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Crystal-induced arthritis & Osteoarthritis

Crystal-induced arthritis & Osteoarthritis. Ira Targoff, MD Division of Rheumatology. “The Gout” James Gillary, 1799. Gout- an evil demon attack the toe. Hyperuricemia. Hyperuricemia is defined as a serum uric acid >7 mg/dl in men and >6 mg/dl in women

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Crystal-induced arthritis & Osteoarthritis

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  1. Crystal-induced arthritis &Osteoarthritis Ira Targoff, MD Division of Rheumatology

  2. “The Gout”James Gillary, 1799 Gout- an evil demon attack the toe

  3. Hyperuricemia Hyperuricemia is defined as a serum uric acid >7 mg/dl in men and >6 mg/dl in women The majority of people with hyperuricemia never develop any clinical problems from it ("asymptomatic hyperuricemia").

  4. Formation of Uric Acid Hypoxanthine  Xanthine  Uric acid • Catalyzed by XanthineOxidase (XO)

  5. Causes of Hyperuricemia Underexcretion of uric acid (90%) Renal insufficiency Medications (diuretics, cyclosporine, salicylates, ethanbutol, pyrazinamide) Ethanol, organic acids (lactic acidosis, ketoacidosis) Lead nephropathy Overproduction (10%) High cell turnover (myeloproliferation, psoriasis) High purine diet, ethanol Genetic causes (X-linked) 1) Hypoxanthine-guanine phosphorybosyl trnaferase (HGPRT) deficiency 2) 5-phosphryboyl-1-pyrophosphate synthetase (PRPP synthetase) over activity

  6. How to distinguish between overproducers and underexecreters? • 24-hr urine collection for uric acid Uric acid >800 mg/24hrs  Overproducer Uric acid <800 mg/24hrs  Underexecreter • Spot urine uric acid

  7. The famous Podagra -Sudden onset of severe pain and swelling at night -Usually single joint (85%) or fewer than 4 joints -Polyarticular gout is a later feature. -Fever and leukocystosis -Spontaneous resolution over 1-2 weeks -The red apple is replaced by purple plum with exfoliating skin.

  8. Gout mimics cellulitis

  9. Chronic Draining Tophi

  10. Gout-epidemiology • The prevalence of gout in the adults is 1.4%, and in men over 75 is 7% (UK General Practice Data). • Gout is rare in males under 30 and in women before menopause • The peak age of onset in men is 40-50 and in women is after 60 • There is an association between hyperuricemia and metabolic syndrome (insulin resistance, hypertension, obesity, dyslipidemia)

  11. Crystal Analysis by Polarized Light Microscopy

  12. Mono-sodium urate crystals A. Perpendicular to Polarizer Axis B. Extinction C. Parallel to Polarizer Axis Polarizing Axis

  13. Axis Uric acid crystals parallel to the polarizing axis are yellow, those perpendicular are blue

  14. Mono-sodium urate: Intracellular Intracellular crystals indicate acute flare

  15. Crystal Analysis by Polarized Light Microscopy Presence of Crystals Shape of crystals Needle vs Rhomboid vs Other Birefringence Sign of birefringence Negative birefringence (yellow): MSU Positive birefringence (blue): CPPD Apatite not visible by this method

  16. Tophi

  17. Tophi

  18. Gout: X-ray Tophus Rat bite erosions with overhanging edges

  19. Gout: X-ray

  20. Gouty erosions and olecranon tophus

  21. Uric Acid Nephrolithiasis

  22. Treatment of gout Acute attack Colchicine NSAIDs Steroids (injection or systemic) Uric acid lowering agents Allopurinol: Xanthine oxidase inhibitor Probenecid: Uricosuric; inhibits urate transporter-1 (URAT-1) Febuxostat: Non-purine xanthine oxidase inhibitor Uricase

