Gouty arthritis

GOUT

1. Gouty arthritis By: Mrs.Keerthi Samuel.K Asst.professor Vijay marie con

2. introduction Gout a type of arthritis that causes inflammation, usually in one joint, that begins suddenly. Gouty arthritis is caused by the deposition of needle-like crystals of uric acid in a joint. Clinically it is characterized by recurring attacks of acute arthritis by interval of freedom from pain In late stages by deforming arthritis, nephritis, urinary calculi.

3. HISTORY OF GOUT 2640 BC: podagra first identified by the Egyptians. 5 th century bc: Hippocrates referred to gout as “unwalkable disease” and noted links between gout & lifestyle, demographics & other variables The word ‘gout’ is derived from the Latin word ‘Gutta’. Earlier it was believed that an acute attack of the disease was the result of poison dropping into a joint Disease of the ‘KINGS’ (rich foods have a higher concentration of protein. This could cause major problems for a person afflicted with gout)

4. DEFINITION Gout is a hereditary condition of disturbed uric acid metabolism in which urate salts gets deposited in articular, periarticular and subcutaneous tissues. Chronic heterogeneous disorder of urate metabolism results in deposition of monosodium urate crystals in the joints and soft tissues, with accompanying inflammation and degenerative consequences

5. INCIDENCE Race : whites> blacks Sex : males >females Age :2 n to 4 th decade common at 40 years. 2.6 million in 2005, projected to increase to 3.6 million in 2025 Most common form of inflammatory joint disease in men aged ≥40 years

6. etiology The crystallization of uric acid, often related to relatively high levels in the blood, is the underlying cause of gout. This can occur because of diet, genetic predisposition, or underexcretion of urate, the salts of uric acid. [4]   The causes include Lifestyle Genetics Drugs Medical conditions

7. ETIOLOGY-lifestyle Dietary causes account for about 12% of gout, and include a strong association with the consumption of alcohol, fructose-sweetened drinks, meat, and seafood. among foods richest in purines yielding high amounts of uric acid are dried anchovies, shrimp, organ meat, dried mushrooms, seaweed, and beer yeast. chicken and potatoes also appear related. other triggers include physical trauma and surgery Physical fitness, healthy weight, low-fat dairy products, and to a lesser extent, coffee and taking vitamin C, appear to decrease the risk of gout; 

8. ETIOLOGY-genetics Gout is partly genetic, contributing to about 60% of variability in uric acid level. the  SLC2A9 ,  SLC22A12 , and  ABCG2  genes have been found to be commonly associated with gout and variations in them can approximately double the risk.  loss-of-function mutations in  SLC2A9  and  SLC22A12  causes low blood uric acid levels by reducing urate absorption and unopposed urate secretion. the rare genetic disorders familial juvenile hyperuricemic nephropathy,  hypoxanthine-guanine medullary cystic kidney disease.

9. ETIOLOGY-MEDICAL CONDITIONS Out frequently occurs in combination with other medical problems.  Metabolic syndrome, a combination of abdominal obesity, hypertension, insulin resistance, and abnormal lipid levels, occurs in nearly 75% of cases.  other conditions commonly complicated by gout include lead poisoning, kidney failure, hemolytic anemia, psoriasis, solid organ transplants, and myeloproliferative disorders such as polycythemia.  A body mass index greater than or equal to 35 increases male risk of gout threefold. chronic lead exposure and lead-contaminated alcohol are risk factors for gout due to the harmful effect of lead on kidney function.

10. ETIOLOGY-DRUGS Have been associated with attacks of gout, but a low dose of hydrochlorothiazide does not seem to increase risk. other medications that increase the risk include niacin, aspirin (acetylsalicylic acid), ACE inhibitors, angiotensin receptor blockers, beta blockers, ritonavir, and pyrazinamide. the immunosuppressive drugs ciclosporin and tacrolimus are also associated with gout, the former more so when used in combination with hydrochlorothiazide.

