A 31-Year-Old Army Specialist Presenting with Acute Oligoarthritis

INTRODUCTION

A 31-year-old, Caucasian, active duty, male specialist presented to Walter Reed Army Medical Center for evaluation of left hand pain and swelling. His symptoms had begun 3 days earlier with a painful, stiff, left middle finger. There was no history of trauma. When the patient sought medical attention, screening laboratory tests were performed, and radiographs of the involved finger were negative for fracture. The patient was treated with ibuprofen (400 mg, three times daily), with mild improvement in his symptoms.

At the initial evaluation in the rheumatology clinic, the patient's symptoms had progressed to include pain and swelling in the metacarpophalangeal and proximal intraphalangeal joints of the left index and middle fingers. Morning stiffness was present for 2 hours. The patient denied symptoms in other joints or any history of similar symptoms. He reported no fever, sore throat, weight loss, rash, nail changes, eye pain or redness, or back pain. There had been no antecedent gastrointestinal or genitourinary illnesses. The patient was married and denied extramarital sexual encounters. There was no family history of rheumatoid arthritis, gout, psoriasis, or inflammatory bowel disease. The patient's medical history was unremarkable except for empiric treatment of tuberculosis because of hemoptysis and positive skin test results. The patient's treatment regimen for tuberculosis included isoniazid, rifampin, pyrazinamide, and ethambutol. He had been taking this medical regimen for 6 weeks before the onset of his joint symptoms. Bronchoscopy was performed twice, culture results were negative, and the antibiotics were discontinued except for isoniazid, which was continued for the treatment of latent tuberculosis infection.

APPROACH TO THE PATIENT

Acute oligoarticular arthritis is defined as the presence of inflammation in two to four joints for <6 weeks. There may be substantial overlap with monoarticular and polyarticular causes of arthritis, because these conditions sometimes present as oligoarthritis. Broad diagnostic categories of oligoarthritis include crystalline arthritis, infectious causes, and inflammatory causes.

Although acute gouty arthritis typically presents as intense monoarthritis of the lower extremities, particularly of the first metatarsophalangeal joint, oligoarticular presentations may occur. Other common sites of lower-extremity involvement include the mid-foot, ankle, and knee. The typical patient is a middle-aged man, although younger men and postmenopausal women may be affected. Upper-extremity involvement is uncommon at disease onset but may occur, particularly in postmenopausal women or elderly patients.1

Other inflammatory conditions to consider in acute oligoarthritis include rheumatoid arthritis and arthritis associated with a connective tissue disease, such as systemic lupus erythematosus. These conditions are more commonly polyarticular but may be oligoarticular at disease onset, with the more characteristic, symmetric polyarthritis developing over time. Finally, acute sarcoidosis may present as symmetric oligoarthritis of the ankles, particularly in Lofgren's syndrome, with erythema nodosum and hilar adenopathy.

Medications may be an important predisposing factor for gout and may lead to symptoms at an earlier age than is typical. Many medications that affect serum urate levels activate a recently identified urate-anion exchange pump (URAT1).2 Both pyrazinamide and ethambutol have been associated with hyperuricemia. Pyrazinamide stimulates URAT1, leading to increased urate absorption in the proximal tubule.3 Other drugs that cause hyperuricemia, such as niacin and furosemide, also activate URAT1, leading to hyperuricemia. Although ethambutol does not affect URAT1, it contributes to hyperuricemia by decreasing renal urate excretion.3 Several uricosuric drugs inhibit this transporter, including probenecid, sulfinpyrazone, losartan, and high-dose aspirin, leading to reduced serum uric acid levels.

Military operational requirements may potentially precipitate gout attacks. Current desert operating environments predispose service members to dehydration, a known precipitant of gouty arthritis.4 Strenuous exercise leads to increased adenine nucleotide breakdown, with a resultant increase in serum uric acid levels.5 This sudden change in uric acid levels may also precipitate acute gout.

