MILITARY MEDICINE, 173, 10:1044, 2008

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

LCDR Michael P. Keith, MC USN*; LTC Jonathan D. Roebuck, MC USA†

ABSTRACT A 31-year-old Army specialist was evaluated at Walter Reed Army Medical Center for an acute attack of arthritis in the left hand. After an initial evaluation, the patient was referred to the rheumatology service, and gout was diagnosed on the basis of synovial fluid analysis. This case demonstrates an uncommon presentation of a common disorder in an active duty soldier. The discussions presented following the clinical data are meant to expand diagnostic Downloaded from https://academic.oup.com/milmed/article/173/10/1044/4283056 by guest on 23 September 2021 considerations for patients with similar symptoms, to address risk factors for gout relevant to the military, and to clarify the management of gout.

INTRODUCTION continued except for isoniazid, which was continued for the A 31-year-old, Caucasian, active duty, male specialist pre- treatment of latent tuberculosis infection. sented to Walter Reed Army Medical Center for evaluation of left hand pain and swelling. His symptoms had begun 3 days APPROACH TO THE PATIENT earlier with a painful, stiff, left middle finger. There was no Acute oligoarticular arthritis is defined as the presence of history of trauma. When the patient sought medical attention, inflammation in two to four joints for Ͻ6 weeks. There screening laboratory tests were performed, and radiographs may be substantial overlap with monoarticular and polyartic- of the involved finger were negative for fracture. The patient ular causes of arthritis, because these conditions sometimes was treated with ibuprofen (400 mg, three times daily), with present as oligoarthritis. Broad diagnostic categories of oli- mild improvement in his symptoms. goarthritis include crystalline arthritis, infectious causes, and At the initial evaluation in the rheumatology clinic, the inflammatory causes. patient’s symptoms had progressed to include pain and swell- Although acute gouty arthritis typically presents as intense ing in the metacarpophalangeal and proximal intraphalangeal monoarthritis of the lower extremities, particularly of the first joints of the left index and middle fingers. Morning stiffness metatarsophalangeal joint, oligoarticular presentations may was present for 2 hours. The patient denied symptoms in occur. Other common sites of lower-extremity involvement other joints or any history of similar symptoms. He reported include the mid-foot, ankle, and knee. The typical patient is a no fever, sore throat, weight loss, rash, nail changes, eye pain middle-aged man, although younger men and postmeno- or redness, or back pain. There had been no antecedent pausal women may be affected. Upper-extremity involvement gastrointestinal or genitourinary illnesses. The patient was is uncommon at disease onset but may occur, particularly in married and denied extramarital sexual encounters. There postmenopausal women or elderly patients.1 was no family history of rheumatoid arthritis, gout, psoriasis, Other inflammatory conditions to consider in acute oligo- or inflammatory bowel disease. The patient’s medical history arthritis include rheumatoid arthritis and arthritis associated was unremarkable except for empiric treatment of tuberculo- with a connective tissue disease, such as systemic lupus sis because of hemoptysis and positive skin test results. The erythematosus. These conditions are more commonly poly- patient’s treatment regimen for tuberculosis included isonia- articular but may be oligoarticular at disease onset, with the zid, rifampin, pyrazinamide, and ethambutol. He had been more characteristic, symmetric polyarthritis developing over taking this medical regimen for 6 weeks before the onset of time. Finally, acute sarcoidosis may present as symmetric oligoarthritis of the ankles, particularly in Lofgren’s syn- his joint symptoms. Bronchoscopy was performed twice, drome, with erythema nodosum and hilar adenopathy. culture results were negative, and the antibiotics were dis- Medications may be an important predisposing factor for gout and may lead to symptoms at an earlier age than *Department of Rheumatology, National Naval Medical Center, Bethesda, MD 20889. is typical. Many medications that affect serum urate levels †Division of Rheumatology and Clinical Immunology, Walter Reed activate a recently identified urate-anion exchange pump Army Medical Center, Washington, DC 20307. (URAT1).2 Both pyrazinamide and ethambutol have been as- The opinions and assertions contained herein are the private views of sociated with hyperuricemia. Pyrazinamide stimulates URAT1, the authors and are not to be construed as reflecting the views of the leading to increased urate absorption in the proximal tubule.3 Department of the Army, the Department of the Navy, or the Department of Defense. Other drugs that cause hyperuricemia, such as niacin and This manuscript was received for review in January 2008. The revised furosemide, also activate URAT1, leading to hyperuricemia. manuscript was accepted for publication in July 2008. Although ethambutol does not affect URAT1, it contributes to

