Crystal Arthritis Amh

1,552 views

Published on

Diagnosis and management of Gout and CPPD

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,552
On SlideShare
0
From Embeds
0
Number of Embeds
13
Actions
Shares
0
Downloads
73
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Crystal Arthritis Amh

  1. 1. Crystal Arthritis
  2. 2. AgendaHistory of crystal arthritisIntroduction to GoutGout pathophysiology, risk factors, clinicalstages, joint destruction and extra articular goutTreatment options and targetsCPPD
  3. 3. Crystal ArthritisGout : oldest diseases in the medical literatureGreeks authors have written about gout as the result of personalexcessAssociation with a diet rich in meat and alcohol gained it thereputation, “the king of diseases and the disease of kings”.Lowenhook described symptoms of gout in the 1600s.In 1848, Sir Alfred Garrod linked gout with hyperuricemiaPathophysiology of acute gouty arthritis was not described fullyuntil 1962Pseudogout, which may be clinically indistinguishable from gout,was recognized as a distinct disease entity in 1962
  4. 4. GoutInflammatory arthritis mediated by the crystallization ofuric acid within joints and soft tissues forming tophiOften associated with prolonged periods ofundiagnosed hyperuricemiaClinically undetectable tophi can only seen on advancedimagingPrevalence is rising in US; 8.3 million, only 3.1 milliongetting treatment
  5. 5. Gout Epidemiology40% are not adequately treated to bring targeturic acid below 6mg/dlPoor treatment adherence is a huge problem;56%Most labs list upper limit 8mg or 8.5mg/dl,ignore that, simply the results of changingdemographics, obesityAsymptomatic hyperuricemia >6.8mg/dlTarget serum urate <6mg/dl
  6. 6. The Cycle of GoutLancet, Volume 377, Issue 9760, 8–14 January 2011, Pages 165–177
  7. 7. Hyperuricemia – Preclinical Period>6.8mg/dl – super saturationOnset males age 30, females postmenopausalDuration 10-15 yrs before “gout”80% due to under secretion20% due to over production – Determined by 24 hr urine collection BUT Spot urine fractional excretion can be usedUric acid above 9mg/dl carries 22% risk offuture attack in 5 years
  8. 8. Intercritical Period70% prevalence of MSU crystals remain in the joint so,joint aspiration can be attempted to prove diagnosis ifnot done in the pastThis phase lasts months to years for 75-80%20% never have another attack
  9. 9. Chronic Gout> 10 yearsTophiChronic joint swellingJoint destructionFrequent and more severe attacksUrate precipitation leads to acute gouty arthritis – Local factors – temperature, pH, trauma – Systemic factors – hydration state, infections, meds, alcohol, co-morbid conditions-CHFDon’t ignore asymptomatic hyperuricemia, needs noticeand monitoring for metabolic conditions but literaturedoesnt support uricosuric therapy
  10. 10. Typical Acute Attack
  11. 11. Atypical is not very uncommon Pseudo-rheumatoid goutThe patient, a 68-year-old man with a 30-year history ofseronegative yet nodular rheumatoid arthritis, presentedfor reevaluationHand radiography revealed soft tissue swelling andextensive joint destruction with erosionsMost of the erosions were “punched out” oroverhanging
  12. 12. Pseudorheumatoid goutArthritis & RheumatismVolume 60, Issue 6, pages 1850-1850, 28 MAY 2009 DOI: 10.1002/art.24528http://onlinelibrary.wiley.com/doi/10.1002/art.24528/full#ill1
  13. 13. Polyarticular Gout OR RA
  14. 14. Pseudo-rheumatoid goutInvolvement of some of the distal interphalangeal jointsLack of osteopenia, over hanging margins and theoverall findings were more suggestive of goutAspirated material from a subcutaneous nodulerevealed colored broad plates of cholesterol crystalsHowever, the presence of admixed needle-shapednegative birefringent crystals of monosodium uratemonohydrate confirmed the diagnosis of gout in thispatient
  15. 15. Co morbiditiesDMHTNMetabolic syndromeObesityCVDCRFAlcoholMedications
  16. 16. Iatrogenic , Diuretic induced Gout †Diuretic use, increased serum urate levels, and risk of incidentgout in a population-based study of adults with hypertension:5,789 pts hypertension; 37% were treated with a diureticUse of any diuretic (HR 1.48 [95% CI 1.11, 1.98])Thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10])Loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associatedwith incident goutUse of antihypertensive medication other than diureticagents was associated with decreased gout risk (adjusted HR0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension Arthritis & Rheumatism, Volume 64, Issue 1, pages 121–129, January 2012
