LO STATO DELL ARTE NELLA GESTIONE DELLA GOTTA

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1 55 Congresso Nazionale SIGG LA GOTTA: UNA MALATTIA MISCONOSCIUTA NELL ANZIANO? LO STATO DELL ARTE NELLA GESTIONE DELLA GOTTA Marco A Cimmino Clinica Reumatologica, DI.M.I. UNIVERSITA DI GENOVA cimmino@unige.it

2 WHY IS GOUT OF PARTICULAR IMPORT IN PRESENT TIMES? Frequency Changing clinical spectrum (more women, more old aged, more often the upper limb) Metabolic implications Underdiagnosis and undertreatment New mechanisms (inflammasome, IL 1) New treatments (anti IL 1, febuxostat, uricase) Potential usefulness of imaging 2

3 INFLAMMATION DAMAGE Asymptomatic hyperuricaemia Acute intermittent attacks Chronic tophaceous gout

4 INFLAMMATION DAMAGE Asymptomatic hyperuricaemia Acute intermittent attacks Chronic tophaceous gout?

5 Criteri ACR per la diagnosi di artrite gottosa: 1. Presence of monosodium urate crystals in synovial fluid AND/OR 2. Tophus that contains urate crystals by chemical or polarized light microscopy AND/OR 3. The presence of six of the following: a. One attack of acute arthritis b. Maximal inflammation occurring within one day c. Attack of monoarticular arthritis d. Presence of joint redness e. First metatarsophalangeal joint painful or swollen f. Unilateral attack involving first metatarsophalangeal joint g. Unilateral attack involving tarsal joint h. Suspected tophus i. Hyperuricemia j. Radiographic evidence of joint swelling k. Radiographic evidence of subcortical cysts without erosions l. Negative synovial fluid culture during acute attack 4

6 Radiologo di 50 anni con iperuricemia asintomatica da almeno 20 e recente riscontro di nodulo artrosico dell interfalangea distale del 5 dito. Mai attacchi acuti, non dolorabilità locale. 5

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11 In corso di iperuricemia si può verificare un danno articolare cronico asintomatico con lesioni anatomiche erosive *

12 7/ /2007 2/2008 artrite acuta remissione colchicina Uomo di 43 anni con una storia di gotta da 6 anni, che ha presentato una artrite oligoarticolare interessante anche il polso per la prima volta a luglio 2007

13 INFLAMMATION DAMAGE Asymptomatic hyperuricaemia Acute intermittent attacks Chronic tophaceous gout

14 INFLAMMATION DAMAGE Asymptomatic hyperuricaemia Acute intermittent attacks Chronic tophaceous gout US? MRI? wrist? Tendons? Asymptomatic hyperuricaemia Asymptomatic gout

15 COME COMPORTARSI DI FRONTE AD UN PAZIENTE GOTTOSO Terapia dell artrite gottosa acuta Suggerimenti di stile di vita Terapia della gotta cronica Profilassi degli attacchi acuti Asymptomatic hyperuricaemia Acute intermittent attacks Chronic tophaceous gout 9

16 Treatment options during acute attack Nonpharmacological Colchicine NSAIDs or coxibs Corticosteroids (systemic and i.a.) Rest Cold packs Considerations Caution with renal or hepatobiliary dysfunction, active infection Drug interactions Can cause diarrhoea, GI upset with high doses IV colchicine should not be used Ulcer disease, GI bleeds, NSAID-induced asthma or renal dysfunction Interaction with warfarin No relevant side effects in acute use Chronic use complications GI toxicity Potential for serious side effects Hypertension Hyperglycaemia Osteoporosis Anakinra IPOURICEMIZZANTI? 10

17 Treatment options during acute attack Nonpharmacological Colchicine NSAIDs or coxibs Corticosteroids (systemic and i.a.) Rest Cold packs Considerations Caution with renal or hepatobiliary dysfunction, active infection Drug interactions Can cause diarrhoea, GI upset with high doses IV colchicine should not be used Ulcer disease, GI bleeds, NSAID-induced asthma or renal dysfunction Interaction with warfarin No relevant side effects in acute use Chronic use complications GI toxicity Potential for serious side effects Hypertension Hyperglycaemia Osteoporosis Anakinra IPOURICEMIZZANTI? 10

