The following cases and commentary, which focus on gout and similar conditions, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Treating acute knee pain
A 52-year-old man is evaluated in the emergency department for a 2-day history of acute pain and swelling in the left knee. He lives in Memphis, works in an office, and does not participate in outdoor recreational activities. There is no history of skin rash or trauma. He has type 2 diabetes mellitus. Medications are insulin glargine and insulin lispro.
On physical examination, temperature is 38.0°C (100.4°F), blood pressure is 144/88 mm Hg, pulse rate is 88/min, and respiration rate is 18/min. The left knee is swollen and warm, has overlying erythema, and is tender to palpation. Range of motion of the left knee elicits pain and is limited. The remainder of the musculoskeletal examination is normal.
Laboratory studies reveal hemoglobin 10 g/dL (100 g/L) (normal indices), leukocyte count 11,300/µL (11.3 × 109/L) (76% neutrophils), erythrocyte sedimentation rate 78 mm/h, uric acid 8.2 mg/dL (0.48 mmol/L) and serum creatinine 2.0 mg/dL (152.6 µmol/L).
Which of the following is the most appropriate next step in this patient's management?
B. Prednisone and allopurinol
C. Radiography of the left knee
D. Serologic testing for Lyme disease
Case 2: Severe pain and swelling
A 78-year-old man with a 15-year history of osteoarthritis is evaluated for severe pain and swelling of the left knee of 4 days' duration. He also has hypertension, type 2 diabetes mellitus, and chronic kidney disease. Medications are glyburide, lisinopril, and low-dose aspirin.
On physical examination, vital signs are normal. He is unable to bear weight on the left leg because of pain. The left knee is swollen and warm, and range of motion of this joint is limited and elicits pain. There are no tophi.
Laboratory studies reveal leukocyte count 15,600/µL (15.6 × 109/L) (90% polymorphonuclear cells, 10% lymphocytes), glucose (random) 210 mg/dL (11.7 mmol/L), serum creatinine 2.2 mg/dL (167.9 µmol/L), serum uric acid 10.7 mg/dL (0.63 mmol/L) and normal urinalysis.
Arthrocentesis of the left knee is performed. Synovial fluid leukocyte count is 24,000/µL (90% polymorphonuclear cells, 10% lymphocytes). Polarized light microscopy reveals intra- and extracellular monosodium urate crystals. Gram stain is negative.
Which of the following is the most appropriate treatment for this patient?
D. Intra-articular methylprednisolone
Case 3: Knee pain with fever
A 53-year-old man is evaluated in the emergency department for a 2-day history of acute swelling and pain in the right knee. He also has had fever up to 38.3°C (101.0°F). Three weeks ago, he was evaluated in the emergency department for cellulitis. Medical history is significant for chronic tophaceous gout and hypertension. Medications are allopurinol, atenolol, and enalapril. He has a monogamous sexual relationship with his wife of 30 years.
On physical examination, temperature is 38.1°C (100.5°F), blood pressure is 124/50 mm Hg, and pulse rate is 88/min. Cardiopulmonary examination is normal. Tophi are present on both elbows. The right fourth proximal interphalangeal joint and left third metacarpophalangeal joint have soft-tissue swelling but no warmth or erythema. The right knee is markedly swollen and has overlying warmth and erythema. Palpation of this joint elicits pain.
Laboratory studies reveal a leukocyte count of 15,000/µL (15 × 109/L).
Arthrocentesis is performed. The synovial fluid leukocyte count is 110,000/µL (95% neutrophils). Polarized light microscopy of the fluid reveals negatively birefringent monosodium urate crystals. Gram stain of the aspirated fluid is negative. Culture results are pending.
Which of the following is the most appropriate treatment for this patient?
B. Intra-articular corticosteroids
Case 4: Hip prosthesis with pain
A 67-year-old man is evaluated in the emergency department for a 2-week history of pain involving the left hip. He has had no fever. Four years ago, he underwent total arthroplasty of the left hip joint to treat osteoarthritis. One month ago, he underwent tooth extraction for an abscessed tooth.
On physical examination, temperature is 36.6°C (98.0°F), blood pressure is normal, and pulse rate is 90/min. Cardiopulmonary examination is normal. A well-healed surgical scar is present over the left hip, and there is no warmth or tenderness. External rotation of the left hip joint is markedly painful.
Laboratory studies reveal an erythrocyte sedimentation rate of 88 mm/h.