  17. 17. Ask patient if he is having a gout flare Developing a provisional definition of a flare in patients with established gout† Patient-reported flare is as good as study gold standard Joint pain at rest Presence of warm joints Swollen joints were most strongly associated with presence of a gout flareArthritis & RheumatismAccepted Article (Accepted, unedited articles published online for future issues)
  18. 18. ACUTE FLARE OF TOPHUS
  19. 19. Can Gout affect womenEpidemiology of gout in women: Fifty-two–year follow-up ofa prospective cohort Higher levels of serum uric acid increase the risk of gout in a graded manner among women, but the rate of increase is lower than that among men Risk factors – Increasing age – Obesity – Alcohol consumption – Hypertension – Diuretic use Arthritis & Rheumatism Volume 62, Issue 4, pages 1069–1076, April 2010
  20. 20. DiagnosisAspiration always recommended if possiblePrompt polarized microscopic analysisDefinitive diagnosis– requires crystalconfirmationGout and Sepsis can coexist – fluid should besent Gram’s stain, cultureSerum uric acid levels neither confirm norexclude gout
  21. 21. MSU CRYSTALS
  22. 22. Gout Can Coexist With Septic Arthritis WHO IS AT RISK? Diabetic Alcoholic Old age
  23. 23. MSU AND STAPH
  24. 24. PREDICT AN ATTACK
  25. 25. TREATMENT OF ACUTE ATTACKTHERAPY (for all crystal diseases): – Corticosteroids: intrarticular > systemic – NSAIDs – fast acting full dose if no contraindications – Colchicine (PO, NOT IV route dangerous) narrow therapeutic window – Bone marrow suppression, myopathy, neuropathy purgative effects – “Pt often run before they walk” – NEVER ALLOPURINOL
  26. 26. LOW VS HIGH COLCHICINE
  27. 27. LESS IS MORE
  28. 28. MEDS- Increased Urate PoolDiuretics (RR 1.77, CI 1.4-2.2)Low dose AspirinB-blockersPZAEthambutolCyclosporinTacrolimusInsulin
  29. 29. Diet for GoutPurine-containing foods to be avoided include• Beer, other alcoholic beverages.• Anchovies, sardines in oil, fish roes, herring.• Yeast.• Organ meat (liver, kidneys, sweetbreads)• Meat extracts, consomme, gravies.Foods which are very high in purines include:• hearts• herring• mussels• yeast• smelt• sardines• sweetbreads
  30. 30. Treat to target : GoutA two-stage approach to the treatment ofhyperuricemia in gout: The “dirty dish” hypothesisMaintaining serum urate levels at less than 6 mg/dL isnecessary for clearing tophi and dissolvingmonosodium urate monohydrate crystals in goutOnce target has been achieved, keeping serum uratejust below the threshold for saturation (6.0 - 6.9mg/dL) is likely to be enough to prevent goutrecurrence Arthritis & Rheumatism Volume 63, Issue 12, pages 4002–4006, December 2011
  31. 31. Hyperuricemia and xanthine oxidase - toxic to the vasculature?Uric acid : Antioxidant or Pro oxidant.Xanthine Oxidase induces oxidative stressUric acid and XOD may promote inflammationPromote endothelial dysfunction and vascular pathologiesEpidemiologic evidence supports the hypothesis;hyperuricemia is an independent risk factor for certainvascular diseases and complications of atherosclerosis.Intrinsic inflammation and oxidative stress in gout, CHF,metabolic syndrome, diabetes, and chronic kidney disease,are likely major determinants of outcomes
  32. 32. Tophaceous Gout
  33. 33. BULKI TOPHI
  34. 34. EAR TOPHI
  35. 35. OLECRNON BURSITIS
  36. 36. SYNVIAL TISSUE DEPOSITS
  37. 37. Erosions with overhanging margins
  38. 38. Punched out erosions
  39. 39. Extra articular complications
  40. 40. Spinal Gouty Tophus
  41. 41. CT spine showing tophus causing destruction of spinous process
  42. 42. Urate nephropathy
  43. 43. Cardiac tissue deposits
  44. 44. Treatment of acute and chronic gout
  45. 45. Acute AttackColchicineNsaidsPrednisoneIntra articular steroids
  46. 46. Uric Acid Lowering TherapyLifestyle, dietary modificationDiet high in vegetables, dairy, water beneficialInitiate uric acid lowering therapy after 1(?) or 2episodes of acute gouty arthritisAlways prophylaxis for first 6 months with lowdose steroids, NSAIDs, or Colchicine
