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Rheumatoid arthritis in adults Implementing NICE guidance Prof. Dr. R V S N Sarma MD (Med), MSc (Canada), FCGP, FIMSA Senior Consultant Physician and Cardio-Metabolic.

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Presentation on theme: "Rheumatoid arthritis in adults Implementing NICE guidance Prof. Dr. R V S N Sarma MD (Med), MSc (Canada), FCGP, FIMSA Senior Consultant Physician and Cardio-Metabolic."— Presentation transcript:

1 Rheumatoid arthritis in adults Implementing NICE guidance Prof. Dr. R V S N Sarma MD (Med), MSc (Canada), FCGP, FIMSA Senior Consultant Physician and Cardio-Metabolic & Chest Specialist Hon. National Professor of Medicine Visiting Professor of Internal Medicine at Sri Balaji Medical College, Chennai and Visiting Faculty at Frontier Life Line, Chennai drsarmaji YouTube drsarmaji YouTube

2 Purine nucleotides hypoxanthine xanthine Uric acid Xanthine oxidase (XO) Alimentary excretion Urinary excretion Tissue deposition in excess Urate crystalmicrotophi Phagocytosis with acute inflammation and arthritis uricosurics colchicine NSAID Allopurinol Oxypurinol Dietary 34%, Endogenous 66%, 2/3 1/3

3 Gout: Over View Gout is a systemic illness – a metabolic disease Defined as a peripheral arthritis resulting from the deposition of sodium urate crystals in one or more joints deposition of uric acid in soft tissue as mono sodium urate deficient purine metabolism – serum uric acid elevation Demonstration of intra-articular mono sodium urate (MSU) crystals -to establish a definitive diagnosis of gouty arthritis Prevalence is about 0.8 to 1.5% of the population Gout is 5 x more in males than premenopausal women Prevalence increases with age and increasing serum UA Strong familial predisposition – 80% of family members

4 The Spectrum of Gout Serum hyper uricemia > 7 mg % Acute Inflammatory Mono Arthritis Tophaceous urate crystal deposit Interstitial Renal urate deposition Urolithiasis and Nephropathy

5 Pathophysiology Urate saturates in plasma at 7 mg/dL Assuming pH, temp, Na are WNL MSU deposits in less vascular tissue Cartilage Tendons and / or ligaments There is a predilection for peripheral joint / tissue

6 Etiology of Gout Primary gout Overproduction: 10% Under excretion: 90% Secondary gout Excess nucleoprotein turnover (lymphoma, leukemia) Increased cell proliferation or death (psoriasis) Rare genetic disorder Lesch-Nyhan Syndrome (HGPRT) Drugs – Thiazides, loop diuretics, PZA, Cyclosporine Ethanol abuse – habitual beer drinkers Dehydration – fluid deprivation

7 Predisposing Factors Heredity Drug usage Renal failure Hematologic Disease Trauma Alcohol use Psoriasis Poisoning Obesity Hypertension Organ transplantation Surgery

8 Signs and Symptoms Acute attack With in few hours - frequently nocturnal Excruciating pain – worst pain ever experienced Swelling, redness and tenderness Podagra: 1 st MTP classic presentation May effect knees, wrist, elbow, and rarely SI and hips. Chronic Destructive Tophaceous Gout Much greater chance if untreated Rarely presents as a chronic illness

9 Sequence of Progression Asymptomatic Hyperuricemia Acute Gouty Monoarthritis Interval or Intercritical Gout Chronic Tophaceous Gout

10 Tophaceous Gout Incidence has decreased over last few decades Seen in 25-50% of untreated patients (after 10-20yrs) Location: Olecranon, bursae, digits, helix of ear Damages bone, peri articular structures and soft tissues Palpable measure of total body urate load Other Extra articular Complications Uric acid calculi (seen in10-15% of gout pts) Chronic urate nephropathy (in those with tophi) Acute uric acid nephropathy (in pts undergoing chemotherapy) Hypertensive Renal disease is the most common in gout