Radiograph of the left hip shows a normally seated left hip prosthesis. Fluoroscopic-guided arthrocentesis is performed. The synovial fluid leukocyte count is 38,000/µL (90% neutrophils). Polarized light microscopy of the fluid shows no crystals, and Gram stain is negative. Culture results are pending.
Which of the following is the most likely diagnosis?
A. Aseptic loosening
C. Pigmented villonodular synovitis
D. Prosthetic joint infection
Answers and commentary
Correct answer: A. Arthrocentesis.
Acute monoarticular arthritis should be presumed to be infectious until proven otherwise by synovial fluid analysis and culture via arthrocentesis; the presence of a synovial fluid leukocyte count higher than 50,000/µL would strongly suggest an infectious process. The most appropriate next step in this patient's management is therefore arthrocentesis of the left knee. Because infectious arthritis is associated with significant morbidity and mortality, patients whose clinical presentation is suspicious for this condition should be treated immediately with empiric antibiotic therapy until culture results are available.
This patient's diabetes mellitus places him at increased risk for infectious arthritis, and the presence of fever as well as erythema and swelling of the involved joint further raises suspicion for this condition.
The differential diagnosis of acute monoarticular arthritis includes gouty arthritis, fracture, and Lyme disease. Allopurinol therapy would not be indicated for a first attack of gout or during an acute flare of gout. Also, crystal-induced arthritis and infectious arthritis may coexist, and infection must be excluded via synovial fluid analysis before beginning therapy for gout.
In patients with long-standing gout, joint radiographs may reveal accumulated effects of inflammation, such as joint-space narrowing and destruction of the joint surface. Although highly suggestive of gout, radiographic abnormalities are not diagnostic of this condition and are usually absent in a first attack of acute gouty arthritis. Patients with acute calcium pyrophosphate deposition disease may have no radiographic abnormalities, and, conversely, chondrocalcinosis may be present in asymptomatic patients. In infectious arthritis, changes seen on joint radiographs may include bone damage but are relatively late findings. Early in the course of septic arthritis, soft-tissue fullness and joint effusions are often the only initial radiographic findings.
Serologic testing for Lyme disease would not be the most appropriate next step in the management of a patient who does not have definite risk of exposure for this condition, such as living in an endemic area. Furthermore, arthritis typically is a late manifestation of Lyme disease and manifests subacutely. In patients with Lyme arthritis, swelling is usually more prominent than pain and significant erythema is rare.
- Acute monoarticular arthritis should be presumed to be infectious until proven otherwise by synovial fluid analysis and culture via arthrocentesis.
Correct answer: D. Intra-articular methylprednisolone.
This patient has gout, which manifests as acute, intermittent attacks of severe pain, redness, and swelling of a joint accompanied by intracellular urate crystals seen on polarized light microscopy of the synovial fluid. The most appropriate treatment for this patient is an intra-articular corticosteroid injection. Early attacks of gout are typically monoarticular and usually involve a joint in the lower extremities, particularly the first metatarsophalangeal joint. Affected joints may be exquisitely tender to the touch and have a painful range of motion. Gout also is associated with an inflammatory synovial fluid leukocyte count during an acute attack and an elevated serum uric acid level, although many patients with hyperuricemia do not develop gout.
Intra-articular corticosteroid injection has been shown to rapidly treat acute gout. This therapy is particularly useful in patients in whom NSAIDs or oral or parenteral corticosteroids are contraindicated. Furthermore, local injection therapy with a corticosteroid only minimally affects glycemic control. However, infectious arthritis must be excluded before this treatment is administered.
Allopurinol would help to decrease this patient's uric acid level. However, use of uric acid-lowering agents during an acute attack does not ameliorate the attack of gout and may prolong an attack or cause a more frequent attack rate. Furthermore, allopurinol may cause a rare but serious hypersensitivity syndrome in patients who have renal insufficiency. Therefore, this agent should be used with caution starting at a low dose in this population group.
Effective treatment of acute attacks of gout involves high-dose therapy with NSAIDs, corticosteroids, or colchicine. Immediately initiating NSAID treatment at anti-inflammatory doses is most likely more important than the specific agent used. However, NSAIDs are contraindicated in this patient because of his chronic kidney disease.
Colchicine is most effective for the treatment of acute gout when used within the first 24 hours of symptom onset but would be less efficacious in this patient, whose symptoms began 4 days ago. Corticosteroids may be given orally, intramuscularly, or by intra-articular injection. These agents have similar efficacy to NSAIDs, but a high-dose oral or parenteral corticosteroid may exacerbate this patient's diabetes mellitus and is relatively contraindicated.