1044 MILITARY MEDICINE, Vol. 173, October 2008 Acute Oligoarthritis hyperuricemia by decreasing renal urate excretion.3 Several ROLE OF SERUM URIC ACID MEASUREMENT IN uricosuric drugs inhibit this transporter, including probene- ACUTE ARTHRITIS cid, sulfinpyrazone, losartan, and high-dose aspirin, leading Gout is an acute arthritis caused by the immune response to to reduced serum uric acid levels. the presence of uric acid crystals, a product of purine metab- Military operational requirements may potentially precip- olism, in the joint. Approximately 90% of patients with gout itate gout attacks. Current desert operating environments pre- are uric acid-underexcreters, and the remaining 10% of pa- dispose service members to dehydration, a known precipitant tients are uric acid-overproducers. A normal serum uric acid 8 of gouty arthritis.4 Strenuous exercise leads to increased level does not exclude the diagnosis of gout. Although ϳ adenine nucleotide breakdown, with a resultant increase in physiologic saturation is 6.4 mg/dL at 37°C, many labora- serum uric acid levels.5 This sudden change in uric acid levels tories report uric acid levels of up to 8.0 mg/dL as normal. Therefore, some patients with normal uric acid levels accord- may also precipitate acute gout. Downloaded from https://academic.oup.com/milmed/article/173/10/1044/4283056 by guest on 23 September 2021 ing to the laboratory have urate concentrations above the The contribution of alcohol to gout is relevant to military physiologic saturation point. Furthermore, the interpretation medicine, because personnel on active duty may consume of uric acid levels in the setting of an acute gout attack may alcohol regularly. Alcohol consumption contributes to hyper- be unreliable because of increased renal excretion of uric acid uricemia in several ways, possibly increasing the risk of a mediated by the inflammatory response.9 Similarly, an ele- gout attack. The type of alcohol consumed may play a role in vated serum uric acid level is not diagnostic of gout, because gout, in that beer and liquor, but not wine, have been shown the majority of patients with asymptomatic hyperuricemia do 6 to increase serum uric acid levels. Furthermore, alcohol not develop gouty arthritis. ingestion increases the production of lactate, and fasting On physical examination, our patient had normal vital associated with heavy drinking may enhance the production signs and appeared well. His examination was unremarkable of ketoacids, which can compete with urate for proximal except for the left hand. The patient was unable to make a tubular secretion.7 Ketoacids produced during alcohol con- clenched fist, and the dorsum of the hand was warm. Syno- sumption also activate URAT1, increasing proximal tubular vitis was present in the left second, third, and fourth meta- reabsorption of urate and compounding the hyperuricemic carpophalangeal joints and the left third proximal intrapha- effect of alcohol.7 langeal joint. Inflammatory oligoarthritis of the lower limbs is typical of the seronegative spondyloarthropathies, such as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and entero- ADDITIONAL DIAGNOSTIC CONSIDERATIONS pathic arthritis. Almost one-third of patients with psoriasis Arthrocentesis should be performed in all cases of acute may present with asymmetric oligoarthritis. Both ankylosing monoarthritis, for the purpose of excluding septic arthritis. spondylitis and enteropathic arthritis may present with oligo- Arthrocentesis should also be considered in the setting of arthritis before the development of axial skeleton or bowel oligoarticular arthritis when clinical data suggest the possi- symptoms. Dactylitis (sausage digit) is a hallmark clinical bility of crystal-induced arthritis. In this case, data that sug- feature common to these diseases and may affect one or more gested the possibility of gout included an elevated serum uric fingers and/or toes. acid level and the use of multiple medications that are asso- ciated with hyperuricemia. Although plain radiographs may The absence of rash does not exclude psoriatic arthritis show soft tissue swelling in acute arthritis, they are unlikely from consideration. In fact, a minority of patients may de- to demonstrate bony changes that would allow differentiation velop arthritis before the onset of psoriasis. A family history of the cause of the arthritis. Synovial biopsy is usually re- of psoriasis is usually present in these patients. served for the evaluation of persistent monoarthritis of un- Infectious causes of acute oligoarthritis in young adults are known cause. This intervention is too invasive in the acute similar to those that cause acute monoarthritis. Gonococcal setting, when other tests can be used to make the diagnosis. septic arthritis often presents as migratory arthritis with Although the C-reactive protein level may be elevated in prominent tenosynovitis of the wrists. Nongonococcal septic acute inflammatory arthritis of any cause, this does not add arthritis typically involves one joint, most commonly the information beyond the physical examination findings in this knee. However, additional joints may be involved for patients case. Magnetic resonance imaging of the hands is useful for with bacteremia (especially attributable to Staphylococcus the detection of subclinical synovitis and early erosions but is aureus), immunosuppression, or preexisting arthritis involv- not required when synovitis is readily palpable on physical ing multiple joints. examination. For our patient, laboratory data available from the previ- For our patient, arthrocentesis of the left third metacarpo- ous evaluation included a normal complete blood count, a phalangeal joint was performed, and a trace amount of fluid normal complete metabolic profile, an erythrocyte sedimen- was obtained. Polarized light microscopy revealed moderate tation rate of 21 mm/h, and a uric acid level of 10.0 mg/dL leukocytes with the presence of intracellular monosodium (normal range, 3.5–8.5 mg/dL). urate crystals.

