13):1120-1126.
7. Pelaez-Ballestas I, Hernandez Cuevas C, Burgos-Vargas R, et al. Diagnosis of chronic gout: Evaluating the American College of Rheumatology Proposal, European League Against Rheumatism Recommendations, and clinical judgment. J Rheumatol. 2010; 37(8):1743-1748.
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11. Scalapino JN, Edwards WD, Steckelberg JM, et al. Mitral stenosis associated with valvular tophi. Mayo Clin Proc. 1984; 59(7):509-512.
12. Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee For International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006; 65(10):1312-1324.
13. Pascual E, Batlle-Gualda E, Martinez A, et al. Synovial fluid analysis for diagnosis of intercritical gout. Ann Intern Med. 1999; 131(10):756-759.
14. Stamp LK, Jordan S. The challenges of gout management in the elderly. Drug Aging. 2011; 28(8):591-603.
15. Nuki G, Simkin P. A concise history of gout and hyperuricemia and their treatment. Arthritis Res Ther. 2006; 8(Suppl1):S1.
16. Singh D, Huston KK. IL-1 inhibition with anakinra in a patient with refractory gout. J Clin Rheumatol. 2009; 15(7):366.
17. So A, DeSmedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007; 9(2):R28.
18. So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. Arthritis Rheum. 2010; 62(10):3064-3076.
19. Pascual E, Sivera F. Therapeutic advances in gout. Curr Opin Rheumatol. 2007; 19(2):122-27.
20. Schumacher HR Jr, Becker MA, Wortmann RL, et al. Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week phase III randomized, double-blind, parallel-group trial. Arthritis Rheum. 2008; 15:59(11):1540-8.
21. Ernst ME, Fravel MA. Febuxostat: A selective xanthine-oxidase/xanthine-dehydrogenase inhibitor for the management of hyperuricemia in adults with gout. Clin Ther. 2009; 31(11):2503-2518.
22. Barber C, Thompson K, Hanly JG. Impact of rheumatology consultation service on the diagnostic accuracy and management of gout in hospitalized patients. J Rheumatol. 2009; 36(8):1699-1704.
23. Schlesinger N. Diagnosis of gout: Clinical, laboratory, and radiologic findings. Am J Manag Care. 2005; 11(Suppl 15):S443-S450.
24. Mandell BF, Edwards NL, Sundy JS, et al. Preventing and treating acute gout attacks across the clinical spectrum: A roundtable discussion. Cleve Clin J Med. 2010; 77(Suppl 2):S2-S25.
Editor’s note: For further reading, see “Managing Gout In The Lower Extremity” in the May 2009 issue of Podiatry Today or “Study Says Poor Footwear Is Common In Gout Patients” in the “News And Trends” section of the November 2011 issue.