11 Diagnosis Based on history and physical Confirmed by arthrocentesis Urate crystals: needle-shaped negatively birefringent either free floating or within neutrophils & macrophages. Uric acid level is non specific. 30% may show normal level 24 hour Urine collection for urine uric acid estimation > 800 mg – Over producer (XO inhibitors) < 800 mg - under excretor (uricosuric) < 600 mg - purine-free diet Polarizing Light Microscopy

12 X-ray Findings in Gout Acute: Soft tissue swelling Chronic Chronic Tophaceous gouty arthritis, extensive bony erosions are noted throughout the carpal bones Sclerosis and joint-space narrowing are seen in the first metatarsophalangeal joint, as well as in the fourth interphalangeal joint. Punched out bony defects Retained bone density


14 ACR Criteria for Diagnosis Any 6 of following 1. More than one attack acute arthritis 2. Max. inflammation with in 1day 3. Erythema over joint 4. Podagra 5. H/o of Podagra 6. Unilateral tarsal involvement 7. Tophus 8. Hyperuricemia – serum uric acid > 7 mg% 9. Asymmetric swelling on X-ray 10. Subcortical cyst without erosion 11. Negative Culture for infective arthritis

15 Septic ArthritisCPPD – Pseudo GoutAcute Rheumatic FeverPalindromic RheumatismPsoriatic Arthritis Differential Diagnosis

16 Treatment Acute Attack NSAID’s in anti-inflammatory doses Colchicine 0.5 mg oral every 2 hours, may require 6 mg. Neutrophil micro tubular assembly inhibitor Stop with response or side effect (diarrhea, vomiting) Can be used for chronic disease, risk of BM suppression Joint aspiration followed by administration of IAS Oral Prednisone 30 – 60 mg/day for 1-2 weeks - taper ACTH IM/IV or Solumedrol Opiates and Tylenol for analgesia

17 Treatment Acute Gout NSAIDs Contraindicated?  Renal insufficiency  Peptic ulcer disease  Congestive heart failure  NSAID intolerance NSAIDs Contraindicated?  Renal insufficiency  Peptic ulcer disease  Congestive heart failure  NSAID intolerance Are Corticosteroids Contraindicated? Are Corticosteroids Contraindicated? NSAIDs Anti inflammatory doses NSAIDs Anti inflammatory doses Corticosteroids Oral Colchicine Oral or Intra articular Steroid Oral or Intra articular Steroid No # Joints Involved? # Joints Involved? Yes No Yes Lipsky PE, Alarcon GS, Bombardier C, Cush JJ, Ellrodt AG, Gibofsky A, Heudebert G, Kavanaugh AF, et al. Am J Med 103(6A):49S-85S, 1997 Intra articular PO Steroid Intra articular PO Steroid >1 1

18 High Purine Foods All meats, including organ meats Meat extracts and gravies, Sea foods Yeast and Yeast extracts Beer and other Ethanol containing beverages Beans, peas, lentils, oatmeal Spinach, Asparagus, Cauliflower, Mushrooms

19 Treatment Prophylaxis of Chronic Gout Diet low in purine - sea foods, meet Will decrease uric acid 1 mg/dL at best Weight loss is essential Limit consumption of Ethanol Modification of medications Avoid Salicylates, Diuretics, Niacin

20 Uric Acid Lowering Therapy (ULT) Never useful to treat acute attacks Two Approaches if SUA is more than 7 mg% Uricosuric therapy – Increasing UA excretion If the 24 hour uric acid excretion is < 800 mg Probenecid 500 mg, Sulfinpyrazone mg bid Urine out put of 2000 ml must be maintained Xanthine Oxidase (XO) inhibitors  UA Production Useful in over producers – urinary UA > 800 mg/24 Two drugs – Allopurinol, Febuxostat Precipitation of acute attack is problem

21 Treatment Chronic Uricosuric: for under excretors Probenecid (Benemid) Sulfinpyrazone (Anturane) - toxic side effects Avoid in patients with renal disease Consider NSAIDs to avoid exacerbation of gout Benzbromarone is a good agent

