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Rheumatoid arthritis in adults

Gout - Management. 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

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Rheumatoid arthritis in adults

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  1. Gout - Management 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 Rheumatoid arthritis in adults Implementing NICE guidance www.drsarma.in drsarmaji YouTube

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

  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 Acute Inflammatory Mono Arthritis Serum hyper uricemia > 7 mg % Tophaceous urate crystal deposit GOUT Interstitial Renal urate deposition Urolithiasis and Nephropathy

  5. 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

  6. Signs and Symptoms • Acute attack • With in few hours - frequently nocturnal • Excruciating pain – worst pain ever experienced • Swelling, redness and tenderness • Podagra: 1st 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

  7. Sequence of Progression

  8. 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

  9. 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

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

  11. 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 40-80 IM/IV or Solumedrol • Opiates and Tylenol for analgesia

  12. No Yes No Yes # Joints Involved? 1 >1 NSAIDs Contraindicated? • Renal insufficiency • Peptic ulcer disease • Congestive heart failure • NSAID intolerance NSAIDs Anti inflammatory doses Corticosteroids Are Corticosteroids Contraindicated? Treatment Acute Gout Oral Colchicine Intra articular PO Steroid Oral or Intra articular Steroid 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

  13. 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

  14. 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

  15. 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 50-100 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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 • 100-300 mg/day orally as a single or divided doses • Moderate to severe - Allopurinol • 400-600 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

  21. 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

  22. Newer Drugs for Gout • Febuxostat • Pegloticase • Losartan • Fenofibrate • Dietary supplements: Vitamin C

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

  24. 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

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

  26. 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.

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

  28. Thank you all

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