Managing Gout In The Lower Extremity
Initial attacks of gout often affect the first metatarsophalangeal joint (MPJ). Accordingly, this author discusses the differential diagnosis of lower extremity gout, keys to managing acute attacks and how to get a handle on the disease’s metabolic causes. He also discusses current and emerging pharmaceutical options for treating the disease.
Gout is a metabolic condition characterized by excessive levels of serum urate. The consensus is that a serum urate level above 6.0 mg/dL, the saturation point of urate in biological fluids, is the cause of gout.
Elevated levels of serum urate over time lead to deposits of monosodium urate crystals within joints. Attacks of gout are due to the sudden release of these crystals into the joint, where they elicit an acute inflammatory response characterized by warmth, redness, swelling and excruciating pain.
The pain often starts at night or early in the morning. Patients will state that they awaken from foot pain so severe that they cannot “bear the weight of the sheet” on the foot. Walking is next to impossible. In addition to these symptoms, fatigue, malaise and a low-grade fever may be present.
Most gout attacks resolve, at least early on, within three to 14 days, even without treatment. However, with time, the attacks become more frequent, last longer and spread to involve other joints.
Ninety percent of first attacks affect one joint, usually the first metatarsophalangeal joint (MPJ). This condition is called podagra.
However, other types of arthritis such as calcium pyrophosphate arthropathy (CPPD), Reiter’s disease, septic arthritis and psoriatic arthritis can produce a similar clinical picture. The instep of the foot may also be a target for a first attack and patients may think they have “turned their ankle.”
When it comes to other conditions to consider in the differential diagnosis, we know that osteoarthritis may affect the first MPJ and possibly lead to a bunion. One may mistake this condition for gout. In cases in which septic arthritis is a possibility, joint aspiration is mandatory. Finally, cellulitis is another condition that can be confused with acute gout.
A Closer Look At The Criteria For Diagnosing Gout
When it comes to the classification of acute arthritis with primary gout, the American College of Rheumatology notes there are a variety of possible criteria.1 These criteria may include:
• more than one attack of acute arthritis
• maximum inflammation developing within a day
• monoarthritis attack
• redness over joints
• painful or swollen first MPJ
• unilateral first MPJ attack
• unilateral tarsal joint attack
• asymmetric swelling within a joint on radiography
• subcortical cysts without erosions on radiography
• monosodium urate crystals in joint fluid during an attack
• joint fluid culture negative for organisms during an attack
A diagnosis of gout is highly likely if:
• monosodium urate crystals are detected in joint fluid
• a tophus containing urate crystals is identified
• six or more of the aforementioned criteria are present.
Measurement of serum uric acid during an attack may be helpful. Although a highly elevated level of serum uric acid supports the diagnosis, a normal level does not exclude the diagnosis. Keep in mind that serum urate levels do tend to be elevated two weeks after an attack.
One study demonstrated that measuring serum urate during an attack and then measuring two weeks later yields two serum urate levels that one can compare to help with the diagnosis. The authors concluded that patients were unlikely to have gout if they had low serum urate levels (2
The patient history may also provide clues as to etiology. These clues include a family history of documented gout, cold exposure, history of excessive alcohol ingestion and a history of hyperuricemia. Another possible etiology is overindulgence in high purine-containing foods such as shellfish or red meat immediately preceding the attack. Patients treated with thiazide diuretics and cyclosporines are also at risk for hyperuricemia and gout.
When a patient presents with monoarticular arthritis at our clinic, we tend to perform an arthrocentesis in order to ensure an accurate diagnosis.
What You Should Know About Treating Acute Gout
One can treat acute gout effectively with any number of nonsteroidal anti-inflammatory drugs (NSAIDs). Physicians should exercise caution with these drugs in patients who have significant renal, cardiovascular or gastrointestinal diseases. The use of NSAIDs is contraindicated in patients who have an aspirin allergy. The concomitant use of a proton pump inhibitor may be helpful for gastric prophylaxis.
Of all the NSAIDs, indomethacin (Indocin, Merck) is the one to avoid in elderly patients because of the high incidence of potential side effects including dizziness, headaches and confusion. One should not use NSAIDs in patients who are on anticoagulation therapy with warfarin (Coumadin, Bristol-Myers Squibb).
