Gout Asad Khan Consultant Rheumatologist Heart of England NHS Foundation Trust

Overview Background Diagnosis Risk factors Acute treatment Long-term treatment Pseudogout

Gout Inflammatory arthritis due to monosodium urate crystal deposition Presents with acute self-limiting attacks of severe pain Chronic – causes tophaceous deposits, joint damage and chronic pain Rising prevalence (2.49% in 2012) Curable!

Blue: men Red: women Green:overall (Kuo et al, Ann Rheum Dis Blue: men Red: women Green:overall (Kuo et al, Ann Rheum Dis. 2015 Apr; 74(4): 661–667.)

Neutrophil activation Purine Hypoxanthine Adenine Xanthine Chemistry Inosine Uric acid Guanosine Deposition Excretion Neutrophil activation

Risk factors Male/post menopausal Metabolic syndrome Diet High purine intake Alcohol (beer/spirits) Fructose Drugs, including: Diuretics Low dose aspirin Ciclosporin Increased cell turnover (malignant/haematological) Genetic predisposition/disease Lead (saturnine gout)

Diagnosis Gold standard In clinical practice Diagnostic aspiration and polarised light microscopy In clinical practice Characteristic patterns of disease presentation Can be difficult to distinguish from septic arthritis

Microscopy

Podagra

Tophi

Othe tests Bloods XRs Ultrasound/CT? Urate in “intercritical” period Punched out periarticular erosion Ultrasound/CT?

Treating acute attacks Full dose NSAID Beware of comorbidities, especially renal impairment Colchicine 500mcg 2-4 day Adjust if low GFR Drug interactions – including statins Prednisolone Non genomic vs genomic doses (30-35mg is evidence based) Intrarticular glucocorticoid injection Combination

Neutrophil activation Xanthine Oxidase Purine Hypoxanthine Adenine Xanthine Chemistry Inosine Uric acid Uricase Anti IL-1 Guanosine (Allantoin) Uricosuric Neutrophil activation Excretion

Dietary exclusion High purine content – avoid Oily fish, shellfish Game Offal Marmite/yeast extract Moderate purine content – in moderation Meat/chicken Beans/legumes/peas Spinach/cauliflower/asparagus Mushrooms Wholegrains Alcohol

Dietary inclusion Low purine – fine to eat Bread/pasta Milk (milk protein uricosuric?) Eggs Other fruit and vegetables Butter, cheese, ice cream, chocolate, cake (beware comorbidities…) Low fat dairy and vegetable protein sources Black cherry

Pharmacological treatment Review regular medications Treat acute attack first Discuss urate lowering therapy at first attack, offer if >1 attack/year Reducing uric acid can precipitate/extend attack Prophylactic therapy along with urate lowering drug Target uric acid <300 umol/l (or <360)

Prophylactic treatment Up to 6 months Low dose colchicine 500mcg once daily Long term NSAID IM depomedrone 120mg

Xanthine oxidase inhibitors Allopurinol Start at 100mg, build up to 300mg Up to 900mg titrated against serum uric acid Adjust dose in CKD Beware drug reactions (inc DRESS) Febuxostat 80mg or 120mg Safe in mild/moderate renal impairment Contraindicated in ischaemic heart disease/heart failure

Uricosuric Formulary – probenecid Others – sulfinpyrazone, benzbromarone (latter associated with liver toxicity) Coming soon – lesinurad? Locally initiated in secondary care

Medication review Reduce/avoid diuretics Uricosuric drugs Bumetanide? Losartan Fenofibrate Atorvastatin

Others IL-1 inhibitors Uricase Eg Anakinra, canakinumab Not NICE approved (anakinra not licensed) Uricase Pegloticase – not NICE approved Rasburicase – to prevent tumour lysis syndrome

Uric acid and cardiovascular risk Noted association between gout and cardiovascular disease Is serum uric acid an independent risk factor? Trend of association with: Hypertension IHD/heart failure CKD Diabetes Only proven associations: gout, nephrolithiasis Is low serum uric acid harmful? Reactive oxygen species scavenger, possible association with neurodegenerative diseases Currently – raised serum uric acid not an indication for treatment But diagnosis of gout should prompt for assessment of cardiovascular risk

Pseudogout Calcium pyrophosphate crystal deposition Large joints – knee, wrist, hip Risk factors Age Hyperparathyroidism Haemochromatosis Other calcium haemostasis disoders Acute attacks – treat as for gout Prophylaxis – none available

(University of California, San Diego)

Summary Commonest inflammatory arthritis Generally diagnosed by pattern of disease rather than joint aspiration Treatment: Acute Followed by urate lowering therapy Lifestyle Pharmacological With prophylaxis See BSR (2017) and EULAR (2016) guidelines