crystal associated arthropathies
TRANSCRIPT
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CRYSTAL ASSOCIATED ARTHROPATHIES
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Crystalline particles in joint disease• Intrinsic
• Monosodium urate monohydrate (Gout)• Calcium pyrophosphate dihydrate (Pseudogout)• Calcium phosphates
• • Basic—hydroxyapatite, octacalcium phosphate, tricalcium phosphate• • Acidic—brushite, monetite
• Calcium oxalate• Lipids• Cholesterol• Lipid liquid crystals• Charcot–Leyden (phospholipase) crystals• Cystine• Xanthine, hypoxanthine• Protein precipitates (e.g. cryoglobulins)
• Extrinsic• Synthetic corticosteroids• Plant thorns (semicrystalloid cellulose), especially blackthorn, rose, dried palm fronds• Sea urchin spines (crystalline calcium carbonate)• Methylmethacrylate
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COMMON DISEASES• Gout
• Monosodium urate monohydrate
• Pseudogout or Chondrocalcinosis• Calcium pyrophosphate dihydrate
• Basic calcium phosphate• Hydroxyapatite
• Calcium oxalate
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GOUT
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GOUT• Metabolic disease• ↑ Body pool of urate• Hyperuricemia• Monosodium urate monohydrate deposition
• Joints• Connective tissue• Kidney interstitium• Uric acid nephrolithiasis
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GOUT• Affects:-
• Middle aged to elderly males• Postmenopausal women
• Precipitants:-• Purine rich foods• Alcohol intake• Trauma, surgery• Hypouricemic drugs• Serious illness – MI, stroke
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GOUT RISK FACTORS• Primary:-
• Hyperuricemia• Male sex• Hypertension• Obesity• Insulin resistance• Metabolic syndrome• Alcohol• Purine rich diet• ↓ uric acid excretion
• Secondary:-• Diuretics• CKD• Osteoarthritis • Chronic renal failure • Lead poisoning (rare) • Ciclosporin (rare) • Myeloproliferative disorders (rare)
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GOUT PHASES1) Asymptomatic hyperuricemia2) Acute gout
• Single peripheral joint – 50% podagra (big toe)• Midtarsal, ankle, knee, small hand joints, wrist, elbow• Swollen, red, hot, shiny, tender joint
3) Intercritical gout• Repeated attacks• Turns chronic by 10 years
4) Chronic tophaceous gout• Tophi – large crystal deposits• Irregular firm nodule• Joint deformity & damage
• Associated – Uric acid stones, c/c urate nephropathy
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GOUT• Diagnosis:-
• Synovial fluid aspirate / tophi• Birefringent crystals – polarized light
• Radiological:-• Soft tissue swelling• Cystic changes• Erosion of articular surfaces• Sclerotic margins
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GOUT TREATMENT• ↓ inflammation:-
• NSAIDs• Colchicine low dose• Joint aspiration• Steroids – intra-articular, systemic• Icepacks
• Long term:-• Lifestyle modification
• Avoid alcohol• Avoid purine rich foods• Weight reduction
• Urate lowering• Allopurinol, febuxostat
• Uricosuric + Fluid intake + Alkalinization• Probenecid , sulfinpyrazone
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PSEUDOGOUT ALIASCHONDROCALCINOSISALIASCPPD DEPOSITION DISEASE
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CPPD DEPOSITION• Elderly-
• 65-75 years = 10-15%• >85 years = 30-50%
• Cause – uncertain• ↑ ATP degradation to adenosine+pyrophosphate• ↑ Extracellular pyrophosphate transport (genetic mutation)• Calcium pyrophosphate formed and deposited• Crystals phagocytosed (monocytes, macrophages, neutrophils)• Inflammation• Destruction
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CPPD DEPOSITION• Associated with –
• Aging• Disease-associated
• Primary hyperparathyroidism• Hemochromatosis• Hypophosphatasia• Hypomagnesemia• Chronic gout• Postmeniscectomy• Gitelman's syndrome
• Epiphyseal dysplasias
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CPPD DEPOSITION CLINICAL• MC asymptomatic• A/c, sub a/c, c/c, a/c on c/c arthritis• Presentations mimic-
• Gout – pseudogout• Osteoarthritis – atypical joints, age, progression• Neuropathic arthritis – severe destruction• Rheumatoid arthritis – symmetrical arthritis• Ankylosing spondylitis – IVD & lig flavum calcific, spine immobility• Spinal stenosis• Periarticular tophus-like nodule – very rare
