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Gout

Gout ( podagra ) is the most common cause of inflammatory arthritis worldwide characterized by a raised uric acid level in the blood and deposition of urate crystals in joints and other tissues.
Background-Purines→ cyclical organic molecules Disorder of purine metabolism ↑ uric acid level in blood When plasma saturated with UA , UA crystals are liable to form
( usually > 0.415 mmol/ L or 6.8 mg / dL ) in joints & other tissues as connective tissues or the urinary tract Gout may present without hyperuricaemia and hyperuricaemia may occur without gout Clinical manifestation of gout may include
♦ Tophi ♦ Chronic arthritis ♦ Urolithiasis ♦ Renal disease ♦ Recurrent acute arthritis ♦ Bursitis ♦ Cellulitis
Excessive uric acid formation –Dietary → 
High purine diet
Alcohol excess Endogenous overproduction- several complex mechanisms may cause this Obesity Paget’s dis Haemolysis Myeloproliferative disorder Polycythemia vera Severe psoriasis Tissue necrosis Solid tumours
Reduced uric acid excretion-Excretion of UA is almost entirely by the kidney Reduced GFR ( any reason ) Hypertension Acidosis 
( Ketoacidosis , Lactic acidosis ) Starvation Polycystic kidney dis Hypothyroidism Hyperparathyroidism Diabetes insipidus Lead nephropathy Drugs ( aspirin , cyclosporine , L dopa , diuretics, ethambutol , pyrazinamide , nicotinic acid )
Both-↓ ed excretion and ↑ ed production Glucose 6 Phosphate dehydrogenase deficiency Alcohol ingestion Shock
risk factors –Alcohol ( ↑ with beer ) Age and sex 
( ↑ increasing age, Males , rare in pre menopausal women ) Diet → meat ↑ risk , consuming ↑ dairy products ↓ the risk Drugs ( eg diuretics , low dose aspirin ) Family history ( 20 % have a family hx ) Co-morbidities as
Hypertension , renal impairment , diabetes , myeloproliferative dis , hyperlipidaemia , vascular disease , severe psoriasis , enzyme defects
History-Previous attacks , frequency , duration
○ Big toe in 70% as 1st presentation
 In 90 % at some time during the disease
 Previous treatment
 Age of onset
○ Onset < 30 can suggest renal disease or enzymatic disorders 
 Can be associated with genetic causes
 May require more aggressive investigation and Rx
Acute gout-Monoarthritis with 1st Metatarsophalyngeal jt affected in over 70 % cases Begins early hrs of morning and can affect great toe , ankle , fingers , elbow or ocassionally knee Predisposition to affect colder peripheral jts Trauma or local metabolic changes → crystals of monosodium urate to be shed into the joint cavity Release of mediators ( cytokines , prostaglandins , free radicals etc ) causing local and systemic manifestations Jt is swollen , red and tender , overlying skin erythematous Resolves within 7-10 days even with no specific treatment Can also present as acute bursitis , tenosynovitis and polyarticular arthritis
Diagnosis- Joint aspirate in association with elevated plasma UA Plasma uric acid may ↑ during an acute attack but 1/3rd may have normal plasma levels WCC modest elevation ( very raised ct suspect septic arthritis )
Differential –Septic arthritis Non-urate crystal arthropathy as
○ Pseudogout ( CPPD )
○ Hysroxyapatite crystal deposition disease
○ Combined ( above two ) Psoriatic arthritis Reactive arthritis Rheumatoid arthritis Seronegative spondyloarthropathy Haemochromatosis
Further assessment –Assess CV risk Diabetes risk- fasting BM/ Hba1c Check FBC Renal profile Lipids Blood pressure BMI Smoking Alcohol
management acout gout-Full dose NSAID + PPI cover → cont treatment until 48 hrs after attack has resolved
OR
 Colchicine ( 500 mcgm 2-4 /day )
○ works by decreasing phagocytosis of UA crystals by neutrophils → limits inflammatory response
○ Works best when started within 1st day or two
-Can cause diarrhoea nausea and vomiting
-Requires adjustment in renal dis
-No
intrinsic analgesic effect

OR
 Corticosteroids → IM , intra-articular or Oral
Single dose of 80-120mg Methylprednisolone or 
Course of prednisolone starting with 30-60 mg / day
 Give Paracetamol with or without Codeine – if all of the above contra-indicated
 Advice to return in 3-4 days if symptoms worse or if no improvement

