CRYSTAL ASSOCIATED DISEASE

1. CRYSTAL ASSOCIATED DISEASE Dr. Alka Stoelinga

2. CRYSTAL ASSOCIATED DISEASES Dr. Alka Stoelinga

3. GOUT Dr. Alka Stoelinga

4. GOUT • Also known as podagra when it involves the big toe • Is medical condition usually characterized by recurrent attacks of acute inflammatory arthritis • Gout is an abnormality of uric acid metabolism that results in the deposition of Monosodium urate Monohydrate crystals • It is caused by elevated levels of uric acid in the blood which crystallize and are deposited in joints, tendons, and surrounding tissues. • The metatarsal- phalangeal joint at the base of the big toe is the most commonly affected • Results in pathological reaction in: • Joints: Gouty arthritis • Soft tissue: Tophi and Tenosynovitis • Urinary tract: Urate stones/ Urate nephropathy. • M:F=10:1 • Prevalence rate increase with: --Age --Serum uric acid concentration Dr. Alka Stoelinga

5. Hyperuricemia is the underlying cause of gout. • Hyperuricemia is defined as • A plasma urate level • > 420 μmol/L (7.0 mg/dL) in males and • > 360 μmol/L (6.0 mg/dL) in females. • This can occur for a number of reasons, including • Diet • Genetic predisposition • Underexcretion of urate, the salts of uric acid • Renal underexcretion of uric acid is the primary cause of hyperuricemia in about 90% of cases • Overproduction is the cause in less than 10% • About 10% of people with hyperuricemia develop gout at some point in their lifetimes • The risk varies depending on the degree of hyperuricemia. • When levels are between 415 and 530 μmol/L (7 and 8.9 mg/dL), the risk is 0.5% per year • In those with a level greater than 535 μmol/L (9 mg/dL), the risk is 4.5% per year Dr. Alka Stoelinga

6. PATHOPHYSIOLOGY Dr. Alka Stoelinga

7. Pathophysiology • Disorder of purine metabolism • Final metabolite uric acid • Crystallizes in the form of monosodium urate, precipitates in joints, on tendons, and in the surrounding tissues. • These crystals then trigger a local immune-mediated inflammatory reactionwith interleukin 1β • An evolutionary loss of uricase (breaks down uric acid) • Uric acid crystallizes as levels increase • Other factors triggering an acute episode of arthritis include • cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration, and extracellular matrix proteins, such as proteoglycans, collagens, and chondroitin sulfate. • Rapid changes in uric acid may occur due to a number of factors, including • trauma, surgery, chemotherapy, diuretics, and stopping or starting allopurinol. Dr. Alka Stoelinga

8. Types: • Primary Gout: • Exclusively in male • Common cause of inflammatory arthritis in men>40 years • Secondary Gout: • Due to renal impairment • Drugs Dr. Alka Stoelinga

9. Predisposing factors for Hyperuricemia: • Diminished renal excretion of uric acid • Inherited isolated renal tubular defect • Renal failure • Drugs: Diuretics, Pyrazinamide, Low dose of aspirin • Lead poisoning • Hyperparathyroidism • Myxedema • Down’s syndrome • Lactic Acidosis: Alcohol, Exercise, Starvation, Vomiting, Toxemia of pregnancy Dr. Alka Stoelinga

10. Predisposing factors for Hyperuricemia: 2. Increased production of Uric acid: • Increased turnover of Purines --Chronic Myeloproliferative disorders e.g. Polycythaemia Vera --Chronic Lymphoproliferative disorders e.g. CLL --Psoriasis • Increased purine synthesis de novo --Unidentified abnormality --Specific enzyme defect --HGPRT deficiency --PRP deficiency Dr. Alka Stoelinga

11. Predisposing factors for Hyperuricemia: • MSUM crystal deposition: • Around synovial joints • Initially lower limb joints • Especially 1st Metatarsophalangeal joint • Small joints of feet and hand • Crystal induces: • Inflammation of the joints/Periarticulartissue • Pressure effect • Secondary osteoarthritis Dr. Alka Stoelinga

12. Gout with Tophi on elbow and knee. Dr. Alka Stoelinga

13. Clinical features: ACUTE GOUTY ARTHRITIS: • Peak age of onset in men is 45 years • Usually after 20-30 years of sustained Hyperuricemia • Usually single joint involvement at first, common is 1st Metatarsophalangeal joint of great toe. • Other joints : Ankle, Midfoot, Knee, small joints of hands and wrist • Severe pain and extreme tenderness • The joint is red, hot, swollen with shiny overlying skin and dilated veins • Fever, malaise • Pruritis, desquamation • Initial attacks are usually self limited over 5-14 days Dr. Alka Stoelinga

14. Interictal period: • More than 50% of patients experience recurrent arthritis within 1 year of first attack, subsequently frequency increases, attacks will be more prolonged and severe and involve multiple joints. • Precipitating factors: • Dietary excess • Alcohol • Starvation • Diuretics • Trauma, unusual physical exercise • Systemic infection Dr. Alka Stoelinga

15. Acute gouty arthritis on the big toe of an elderly man. Dr. Alka Stoelinga

16. CHRONIC TOPHACEOUS GOUT: • Recurrent attacks are followed by chronic gout in which there is progressive cartilage and bone erosions in association with deposition of Tophi and secondary degenerative changes • They appear 10-15 years after initial attack • Tophi is firm, painless, irregular nodules, due to deposition of large MSUM crystals • Found around extensor surfaces of joints and their presence cause immobility of joints and severe joint deformities • Usual sites: Fingers, hand, forearm, elbow, Achilles tendon, cartilage of ear. • May ulcerate, discharge of white gritty material Dr. Alka Stoelinga

17. Severe gout in the fingers resulting in large, hard deposits of crystals of uric acid. These deposits are called Tophi Dr. Alka Stoelinga

18. Dr. Alka Stoelinga

19. OTHER MANIFESTATIONS: • Synovitis • Deformity of joints • Urolithiasis: Uric acid Calculi • Chronic urate nephropathy Dr. Alka Stoelinga

20. INVESTIGATIONS: 1. Synovial fluid examination • A definitive diagnosis of gout is based upon the identification of monosodium urate (MSU) crystals in synovial fluid or a tophus • Under polarized light microscopy, they have a needle-like morphology and strong negative birefringence. • The fluid must also be examined relatively quickly after aspiration, as temperature and pH affect their solubility. • Increased cells: Neutrophils • Turbid 2. Blood tests • Hyperuricemia is a classic feature of gout • However, Gout occurs nearly half of the time without hyperuricemia, and most people with raised uric acid levels never develop gout. • Other blood tests commonly performed are • White blood cell count • Electrolytes • Renal function test • Liver function test • Erythrocyte sedimentation rate (ESR). • Both the white blood cells and ESR may be elevated due to gout in the absence of infection 3. Joint X-ray/ KUB 4. Dual-energy CT scanning (DECT) Dr. Alka Stoelinga

21. Using a sterile syringe and needle, fluid is withdrawn from the inflamed joint and then analyzed for uric acid crystals Dr. Alka Stoelinga

22. Fluid obtained from crystal deposits in a patient with gout Dr. Alka Stoelinga

23. A purulent knee aspirate from a person with presumed gout Dr. Alka Stoelinga

24. Needle-shaped urate crystals diagnostic of gout from an acutely inflamed joint (left) as seen under polarized microscopy and unpolarized microscopy (right) Dr. Alka Stoelinga

25. Gouty Tophi Dr. Alka Stoelinga

26. MANAGEMENT Treatment of Acute attack: • NSAIDS • Indomethacin and Naproxen • Colchicine • Joint aspiration • Intra-articular steroids • Analgesics: Opioids may be required for pain and aspirin should be avoided • Bed rest for 24 hours Dr. Alka Stoelinga

27. Long term therapy: • Long term therapy should be started when acute attack has settled. • Indications of Hypourecemic drug: • Recurrent attack of acute gout • Presence of Tophi • Increased uric acid level • Evidence of bone or joint damage • Associated with renal disease Dr. Alka Stoelinga

28. Drug therapy: • Allopurinol: --Indicated In overproduction of uric acids • Xanthine oxidase inhibitor • Can precipitate acute attack • Start with low dose/combine with Colchicine • Not to be used during acute attack 2. Uricosurics: --Indicated in undersecretors of uric acid --when increased frequency or severity of acute Gout. • Probenecid • Sulfinpyrazone Dr. Alka Stoelinga

29. Dr. Alka Stoelinga

30. LIFE STYLE MODIFICATION: • Weight reduction • Reduction of alcohol intake • Avoidance of foods containing high levels of Purine E.g. Meat, organ meat, seafood, beans, spinach, alcohol • Adequate fluid intake • Withdrawal of drugs such as Diuretics and salicyclates. Dr. Alka Stoelinga

31. Relationship of Hyperuricemia with other diseases: Patients with Hyperurecemiaand Gout have and increased incidence of: • Hypertension • Renal disease (Nephrosclerosis, Tophi, Pyelonephritis) • Diabetes mellitus • Hypertriglyceridemia • Atherosclerosis Dr. Alka Stoelinga

32. Dr. Alka Stoelinga