Gout

Crystal-induced arthritides

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MSU (monosodium urate)CPPD (calcium pyrophosphate dihydrate)HA (calcium hydroxyapatite)Calcium oxalate (CaOx)

DefinitionGout is an inflammatory arthritis associated with hyperuricaemia

Acute and chronic arthritis


Acute arthritis is the most frequent early clinical manifestation of MSU gout.

Usually only one joint is affected initiallyPolyarticular acute gout is also seen in male

hypertensive patients with ethanol abuse as well as in postmenopausal women.


The metatarso phalangeal joint of the first toe is often involved.

Ankles, and knees are also commonly affected.

In elderly patients, finger joints may be inflamed.

Epidemiology

Prevalence of hyperuricaemia 5%Prevalence of Gout 0.2%M:F ratio 10:1Hyperuricaemia is defined as >2 SD from

mean 420 μmol in males and 360 μmol/l in females.


Urate production varies with the purine content of the diet and the rates of purine biosyntesis, degradation and salvage.


2/3 to ¾ of urate is excreted by kidneys, and most of the remainer is eliminated through the intestines.

Factors associated withHigh Uric acid

1. Increasing age2. Obesity3. High protein diet4. High alcohol consumption5. Combined hyperlipidemia6. Diabetes mellitus7. Ischaemic heart disease8. Hypertension

Causes of hyperuricaemia

Impaired excretion of uric acid

Increased production of uric acid

Cause of hyperuricaemia

90% have decreased excretion10% have increased production1% have in born error of metabolism like

HGPRT def or PRPP overactivity

Uric acid synthesis

Uric acid is the last step in purine breakdownConversion of hypoxnthine to xanthine and

xanthine to Uric acid is catalysed by Xanthine Oxidase


Serum urate levels vary with age and sex.Children: 3 to 4 mg/dlAdult men: 6 to 6.8 mg/dl

Hyperuricemia


Defined as a plasma urate concentration > 7.0 mg/dl

Combined Mechanisms


Alcohol intake promotes hyperuricemia:

Fast hepatic breakdown of ATP and increases urate production.

Can induce hyperlacticacidemia, and inhibition of uric acid secretion.

The higher purine content in some alcoholic beverages such as beer may also be a factor.

Causes of hyperuricemia


PrimaryNo recognized causeHypoxanthine

phosphoribosyltransferase deficiency

Increased phosphoribosyl pyrophosphatase activity.

SecundaryHereditary fructose

intoleranceMieloproliferative

diseaseLinfoproliferative

diseaseHemolitic anemiaDrugs: Low-doses

salicylate, diuretis, pyrazinamide, ethambutol, nicotinamide, etanol


Several events may precipitate acute gouty arthritis: Dietary excess Trauma Surgery Excessive ethanol ingestion Glucocorticoid withdrawal

Uric acid excretion

UA is completely filtered by glomerulusAlmost 100% is reabsorbed by proximal

tubule50% is re-excreted by distal tubuleLow dose aspirin blocks secretionHigh dose aspirin blocks reabsorption

Impaired excretion

Chronic renal failureDrugs: thiazides, low dose aspirinHypertenionLead toxicityPr. HyperparathroidismHypothyroidism↑lactic acid production: alcohol,

exercise,starvationG 6 PD deficiency

Increased production

Lesch Nyhan Syndrome (HGPRT deficiencyPRPP overactivityG6 PD deficiencyIncreased purine turnoverMyeloproliferative disorders eg

Polycythemia rubra veraLymphoproliferative disorders like leukemiaCarcinoma esp after chemo, severe

psoriasis

CLINICAL FEATURES OF HYPERURICAEMIA

Acute Urate synovitis-goutChronic polarticular goutChronic tophaceous goutUrate renal stones

Acute Gout

Sudden onset of severe agonizing pain, swelling of 1st MTP joint

Too painful to touch or movePrecipitated by food, exercise, alcohol or

diureticUsually recovers in 7 daysTypically associated with desquamation of

overlying skin

Investigations

Joint fluid microscopySpecificTechnically difficultSerum Urate usually raised, may fall after an

acute attackte and creatinineMonitor serum ur

Treatment

High Dose NSAIDsRapid responseNaproxen 750 mg initially then 500mg bidDiclofenac 75-100 mg intially then 50 mg bid

or tidIndomemethacin 75 mg initially the 50 mg

bid or qid

Alternative treatments

Colchisine 1000mg initially then 500mg bid to qid ((DIARRHOEA))

Corticosteroids ((intramuscular or intra articular))– depot methylpredisolone

Reduction of Serum Urate

Dietary adviceWeight reductionAdvice on alcohol consumption

Pharmacological agents

Decrease Uric acid production ((ALLOPURINOL))

Increase Uric acid excretion((PROBENECID))

A word about Allopurinol

Relatively safe drugCan cause rashes and rarely bone marrow

suppressionUse only in frequent and severe attacks

when diet and life style modification has failed to prevent acute attacks

DO NOT USE within ONE MONTH of acute attack

Started under cover of NSAIDs

Chronic polyarticular gout

Elderly on long term diuretic treatmentRenal failureAllopurinol treatment started soon after

acute to gout

Chronic tophaceous gout

Sodium urate forms white smooth deposits in skin and around joints

Typical sitesEar lobes, fingers and Achilles tendonCan ulcerateCauses bone destruction (punched out) bone

cysts on x-raysOften accom. by renal impairmrnt

Psudogout ((Pyrophosphate athropathy))

1. Another form of crystal arthropathy2. Can resemble acute gout3. Affects elderly women 4. Usually affects knees and wrists

5. Caused by deposition of Calcium pyrophosphate crystals

Associations of pseudogout

HaemochromotosisHyperparathyoidismWilson’s diseasealkaptonuria

Diagnosis

Chondrocalcinosis on xraysJoint aspiration and polarised microscopy to

reveal WEAKLY POSITIVE RHOMBOIDAL crystals

Gout

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