18 Arthritis Rheum 2010; 62:

19 Lifestyle changes recommended in gout Diet Reduce purine intake (reduce red meat, butter, avoid liver, kidneys, shellfish and pulses Hülsenfrüchte ) Reduce fructose containing drinks Include skimmed milk, low fat yoghurt, vegetable protein and cherries every day, vitamin C rich food Decrease alcohol consumption (especially beer) Weight loss 1 kg/month (avoid crash diets) Avoid high protein diets Patients with urolithiasis should be encouraged to drink >2 L of water/day Moderate exercise Lifestyle changes have only modest effects on sua (eg 10 15% reduction with a low purine diet), hence drug therapy is usually required 12

20 Choi HK, Curhan G. Curr Opin Rheumatol 2005; 17: Choi HK, et al. Lancet 2004; 363: Choi HK, et al. N Eng J Med 2004; 350:

21 Induction of acute gouty arthritis by intra articular injection of MSU + free fatty acids C18:0. Inflammation dependent on ASC and caspase 1, but not on NLRP3 Joosten et al. Arthritis Rheum 2010; 62:

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24 Ann Rheum Dis 2010; 69: Ann Rheum Dis 2010; 69:

25 EVIDENZA DELL UTILITA DI DIMINUIRE L URICEMIA Una uricemia inferiore a 5 mg/dl determina: Scomparsa o diminuzione degli attacchi acuti Becker at al (Arthritis Rheum, 2004) Meno cristalli nelle articolazioni LiYu et al (J Rheumatol, 2001) Riduzione del volume dei tofi Perez Ruiz et al (Arthritis Rheum, 2002) Assenza di recidive dei depositi tofacei Gast et al (Clin Rheumatol, 2000) % incidence of recurrent gouty attack more than 1 year after each patient s first visit 100% 80% 60% 40% 20% 0% Urate solubility at: 35 o C 37 o C Observed Logistic regression 0.30 (5) 0.36 (6) 0.42 (7) 0.48 (8) 0.54 (9) 0.60 (10) Average serum urate level during the whole investigation period in mmol/l (mg/dl) Shoji A, et al. Arthritis Rheum. 2004; 51(3):

26 TERAPIA IPOURICEMIZZANTE Allopurinolo Dosaggio fino a 900 mg! Febuxostat Sulfinpirazone off label Uricase se non efficace, causa di effetti collaterali, o in pazienti difficili 18

27 Differences Between Febuxostat and Allopurinol Chemical structure and activity Efficacy Excretion Dosing Dosing in renal insufficiency Febuxostat Non-purine, selective inhibitor of xanthine oxidase Effective at achieving <6 mg/dl (<0.36 mmol/l) Primarily eliminated through the liver* Effective at the lowest dose (80 mg) Safe at standard doses Allopurinol Purine, nonselective inhibitor of xanthine oxidase Less effective at achieving <6 mg/dl (<0.36 mmol/l) Primarily eliminated through the kidney Needs to be titrated up (from 100 mg) Dosage adjustment required *No dosage adjustments required in mild to moderate hepatic impairment. 19

28 Phase II Dose Response Study TMX % of Subjects Proportion of Subjects With sua <6 mg/dl (<0.36 mmol/l) at Final Visit % Placebo (N=35) * 56% 40 mg (N=34) * 76% 80 mg (N=37) * 94% 120 mg (N=34) *p<0.001 vs placebo Becker MA, et al. Arthritis Rheum. 2005; 52:

29 Schumacher HR, et al. Arthritis Rheum 2008; 59:

30 PEGLOTICASE TREATMENT IN GOUT Baraf HSB et al. Arthritis Rheum 2008; 58:

31 Colchicine for prophylaxis Colchicine prophylaxis during initiation of ULT for chronic gout: Reduces the frequency and severity of acute flares Reduces the likelihood of recurrent flares Evidence supports the use of low dose colchicine for up to for 6 months following initiation of urate lowering therapy Borstad GC, et al. J Rheumatol. 2004; 31(12):

32 Harrod LR, et al. Arthritis Res Ther 2009; 11R46 24

33 GLI IPERURICEMICI SONO PIU INTELLIGENTI? Acido urico tipico dei primati tra i mammiferi Possibile stimolante corticale Numerosi uomini famosi della storia erano gottosi JAMA 1966; 195: