Gout

introduction , clinical manifestation, diagnosis and treatment of gout ,,,,, differentiation with pseudogout...

1. Gout Dr. Sunil pahari 3rd Year Resident Department of Orthopedic surgery, Yangtze University jingzhou , hubei , P.R. China

2. Definition Acute inflammatory monoarthritis caused by precipitation of monosodium urate (MSU ) crystals in joints Uric acid is the normal end product of the degradation of purine compounds. Major route of disposal is renal excretion Humans lack the enzyme uricase to break down uric acid into more soluble form.

3. Epidemiology Most common of microcrystalline arthropathy Affects about 2.1million worldwide Gout is 5 times more common in males Acute attack tend to occur after a large meal or alcohol consumption ( alcohol metabolites compete for same excretion sites in kidney as uric acid, causing decrease uric acid secretion and subsequent build up in blood )

4. Classification of Hyperuricemia Uric acid overproduction Accounts for 10% of hyperuricemia Acquired disorders Excessive cell turnover rates such as myleoproliferative disorders, Paget’s disease, hemolytic anemias Uric acid underexcretion Accounts for >90% of hyperuricemia Diminished tubular secretory rate, increased tubular reabsorption, diminished uric acid filtration Can be exacerbated by certain medication ( thiazide diuretics)

5. Stages of Classic Gout Asymptomatic hyperuricemia Very common biochemical abnormality Majority of people with hyperuricemia never develop symptoms of uric acid excess Acute Intermittent Gout (Gouty Arthritis) Episodes of acute attacks. Symptoms may be confined to a single joint or patient may have systemic symptoms. Intercritical Gout Symptom free period interval between attacks. May have hyperuricemia and MSU crystals in synovial fluid Chronic Tophaceous Gout Results from established disease and refers to stage of deposition of urate , inflammatory cells and foreign body giant cells in the tissues. Deposits may be in tendons or ligaments. Usually develops after 10 or more years of acute intermittent gout.

6. Presenting Symptoms Systemic : may have fever, chills and malaise Musculoskeletal : Asymmetric joint distribution Joint is swollen ,red and painful. Classic manifestation is painful MTP joint of the big toe ( podagra ) Tophus formation (often on external ear,olecranon bursa , Achilles tendon ) Tophi achilles

7. Differential Diagnosis Trauma Infections septic arthritis, gonococcal arthritis, cellulitis Inflammatory Rheumatic arthritis, Reiter’s syndrome, Psoriatic arthritis Metabolic pseudogout ( calcium pyrophosphate crystal ) Miscellaneous Osteoarthrtis

8. Diagnosis Definitive diagnosis only possible by aspirating and inspecting synovial fluid or tophaceous material and demonstrating MSU crystals. yellow crystals

9. Synovial Fluid Findings Needle shaped crystals of monosodium urate monohydrate that have been engulfed by neutrophils

10. Diagnostic Studies Uric Acid Rise CBC Mild leukocytosis in acute attacks, but may be higher than 25,000/mm ESR mild elevation or may be 2-3x normal 24hr urine uric acid Only useful in patients being considered for uricosuric therapy or if cause of marked hyperuricemia needs investigation .

11. Treatment Goals Gout can be treated without complications. Therapeutic goals include terminating attacks providing control of pain and inflammation preventing future attacks preventing complications such as renal stones, tophi, and destructive arthropathy

12. Treatment mechanism

13. Acute Gout Treatment NSAIDs Most commonly used. No NSAID found to work better than others Regimens: Indocin 50mg po bid-tid for 2-3 days and then taper Ibuprofen 400mg po q4-6 hr max 3.2g/day Ketorolac 60mg IM or 30mg IV X1 dose in patients<65 30mg IM or 15mg IV in single dose in patients >65yo, or with patients who are renally impaired Continue meds until pain and inflammation have resolved for 48hr

14. Acute Treatment Colchicine Inhibits microtubule aggregation which disrupts chemotaxis and phagocytosis Inhibts crystal-induced production of chemotatic factors Administered orally in hourly doses of 0.5 to 0.6mg until pain and inflammation have resolved or until GI side effects prevent further use. Max dose 6mg/24hr 2mg IV then 0.5mg q6 until cumulative dose of 4mg over 24hr

15. Acute treatment cont’d Corticosteriods Patients who cannot tolerate NSAIDs, or failed NSAID/colchicine therapy Daily doses of prednisone 40-60mg a day for 3-5 days then taper 1-2 weeks Improvement seen in 12-24hr Intra-articular injection with steroids Beneficial in patient with one or two large joints affected Good option for elderly patient with renal or PUD or other illness Triamcinolone 10-40mg or Dexamethasone 2-10mg alone or in combination with Lidocaine

16. Chronic gout drugs (preventive) Allopurinol- MoA – inhibit xanthine oxidase, decrease conversion of xanthine to uric acid . Febuxostat - inhibit xanthine oxidase Probenecid ( uricosuric drug )- inhibit reabsortion of uric acid in PCT.

17. Non- Pharmacologic Treatments Immobilization of Joint Ice Packs Abstinence of Alcohol Consumption can increase serum urate levels by increasing uric acid . When used in excess it can be converted to lactic acid which inhibits uric acid excretion in the kidney Dietary modification Low carbohydrates Decrease in dietary purine-meat and seafood Dairy and vegetables do not seem to affect uric acid

18. Newer Therapies Uricase Enzyme that oxidizes uric acid to a more soluble form Natural Uricase from Aspergillus flavus and Candida utilis under investigation Febuxostat New class of Xanthine Oxidase inhibitor More selective than allopurinol Little dependence on renal excretion Losartan Fenofibrate

19. Complications Renal Failure ARF can be caused by hyperuricemia, chronic urate nephropathy Nephrolithiasis Joint deformity Recurrent Gout

20. Pseudo gout