CRYSTAL ASSOCIATED DISEASE 4/23/2017 Dr. Alka Stoelinga

CRYSTAL ASSOCIATED DISEASES ASSOCIATION COMMON Monosodium urate monohydrate Calcium pyrophosphate dihydrate Basic calcium phosphates Acute gout Chronic tophaceous gout Acute pseudogout Chronic arthropathy Chondrocalcinosis Calcific periarthritis Calcinosis UNCOMMON Cholesterol Calcium oxalate Extrinsic crystals/ semi-crystalline particles Synthetic crystals Plant thorns/ sea urchin spines Chronic effusions in rheumatoid arthritis Acute arthritis in Dialysis patient Acute synovitis Chronic monoarthritis, tenosynovitis 4/23/2017 Dr. Alka Stoelinga

GOUT 4/23/2017 Dr. Alka Stoelinga

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 4/23/2017 Dr. Alka Stoelinga

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 4/23/2017 Dr. Alka Stoelinga

PATHOPHYSIOLOGY 4/23/2017 Dr. Alka Stoelinga

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 reaction with 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. 4/23/2017 Dr. Alka Stoelinga

Types: Primary Gout: Exclusively in male Common cause of inflammatory arthritis in men>40 years Secondary Gout: Due to renal impairment Drugs 4/23/2017 Dr. Alka Stoelinga

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 4/23/2017 Dr. Alka Stoelinga

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 4/23/2017 Dr. Alka Stoelinga

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/Periarticular tissue Pressure effect Secondary osteoarthritis 4/23/2017 Dr. Alka Stoelinga

Gout with Tophi on elbow and knee. 4/23/2017 Dr. Alka Stoelinga

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 4/23/2017 Dr. Alka Stoelinga

Precipitating factors: Dietary excess Alcohol Starvation Diuretics 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 4/23/2017 Dr. Alka Stoelinga

Acute gouty arthritis on the big toe of an elderly man. 4/23/2017 Dr. Alka Stoelinga

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 4/23/2017 Dr. Alka Stoelinga

Severe gout in the fingers resulting in large, hard deposits of crystals of uric acid. These deposits are called Tophi 4/23/2017 Dr. Alka Stoelinga

4/23/2017 Dr. Alka Stoelinga

OTHER MANIFESTATIONS: Synovitis Deformity of joints Urolithiasis: Uric acid Calculi Chronic urate nephropathy 4/23/2017 Dr. Alka Stoelinga

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) 4/23/2017 Dr. Alka Stoelinga

Using a sterile syringe and needle, fluid is withdrawn from the inflamed joint and then analyzed for uric acid crystals 4/23/2017 Dr. Alka Stoelinga

Fluid obtained from crystal deposits in a patient with gout 4/23/2017 Dr. Alka Stoelinga

A purulent knee aspirate from a person with presumed gout 4/23/2017 Dr. Alka Stoelinga

Needle-shaped urate crystals diagnostic of gout from an acutely inflamed joint (left) as seen under polarized microscopy and unpolarized microscopy (right) 4/23/2017 Dr. Alka Stoelinga

Gouty Tophi 4/23/2017 Dr. Alka Stoelinga

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 4/23/2017 Dr. Alka Stoelinga

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 4/23/2017 Dr. Alka Stoelinga

--Indicated In overproduction of uric acids Xanthine oxidase inhibitor 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 4/23/2017 Dr. Alka Stoelinga

4/23/2017 Dr. Alka Stoelinga

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. 4/23/2017 Dr. Alka Stoelinga

Relationship of Hyperuricemia with other diseases: Patients with Hyperurecemia and Gout have and increased incidence of: Hypertension Renal disease (Nephrosclerosis, Tophi, Pyelonephritis) Diabetes mellitus Hypertriglyceridemia Atherosclerosis 4/23/2017 Dr. Alka Stoelinga

4/23/2017 Dr. Alka Stoelinga