CRYSTAL ARTHRITIS

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CRYSTAL ARTHRITIS

• Mark Jarek MD,FACP,FACR

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CRYSTAL ARTHRITIS

• GOUT (monosodium urate)
• PSEUDOGOUT (calcium pyrophosphate)
• HYDROXYAPATITE

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GOUT

• Inflammatory arthritis mediated by the
  crystallization of uric acid within joints, tophi
• Often associated with hyperuricemia
• Prevalence in US 2.7 (6 million)
• Incidence 62.3 /100,000 (2-fold increase)
• Associations DM, HTN, metabolic syndrome,
  obesity, CVD, renal stones, CPPD
• Risk Factors genetics, age, CRF, serum uric
  acid, diet, alcohol, medications

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MEDS- Increased Urate Pool

• DIURETICS (RR 1.77, CI 1.4-2.2)
• Low Dose salicylates
• B-blockers
• PZA, ethambutol
• Cyclosporin, tacrolimus
• Insulin

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MEDS- Decreased Urate Pool

• High dose Salicylate
• Losartan
• Fenofibrate
• Amlodipine
• Vitamin C
• Probenecid, sulfinpyrazone, benzbromarone
• Allopurinol, uricase, febuxostat

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Hyperuricemia Preclinical Period

• 6.8mg/dl based on urate supersaturation
• 5-8 - most asymptomatic 20 get gout
• Onset males age 30, females postmenopausal
• Duration 10-15 yrs before gout
• 80 due to undersecretion, 20 due to
  overproduction
• Determined by 24 hr urine collection

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GOUT

• Urate precipitation leads to acute gouty
  arthritis
• Local factors temperature, pH, trauma, joint
  hydration
• Systemic factors hydration state, fevers, meds,
  alcohol, co-morbid conditions
• Attack resolves spontaneously 10-15 days

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GOUT

• ACUTE GOUT
• First attack 4th-6th decade for men
• Women almost always postmenopausal
• Classically monoarticular LE podagra (50), (vs
  pseudopodogra) gtankle gtgonagra gtupper extremity.
  
• Proximal joint, central arthropathy uncommon

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Diagnosis

• Evidence-based medicine based on EULAR (ESCISIT)
  10 key points
• Acute attack 6-12 peak intensity with S/W/E/T
• Aspiration always recommended if possible
• Prompt polarized microscopic analysis performed
• Definitive Dx requires crystal confirmation
• Gout and Sepsis can coexist fluid should be
  sent Grams stain, culture
• Serum uric acid levels neither confirm nor
  exclude gout
• Radiographs not necessary
• Risk factor assessment

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ACUTE GOUT

• THERAPY (for all crystal diseases)
• Corticosteroids intrarticular gt systemic
• NSAIDs fast acting full dose if no
  contraindications
• Colchicine (PO,IV route dangerous)
• narrow therapeutic window
• Bone marrow suppression, myopathy, neuropathy
• purgative effects Pt often run before they
  walk
• ACTH
• NEVER ALLOPURINOL

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Intercritical Period

• 70 prevelance of MSU crystals remain in the
  joint
• Lasts months to years for 75-80, 20 never have
  another attack

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Uric Acid Lowering Therapy

• Lifestyle, dietary modification
• Diet high in vegetables, dairy, water beneficial
• Initiate uric acid lowering therapy after 1(?)
  or 2 episodes of acute gouty arthritis
• Always prophylaxis for first 6 months with low
  dose steroids, NSAIDs, or colchicine

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URICOSURICS

• Uricosurics
• probenecid 1-3 grams / day
• sulfinpyrazone 200-400 mg / day
• Benzbromarone 100-200 mg / day (not available)

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URICOSURICS

• Contraindications
• Tophi
• CRI (GFR gt35ml/min)
• H/O urolithiasis
• Intolerance
• Rapid cell turnover states
• 25 failure rate mild CRI
• Interact with ASA, NSAIDs, PCN, captopril
• Watch for rash , GI,HA, dyscrasias,nephrosis

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Uricostatic Drugs

• Allopurinol - developed 1957
• Reduce annual gout attacks 4.4 to .06 / yr
• Gradual resolution of tophi w/ uric acid lt 6
• Titrate dose up to 600 mg /day
• Uncreased toxicity with CRI
• Allopurinol hypersensitivity rxn rare but can be
  fatal
• Densensitization can be useful for mild SEs
• Oxypurinol is an option but 50 intolerance
• Multiple interactions imuran, 6MP, warfarin,
  theophylline, ampiciliin, diuretics
• Treatment is lifelong

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URICOSTATICS

• FEBUXOSTAT
• Not yet FDA approved
• ?? Hepatic toxicity, HA, diarrhea
• 80-120 day safer, more effective
• No dose reduction for renal, hepatic
  insufficiency
• Combination uricourics and uricostatics offer
  additional benefit
• URICASE converts uric acid to allantoin
• Recombinant uric acid oxidase RASURICASE
• parenteral route can be given only once due to
  antibody production
• Black box warning anaphylaxis, hemolysis,
  methemoglobinemia
• Pegylated preparation approved for urate
  nephropathy in tumor lysis syndrome.
• Expensive
• Sq administration
• Fenofibrate, Lozartan
• E3040 new class of antiinflammatory compounds
• Y-700, scopoletin

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CHRONIC GOUT

• USUALLY PRESENT AFTER 10 YEARS OF ACUTE
  INTERMITTANT GOUT
• TOPHI DEPOSITION
• CHRONIC SWOLLEN JOINTS
• JOINT DESTRUCTION
• ABSOLUTELY REQUIRES ALLOPURINOL

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CHRONIC GOUT
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CPPD DISEASE
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CPPD Presentations

• Acute Pseudogout
• Positive birefringent rod shaped crystals
• More likely in OA joint kneegt wristgt MCPsgt
  hips,shoulders,ankles
• Pseudo-rheumatoid pattern
• Osteoarthritis with/out pseudogout
• Chondrocalcinosis
• Neuropathic joint
• Tumoral CPPD deposition

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CPPD Presentations

• Acute Pseudogout
• Positive birefringent rod shaped crystals
• More likely in OA joint kneegt wristgt MCPsgt
  hips,shoulders,ankles
• Pseudo-rheumatoid pattern
• Osteoarthritis with/out pseudogout
• Chondrocalcinosis
• Neuropathic joint
• Tumoral CPPD deposition

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CPPD Presentations

• Acute Pseudogout
• Positive birefringent rod shaped crystals
• More likely in OA joint kneegt wristgt MCPsgt
  hips,shoulders,ankles
• Pseudo-rheumatoid pattern
• Osteoarthritis with/out pseudogout
• Chondrocalcinosis
• Neuropathic joint
• Tumoral CPPD deposition

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PSEUDOGOUT

• HYPERPARATHYROIDISM
• HEMOCHROMATOSIS
• HYPOTHYROIDISM
• HYPOMAGNESIEMIA
• HYPERCALCEMIA
• HYPOPHOPHATASIA

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CPPD Associations

• Chondrocalcinosis
• Heriditary (rarely )

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Basic Calcium Phosphate BCP Dz

• Usually in the form of hydroxyapatite
• Age related arthropathy except for pseudopodagra
  in young women
• Milwaukee Shoulder
• Calcific Periarthritis
• Soft tissue calcification
• Osteoarthritis (found in 70 of OA synovial fluid)

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BCP Long-Term Treatment

• ? Role for bisphosphonates
• ? Role for low dose warfarin