11. ETIOLOGY/PREDISPOSING FACTORS Purine rich foods – meat, kidney, liver, seafood, anchovies, oatmeal, certain vegetables (peas, beans, lentils, mushrooms, cauliflower, spinach), sweetbreads Caffeine Drugs – loop diuretics, NSAIDS, corticosteroids, niacin, cyclosporine,salicylates,ethambutol, pyrazinamide Trauma Infection

12. ETIOLOGY/PREDISPOSING FACTORS Other disease – DM, HTN, vascular dx, renal dx, thyroid dx, sarcoidosis, etc. overweight kidney disease taking diuretics drinking alcohol in excess diabetes underactive thyroid

13. STAGES OF GOUT

14. STAGE-I :ASYMPTOMATIC URICEMIA In this beginning stage of gout, uric acid is building up in the blood and starting to form crystals around joints, most often in the foot. In this stage of gout, the person has no joint pain, no red or swollen joints, just an elevated uric acid blood test This is the time that the uric acid, or urate, crystals are collecting in the joints and can cause inflammation later on.” uric acid is created when body breaks down substances called purines, which are produced in body and can also be found in certain foods and drinks. but high uric acid isn’t enough for a diagnosis of gout itself. “most people with hyperuricemia never develop clinical gout

15. STAGE-II :ACUTE GOUT At this point, that sudden, unexpected nighttime attack of gout symptoms might occur. “This is when the person has pain, redness, and swelling of a joint, most commonly in the big toe, the foot, the ankle or the knee, but gout can start in other joints as well.“ The urate crystals are released into the joint fluid and cause an inflammatory reaction, bringing in many white blood cells and releasing inflammatory chemicals that cause the pain, redness, and swelling called GOUT FLARE. Identifying uric acid crystals in joint fluid helps confirm a gout diagnosis which can be done in this stage

16. STAGE-IIi :INTERCRITICAL GOUT after a first gout flare, 75 percent of people will have a second within a year; but some people can go years before another attack, since it is the nature of gout to have flares and then quiet down for a period of time before the next flare.” Even though it may seem like nothing is happening, this is the point in which patients should begin long-term treatment. lowering uric acid levels with medication can prevent future gout flares and long-term complications .

17. STAGE-IV :CHRONIC GOUT This stage is also called “ TOPHACEOUS GOUT” because the uric acid deposits can form nodules called “tophi,” often at the bunion point of the big toe or at the elbow. But tophi can form anywhere in the body. “This stage is where a person can have some joint pain from gout just about all the time. “It usually takes many years of uncontrolled gout for someone to get into this stage.” During this stage, progressive joint damage develops, so patients with gout should be treated before this starts happening.

18. PATHOPHYSIOLOGY Disturbed metabolism of uric acid causes accumulation in the joints. The pathogenesis can be explained at three levels: INITITATION AMPLIFICATION RESOLUTION

19. PATHOPHYSIOLOGY-INITITATION PHASE

20. PATHOPHYSIOLOGY-AMPLIFICATION PHASE

21. PATHOPHYSIOLOGY-RESOLUTION PHASE It May resolve & become asymptomatic (INTERCRITICAL GOUT)

22. PATHOPHYSIOLOGY

23. CLINICAL FEATURES-ACUTE GOUT Acute gout is a painful condition that typically affects only one or a few joints. The big toe, knee, or ankle joints are most often affected. Throbbing, crushing, or excruciating pain Joint appears warm and red. Fever may be there. The attack may go away in a few days, but may return from time to time. Additional attacks often last longer. After a first gouty attack, half of the people will have no symptoms. Half of patients have another attack.

24. CLINICAL FEATURES- CHRONIC GOUT Signs and symptoms include: Joint damage Loss of motion in the joints Joint pain and other symptoms most of the time, throughout the day Tophi below the skin around joints or in other places (tophi usually develop only after a patient has had the disease for many years

25. ADVANCED CHRONIC TOPHACEOUS GOUT The tophaceous nodules consists of multicentric deposition of urate crystals and intra cellular matrix and foreign body granulomatous reaction. As they enlarge in size, calcify, they can cause pressure symptoms. The tophi are firm yellow in color and occasionally discharge a chalky material.

26. 1977 ACR Criteria for Acute gout The presence of characteristic urate crystals in the joint fluid, or a tophus proved to contain urate crystals by chemical means or polarized light microscopy, or the presence of 6 of the following 12 clinical, laboratory, and radiographic phenomena: More than one attack of acute arthritis Maximum inflammation developed within 1 day Monoarthritic attack Redness observed over joints

27. 1977 ACR Criteria for Acute gout First metatarsophalangeal joint painful or swollen Unilateral first metatarsophalangeal joint attack Unilateral tarsal joint attack Tophus (proven or suspected) Hyperuricemia Asymmetric swelling within a joint on x ray/exam Subcortical cysts without erosions on x ray Joint fluid culture negative for organisms during attack

