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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
  • 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

  • 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
    • 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 discontinue allopurinol during an acute gout attack
  • 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)
  • 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.
  • Steroids
    • Ideally intra-articular if single joint affected and infection has been ruled out
    • Oral prednisone, dose 0.5mg/kg/day until clinical improvement then taper over 7-14 days
  • Anakinra 100mg QD for three days (or QOD for CrCl <30). Requires rheumatology consult. For pts with contraindications to all other treatments

Chronic

  • Urate Lowering Therapy (ULT)
    • Strong indication: >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
    • 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)
      • Prophylaxis should be continued for at least 6 months until uric acid is at goal and tophi have resolved
    • Allopurinol (xanthine oxidase inhibitor): start low at 100 mg per day (sometimes even 50mg daily in those with advanced CKD) and increase as needed for target uric acid <6 (most pts will need 400-800 mg daily)
      • Adjust dose monthly (3-4 weeks). In kidney dysfunction go slower.
      • Titration of allopurinol ↓ both the risk of acute gout attacks 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
    • Febuxostat: alternative xanthine oxidase inhibitor that is metabolized by the liver for pts at risk for DRESS or SJS related to allopurinol. Black box warning for ↑ cardiovascular risk; more expensive than allopurinol
  • Prophylaxis: typically colchicine 0.6mg QD if normal renal function; NSAIDs may also be used
  • Should be continued for at least 6 months until uric acid is at goal and tophi have resolved to reduce incidence of flares
  • Consider Rheumatology consult for pts with refractory serum urate levels >6.0 on XOI 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 from gout based on clinical features alone (red, hot, swollen joint)
  • Can present as “pseudo OA”: wrists, MCP, glenohumeral joints
  • Can present as “pseudo RA”: chronic inflammatory arthritis of the wrist and MCPs that may be punctuated by flares

Evaluation

  • Synovial fluid analysis: See “Arthrocentesis Quick Look” section for more detail
    • Cell count and differential: WBC 20,000 to 100,000, >50% neutrophils
  • X-ray: chondrocalcinosis (thin calcified line present in fibrocartilage) in the joint space; specifically seen in the meniscus of the knee joint or triangular fibrocartilage just distal to the ulna in the wrist Management
  • Typically follows the same treatment used for acute gout attacks (see above, little evidence)
  • Treatment based on symptoms ranges from NSAIDs (1st line) to colchicine, HCQ, and steroids. Can also use anakinra in acute cases with consult to rheumatology.

Additional Information

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