Crystalline Arthropathies¶

Thomas Horton

Gout¶

Red, hot, swollen joint (classically affects 1^st 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

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 (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

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

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

Evaluation

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 (1^st line) to Colchicine, HCQ, and steroids. Can also use anakinra in acute cases, with consult to rheumatology

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