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Crystalline Arthropathies

Thomas Horton



  • 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
  • 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 (ex: thiazides)


  • Synovial Fluid Analysis: 

    • Cell count and differential: WBC 20,000-100,000, > 50% neutrophils

    • Order gram stain/culture (It is possible to have septic arthritis and gout)

    • Examination for crystals under polarizing light microscopy: (order “Synovial Fluid Eval” so the lab knows to look for crystals)

      • Monosodium urate crystals: needle-shaped and negatively birefringent and appear yellow when parallel to the polarizer
  • 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: gout crystal aggregates appear green. Not routinely necessary; Do not order without rheumatology consult



  • 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 (IL-1 receptor antagonist): 100mg once daily for three days (or QOD for CrCl \<30). Requires rheumatology consult. For patients with contraindications to all other treatments


  • Urate Lowering Therapy (ULT)

    • Indications: Strong: >2 attacks/year, one or more subcutaneous tophi, radiologic changes. Conditional: CKD 3 or worse, urolithiasis, serum urate >9

    • Goal serum urate: \<6.0 mg/dL, or \<5.0 mg/dL in patients 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 patients 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

  • Consider Rheumatology consult for patients 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

  • Eliminating uric acid from the diet only reduces uric acid by ~1 mg/dL. Urate lowering therapy will be needed in most patients even if diet changed

  • VA specific guidance:

    • Colchicine is non-formulary but is easily approved

    • For steroid intra-articular injections triamcinolone is the formulary option

Pseudogout- Calcium pyrophosphate dihydrate crystal deposition disease (CPPD)


  • Red, hot, swollen joint usually in the wrists, knees, or MCP joints

  • Cannot distinguish from gout based on clinical features alone. Like gout, diagnosis is based on exam and arthrocentesis

  • More prevalent in the elderly populations


  • Synovial Fluid:

    • Cell count and differential: WBC 20,000 to 100,000, >50% neutrophils

    • Order gram stain/culture (It is possible to have septic arthritis and CPPD)

    • Examination for crystals under polarizing light microscopy

      • CPPD crystals: rhomboid-shaped, weakly positively birefringent and appear blue when parallel to the polarizer
  • Imaging: 

    • XR: chondrocalcinosis (thin calcified line present in fibrocartilage) in the joint space (easiest to see in knee and wrists)


  • Typically follows the same treatment used for acute gout attacks (see above, little evidence)

  • Some patients may develop Chronic CPP Crystal Inflammatory Arthritis.

    • Resembles RA in presentation

    • Treatment base on symptoms and 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 patient.

Last update: 2022-06-27 03:22:52