Crystalline Arthropathies

Thomas Horton

Gout

Presentation

  • Red, hot, swollen joint (classically affects 1st metatarsal phalangeal joint [podagra])
  • May progress to involve ankles, knees, elbows, and small joints of hand if untreated
    • Flares may also become polyarticular over time and include systemic symptoms like fever
    • Tophi (firm, yellow deposits of monosodium urate in soft tissue) may develop over time in olecranon, Achilles tendon, ear helix
  • Gout is diagnosed with combination of clinical presentation and arthrocentesis results
  • Lifestyle factors:
    • Protective: Low fat dairy, hydration, weight loss, smoking cessation
    • Promoting: Meat, seafood, alcohol, high fructose corn syrup, medications that lead to hyperuricemia (e.g. thiazides)

Evaluation

  • Diagnosis: arthrocentesis remains gold standard but typically a clinical diagnosis. If arthrocentesis is unavailable or presentation is atypical, can use 2015 ACR/EULAR classification criteria: ≥1 episode of peripheral joint or bursa swelling, pain, or tenderness + scoring system based on uric acid level, clinical features (e.g. 1st MTP involvement, erythema over joint, tophus), imaging
  • Synovial fluid analysis: See “Arthrocentesis Quick Look” section for more detail
    • Cell count and differential: WBC 20,000-100,000, > 50% neutrophils
    • Examination for crystals under polarizing light microscopy: (order “Synovial Fluid Eval” so the lab knows to look for crystals)
  • Imaging: generally unnecessary but can be helpful (especially if no active flare or polyarticular flares)
    • MSK ultrasound: "Double contour sign" (hyperechoic band = urate crystals deposits)
    • Radiographs: Punched out erosions or lytic areas with overhanging edges
    • Dual energy CT scan: crystal aggregates appear green. Not routinely necessary but may be helpful to identify extraarticular locations. Do not order without rheumatology consult.

Management

Acute

  • Do not hold allopurinol during an acute flare if the patient is already taking chronically
  • 1st line: NSAIDs (if not contraindicated): short course (2-5 days) at full anti-inflammatory dose (ibuprofen 800 mg TID, indomethacin 50 mg TID, naproxen 500 mg BID) with colchicine
  • 1st line: colchicine (avoid if GFR <10 mL/min. Dose reduce by 50% if GFR <50 mL/min)
    • Best if used within the first 36 hours of an attack. Much less effective if started later.
    • Dosing: 1.2 mg then 0.6 mg one hour later, then 0.6 mg daily until clinical improvement
    • Note drug interactions that may require dose adjustment of colchicine: Statins, diltiazem, fluconazole, cyclosporine, tacrolimus, clarithromycin, etc.
  • 2nd line: steroids (use if NSAIDs and colchicine are contraindicated or ineffective)
    • Ideally intra-articular if 1-2 joints affected and infection has been ruled out
    • Oral prednisone 0.5mg/kg/day until clinical improvement, then taper over 7-14 days
  • 3rd line: IL-1 inhibitors (anakinra 100mg QD x3 days or canakinumab) if flare refractory to 1st line treatment or other treatments contraindicated. Requires rheumatology consult.

Chronic

  • Urate Lowering Therapy (ULT)
    • Indications: strong= >2 attacks/year, one or more subcutaneous tophi, radiologic changes. Conditional indication= CKD 3 or worse, urolithiasis, serum urate >9
    • Goal serum urate: <6.0 mg/dL, or <5.0 mg/dL in pts with tophi
    • Prophylaxis: ULT can precipitate an acute gout flare and should always be started with low-dose NSAIDs, colchicine (0.6 mg) or prednisone (5 mg daily or QOD). This should be continued for at least 3 months after reaching urate goal with no tophi or 6 months if tophi present
    • 1st line: allopurinol (xanthine oxidase inhibitor)
      • Start at 100 mg daily (sometimes even 50mg daily in those with advanced CKD) and titrate monthly by 100mg to target uric acid <6 (most pts will need 400-800 mg daily; consider deferring uric acid recheck until at least reaching 300mg). Slow titration decreases risk of flare and DRESS syndrome.
      • Genetic testing (HLA-B*5801) recommended prior to starting for pts of Asian and African descent given ↑ incidence of allopurinol hypersensitivity if + positive allele
      • Allopurinol can be started during a flare if the flare is being treated.
    • 2nd line: febuxostat (alternative xanthine oxidase inhibitor); consider for pts at risk for DRESS or SJS related to allopurinol. Black box warning for ↑ cardiovascular risk; more expensive than allopurinol
    • 3rd line: probenecid (uricosuric); consider in patients failing XOI. Avoid in renal disease or nephrolithiasis
    • 4th line: pegloticase (uricase); for severe, refractory gout with tophi
  • When to refer: consider Rheumatology consult for pts with refractory serum urate levels >6.0 despite 1st or 2nd line ULT

Additional pearls

  • There is a microscope in the rheumatology clinic at VUMC (TVC 2). You can page the rheumatology fellow and they are happy to help you use it
  • Uric acid level is often normal during acute gout flare
  • Shifts in uric acid may be the trigger of the flare: diuresis, dietary changes, hospital stays

Pseudogout – Calcium Pyrophosphate Dihydrate Crystal Deposition Disease (CPPD)

Presentation

  • More prevalent in the elderly populations
  • Cannot distinguish acute episodes from gout based on clinical features alone (red, hot, swollen joint)
  • Can mimic OA with multiple joints affected without inflammatory arthritis (“pseudo OA” ), RA with acute flare of polyarthritis (pseudo RA”), or septic arthritis

Evaluation

  • No formal diagnostic criteria; clinical diagnosis +/- crystals +/- imaging
  • Synovial fluid analysis: See “Arthrocentesis Quick Look” section for more detail
    • Cell count and differential: WBC 20,000 to 100,000, >50% neutrophils
      • + Rhomboid-shaped, positively birefringent.
  • X-ray: chondrocalcinosis (thin calcified line present in fibrocartilage) in the joint space; specifically often seen in the meniscus of the knee joint or triangular fibrocartilage just distal to the ulna

Management

  • Acute: typically mirrors gout flare treatment; ranges from NSAIDs (1st line) to colchicine (2nd line) to steroids (3rd line). Can also use anakinra in acute cases with consult to rheumatology.
  • Chronic: IL-1 inhibition (off-label) can be useful in chronic inflammatory CPPD. For those with frequent flares, consider daily colchicine prophylaxis

Additional Information

  • CPPD can be associated with other disorders: hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatemia, and familial hypocalciuric hypercalcemia, hypothyroidism, Wilson disease
  • Consider further workup for these conditions, especially in a younger pt.
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