CRYSTAL ARTHRITIS

1. CRYSTAL ARTHRITIS Mark Jarek MD,FACP,FACR

2. CRYSTAL ARTHRITIS • GOUT (monosodium urate) • PSEUDOGOUT (calcium pyrophosphate) • HYDROXYAPATITE

3. 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

4. MEDS- Increased Urate Pool • DIURETICS (RR 1.77, CI 1.4-2.2) • Low Dose salicylates • B-blockers • PZA, ethambutol • Cyclosporin, tacrolimus • Insulin

5. MEDS- Decreased Urate Pool • High dose Salicylate • Losartan • Fenofibrate • Amlodipine • Vitamin C • Probenecid, sulfinpyrazone, benzbromarone • Allopurinol, uricase, febuxostat

6. 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

7. 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

8. 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

9. 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

10. 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

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

12. 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

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

14. 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

15. 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

16. 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

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

18. CHRONIC GOUT

19. CPPD DISEASE

20. 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

21. 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

22. 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

23. PSEUDOGOUT • HYPERPARATHYROIDISM • HEMOCHROMATOSIS • HYPOTHYROIDISM • HYPOMAGNESIEMIA • HYPERCALCEMIA • HYPOPHOPHATASIA

24. CPPD Associations • Chondrocalcinosis • Heriditary (rarely )

25. 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)

26. BCP Long-Term Treatment • ? Role for bisphosphonates • ? Role for low dose warfarin