22 Probenecid Prophylaxis Initial 250 mg oral twice daily for 1 week Maintenance – uricosuric drug 500 mg oral twice daily If symptoms persist or If 24 h urate excretion below 700 mg Incrementally increase by 500 mg every 4 wks. Maximum of 2000 mg/day

23 Benzbromarone Benzbromarone (Benzarone) retains its uricosuric effect at doses of 25–150 mg/day in patients who have a creatinine clearance >25 mL/min. Good uricosuric effective and safe It is effective in mild to moderate disease May cause hepatotoxicity Limited availability

24 Treatment Chronic Indications for Allopurinol (Zyloric, Zyloprim) Tophaceous deposits Uric acid consistently > 9 mg% Persistent Symptoms with moderate UA levels Impaired renal function Prophylaxis for tumor-lysis syndrome Consider NSAID’s to avoid exacerbation

25 Allopurinol Indications for urate lowering therapy (ULT) Recurrent attacks, tophi, bone / joint damage Renal disease and/or nephrolithiasis,   SUA Mild Disease – Allopurinol is the drug of choice mg/day orally as a single or divided doses Moderate to severe - Allopurinol mg/day orally as a single or divided dose (2-3 times daily); maximum dose 800 mg/day It is a non selective Xanthine Oxidase (XO) inhibitor

26 Febuxostat It is recent selective XO inhibitor (Uloric) given as 80 mg daily single dose In those intolerant to Allopurinol In Renal insufficiency If target serum uric acid is not achieved High baseline serum uric acid levels Severe Tophaceous gout

27 Newer Drugs for Gout Febuxostat Pegloticase Losartan Fenofibrate Dietary supplements: Vitamin C

28 Pigloticase Intolerant to Allopurinol & Febuxostat Do not achieve target serum urate High baseline serum urate levels Severe Tophaceous gout Induction therapy

29 Other Drugs Losartan and Fenofibrate Hypertension or Hyperlipidemia present Mild effect Therapy for borderline Hyperuricemia Adjuvant therapy while on allopurinol Vitamin C Mild effect, not replicated instudies Borderline Hyperuricemia

30 Prognosis Generally good Acute attacks subside in weeks More severe course when Sx present < 30 y/o Up to 50% progress to chronic disease if untreated. Surgical intervention may be required for tophi. Secondary Osteoarthritis in chronic joint Tophi

31 Hyperuricemia Hyperuricemia is linked to comorbidities Obesity Hyperlipidemia Metabolic syndrome Hypertension Diabetes mellitus Renal disease Heart failure

32 Ten Commandments Fast acting NSAIDs are the drugs of choice for Acute Gout Anti inflammatory drug Rx. must be continued for 1-2 wks. Colchicine an effective alternative for NSAIDs. Slow to work IAS are highly effective in acute mono arthritis of Gout Oral or parenteral corticosteroids in NSAID intolerance Allopurinol should not be used in acute attack of Gout Allopurinol should be continued if the pt. is already receiving Diuretic use for hypertension to be changed to other agents Uricose uric Rx. Must be started after a second attack Newer drugs in refractory cases with high serum UA levels.

33 Hippocrates described gout as “the king of diseases and the disease of kings”

34 “The Management of Gout: It Should Be Crystal Clear” Robert L. Wortmann Editorial in J of Rheumatology Oct 2006

35 Case 1 56 yr postmenopausal female with sudden onset of acute pain in her right toe and knee. She had 3 previous episodes of the same symptoms lasting 4-5 days and treated. PM Hx HTN treated with thiazide diuretic and patient is trying to lose weight. BP138/86 BMI 32. PE remarkable for swollen & tender right great toe and knee. UA 8.3mg/dL, aspiration of her knee demonstrated WBC 15K and presence of urate crystals. Treatment includes all of the following except: A.Starting Allopurinol at 300mg/day with an NSAID for acute pain B.Discuss risk factors for gout to include obesity, but continue with weight loss and switching of the HTN medication. C. Start colchicine at 0.6mg bid and start uricosuric Rx. in 4 weeks D. Start Rx. for acute pain with NSAIDs, but withhold uricosuric Rx.

36 Case 2 50 yr. male with long-standing gouty arthritis. He had several attacks a year treated by OTC NSAIDs. The attacks have become more frequent and the NSAIDs are not controlling the pain. He has HTN for which he takes Captopril. On PE BP 135/85, BMI 31, Temp N. Exam remarkable for a small effusion over right knee and tophi noted over both olecranons. Labs UA 7.5mg/dL, ESR 23mm/hr WBC count N. X-rays of his knees noted narrowing of joint space with effusion. Best treatment option for this patient is A.Start colchicine 0.6mg bid and urate lowering Rx. with allopurinol B.Advise patient to discontinue NSAID therapy and use low dose prednisone daily for prophylaxis. C. Colchicine 0.6 mg bid and uricosuric Rx. with Probenecid D. Since patient is between attacks, just start urate lowering Rx.

37 Case 3 60 yrs male with persistent gout despite taking allopurinol daily at 100mg/day for the past year. He has a 20 year h/o of gout and was treated with NSAIDs for his acute flairs. However, once the attacks became more common, he was placed on chronic NSAID therapy. PM Hx significant for HTN and chronic renal insufficiency SCr PE: BP 125/73 BMI 34. No acute symptoms. Chronic synovial changes over wrists & left first MTP. Tophi over olecranon. UA 9.5 Best treatment option for this patient is A. Replace NSAIDs with prednisone. Do not change allopurinol dose B. Continue to increase allopurinol despite his renal issues to a dose that keeps UA level below 6.0mg/dL and replace NSAIDs C. Continue NSAID therapy for prophylaxis. Counsel pt. long term NSAID use and HTN can contribute to increasing renal disease. D. Discontinue all current meds and replace them with Colchicine E. None of the above

38 Case 4 A 62 yrs. male comes to you with pain and swelling over left great toe at MTP joint. Exam shows it is erythematous, warm swollen, tender to touch. No h/o previous such attacks. The patient has a history of DM controlled by diet and has HTN. His medications include HCTZ 25mg daily. A CBC and blood chemistry profile are normal except SUA 9.2 mg/dL. Which of the following is true in this situation A. This attack should resolve spontaneously in 2 days B. Allopurinol therapy should be started C. The elevated uric acid level establishes diagnosis of gout D. Intra-articular injection should be avoided E. Stopping the HCTZ may control Hyperuricemia

39 Case 5A A 32 yrs. male complains of pain of 12 hr duration in the MTP joint of large left toe. He states that the joint is very tender to touch and denies history of trauma. He is on no meds. Exam is within normal limits except for large area of erythema over his left large toe and up onto the dorsum of his foot. No lymphangitis or cellulitis is noted. Which of the following tests help you in a definitive diagnosis A. A gram stain of the fluid aspirated from the joint B. 24hr urine collection for protein C. An X-ray of foot and ankle D. Microscopic examination for crystals in the synovial fluid aspirate E. Intravenous pyelography

40 Case 5B A 32 yrs. male complains of pain of 12 hr duration in the MTP joint of large left toe. He states that the joint is very tender to touch and denies history of trauma. He is on no meds. Exam is within normal limits except for large area of erythema over his left large toe and up onto the dorsum of his foot. No lymphangitis or cellulitis is noted. Appropriate treatment choices may include which of the following A. Colchicine B. Probenecid C. Prednisone D. Indomethacin E. Allopurinol

41 Case 5C You are able to aspirate synovial fluid from the joint, to establish diagnosis of gout, which of the following joint findings will establish the diagnosis of gout? A. Negatively birefringent needle shaped crystals B. Positively birefringent needle shaped crystals C. Snowball like aggregate crystals D. Dumbbell and octahedron shaped crystals


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