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MANAGEMENT OF ACUTE GOUT use of probenecid include chronic kidney disease, low-dose The finding of intracellular monosodium urate crystals in aspirin use, and age of Ͼ60 years. synovial fluid is diagnostic of gout. Treatment options for A new option for urate-lowering therapy that may become acute gout include colchicine, nonsteroidal anti-inflammatory available is febuxostat, a nonpurine inhibitor of xanthine drugs (NSAIDs), and corticosteroids. Colchicine, a plant de- oxidase that is currently awaiting Food and Drug Adminis- rivative, inhibits leukocyte activation and migration and is tration approval.14 Although it is likely to be more expensive most effective when given in the first 24 to 48 hours of the than currently available agents, febuxostat may be useful for attack. NSAIDs are also effective, but full anti-inflammatory patients for whom probenecid is contraindicated or those who doses are required. Corticosteroids may be given as an intra- cannot tolerate allopurinol because of hypersensitivity. articular injection in the case of monoarthritis or systemically in the case of oligoarticular or polyarticular disease. Starting

CONCLUSIONS Downloaded from https://academic.oup.com/milmed/article/173/10/1044/4283056 by guest on 23 September 2021 doses of 40 mg of prednisone or equivalent, with tapering Gout is the most common crystal-induced arthritis and is over 7 to 10 days, are commonly recommended when col- caused by the immune response to the presence of uric acid chicine and NSAIDs are ineffective or are contraindicated crystals in the synovial space. Gouty arthritis most commonly because of comorbid medical conditions.10 presents as acute monoarthritis of the lower extremities. Po- Allopurinol is the most commonly used urate-lowering dagra is the term for the classic presentation of gouty arthritis agent, and administration should not be initiated during an of the first metatarsophalangeal joint. Patients often have acute attack. When used mistakenly in the acute setting, recurrent attacks, although these may occur with an asym- allopurinol can lengthen the attack or lead to a recurrence metric distribution. Less common presentations include in- once treatment of the attack is complete. Prophylaxis of gout volvement of more than one joint at onset.1 with colchicine or a NSAID is generally recommended when Although gout most commonly affects middle-aged men allopurinol treatment is initiated, but with doses that are and postmenopausal women, military providers should be lower than those used in the treatment of an acute attack.11 familiar with its diagnosis and management because some Allopurinol should be continued during a gout attack, exposures related to military service may predispose younger however, for patients who are already receiving it as urate- patients to gout. Both dehydration in desert operating envi- lowering therapy. A serum uric acid level of 6 mg/dL is ronments and strenuous exercise can predispose patients to commonly the initial goal of urate-lowering therapy. gout. Alcohol use remains common in active duty popula- Our patient was treated with a course of prednisone (40 tions and, for the reasons discussed above, may be an impor- mg daily, tapered over 14 days), with resolution of his gouty tant contributor to incident gout. arthritis. At a follow-up visit, a patient may state that he has Overseas deployments to areas of high tuberculosis prev- read about gout on the Internet and wants to know if he is a alence are likely to be associated with increased rates of latent candidate for urate-lowering therapy. and active tuberculosis infections. This will necessitate in- creased exposure to antituberculosis medications, with a re- sultant (although probably small) increase in gout in patients INDICATIONS FOR URATE-LOWERING THERAPY treated with multidrug regimens containing ethambutol Urate-lowering therapy consists of treatment with allopuri- and/or pyrazinamide. nol, a xanthine oxidase inhibitor, or probenecid, a uricosuric Furthermore, recent reports suggest that the substantial agent, for the purpose of reducing the number of gouty disease burden of gout may be increasing,3,7 partly because of attacks and/or reducing end-organ damage related to gout. the increase in obesity and the metabolic syndrome. The Although hyperuricemia is a risk factor for the development prompt recognition and appropriate treatment of gout should of gout, most patients with asymptomatic hyperuricemia do decrease disability in the acute and long-term settings, im- not develop gout and therefore should not be treated. Recur- proving the readiness of the individual service member. rent gout attacks are an indication for urate-lowering therapy. As in the present case, gout may occur in young, active Patients should be offered urate-lowering therapy if they have duty patients. A family history of gout may be present in two or more attacks per year. Reports have shown that reduction these patients. In the absence of family history, military of serum uric acid levels to Յ6 mg/dL reduces the frequency providers should consider gout in the differential diagnosis of of, and in many cases prevents, further gout attacks.12,13 acute oligoarthritis, especially when factors that contribute to Patients with tophaceous gout or evidence of erosive arthritis hyperuricemia, such as dehydration, alcohol consumption, on radiographs should be treated with allopurinol. and use of certain prescription drugs, are present. The dose of allopurinol must be reduced for patients with chronic kidney disease and those taking azathioprine or REFERENCES 6-mercaptopurine, because both of those drugs are metabo- 1. Rott KT, Agudelo CA: Gout. JAMA 2003; 289: 2857–60. lized by xanthine oxidase. Probenecid is contraindicated for 2. Enomoto A, Kimura H, Chairoungdua A, et al: Molecular identification patients with a history of uric acid nephrolithiasis, because it of a renal urate anion exchanger that regulates blood urate levels. Nature increases urine uric acid levels. Other contraindications to the 2002; 417: 447–52.

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