- Intra-articular injections of corticosteroids have been shown to be effective in the treatment of acute gout attacks and are useful in patients who cannot take NSAIDs or oral and parenteral corticosteroids.
Correct answer: D. Vancomycin.
This patient may have septic arthritis and should begin treatment with intravenous vancomycin. He has a history of chronic tophaceous gout but also has a history of cellulitis and the new onset of acute monoarthritis of the knee, fever, peripheral leukocytosis, and a markedly elevated synovial fluid leukocyte count. This constellation of symptoms is consistent with an acute flare of gout but also raises strong suspicion for septic arthritis. A diagnosis of septic arthritis should be considered in any patient who presents with the sudden onset of monoarthritis or the acute worsening of chronic joint disease. In patients with gout or pseudogout, the presence of crystals on polarized microscopic analysis of the synovial fluid does not exclude a concomitant infection. Therefore, until culture results are available, empiric antibiotic treatment is indicated for this patient.
Infection with gram-positive pathogens such as staphylococci or streptococci is the most common cause of septic arthritis in older patients. Thus, vancomycin, which has broad gram-positive coverage, is the empiric therapy of choice in patients with suspected septic arthritis whose Gram stain reveals gram-positive organisms. Further, many experts recommend empiric antibiotic therapy with vancomycin for immunocompetent patients with suspected septic arthritis and a negative Gram stain, while vancomycin and a third-generation cephalosporin such as ceftriaxone are recommended for patients who are immunocompromised or have trauma-associated infection. Also, experts suggest careful joint management with repeated arthrocenteses or drainage until the inflammatory component is resolved. If disseminated gonococcal infection is in the differential diagnosis, ceftriaxone may be added to vancomycin.
Gram-negative organisms account for 9% to 20% of cases of septic arthritis, and certain pathogens occur more frequently in specific patient groups. For example, Salmonella infection has been reported in patients with systemic lupus erythematosus, AIDS, or sickle cell anemia, whereas patients who use illicit injection drugs often have infection with Pseudomonas aeruginosa. Comorbid medical conditions, a history of antibiotic use, and extra-articular infections (particularly urinary tract infections and decubitus ulcers) predispose patients to gram-negative septic arthritis.
Neither prednisone nor intra-articular corticosteroids are effective for treating infections.
- Pending culture results, empiric vancomycin is recommended for patients with suspected septic arthritis whose synovial fluid Gram stain reveals gram-positive organisms and for immunocompetent patients with a negative synovial fluid Gram stain.
Correct answer: D. Prosthetic joint infection.
This patient most likely has prosthetic joint infection, which may occur at any time in the postoperative period. Prosthetic joint infections that occur after the first postoperative year are most frequently caused by hematogenous spread of organisms to the prosthetic joint. The source of infection in this setting is often obvious and includes skin or genitourinary tract infection or, as in this patient, an abscessed tooth. Pain is the predominant or only symptom in patients with prosthetic joint infection, and fever and leukocytosis are frequently absent. Patients with prosthetic joint infection usually have an elevated erythrocyte sedimentation rate. Radiography may reveal prosthetic loosening, but hardware loosening may occur in patients without infection, as well.
The gold standard for diagnosing prosthetic joint infection is arthrocentesis or intraoperative tissue sampling with culture before antibiotic therapy is initiated. The synovial fluid leukocyte count in patients with prosthetic joint infection is usually lower compared with that in patients with other forms of septic arthritis.
Aseptic loosening refers to loss of fixation of the arthroplasty components, which is a major long-term complication of hip arthroplasty. The most striking manifestation of this condition is pain in the proximal and medial aspect of the thigh that is worse with weight bearing. Osteolysis is typically seen on radiographs of affected patients, which this patient does not have. Aseptic loosening also would not explain this patient's inflammatory synovial fluid.
This patient's elevated synovial fluid leukocyte count with a predominance of neutrophils is suggestive of gout, but this condition does not have a subacute onset and does not commonly affect the hips. An acute attack of gout also would be associated with crystals visible on polarized light microscopy of the synovial fluid.
Pigmented villonodular synovitis is a rare proliferative synovitis that most commonly involves the hip or knee. Radiographs in patients with this condition may reveal bone erosions or may be normal. Pigmented villonodular synovitis typically develops in young patients and is not associated with prosthetic joint placement.
- In patients with prosthetic joint infection, pain is the predominant or only symptom, and fever and leukocytosis are frequently absent.