Rheumatoid arthritis, seronegative spondylarthritides and gout. György Nagy

Transcription

1 Rheumatoid arthritis, seronegative spondylarthritides and gout György Nagy Dec 4, 2017

2 Rheumatoid arthritis

3 Rheumatoid arthritis Chronic, progressive, autoimmune disorder of the joints with extra-articular features. Prevalence: 1% ( %) Female/male = 3:1 Age at onset years

4 Early RA

5 Advanced RA

6 End stage RA

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8 Extra-articular features

9 Extra-articular features

10 The pathogenesis of rheumatoid arthritis Iain B. McInnes, F.R.C.P., Ph.D., and Georg Schett, M.D. N Engl J Med 2011;

11 The pathogenesis of rheumatoid arthritis Iain B. McInnes, F.R.C.P., Ph.D., and Georg Schett, M.D. N Engl J Med 2011;

12 Autoantibodies in RA Rheumatoid factor - against the Fc portion of IgG - occurs in 70% of the RA patients - not specific for RA Autoantibodies targeting citrullinated proteins - highly specific for RA - occurs in 70% of the RA patients

13 The pathogenesis of rheumatoid arthritis Baka Z, Buzás E, Nagy G - Arthritis Res. Ther. (2009)

14 DAS 28 = disease activity score Swollen and tender joints, patient s global opininion, CRP or We

15 Synthetic DMARD, NSAID and steroid therapy in RA Philip S. Hench and Edward C. Kendall Mayo Clinic, 1950 Nobel Prize

16 Biological therapy in RA & side effects Ronald F. van Vollenhoven Nature Reviews Rheumatology 7, (April 2011)

17 Ankylosing spondylitis

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32 Ankylosing spondylitis

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35 Gout

36 Gout 400 BC. Hippokrates podagra- foot pain (greek) 190 AD. Galenus: tophus 1679 Antonij van Leeuwenhoek, crystal identification from tophus Sydenham: description of the disease Antonij van Leeuwenhoek Heberden arthrosis

37 Gout acute or chronic arthritis primary or secondary hyperuricaemia >10% of the adult population male: >420umol/l female:>360 umol/l increased production, or decreased excretion of uric acide prevalance of gout: % acute disease affects I. MTP in 75% of cases

38 Diagnosis of gout monosodium urate monohydrate crystals in joint fluid or 6 from 1. more than one attack of acute arthritis 2. maximum inflammation developed within 1 day 3. monoarthritis attack 4. redness observed over joints 5. first metatarsophalangeal joint painful or swollen 6. unilateral first metatarsophalangeal joint attack 7. unilateral tarsal joint attack 8. tophus (proven or suspected) 9. hyperuricemia 10. asymmetric swelling within a joint on x ray* 11. subcortical cysts without erosions on x ray 12. Wallace SL joint et al Arthritis fluid Rheum culture 1977;20: negative for organisms during attack

39 Drug and lead induced gout diuretics (tubular reabsorption ) cyclosporine (uric acid excretion ) aspirin heparin chronic lead intoxication

40 Serum uric acid level influenced by: serum creatinine (GFR) weight age blood pressure alcohol consumption beer consumption (high guanosine cc.)

41 EULAR recommendations 1. Zhang W, Doherty M, Pascual E et al.: EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the standing committee for international clinical studies including therapeutics (ESCISIT). Ann Rheum Dis 2006; 65: Zhang W, Doherty M, Bardin T et al.: EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the standing committee for international clinical studies including therapeutics (ESCISIT). Ann Rheum Dis 2006; 65:

42 Diagnosis of gout 10 recommendations 1. in acute attacks the rapid development of severe pain, swelling, and tenderness that reaches its maximum within just 6 12 hours, especially with overlying erythema, is highly suggestive of crystal inflammation though not specific for gout

43 Definitive diagnosis 2. for typical presentations of gout (such as recurrent podagra with hyperuricaemia) a clinical diagnosis alone is reasonably accurate but not definitive without crystal confirmation 3. demonstration of MSU crystals in synovial fluid or tophus aspirates permits a definitive diagnosis of gout

