Residency · Residency · Internal Medicine

Acute Monoarthritis: Gout, Pseudogout, and Septic Arthritis

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Alright, intern, it’s 3 AM and the pager just went off for a swollen, painful knee. You walk into the room, and there’s a grimacing patient, leg propped up, looking utterly miserable. Your first thought, before anything else, needs to be: could this be infected? Because if it is, we’re talking about an emergency that can permanently damage a joint. This isn't just about pain; it's about preserving function.

So, you take a quick history: fever? Trauma? Any prior joint issues? Then you examine that knee – is it red, hot, exquisitely tender, limited range of motion? All those clues are important, but none of them definitively rule out an infection. That’s where arthrocentesis – sticking a needle in to get some fluid out – becomes your best friend. Don't wait for morning rounds; if there’s any suspicion of septic arthritis, that joint fluid needs to be analyzed now. Send it for cell count with differential, Gram stain, culture, and crystal analysis.

While you're waiting for those crucial results, your job is to make the patient comfortable and prepare for the worst. If you have a high suspicion for infection, start empiric intravenous antibiotics, typically vancomycin and ceftriaxone, right after you’ve tapped the joint. Then, consult orthopedics to discuss drainage options. If the fluid comes back with crystals, whether it’s needle-shaped monosodium urate (gout) or rhomboid-shaped calcium pyrophosphate (pseudogout), you can then tailor your anti-inflammatory treatment with NSAIDs, colchicine, or corticosteroids. But remember, the golden rule: even if you see crystals, always, always send cultures. Infection and crystals can coexist, and you don’t want to miss a joint-destroying infection because you got tunnel vision on the crystals.

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

• 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

1. Neogi T, Jansen TL, Dalbeth N, et al. 2015 Gout classification criteria: an ACR/EULAR collaborative initiative. Arthritis Rheumatol. 2015;67(10):2557-2568.
2. 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.
3. 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.
4. Rosenthal AK, Ryan LM. Calcium pyrophosphate deposition disease. N Engl J Med. 2016;374(26):2575-2584.

For the intern

At 3am, your priorities are to exclude septic arthritis and provide analgesia. Tap any joint when infection is possible—synovial fluid analysis cannot wait until morning. Send cell count, Gram stain, culture, and crystals. Start empiric IV antibiotics (vancomycin plus ceftriaxone or cefepime) immediately after aspiration if concerned for septic arthritis; consult orthopedics for drainage planning. For crystal arthropathy, give NSAIDs, colchicine, or steroids for pain control. The rest—urate-lowering therapy, screening for pseudogout-associated conditions, and HLA-B*5801 testing—can be addressed during daylight rounds. Document range of motion and neurovascular status carefully.

Common pitfalls

• Assuming crystals exclude infection: Gout and septic arthritis coexist in up to 5% of cases. Always send cultures even when crystals are seen. A synovial fluid WBC over 50,000 should raise concern for possible infection regardless of crystal presence.

• Starting allopurinol during an acute flare: This worsens and prolongs the attack. Treat the acute episode first, then initiate urate-lowering therapy weeks later with prophylactic colchicine to prevent flares during the titration phase.

• Using high-dose colchicine: The outdated regimen (1.2 mg then 0.6 mg hourly) causes severe diarrhea without improving efficacy. Use low-dose: 1.2 mg followed by 0.6 mg one hour later only.

• Delaying drainage in septic arthritis: Antibiotics alone are insufficient. Repeated aspiration or surgical washout prevents irreversible cartilage destruction.

Make it stick

You're covering the wards overnight, and the ED calls about an acute monoarthritis. Your mind races: gout, pseudogout, or septic arthritis? You know the answer hinges on synovial fluid analysis. You rush to the ED, tap the joint, and immediately send the fluid for cell count, Gram stain, culture, and crystal analysis. While you wait for results, you start empiric antibiotics for potential septic arthritis because delaying treatment can lead to joint destruction. You provide pain relief and consult orthopedics. By dawn, you've ruled out septic arthritis, diagnosed crystal arthropathy, and the patient is resting comfortably.

If you remember one thing

Always tap an acutely inflamed joint if septic arthritis is in the differential, and immediately start empiric broad-spectrum antibiotics after aspiration if infection is suspected. Crystals and infection can coexist; always send cultures.

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