Gout

DefinitionElbow Gout

 

Heterogeneous group of diseases characterised by

- hyperuricaemia

- recurrent attacks of acute arthritis

 

Diagnosis confirmed by

- crystals of Monosodium Urate in synovial fluid

- tophi ("Porous stone") urate in soft tissues

- renal urate stones

 

Epidemiology

 

Adult men

- M:F = 20:1

- peak 40-60 years

 

Part of metabolic syndrome

- obese / HTN / high cholesterol / diabetes

 

Often have positive FHx

 

Physiology

 

Prerequisite is hyperuricaemia at some stage

- determined by balance between production & excretion

 

Production

- breakdown of nucleic acids

- oxidation of Purine bases (Guanine & Adenine)

- converted Inosine > Hypoxanthine > Xanthine > Uric Acid

 

Excretion

- 2/3 excreted into urine

- 1/3 into GIT

- uric acid filtered at glomerulus

- reabsorbed in PCT 

- secreted in subsequent PCT

 

Classification

 

A.  Overproducers ~ 10%

 

Primary

 

Disturbance of Purine biosynthesis secondary to heritable error of metabolism

- usually idiopathic

- some specific enzyme known eg Lesch-Nyhan syndrome

 

Lesch-Nyhan Syndrome

- rare 

- X-linked recessive

- absence of enzyme in purine pathway HGPRT

- leads to excessive uric acid formation & gout

- young boys with mental retardation and self-mutilation

 

Secondary

 

Diet high in purines

- alcohol / meat / seafood

Myeloproliferative disease

- leukaemia

Chronic hemolysis

Chemotherapy

Drugs eg salicylates, thiazide diuretics

Starvation, ketoacidosis

Alcoholism

 

B.  Under-excretors ~ 90%

 

Secondary abnormal renal excretion of Uric acid

- diuretics

- CRF

 

Pathogenesis

 

Acute Gouty Arthritis

 

Sustained hyperuricaemia 

 

Develop monosodium urate deposits

- in synovial lining cells & in cartilage on PG which are inert

- subsequently released into synovial fluid & CT 

- precipitates at > 8 mg/dl (trauma, low pH)

 

Sufficient number of crystals in joint precipitates acute inflammation

- phagocytosis of crystals

- release of chemotactic factors & inflammatory mediators

- activate complement & platelets

- disrupt lysosomes in leucocytes with cell rupture 

 

Chronic Gouty Arthritis

 

Tophi of Monosodium Urate Monohydrate Crystal aggregates

- deposited in synovium, cartilage & tendon sheaths

- lead to cartilage destruction & periarticular cyst formation

 

4 stages

 

1. Initial asymptomatic hyperuricaemia

 

2. First attack of acute gouty arthritis

 

3. When this settles, hyperuricaemia persists

- recurrent attacks

- frequency of attacks varies, may increase

 

4. Chronic gout

- joints no longer recovering from acute attacks

- arthritis & tophi develop

 

NHx

 

Hyperuricaemia

- in men begins at puberty

- in women starts at menopause

 

Risk of gout increases with

- serum urate level

- duration of hyperuricaemia

- usually develops after 20-30 years

 

Only 5% of hyperuricaemic patients develop gout

 

Takes days / weeks to resolve

- pain-free intervals of variable length

 

Clinical presentation

 

Acute Gouty Arthritis

 

Predominantly affects distal lower limb

- 70% initially attack 1st MTPJ (Podagra)

 

May also involve

- Other joints in foot

- ankle

- knee

- hands

 

Usually monoarticular, rapid onset 

- excruciating night pain

- hot red shiny swollen joint

- very painful to touch

- may have systemic features

- fever / leucocytosis / raised ESR

 

Onset may be spontaneous

 

May be precipitated by

- trauma

- excessive activity

- diet excess

- alcohol consumption

- diuretics

- systemic illness

- surgery

 

Chronic Gouty Arthritis

 

Arthritis

- after repeated attacks of gout

- asymmetric destructive arthropathy

- often involves small joints in hand

 