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CPPD DEPOSITION• Joints involved-
• MC knee• Wrist, shoulder, ankle, elbow, hand joints• Rarely TMJ, ligamentum flavum
• Usually polyarticular• Mimic many others• Low grade fever• Precipitated by-
• Trauma• Rapid ↓ serum calcium levels
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CPPD DEPOSITION• Synovial fluid-
• TC = 1000s to 100,000/mm3
• Definitive –• Rhomboid, square, rod-like crystals• Weak birefringent• Inside tissue fragments, clots, neutrophils
• Radiographic-• Chondrocalcinosis• Punctate / linear opacities in cartilaginous tissue
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CPPD DEPOSITION Rx• Acute
• Joint aspiration• NSAIDs• Intra-articular steroids
• Severe• Short course steroids• Anakinra – IL-1β antagonist
• Prophylaxis• Daily low-dose colchicine
• Advanced destruction• Joint replacement
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CALCIUM APATITE DEPOSITION DISEASE
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CA DEPOSITION• aka Basic calcium phosphate deposition disease• Deposition-
• Dystrophic – damaged tissue• Metastatic – hypercalcemia• Unknown cause• CKD – hyperphosphatemia
• Clinical course-• Recurrent acute attacks• Inflammation• Destructive arthropathy
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CA DEPOSITION ASSOCIATIONS• Aging• Osteoarthritis• Hemorrhagic shoulder effusions in the elderly (Milwaukee shoulder)• Destructive arthropathy• Tendinitis, bursitis• Tumoral calcinosis (sporadic cases)• Disease-associated
• Hyperparathyroidism• Milk-alkali syndrome• Renal failure/long-term dialysis• Connective tissue diseases (e.g., systemic sclerosis, idiopathicmyositis, SLE)• Heterotopic calcification after neurologic catastrophes (e.g., stroke, spinal cord injury)
• Heredity• Bursitis, arthritis• Tumoral calcinosis• Fibrodysplasia ossificans progressiva
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CA DEPOSITION• Periarticular/articular deposits• Acute reversible inflammation• +/- chronic damage• Joint capsule, tendon, bursa, articular surface• Knee, shoulder, hip fingers• Presentations-
• Asymptomatic radiographic changes• Acute synovitis, bursitis, tendinitis• Chronic destructive arthropathy
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CA DEPOSITION• Synovial fluid-
• Low TC <2000/mm3
• But dramatic symptoms• Crystal clumps• Individual crystals – electron micro, X-ray diffraction, IR spectroscopy
• Crystal clumps –• 1-20 micrometre• Intra/extracellular• Nonbirefringent• Wright’s stain – purplish• Alizarin red – bright red
• Radiographic-• Intra/peri-articular calcification• +/- erosive/destructive/hypertrophic changes
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CA DEPOSITION Rx• Acute attacks-
• May self limit by days to several weeks• Joint aspiration• NSAIDs• Colchicine• Intra/periarticular depot steroid
• Renal failure-• Phosphate lowering agents
• Severe destruction-• Joint replacement
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CALCIUM OXALATE DEPOSITION DISEASE
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COD DISEASE• Primary oxalosis-
• Rare hereditary disorder• Enzyme defects• Hyperoxalemia – Ca oxalate crystal deposition• Nephrocalcinosis, renal failure, arthritis, periarthritis• Death by 20 years of age
• Secondary-• Complication of ESRD• Pt on haemo/peritoneal dialysis• Ascorbic acid supplements• Visceral organs, blood vessels, bones, cartilages• Arthritis in CKD
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COD DISEASE• Clinical features-
• Mimics other crystal arthropathies• Rptd a/c attacks, later c/c• Bone, articular cartilage, synovium, periarticular tissues• Progressive joint destruction• Fingers, wrist, elbows, knees, ankles, feet
• X-Ray-• Chondrocalcinosis, soft tissue calcification
• Synovial fluid-• TC<2000/mm3
• Crystals- variable shape & birefringence• Characteristic- bipyramidal, strong birefringence• Alizarin red S stain positive
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COD DISEASE• Treatment-
• Medical mildly effective• Joint replacement in end-stage• Liver transplant for Primary oxalosis
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