Algorithm- gout management –First line – Allopurinol
♦ start at low dose 50 to 100 mg / D
♦ Titrate in 50-100 mg increments /4 weeks
♦ Aim for sUA < 300 µmol/L
♦ Max 900 mg ( dependent on renal function )
 Consider prophylaxis with Colchicine 500 µg od-bd or NSAID / coxib + PPI Consider switch to Febuxostat 80 mg od Increase Febuxostat to 120 mg after 4 weeks if target sUA not reached ( < 300 )-Consider switch to Sulfinpyrazone or Probenecid or Benbromarone * Titrate dose every 4 weeks based on sUA-Consider reducing ULT dose to maintain sUA between 300 and 360 Check ULT annually to ensure target still maintained → adjust dose as needed Continue ULT lifelong unless modifiable risk factors successfully addressed and clinical ” cure ” achieved
Referral-If septic arthritis suspected → admit Diagnosis uncertain Suspicion of underlying systemic illness eg Rh arthritis or connective tissue disorder Gout and pregnant < 25 yrs of age Complications present as
♦ urate kidney stones ♦ urate nephropathy
♦ troublesome tophi
Allopurinol or Febuxostat at max dose but recurrent attacks continue Persistent symptoms during an acute attack despite max doses of NSAIDs
 ( alone or in combination ) Intra-articular steroid inj indicated but expertise lacking
The most important change by the British Society for Rheumatology guideline of May 2017 is that ” curative treatment with urate lowering drugs should be offered to all patients with gout early in the course of their disease rather than waiting for them to develop troublesome , disabling symptoms ” . Guideline updated because
 availability of new pharmaceutical treatment options recent increases in the incidence , prevalence and severity of gout continuing suboptimal management in both primary and secondary care better understanding of patient and provider barriers to effective care
Assess lifestyle factors – diet , exercise, alcohol , sugary drinks Assess cardiovascular risk factors
♦ obesity ♦ hypertension ♦ lipids ♦ diabetes Review prescribed medications – eg diuretics Test uric acid , renal function
Patient education Optimise weight Modify diet Reduce alcohol intake Discontinue diuretics ( where relevant / possible ) Treat underlying CV risk factors Discuss uric acid lowering therapy

LINKS AND RESOURCES

INFORMATION FOR PATIENTS
UK Gout Society A concise resource with fact sheets which can be downloaded, a section for health professionals is also very useful http://www.ukgoutsociety.org/resources.htm
Versus arthritis 28 page gout leaflet from Arthritis Research UK https://www.versusarthritis.org/media/1253/gout-information-booklet.pdf
Single page printable information from Arthritis Australia https://arthritissa.org.au/downloads/2015-05-11_222937_Gout.pdf
Arthritis Australia on diet and gout https://arthritisaustralia.com.au/managing-arthritis/living-with-arthritis/healthy-eating/gout-and-diet/
A complete educational resource for those who are internet users from HSS Physicians https://www.hss.edu/conditions_gout-risk-factors-diagnosis-treatment.asp
Arthritis Foundation on gout https://www.arthritis.org/diseases/gout
Render dietary advice on gout using the Oxford University Hospitals sheet on dietary advice https://www.ouh.nhs.uk/patient-guide/leaflets/files/44690Pgout.pdf
A few leaflets on ALLOPURINOL
Arthritis Australia https://rheumatology.org.au/patients/documents/Allopurinol_2016_002.pdf
NHS https://www.nhs.uk/medicines/allopurinol/ 
FEBUXOSTAT – versus arthritis https://www.versusarthritis.org/about-arthritis/treatments/drugs/febuxostat/
FURTHER READING FOR HEALTH CARE PROFESSIONALS

The British Society for Rheumatology Guideline for the Management of Gout Michelle Hui, Alison Carr, Stewart Cameron, Graham Davenport, Michael Doherty, Harry Forrester, Wendy Jenkins, Kelsey M. Jordan, Christian D. Mallen, Thomas M. McDonald … Show more  Rheumatology, Volume 56, Issue 7, July 2017, Pages e1–e20, https://doi.org/10.1093/rheumatology/kex156

American Collge of Rheumatology on Gout https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Gout

Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians FREE Amir Qaseem, MD, PhD, MHA; Russell P. Harris, MD, MPH; Mary Ann Forciea, MD; for the Clinical Guidelines Committee of the American College of Physicians * https://annals.org/aim/fullarticle/2578528/management-acute-recurrent-gout-clinical-practice-guideline-from-american-college

European Medicine Agency -Guideline on clinical investigation of medicinal products for the treatment of gout https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-treatment-gout-first-version_en.pd

2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout https://ard.bmj.com/content/79/1/31

 
References:

  1. Gout treatment algorithm available from http://www.wales.nhs.uk/sites3/documents/814/
gout-abuhbguidelinesfinal%5bjune2015%5d.pdf
  2. Medicine compendium https://www.medicines.org.uk/emc/medicine/21325#PHARMACOLOGICAL_PROPS
  3. Hyperuricemia http://emedicine.medscape.com/article/241767-overview#a6
  4. Crash Course Rheumatology and Orthopaedics Cameron Elias-Jones and Martin Perry
  5. The British Society for Rheumatology Guideline for the Management of Gout Rheumatology ( Oxford ) kex156 may 2017
  6. CKS NHS Gout
  7. Gout from StatPearls by Ardy Fenando and Jason Widrich accessed via https://www.ncbi.nlm.nih.gov/books/NBK546606/

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