44 Joint puncture 4. a routine search for MSU crystals is recommended in all synovial fluid samples obtained from undiagnosed inflamed joints 5. identification of MSU crystals from asymptomatic joints may allow definite diagnosis in intercritical periods

45 Differential diagnosis 6. gout and sepsis may coexist, so when septic arthritis is suspected Gram staining and culture of synovial fluid should still be performed, even if MSU crystals are identified

46 Hyperuricaemia 7. while being the most important risk factor for gout, serum uric acid levels do not confirm or exclude gout, as many people with hyperuricaemia do not develop gout, and during acute attacks serum levels may be normal attack/year <7,0 7,0-7,9 8,0-8,9 >9,0 mg/dl

47 Diagnostics of gout 8. renal uric acid excretion should be determined in selected gout patients, especially those with a family history of young onset gout, onset of gout under age 25, or with renal calculi purin free diet 600mg/day normal diet 800mg/day

48 Radiographs 9. although radiographs may be useful for differential diagnosis and may show typical features in chronic gout, they are not useful in confirming the diagnosis of early or acute gout untreated gout, after 7 years

49 Risk factors 10. risk factors for gout and associated comorbidity should be assessed, including features of the metabolic syndrome (obesity, hyperglycaemia, hyperlipidaemia and hypertension) acidosis rare with gout: RA, SLE, AS

50 20-40% of patients have mild albuminuria urat nephropaty, urat crystals in the medulla interstitium uric acide nephropaty: urate cristals in the collecting ducts, may lead to acute renal failure, eg: during chemotherapy nephrolithiasis Renal involvement

51 Famous gout sufferers. Isaac Newton Henry VIII Benjamin Franklin

52 Treatment of gout 1. optimal treatment of gout requires both non-pharmacological and pharmacological modalities and should be tailored according to: (a) specific risk factors such as levels of serum urate (b) clinical phase (c) general risk factors such as: age, sex, obesity, alcohol consumption

53 2. patient education and appropriate lifestyle advice regarding weight loss if obese, diet, and reduced alcohol (especially beer) are core aspects of management Patient education

54 Comorbidity 3. Associated comorbidity and risk factors such as hyperlipidaemia, hypertension, hyperglycaemia, obesity and smoking

55 Treatment of acute gout 4. oral colchicine and/or NSAIDs are first line agents for systemic treatment of acute gout 5. high doses of colchicine lead to side effects, and low doses (for example 0.5 mg three times daily) may be sufficient colchicine targets neutrofil granulocytes

56 Treatment of acute gout 6. intra-articular aspiration and injection of a long acting steroid is an effective and safe

57 Urate lowering therapy 7. urate lowering therapy is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout

58 Allopurinol

59 Therapeutic goal 8. the therapeutic goal of urate lowering therapy is to promote crystal dissolution serum uric acid below the saturation point for monosodium urate ( 360 µmol/l or 6 mg/dl)

60 Therapy of gout 9. allopurinol is an appropriate long term urate lowering therapy started at a low dose (100 mg daily) and increased by 100 mg every two to four weeks if required 10. uricosuric agents such as probenecid and sulphinpyrazone and can be used in patients with normal renal function but are relatively contraindicated in patients with urolithiasis

61 Dose of allopurinol in case of impaired renal function creatinine clearence ml/min dose of allopurinol 20 1x100 mg 40 1x150 mg 60 1x200 mg >100 1x300 mg

62 Prophylaxis 11. during the first months of urate lowering therapy can be achieved by colchicine (0.5 to 1 mg daily) and/or an NSAID

63 Secondary gout 12. when gout associates with diuretic therapy, stop the diuretic if possible consider the use of losartan and fenofibrate, respectively (both have modest uricosuric effects) secondary gout may be induced by: cyctostatic agents, thiazide, furosemid cyclosporine-a

64 Summary: therapy of gout

65 Thank you for your attention