  47. 47. Uricostatic DrugsAllopurinol - developed 1957NEVER USED IN ACUTE ATTACK– Reduce annual gout attacks 4.4 to .06 / yr– Gradual resolution of tophi w/ uric acid < 6– Titrate dose up to 600 mg /day
  48. 48. Concerns associated with Allopurninol– Increased 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
  49. 49. Allopurinol hypersensitivity syndromeStarting dose is a risk factor for allopurinol hypersensitivity syndrome:A proposed safe starting dose of allopurinol†‡Allopurinol hypersensitivity syndrome (AHS) is a rare but potentially fataladverse event.Dosing guidelines based on creatinine clearance (CrCL) have been proposedthat doses ≥300mg/d may be associated with AHS, particularly in patientswith renal impairmentThe aim of this study was to determine the relationship between allopurinoldosing and AHS.A retrospective case-control study of AHS between January 1998 andSeptember 2010 was undertaken.
  50. 50. Allopurinol hypersensitivity syndrome Fifty-four AHS cases and 157 controls were identified. There was an increase in risk of AHS as the starting dose of allopurinol corrected for eGFR increased. For the highest quintile of starting dose≥eGFR, the odds ratio was 23.2 (p<0.01). ROC analysis indicated that 91% of AHS cases and 36% of controls started on a dose of allopurinol at ≥1.5mg allopurinol per unit eGFR (mg/ml/min). Conclusions: Starting allopurinol at a dose of 1.5mg per unit eGFR may be associated with a reduced risk of AHS. In patients who tolerate allopurinol the dose can be gradually increased to achieve the target SUArthritis & RheumatismAccepted Article (Accepted, unedited articles published online for future issues)
  51. 51. FebuxostatFebuxostat was approved by the U.S. Food and DrugAdministration on February 16, 2009Urate lowering drug, an inhibitor of xanthine oxidaseXanthine oxidase is needed to successively oxidize bothhypoxanthine and xanthine to uric acid.Febuxostat inhibits xanthine oxidase, thereforereducing production of uric acidFebuxostat inhibits both, oxidized and reduced form ofxanthine oxidase because of which febuxostat cannotbe easily displaced
  52. 52. New kid on the block (not so new)
  53. 53. RESULTS
  54. 54. CONCLUSION
  55. 55. Newer and stronger drugsURICASE – 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 administrationPEGOLITICASE (Krsytexxa) Now approved
  56. 56. PEGLOTICASE
  57. 57. DOSE S AND RESPONSE
  58. 58. NEW TREATMENT ON HORIZON
  59. 59. Anakina (Kinret, IL-1blocker)
  60. 60. Uricosuric agentsUricosurics probenecid 1-3 grams / day sulfinpyrazone 200-400 mg / day Benzbromarone 100-200 mg / day (not available)AtorvastatinLosartanFenofibrateAmlodipine
  61. 61. Advanced Imaging to confirm diagnosis
  62. 62. ULTRASOUND IMAGING
  63. 63. Double contour sign
  64. 64. MRI FOOT FOR TOPHUS
  65. 65. CPPD DISEASE
  66. 66. Acute CPPDAcute Pseudogout– Positive birefringent rod shaped crystals– More likely in OA joint – knee> wrist> MCPs> hips,shoulders,ankles
  67. 67. CPPD CRYSTAL
  68. 68. CPPD PresentationsPseudo-rheumatoid patternOsteoarthritis with/out pseudogoutChondrocalcinosisNeuropathic jointTumoral CPPD deposition
  69. 69. ROD OR RHOMBOID
  70. 70. Coexist with Septic arthritis
  71. 71. ASSOCIATIONSHyper PTHHemochromatosisHypothyroidismHypomagnesiemiaHypercalcemiaHypophatasia
  72. 72. MASSIVE CPPD
  73. 73. TISSUE STAINING
  74. 74. FLUFFY DEPOSITS OF WRIST
  75. 75. CPPD ON LAPRSCOPY
  76. 76. BASIC CALCIUM PHOSPHATEUsually in the form of hydroxyapatite (CHA)Age related arthropathy except for pseudopodagra in youngwomen“Milwaukee Shoulder”Calcific PeriarthritisSoft tissue calcificationOsteoarthritis (found in 70% of OA synovial fluid)
  77. 77. MILAWAUKEE SHOULDER HYDROXAPATITE
  78. 78. Calcium Hydroxyapatite •Coronal oblique T2-weighted fat suppressed image shows a deposit of CHA crystals (arrow) •Prominent subdeltoid bursitis is also present (arrowheads)
  79. 79. •A coronal T-2 weightedimage of the kneedemonstrates a deposit ofCHA crystals adjacent to themedial femoral condyle(arrow)•Prominent soft tissueinflammation is present
  80. 80. CALCIUM OXALATE CRF
  81. 81. CPPD & BCP TreatmentNSAIDSCOLCHICINE ( prophylaxis in cppd)STEROID INJECTIONULTRASOUND GUIDED ASPIRATIONSURGERY

×