28. DIAGNOSTIC FEATURES Plain radiographs (may be normal) Serum Uric acid ARTHROCENTESIS Synovial fluid analysis (shows uric acid crystals) BUN (blood urea nitrogen), Serum Creatinine Synovial biopsy Uric acid – urine

29. RADIOGRAPHIC EXAMINATION To exclude other kinds of arthritis: Tophi Normal mineralization Asymmetric polyarticular distribution Juxta-articular bony erosion associated with periarticular tophi Subchondral erosions with overhanging bony edges

30. SYNOVIAL FLUID ANALYSIS (Polarized Light Microscopy) Joint Fluid analysis : The gold standard Crystals intracellular during attacks Needle & rod shapes Strong negative birefringence ARTHROCENTESIS Polarizing microscopy showing m onosodium urate (MSU) : needle-shaped negatively birefringent either free floating or within neutrophils & macrophages.

31. BIOCHEMICAL TESTS FOR GOUT

32. SYNOVIAL FLUID ANALYSIS (Polarized Light Microscopy) Both have polyarticular, symmetric arthritis Tophi can be mistaken for RA nodules

33. MANAGEMENT Gout can be treated and controlled. Symptoms are often dramatically improved within 24 hours after treatment has begun. Attacks can be prevented with appropriate therapy to lower the blood uric acid levels and change in lifestyle by addressing the modifiable risk factors. The goals of treatment are to: Relieve pain and inflammation Prevent future gout attacks that could lead to permanent joint damage and tophi Prevent the development of tophi Prevent kidney damage from chronically elevated urate levels

34. MANAGEMENT

35. MEDICAL MANAGEMENT

36. 34 Purine nucleotides hypoxanth i ne xanthine Uric acid Xanthine oxidase Alimentary excretion Urinary exc r et i on Tissue deposition in excess Urate crystal microtophi Phagocytosis with acute infla mm at i on and ur i cosu r ics col c hicine N S AID Allopu r inol Oxypurinol

37. MEDICAL MANAGEMENT NSAIDS Inhibits pain & inflammation. Inhibits urate crystal phagocytosis by decreasing the migration of granulocytes into the inflammatory area. Indomethacin, naproxen, ketorolac. COLCHICINE Produces its anti-inflammatory effects by binding to the intracellular protein tubulin, preventing its polymerization leading to the inhibition of leukocyte migration into affected area. Inhibits the synthesis & release of leukotrienes.

38. MEDICAL MANAGEMENT URICOSURIC AGENTS: Probenecid & sulfinpyrazone They are weak organic acids . Sulfinpyrazone is a metabolite of phenylbutazone. Increase the excretion of uric acid Allopurinol/ Febuxostat: Inhibits synthesis of uric acid by inhibiting xanthine oxidase enzyme Uric acid is produced by xanthine and hypoxanthine by xanthine oxidase inhibitor. Uric acid is more toxic than either xanthine or hypoxanthine.

39. MEDICAL MANAGEMENT STEROIDS Glucocorticoids Have been found to be as effective as NSAIDS and may be used if contraindications exist for nsaids.  they also lead to improvement when injected into the joint. A joint infection must be excluded, however, as steroids worsen this condition. there were no short-term adverse effects reported OTHERS Inhibitors, such as canakinumab, showed moderate effectiveness for pain relief and reduction of joint swelling, but have increased risk of adverse events, such as back pain, headache, and increased blood pressure. they, however, may work less well than usual doses of NSAIDS. the high cost of this class of drugs may also discourage their use for treating gout.

40. SURGICAL MANAGEMENT Excision of gout trophy. Arthrodesis of the joint in functional position, Removal of lesion adjacent to the joint preserves joint function.

41. Prevent Disease Progression Lower urate to < 6 mg/dl : Depletes Total body urate pool Deposited crystals Treatment is lifelong & continuous Drug choices : Uricosuric agents Xanthine oxidase inhibitor

42. PREVENTION Maintain the concentration of Uric Acid level within the normal range. Drinking Plenty of Water. Balance your weight with proper diet and exercise Avoid purine rich foods Reducing alcohol consumption Avoid Diuretic Drugs.

43. DIETARY MANAGEMENT Foods known to decrease the occurrence of gout include dairy, foods high in potassium, black cherry juice, blueberries and lemon juice. Immediately treating gout will not allow it worse.

44. RECENT ADVANCEMENTS-NEW DRUGS URICASE ENZYMES: Catabolize urate to allantoin: More soluble, excretable form Currently approved for hyperuricemia in tumor lysis syndrome Some concerns: fatal immunogenicity & unknown long-term effects