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CRYSTAL ARTHRITIS. Mark Jarek MD,FACP,FACR. CRYSTAL ARTHRITIS. GOUT (monosodium urate) PSEUDOGOUT (calcium pyrophosphate) HYDROXYAPATITE. GOUT . Inflammatory arthritis mediated by the crystallization of uric acid within joints, tophi Often associated with hyperuricemia

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crystal arthritis

CRYSTAL ARTHRITIS

Mark Jarek MD,FACP,FACR

crystal arthritis1
CRYSTAL ARTHRITIS
  • GOUT (monosodium urate)
  • PSEUDOGOUT (calcium pyrophosphate)
  • HYDROXYAPATITE
slide3
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
meds increased urate pool
MEDS- Increased Urate Pool
  • DIURETICS (RR 1.77, CI 1.4-2.2)
  • Low Dose salicylates
  • B-blockers
  • PZA, ethambutol
  • Cyclosporin, tacrolimus
  • Insulin
meds decreased urate pool
MEDS- Decreased Urate Pool
  • High dose Salicylate
  • Losartan
  • Fenofibrate
  • Amlodipine
  • Vitamin C
  • Probenecid, sulfinpyrazone, benzbromarone
  • Allopurinol, uricase, febuxostat
hyperuricemia preclinical period
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
slide7
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
slide8
GOUT
  • ACUTE GOUT
    • First attack 4th-6th decade for men
    • Women almost always postmenopausal
    • Classically monoarticular LE– podagra (50%), (vs pseudopodogra) >ankle >gonagra >upper extremity.
    • Proximal joint, central arthropathy uncommon
diagnosis
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 Gram’s stain, culture
    • Serum uric acid levels neither confirm nor exclude gout
    • Radiographs not necessary
    • Risk factor assessment
acute gout
ACUTE GOUT
  • THERAPY (for all crystal diseases):
    • Corticosteroids: intrarticular > 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
intercritical period
Intercritical Period
  • 70% prevelance of MSU crystals remain in the joint
  • Lasts months to years for 75-80%, 20% never have another attack
uric acid lowering therapy
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
uricosurics
URICOSURICS
  • Uricosurics
      • probenecid 1-3 grams / day
      • sulfinpyrazone 200-400 mg / day
      • Benzbromarone 100-200 mg / day (not available)
uricosurics1
URICOSURICS
  • Contraindications
    • Tophi
    • CRI (GFR >35ml/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
uricostatic drugs
Uricostatic Drugs
  • Allopurinol - developed 1957
    • Reduce annual gout attacks 4.4 to .06 / yr
    • Gradual resolution of tophi w/ uric acid < 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
uricostatics
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
chronic gout
CHRONIC GOUT
  • USUALLY PRESENT AFTER 10 YEARS OF ACUTE INTERMITTANT GOUT
  • TOPHI DEPOSITION
  • CHRONIC SWOLLEN JOINTS
  • JOINT DESTRUCTION
  • ABSOLUTELY REQUIRES ALLOPURINOL
cppd presentations
CPPD Presentations
  • Acute Pseudogout
    • Positive birefringent rod shaped crystals
    • More likely in OA joint – knee> wrist> MCPs> hips,shoulders,ankles
  • Pseudo-rheumatoid pattern
  • Osteoarthritis with/out pseudogout
  • Chondrocalcinosis
  • Neuropathic joint
  • Tumoral CPPD deposition
cppd presentations1
CPPD Presentations
  • Acute Pseudogout
    • Positive birefringent rod shaped crystals
    • More likely in OA joint – knee> wrist> MCPs> hips,shoulders,ankles
  • Pseudo-rheumatoid pattern
  • Osteoarthritis with/out pseudogout
  • Chondrocalcinosis
  • Neuropathic joint
  • Tumoral CPPD deposition
cppd presentations2
CPPD Presentations
  • Acute Pseudogout
    • Positive birefringent rod shaped crystals
    • More likely in OA joint – knee> wrist> MCPs> hips,shoulders,ankles
  • Pseudo-rheumatoid pattern
  • Osteoarthritis with/out pseudogout
  • Chondrocalcinosis
  • Neuropathic joint
  • Tumoral CPPD deposition
pseudogout
PSEUDOGOUT
  • HYPERPARATHYROIDISM
  • HEMOCHROMATOSIS
  • HYPOTHYROIDISM
  • HYPOMAGNESIEMIA
  • HYPERCALCEMIA
  • HYPOPHOPHATASIA
cppd associations
CPPD Associations
  • Chondrocalcinosis
  • Heriditary (rarely )
basic calcium phosphate bcp dz
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)
bcp long term treatment
BCP Long-Term Treatment
  • ? Role for bisphosphonates
  • ? Role for low dose warfarin