The contribution of alcohol to gout is relevant to military medicine, because personnel on active duty may consume alcohol regularly. Alcohol consumption contributes to hyperuricemia in several ways, possibly increasing the risk of a gout attack. The type of alcohol consumed may play a role in gout, in that beer and liquor, but not wine, have been shown to increase serum uric acid levels.6 Furthermore, alcohol ingestion increases the production of lactate, and fasting associated with heavy drinking may enhance the production of ketoacids, which can compete with urate for proximal tubular secretion.7 Ketoacids produced during alcohol consumption also activate TJRATl, increasing proximal tubular reabsorption of urate and compounding the hyperuricemic effect of alcohol.7

Inflammatory oligoarthritis of the lower limbs is typical of the seronegative spondyloarthropathies, such as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. Almost one-third of patients with psoriasis may present with asymmetric oligoarthritis. Both ankylosing spondylitis and enteropathic arthritis may present with oligoarthritis before the development of axial skeleton or bowel symptoms. Dactylitis (sausage digit) is a hallmark clinical feature common to these diseases and may affect one or more fingers and/or toes.

The absence of rash does not exclude psoriatic arthritis from consideration. In fact, a minority of patients may develop arthritis before the onset of psoriasis. A family history of psoriasis is usually present in these patients.

Infectious causes of acute oligoarthritis in young adults are similar to those that cause acute monoarthritis. Gonococcal septic arthritis often presents as migratory arthritis with prominent tenosynovitis of the wrists. Nongonococcal septic arthritis typically involves one joint, most commonly the knee. However, additional joints may be involved for patients with bacteremia (especially attributable to Staphylococcus aureus), immunosuppression, or preexisting arthritis involving multiple joints.

For our patient, laboratory data available from the previous evaluation included a normal complete blood count, a normal complete metabolic profile, an erythrocyte sedimentation rate of 21 mm/h, and a uric acid level of 10.0 mg/dL (normal range, 3.5-8.5 mg/dL).

ROLE OF SERUM URIC ACID MEASUREMENT IN ACUTE ARTHRITIS

Gout is an acute arthritis caused by the immune response to the presence of uric acid crystals, a product of purine metabolism, in the joint. Approximately 90% of patients with gout are uric acid-underexcreters, and the remaining 10% of patients are uric acid-overproducers. A normal serum uric acid level does not exclude the diagnosis of gout.8 Although physiologic saturation is ~6.4 mg/dL at 37°C, many laboratories report uric acid levels of up to 8.0 mg/dL as normal. Therefore, some patients with normal uric acid levels according to the laboratory have urate concentrations above the physiologic saturation point. Furthermore, the interpretation of uric acid levels in the setting of an acute gout attack may be unreliable because of increased renal excretion of uric acid mediated by the inflammatory response.9 Similarly, an elevated serum uric acid level is not diagnostic of gout, because the majority of patients with asymptomatic hyperuricemia do not develop gouty arthritis.

On physical examination, our patient had normal vital signs and appeared well. His examination was unremarkable except for the left hand. The patient was unable to make a clenched fist, and the dorsum of the hand was warm. Synovitis was present in the left second, third, and fourth metacarpophalangeal joints and the left third proximal intraphalangeal joint.

ADDITIONAL DIAGNOSTIC CONSIDERATIONS

Arthrocentesis should be performed in all cases of acute monoarthritis, for the purpose of excluding septic arthritis. Arthrocentesis should also be considered in the setting of oligoarticular arthritis when clinical data suggest the possibility of crystal-induced arthritis. In this case, data that suggested the possibility of gout included an elevated serum uric acid level and the use of multiple medications that are associated with hyperuricemia. Although plain radiographs may show soft tissue swelling in acute arthritis, they are unlikely to demonstrate bony changes that would allow differentiation of the cause of the arthritis. Synovial biopsy is usually reserved for the evaluation of persistent monoarthritis of unknown cause. This intervention is too invasive in the acute setting, when other tests can be used to make the diagnosis. Although the C-reactive protein level may be elevated in acute inflammatory arthritis of any cause, this does not add information beyond the physical examination findings in this case. Magnetic resonance imaging of the hands is useful for the detection of subclinical synovitis and early erosions but is not required when synovitis is readily palpable on physical examination.

For our patient, arthrocentesis of the left third metacarpophalangeal joint was performed, and a trace amount of fluid was obtained. Polarized light microscopy revealed moderate leukocytes with the presence of intracellular monosodium urate crystals.