Tophi

- 20% of cases

- white mass of sodium urate crystals

- visible underlying thinned-out skin

- may necrose overlying skin

 

Sites

- periarticular subcutaneous tissue

- helix of ear

- tendon sheaths especially Achilles

- olecranon / prepatellar bursae

 

Renal Stones

- 15% of cases

- radiotranslucent uric acid stones

 

Investigations

 

Serum Uric Acid

 

Attacks of gout occur when levels of serum uric acid change

- not necessary to have increased serum urate during acute attack

- elevated serum urate in patient with painful joint not diagnostic of gout

 

Synovial fluid

 

Specimen must be anticoagulated

- must be very careful with sample as any water or alcohol put into it will dissolve the crystals

 

Monosodium urate crystals 

- diagnostic if found in synovial fluid 

- needle-shaped crystals 10um long

- lying free or in neutrophils 

 

Test

- negatively birefringent under polarised light & parallel to 1st order red compensator

- bright yellow when parallel to compensator

 

Synovial fluid analysis 

- WCC of 1000 to 70 000 x 10.6/ L 

- predominantly neutrophils (< 70%)

 

Note

- presence of crystals doesn't exclude infection

- infection precipitates urate

 

24 hr Urinary Uric Acid Secretion

 

> 1100mg /day 

- 50% chance renal stones

- treat with Allopurinol

 

X-ray

 

Chronic Gouty Arthritis

- usually in feet in phalangeal heads 

- characteristic periarticular bony defects 

- punched out lytic appearance 

- overhanging sclerotic margin (Martell's sign)

- also joint space narrowing & secondary OA 

- no osteopenia compared with RA

 

Wrist Gout Severe

 

DDx 

 

Pseudo-gout

Septic arthritis

Acute bursitis

Cellulitis

RA

OA

Seronegative spondyloarthropathy

 

Management

 

Acute Gout

 

Medications

 

Colchicine

 

Action is as anti-inflammatory

- inhibits activation of inflammatory mediators by crystals

- very effective

- rapid response strongly suggestive of diagnosis

- 1 mg then 0.5 mg q2h up to maximum 6 mg / day

- continue till patient improves / diarrhea occurs / maximum dose

- 80% of patients unable to tolerate optimum dose because of GIT side-effects

 

NSAID

 

Usually better tolerated than colchicine

- indomethacin most commonly used

- 50 mg t.d.s

- side effects include GIT toxicity / Sodium retention / CNS disturbance

 

ACTH

 

Adrenocorticotrophic Hormone

- good for acute attack

- minimal side effects

- single 40 IU IM injection

 

Glucocorticoids

 

Oral Prednisone

- if colchicine not tolerated / NSAID contraindicated

 

Intra-articular steroids

- may be used for severe monoarticular attack

- especially knee

 

Prophylaxis

 

3 Tier Approach

 

Initial 

 

Lose weight

Increase fluids intack

Aim to decrease Purine intake and avoid precipitating factors

- alcohol

- diuretics

- diet - meat, seafood

 

2nd Stage

- Probenecid

 

3rd Stage

- Allopurinol

- beware hypersensitivity / bone marrow suppression

 

Antihyperuricaemics

 

Absolute indications

- CRF secondary to kidney stones 

 

Relative indications

- > 3 acute attacks / year

- polyarticular gout

- tophi

- uric acid > 500 mmol/l

 

Options

 

1. Increase Renal Uric Acid Excretion / Uricosuric

- Probenecid

- require good renal function

 

2. Decrease Uric Acid Synthesis

- Allopurinol

 

Allopurinol

 

Inhibits Xanthine Oxidase

- 300 mg/day (150 if CRF) 

- hypersensitivity side effects in 20% 

 

Causes decrease in serum uric acid & this may precipitate acute attack of gout

- initiation of treatment should be accompanied by Colchicine or NSAIDS

- never used in acute gouty attack

- can shrink tophi if keep serum urate < 0.4mmol/l

 

Side effects can be fatal

- rash

- alopecia

- marrow suppression

- hepatitis