Alternatively, one can use colchicine in a dose of 0.6 mg twice a day. It is contraindicated in patients undergoing dialysis. Avoid using colchicine in patients who have liver or kidney disease. Due to underlying drug interactions, physicians should avoid using colchicine in patients taking statin drugs, macrolide antibiotics and cyclosporines.
When one cannot use NSAIDs or colchicine, use oral corticosteroids instead. Starting a prednisone burst at 30 mg a day and reducing it by 5 mg daily is effective. Another option is direct injection of glucocorticoids into the joint with ultrasound needle guidance. This is very effective for aborting attacks in a single joint.
One should counsel patients with diabetes mellitus about blood sugar elevation. Physicians should avoid the use of high dose oral steroids for treating gout in patients with uncontrolled diabetes. If there is any concern regarding infection, do not use steroids.
Pertinent Pearls On Addressing Metabolic Issues
Bear in mind that treating acute attacks does not treat the underlying disease. Dealing with the metabolic condition requires lowering serum urate levels below 6.0 mg/dL for an extended period of time. (When it comes to reducing serum urate levels, one may want to consult with the patient’s primary care provider or facilitate a referral to an internist.) This reduces the crystal burden and prevents further uric acid crystal deposition.
Extended high levels of hyperuricemia have been associated not only with chronic gouty arthritis but also with chronic renal disease, hypertension and cardiovascular disease.3 Indeed, comorbid conditions such as hyperlipidemia, diabetes, hypertension, chronic renal disease and cardiovascular disease are collectively referred to as the metabolic syndrome. These conditions are associated with the development of gout.4
Over time, tendons can also become inflamed along with joints. Chronic gout, which involves multiple joints, may look like rheumatoid arthritis. This becomes a confounding problem in the older patient who may also develop a positive rheumatoid factor as a result of the aging process. Also bear in mind that the development of tophaceous deposits may be mistaken for rheumatoid nodules.
When weighing the possible use of therapy to lower chronic uric acid, physicians must consider the patient’s lifestyle, comorbid conditions, concomitant medications and willingness to take chronic medicine.
Younger patients with normal renal function who excrete less than 800 mg/dL per 24-hour urine collection are usually treated with uricosuric drugs such as probenecid (Benuryl). Uricosuric drugs cause patients to eliminate uric acid in the urine. There is a risk for the development of kidney stones in patients who overproduce uric acid. In addition, patients need to take the drugs twice daily and increase their fluid intake.
Since abrupt changes in serum uric acid can trigger flares, concomitant colchicine is recommended in a dose of 0.6 mg daily for prophylaxis against acute attacks during the first six months of treatment.
One should carefully monitor patients on chronic colchicine for neuromuscular symptoms. These problems occur more often in patients with renal insufficiency or those who are also taking statin or macrolide drugs.
Another uricosuric agent that one can use is sulfinpyrazone (Anturane). This drug has the added benefit of reducing platelet adhesiveness. Losartan (Cozaar, Merck), an anti-hypertensive drug, is also a mild uricosuric drug.
Patients who excrete more than 800 mg/dL per 24-hour urine collection should receive a xanthine oxidase inhibitor such as allopurinol (Zyloprim, Prometheus Laboratories). This drug inhibits the conversion of purines to uric acid. Allopurinol is effective in patients who are under-excreters and overproducers of urate.
Patients with compromised renal function require an adjustment in dosing. Drug interaction may present a problem. For instance, one should reduce the dose of allopurinol in patients who require azathioprine (Imuran, Prometheus Laboratories). Achieving the target of 6.0 mg/dL is not always easy. Allopurinol also has multiple severe toxicities and a possible risk of death.
Emerging Modalities In Gout Treatment
Recent research has produced two more drugs that will be helpful for managing chronic gout. The first is febuxostat (Uloric, Takeda Pharmaceuticals). This is a xanthine oxidase inhibitor that seems to be as effective as allopurinol but with less toxicity. The U.S. Food And Drug Administration (FDA) approved this therapy in February. There are some concerns regarding cardiovascular safety and the drug is undergoing further clinical study.
The other drug is PEG-uricase (Puricase, Savient). One must administer this medicine intravenously as it is reserved for patients with severe chronic gout. It works by converting urate to a soluble and easily excreted compound called allantoin. Concerns related to infusion reactions are prompting further study.
