# 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

![Algorithm for the diagnostic approach to acute monoarthritis with synovial fluid analysis](/images/residency/monoarthritis-algorithm.jpg)

## 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-B*5801** 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

![Polarized light microscopy showing negatively birefringent urate crystals and positively birefringent CPPD crystals](/images/residency/crystal-microscopy.jpg)

## 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

![Approach to management of suspected septic arthritis including drainage and antibiotic selection](/images/residency/septic-arthritis-management.jpg)

## 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.