  23. Indications for uric acid lowering agents • >2 attacks within 1-2 yrs • Renal stones (urate or calcium) • Tophaceous gout • Chronic gouty arthritis with erosive disease • Asymptomatic hyperuricemia >12 mg/dl or 24 hrs urinary excretion >1100 mg (to decrease risk for uratenephrolithiasis)

  24. Calcium Pyrophosphate Dihydrate (CPPD) Deposition Disease “Pseudogout” : acute attacks may be provoked by pamidronate, G-CSF, intra-articularhyaluronic acid, joint lavage or surgery) Pyrophosphate arthropathy “pseudo-osteoarthritis” OA involving the knees, wrists, metacarpophalangeal joints, (particularly the second and third), shoulders and hips. “Pseudo-rheumatoid” polyarthritis (MCPs and wrists) Asymptomatic (most common)

  25. Calcium Pyrophosphate Dihydrate (CPPD) Deposition Disease Associated predisposing conditions include: • Hemochromatosis • Hyperparathyroidism • Hypomagnesemia • Hypophosphatasia • Increasing age

  26. Calcium Pyrophosphate Dihydrate Deposition Wrap around patella “Fuzzy” calcium in the joint space

  27. CPPD: MCPS Squaring off and large hook-like osteophytes on 2nd and 3rd MCPS

  28. CPPD, wrist Joint destruction Calcium Cystic changes

  29. CPPD Shoulder • High riding • Sclerosis of glenohumeral space

  30. Calcium Pyrophosphate Dihydrate Deposition Rhomboid crystals are faintly blue in parallel Axis

  31. Other Synovial Fluid Crystals • Basic Calcium Phosphate; hydroxyapetite • acute calcificperiarthritis • acute arthritis • destructive arthropathy (Milwaukee Shoulder) • Calcium Oxalate • acute arthritis • Lipid • Cholesterol

  32. A heterogeneous group of conditions that lead to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone at the joint margins. American College of Rheumatology Definition of Osteoarthritis

  33. Rheumatic Disease in US

  34. Osteoarthritis (OA) • Fastest growing disease in the US • Most common arthritis • 16 million patients in US alone • Mainly affects  60 years old • 80% of people  75 have OA symptoms

  35. OA - Clinical Features • Asymmetrical arthritis • Primarily affects weight bearing joints (knees, hips) • Most common joints - knees, hips, DIP’s, 1st MCP, 1st CMC • Little morning stiffness (<30min) • Increased Pain with activity

  36. OA - Diagnosis Clinical and radiographic No elevation of sedimentation rate Normal hematocrit and leukocyte count Non-inflammatory joint tap ( usually <2,000) No crystals in synovial fluid

  37. Inflammatory Osteoarthritis

  38. Heberden and Bouchard nodes

  39. OA of hand Bone on bone loss of joint space PIPs and DIPs 1st Carpal metacarpal at base of thumb Spares MCPs CMC

  40. Histology of OA Loss of articular cartilage and osteophyte formation

  41. Carpometacarpal Joint OA • Loss of joint space • Sclerosis • Subchondral cysts • Subluxation

  42. Osteoarthritis of Left Hip Loss of joint space Sclerosis Osteophytes Normal

  43. OA of knee Osteoarthritis

  44. Pathology of Knee OA Loss of articular cartilage on medial condyle, intercondylar surface and patella

  45. OA Risk factors • Increased age • Positive family history • Obesity

  46. OA - Therapy Patient education Joint safe exercise program Nutritional counseling for obesity Rehabilitation, including joint sparing methods of ADLs, isometric exercises, etc. Nutritional supplements: glucosamine? Pharmacological therapy Joint replacement surgery

  47. OA - Drug Therapy • Simple analgesia • Round the clock acetaminophen • 4000 mg per day (every day, not prn) • Two extra-strength four times a day • Not effective in patients with a “gelling” component (will need NSAID) • Not effective in patients with signifcant morning stiffness • Poor compliance due to large number of pills • NSAIDs: scheduled, once dialy or twice daily have better compliance • Hyaluronic acid injection, steroid injections • Capsacian cream

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