Case Study One: When Uricosuric Drugs Can Benefit Patients
A 52-year-old man presented to the office for evaluation of possible gout. He underwent an executive physical examination a year prior to presentation and had an elevated serum uric acid of 10.5 mg/dL at that time. One month prior to presentation, he noticed pain and swelling in the left foot. The primary care physician diagnosed him with gout.
The patient received two NSAIDs that did not work. The patient then started taking a tapering burst of an oral prednisone and he was still taking this at the time of the initial visit to our clinic. There was no family history of gout nor were there any diet or alcohol triggers. There was no history of lead exposure.
The clinical examination was remarkable for marked swelling involving the left first MPJ.
Since the patient was traveling to Italy, we kept him on the prednisone and advised him to taper it slowly, and make an appointment if he flared again. A urine collection to gauge uric acid was 589.3 mg/24 hours and his creatinine clearance was normal.
Ten days later, the patient presented with an acute flare of pain and swelling in the first MPJ. An ultrasound guided aspiration of the joint yielded 0.5 mL of fluid. We performed a joint injection of 0.25 mL of methylprednisolone acetate (Depo-Medrol, Pfizer) and 0.25 mL of 1 percent lidocaine. Polarized microscopy identified monosodium urate crystals in the aspirate.
We initiated colchicine 0.6 mg and probenecid twice a day. We also prescribed meloxicam (Mobic, Boehringer Ingelheim) to take on an as needed basis.
Since this patient was active, relatively young, had normal renal function and was an under-secretor of urinary uric acid, he was an ideal candidate for a uricosuric drug program. In addition to receiving uric acid lowering therapy, the patient also received the prophylactic colchicines. We generally continue the use of colchicine for six months when starting uric acid lowering therapy.
Case Study Two: When A Patient Presents With Acute Podagra In The First MPJ
A 65-year-old man presented with relatively severe osteoarthritis of the left knee. He was an avid runner and underwent a stem cell procedure on his knee without any difficulty. One week after the procedure, on his follow-up visit, he presented with acute podagra in the right first MPJ.
Aspiration of the joint under ultrasound guidance yielded two drops of synovial fluid. The physician injected the joint with 0.5 mL of methylprednisolone acetate and 0.5 mL of 1% lidocaine. Polarizing microscopy identified both monosodium urate as well as calcium pyrophosphate crystals. The patient did not take any anti-inflammatory drugs because of the recent stem cell procedure.
The patient’s renal function was normal and his serum uric acid was 5.7 mg/dL at the initial presentation.
While the patient’s foot was somewhat better a week later, persistent swelling and pain were present. We initiated colchicine in a dose of 0.6 mg twice a day. Two weeks later, the attack had subsided and we switched the patient to allopurinol 100 mg per day for the first week, 200 mg per day for the second week and finally 300 mg per day. When the patient presented a month later, he was symptom free. Since his serum uric acid was 2.7 mg/dL, we decreased his allopurinol dose to 200 mg per day.
Two issues complicated this patient’s problem. The first is that patients undergoing stem cell procedures should not receive anti-inflammatory drugs for at least four weeks following the procedure. Second, the patient had pseudogout as well as gout. Pseudogout is another microcrystalline-induced disorder due to deposits of calcium pyrophosphate crystals. The clinical picture is similar to that for gout. These two diseases can coexist, making both diagnosis as well as treatment difficult.
Interestingly, the patient’s serum uric acid was normal at the time of his attack. Many physicians make the diagnosis of gout by measuring the serum uric acid. An elevated serum uric acid does not necessarily mean a patient with a swollen toe has gout. By the same token, a normal serum uric acid does not exclude the diagnosis of gout.
We chose allopurinol primarily because of the patient’s age. There is a decline in renal function that occurs with age. Uricosuric drugs such as probenecid are not effective in patients who have less than adequate renal function (
Dr. Wei is a Fellow of the American College of Rheumatology. He is the Clinical Director of the Arthritis and Osteoporosis Center in Frederick, Md.
1. Wallace SL, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 1977; 20(3): 895-900.
2. Rigby AS, Wood PH. Serum uric acid levels and gout: what does this herald for the population? Clin Exp Rheumatol 1994; 12(4): 395-400.
3. Krishnan E, Baker JF, Furst DE, Schumaker HR Jr. Gout and the risk of acute myocardial infarction. Arthritis Rheum 2006; 54(8): 2688-2696.
4. Choi HIK, Mount DB, Reginato AM. Pathogenesis of gout. Ann Intern Med 2005; 143(7):499-516.