Residency · Residency · Internal Medicine
Acute Monoarthritis: Gout, Pseudogout, and Septic Arthritis
Introduction
Acute monoarthritis is a common presentation in the emergency department and hospital wards. The internist must distinguish between crystal arthropathies and septic arthritis, as the latter requires urgent treatment to prevent joint destruction. Arthrocentesis is the cornerstone of diagnosis and should be performed whenever septic arthritis is in the differential.
Approach to Acute Monoarthritis
Differential Diagnosis
- Crystal arthropathies: gout (monosodium urate), pseudogout (calcium pyrophosphate deposition)
- Septic arthritis: bacterial infection of the joint space
- Reactive arthritis: post-infectious, typically post-enteric or urogenital infection
- Trauma: fracture, hemarthrosis, meniscal injury
- Inflammatory arthritis flare: rheumatoid arthritis, psoriatic arthritis
- Osteoarthritis exacerbation: mechanical, but can present with effusion
Initial Evaluation
- History: onset, joint involved, prior episodes, trauma, sexual history, immunosuppression
- Examination: range of motion, effusion, warmth, erythema, assess for polyarticular involvement
- Arthrocentesis is mandatory if septic arthritis cannot be excluded clinically
- Synovial fluid analysis: cell count with differential, Gram stain, culture, crystal analysis
Synovial Fluid Interpretation
| Parameter | Non-inflammatory | Inflammatory | Septic |
|---|---|---|---|
| WBC count | < 2,000 | 2,000-50,000 | > 50,000 |
| PMN % | < 25% | > 50% | > 75% |
| Appearance | Clear, yellow | Cloudy | Purulent |
| Crystals | Absent | May be present | Usually absent |
- Gout and septic arthritis can coexist; always send cultures even if crystals are identified
- Cell counts between 50,000-100,000 may represent either severe crystal arthritis or infection
Gout
Pathophysiology and Clinical Features
- Deposition of monosodium urate (MSU) crystals in joints and soft tissues
- First MTP joint (podagra) is the classic location; also affects ankles, knees, wrists
- Negatively birefringent, needle-shaped crystals on polarized light microscopy
- Risk factors: hyperuricemia, male sex, obesity, diuretic use, chronic kidney disease, alcohol
Acute Gout Management
- NSAIDs (indomethacin, naproxen): first-line if no contraindications
- Colchicine: most effective if started within 12-24 hours of onset; low-dose regimen (1.2 mg then 0.6 mg one hour later)
- Corticosteroids: oral, intra-articular, or IV; preferred in CKD or when NSAIDs contraindicated
- IL-1 inhibitors (anakinra): for refractory flares or when other agents contraindicated
- Do not start or change urate-lowering therapy during an acute flare
Chronic Gout Management
- Urate-lowering therapy (ULT) indicated for recurrent flares (>=2/year), tophi, or urate arthropathy
- Allopurinol: start low (100 mg, 50 mg in CKD), titrate to serum urate target < 6 mg/dL
- Febuxostat: alternative for allopurinol intolerance; monitor cardiovascular risk
- Prophylaxis during ULT initiation: low-dose colchicine 0.6 mg daily for 3-6 months
- Check **HLA-B5801* in Southeast Asian and African American patients before starting allopurinol (risk of DRESS/SJS)
Pseudogout (Calcium Pyrophosphate Deposition Disease)
Clinical Features
- Acute attacks mimic gout; knee is the most commonly affected joint
- Positively birefringent, rhomboid-shaped crystals on polarized microscopy
- X-ray may show chondrocalcinosis (calcification of cartilage), especially in the knee, wrist, and symphysis pubis
- Associated conditions: hyperparathyroidism, hemochromatosis, hypomagnesemia, hypothyroidism
Management
- Acute: NSAIDs, colchicine, or corticosteroids (same approach as gout)
- No equivalent of urate-lowering therapy; no disease-modifying treatment available
- Screen for metabolic associations in younger patients or polyarticular disease
Septic Arthritis
Clinical Features and Risk Factors
- Acute onset of joint pain, swelling, warmth, and severely restricted range of motion
- Fever is present in only ~50-60% of cases; absence does not exclude the diagnosis
- Risk factors: prior joint disease, prosthetic joint, immunosuppression, skin breakdown, bacteremia
- Staphylococcus aureus is the most common organism; Neisseria gonorrhoeae in sexually active young adults
Diagnosis
- Synovial fluid WBC typically > 50,000 with > 75% PMNs
- Gram stain is positive in only 50-75% of non-gonococcal cases
- Blood cultures positive in ~50% of cases
- Gonococcal arthritis: often culture-negative from synovial fluid; send NAAT from urogenital, pharyngeal, and rectal sites
Management
- Empiric IV antibiotics immediately after arthrocentesis: vancomycin (MRSA coverage) +/- ceftriaxone (gram-negative/gonococcal coverage)
- Narrow based on culture results
- Repeated arthrocentesis or surgical drainage for adequate source control
- Orthopedic surgery consultation for prosthetic joint infections and joints not responding to aspiration
- Duration: typically 2-4 weeks of antibiotics; longer for prosthetic joints
Key Clinical Pearls
- When in doubt, tap the joint; synovial fluid analysis is the definitive diagnostic test
- Crystals and infection can coexist; always send cultures regardless of crystal findings
- Low-dose colchicine is as effective and better tolerated than high-dose regimens for acute gout
- Check HLA-B*5801 before starting allopurinol in high-risk populations
- Septic arthritis is a surgical emergency; do not delay drainage and antibiotics
References
- Neogi T, Jansen TL, Dalbeth N, et al. 2015 Gout classification criteria: an ACR/EULAR collaborative initiative. Arthritis Rheumatol. 2015;67(10):2557-2568.
- FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for management of gout. Arthritis Care Res. 2020;72(6):744-760.
- Long B, Koyfman A, Gottlieb M. Evaluation and management of septic arthritis and its mimics in the emergency department. West J Emerg Med. 2019;20(2):331-341.
- Rosenthal AK, Ryan LM. Calcium pyrophosphate deposition disease. N Engl J Med. 2016;374(26):2575-2584.