Gout

Overview

Overview Gout is a common inflammatory arthritis that is increasing in prevalence. Gout (monosodium urate crystal deposition disease) is characterized biochemically by extracellular fluid urate saturation. Tends to occur earlier in life in men than women, and is rare in childhood. Prevalence is increasing. It is associated with many serious comorbidities such as hypertension, chronic kidney disease, obesity, diabetes and cardiovascular disease.

Definition
Gout: Defective metabolism of uric acid can build up in joints causing arthritis, especially in the smaller bones of the feet, deposition of chalk-stones, and episodes of acute pain.
Pseudogout: Deposits of calcium pyrophosphate dihydrate crystals in the fluid and tissues of the joints, leading to intermittent attacks of arthritis

Risk Factors

Risk Factors

Older age

Male sex

Consumption of meat, seafood, alcohol

Menopausal status

Medications (Diuretics, cyclosporine/tacrolimus, pyrazinamide, aspirin)

Genetics

Haematological Malignancies (High cell turn over)

Chemotherapy (High cell turn over)

Diabetes

Signs and Symptoms

Three classic stages in the natural history of progressive urate crystal deposition disease (gout):

Acute gouty arthritis
Intercritical (or interval) gout
Chronic articular and tophaceous gout

Remember Gout does not occur only in the great toe (podagra), although this is a common site for the initial episode. It can affect any joint in the body and can even mimic the polyarthritis of rheumatoid arthritis.

1. Acute gouty arthritis

Monoarthritic joint - 80% (usually big toe podagra or the knee)
Severe pain, redness, warmth, swelling, and disability
Polyarticular gouty arthritis is the initial manifestation in less than 20 percent of patients with gout, but occurs with increasing frequency in later flares.

2. Intercritical gout

Intervals between attacks of acute gouty arthritis are of variable duration
Tophi can already develop bony erosions causing chronic gout arthropathy

3. Chronic articular and tophaceous gout

Polyarthritic joints
Uric acid nephrolithiasis
Tophaceous deposits - Tophi are typically not painful or tender

Differential Diagnosis

Monoarthropathy	Oligoarthropathy	Polyarthropathy
Septic arthritis	Crystal arthritis	Rheumatoid arthritis
Crystal arthritis (Gout or Pseudogout)	Psoriatic arthritis	Viral Arthritis
Osteoarthritis (can be mono-poly)	Reactive arthritis	Autoimmune connective tissue disease (ie. SLE)
Trauma (Haemarthrosis)	Ankylosing spondylititis	Vasculitides (ie. Polymyalgia Rheumatica)

Investigations

Side note The chance of developing gout increases with increasing serum concentrations of uric acid.

Joint aspiration - synovial fluid analysis and view under polarized light
- Cell count
- Crystals
- Gram stain
FBC
EUC
Urate levels
ESR/CRP
X-ray
- Soft-tissue swelling (acute gout)
- Asymmetry
- Punched out 'cyst' in the juxtaarticular bone
- Joint space narrowing
- Secondary osteoarthritis
MRI
Ultrasound

Remember With any monoarthritic presentation, septic arthritis should be ruled out. This can be done with a Joint aspiration.

Synovial fluid analysis
	Aetiology	Colour and Clarity	WBC (mm³)
Normal	Normal	Clear and transparent	<200
Non-Inflammatory	Osteoarthritis	Yellow and transparent	0 to 2000
Inflammatory	Gout	Yellow and traslucent-opaque	2000-100,000
Septic	Bacteria	Yellow/green and opaque	>25,000 - >100,000
Haemorrhage	Trauma	Red and Bloody	200-2000

Diagnosis For a definitive diagnosis of gout, urate crystals must be demonstrated in synovial fluid or in the tophus

Synovial fluid should be analysed by polarised light microscopy

Aetiology

There is a causal relationship between hyperuricaemia (high urate level) and gout.
Factors that increase urate levels are potential causes

Pathophysiology

Increase uric acid concentration in body causes deposition of uric acid crystals in joints
Human lack enzymes capable of degrading uric acid

Management

Acute Attacks

Colchicine
NSAIDs - indomethacin
Oral steroids such as prednisolone if multiple joints
Steroid infection to joint if monoarthritis

Prophylaxis (preventing future attacks)

Diet modification - less seafood
Reduce alcohol intake
Allopurinol
Benzbromarone

Management plan

Set urate target
Start urate-lowering therapy with prophylaxis
Ensure patient has acute flare plan
Monitor serum urate until target reached
Titrate urate-lowering therapy to achieve target
Once target achieved, monitor 6–12 monthly

Side note Allopurinol should not be stopped during acute flares of gout. Stopping allopurinol during an acute flare means therapeutic effect is lost and the urate level will rise. Historically, there has been concern that starting urate-lowering therapy such as allopurinol could worsen or prolong the acute gout flare, now this is not the case.

Pharmacology Allopurinol inhibits the enzyme xanthine oxidase, blocking the conversion of the oxypurines hypoxanthine and xanthine to uric acid. Side effects: arthralgia, joint stiffness or swelling and rash

Pharmacology Colchicine decreases leukocyte chemotaxis and phagocytosis and inhibits the formation and release of a chemotactic glycoprotein that is produced during phagocytosis of urate crystals. Colchicine has no analgesic or antihyperuricemic activity. Colchicine inhibits microtubule assembly in various cells, including leukocytes, probably by binding to and interfering with polymerization of the microtubule subunit tubulin. Side effects: nausea, vomiting, abdominal pain, and diarrhea (maybe bloody) occur first. Burning sensations of the throat, stomach, skin and muscular weakness can occur

Complication and Prognosis

Complications

Nephrolithiasis (kidney stones)
Chronic urate nephropathy

Prognosis

Acute gout attacks is painful and debilitating but self limiting
Appropriate treatment can suppress gout attacks and their recurrence, and prevent long-term consequences of the disease
Chronic articular and tophaceous gout may be associated with renal insufficiency