MANAGEMENT OF ACUTE GOUT

The finding of intracellular monosodium urate crystals in synovial fluid is diagnostic of gout. Treatment options for acute gout include colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. Colchicine, a plant derivative, inhibits leukocyte activation and migration and is most effective when given in the first 24 to 48 hours of the attack. NSAIDs are also effective, but full anti-inflammatory doses are required. Corticosteroids may be given as an intraarticular injection in the case of monoarthritis or systemically in the case of oligoarticular or polyarticular disease. Starting doses of 40 mg of prednisone or equivalent, with tapering over 7 to 10 days, are commonly recommended when colchicine and NSAIDs are ineffective or are contraindicated because of comorbid medical conditions.10

Allopurinol is the most commonly used urate-lowering agent, and administration should not be initiated during an acute attack. When used mistakenly in the acute setting, allopurinol can lengthen the attack or lead to a recurrence once treatment of the attack is complete. Prophylaxis of gout with colchicine or a NSAID is generally recommended when allopurinol treatment is initiated, but with doses that are lower than those used in the treatment of an acute attack.11

Allopurinol should be continued during a gout attack, however, for patients who are already receiving it as uratelowering therapy. A serum uric acid level of 6 mg/dL is commonly the initial goal of urate-lowering therapy.

Our patient was treated with a course of prednisone (40 mg daily, tapered over 14 days), with resolution of his gouty arthritis. At a follow-up visit, a patient may state that he has read about gout on the Internet and wants to know if he is a candidate for urate-lowering therapy.

INDICATIONS FOR URATE-LOWERING THERAPY

Urate-lowering therapy consists of treatment with allopurinol, a xanthine oxidase inhibitor, or probenecid, a uricosuric agent, for the purpose of reducing the number of gouty attacks and/or reducing end-organ damage related to gout. Although hyperuricemia is a risk factor for the development of gout, most patients with asymptomatic hyperuricemia do not develop gout and therefore should not be treated. Recurrent gout attacks are an indication for urate-lowering therapy. Patients should be offered urate-lowering therapy if they have two or more attacks per year. Reports have shown that reduction of serum uric acid levels to ^6 mg/dL reduces the frequency of, and in many cases prevents, further gout attacks.12,13 Patients with tophaceous gout or evidence of erosive arthritis on radiographs should be treated with allopurinol.

The dose of allopurinol must be reduced for patients with chronic kidney disease and those taking azathioprine or 6-mercaptopurine, because both of those drugs are metabolized by xanthine oxidase. Probenecid is contraindicated for patients with a history of uric acid nephrolithiasis, because it increases urine uric acid levels. Other contraindications to the use of probenecid include chronic kidney disease, low-dose aspirin use, and age of >60 years.

A new option for urate-lowering therapy that may become available is febuxostat, a nonpurine inhibitor of xanthine oxidase that is currently awaiting Food and Drug Administration approval.14 Although it is likely to be more expensive than currently available agents, febuxostat may be useful for patients for whom probenecid is contraindicated or those who cannot tolerate allopurinol because of hypersensitivity.

CONCLUSIONS

Gout is the most common crystal-induced arthritis and is caused by the immune response to the presence of uric acid crystals in the synovial space. Gouty arthritis most commonly presents as acute monoarthritis of the lower extremities. Podagra is the term for the classic presentation of gouty arthritis of the first metatarsophalangeal joint. Patients often have recurrent attacks, although these may occur with an asymmetric distribution. Less common presentations include involvement of more than one joint at onset.1

Although gout most commonly affects middle-aged men and postmenopausal women, military providers should be familiar with its diagnosis and management because some exposures related to military service may predispose younger patients to gout. Both dehydration in desert operating environments and strenuous exercise can predispose patients to gout. Alcohol use remains common in active duty populations and, for the reasons discussed above, may be an important contributor to incident gout.

Overseas deployments to areas of high tuberculosis prevalence are likely to be associated with increased rates of latent and active tuberculosis infections. This will necessitate increased exposure to antituberculosis medications, with a resultant (although probably small) increase in gout in patients treated with multidrug regimens containing ethambutol and/or pyrazinamide.

Furthermore, recent reports suggest that the substantial disease burden of gout may be increasing,3,7 partly because of the increase in obesity and the metabolic syndrome. The prompt recognition and appropriate treatment of gout should decrease disability in the acute and long-term settings, improving the readiness of the individual service member.

As in the present case, gout may occur in young, active duty patients. A family history of gout may be present in these patients. In the absence of family history, military providers should consider gout in the differential diagnosis of acute oligoarthritis, especially when factors that contribute to hyperuricemia, such as dehydration, alcohol consumption, and use of certain prescription drugs, are present.

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