DEFINITION OF GOUT

An acute arthritis caused by the inflammatory response to monosodium urate crystals in the joint.
Neutrophils phagocytose the crystals and degranulate. The enzymes released cause the clinical manifestations of inflammation.

Epidemiology
mean age of onset incidence (age 32-64)

men 49 2.8%

women 60 1.5%

the lower incidence and later onset of gout in women is attributed to more efficient urate excretion attack before the age of 30 is rare and suggest a genetic metabolic disorder

Pathophysiology
Gout is caused by disorders of purine metabolism resulting in elevated levels of uric acid
> 7 mg/dl in men > 6 mg/dl in women

prolonged hyperuricemia leads to formation of monosodium urate monohydrate crystals

The 4 stages of gout

Asymptomatic hyperuricemic (but many hyperuricemic people do not develop gout) Acute gouty arthritis (the usual presentation) Intercritical gout (variable symptom-free periods between acute attacks may last weeks or years) Chronic tophaceous gout.

Serum Urate Level

any sudden change in serum urate concentration can provoke an acute gouty attack
sudden increase favors formation of new crystals sudden decrease promotes shedding of previously formed crystals from the synovial membrane

Serum Urate Level

during a gouty attack, serum urate levels are normal in about 20% of cases repeat blood tests eventually detect hyperuricemia

Manifestations of Hyperuricemia
subcutaneous tophaceous deposits urolithiasis nephrolithiasis renal diseases involving the tubules, interstitium, or glomeruli

CLASSIFICATION OF HYPERURICEMIA
OVERPRODUCTION (METABOLIC) (10%) PRIMARY SECONDARY RENAL UNDEREXCRETION (90%) PRIMARY SECONDARY

OVERPRODUCTION
PRIMARY 1. IDIOPATHIC
2. SPECIFIC ENZYME DEFECTS

(<1% of Primary Gout) a. PRPP synthetase overactivity b. Partial deficiency of HGPRTase c. Complete deficiency of HGPRTase

OVERPRODUCTION cont.

SECONDARY
INCREASED NUCLEIC ACID TURNOVER a. Lymphoproliferative or myeloproliferative disorders or their chemotherapy b. Chronic hemolysis c. Psoriasis

Underexcretion (Renal Handling of urate)

PRIMARY 1. Idiopathic SECONDARY 1. Acute or chronic renal failure 2. Volume depletion 3. Altered renal tubular handling of uric acid due to drugs, volume status or endogenous metabolic products

A. Filtration B. Reabsorption
C. Secretion

Underexcretion- Filtration

Almost 100% urate is filtered.

Decreased filtration causes increased serum uric acid such as in: Renal failure Volume depletion

Underexcretion- Reabsorption
Increased reabsorption causes increased serum uric acid as in: Volume depletion

Decreased reabsorption causes decreased uric acid = uricosuria.

Medications which cause uricosuria are: Probenecid Sulfinpyrazone High-dose salicylate

Underexcretion- Secretion
Decreased secretion causes increased serum uric acid. Conditions which contribute to this: Diuretic therapy Low-dose salicylate therapy Lactic acid Ketoacidosis Ethanol

Acute gouty arthritis.

Acute onset of severely painful arthritis usually in lower extremities. Often early attacks in 1st MTP joint (podagra). May be precipitated by trauma, surgery or major medical illness, alcohol ingestion, or systemic infections. Initial attacks self-limited but may become chronic. Synovial fluid is inflammatory with needleshaped monosodium urate crystals with strong negative birefringence.

1. Arthritis (Joint

inflammation): redness warmth tenderness swelling 2. Surrounding soft tissue inflammation

Source: WebPath

Gouty arthritis results from deposition of sodium urate crystals in joints. The joint most often affected is the first MP joint (big toe) as seen here. Acute attacks are characterized by severe pain, swelling, and erythema of the joint.

Chronic tophaceous gout.

If untreated, mono- sodium urate may deposit in cartilage, tendons, bursae, soft tissue and synovium in deposits called tophi. These are commonly found in olecranon bursae, Achilles tendon, around joints and ear. May extrude white pasty material and can limit joint mobility.

Chronic tophaceous gout

persistent gout chronic tophaceous gout produces tophi, solid deposits of of monosodium urate crystals form in the joints, cartilage, bones, and elsewhere in the body. develop on average about 10 years after the onset

Gouty tophi project from the fingers as rubbery nodules. Below: A section from a tophus shows extracellular masses of urate crystals with accompanying foreign body giant cells.

What are the typical laboratory findings in gout?

1. Inflammatory synovial fluid a. Cloudy b. 20,000 to 100, 000 WBC/mm c. Predominately PMN 2. Monosodium urate crystals in synovial fluid a. Needle-shaped b. Strong, negative birefringence with compensated polarized light 3. Serum uric acid is elevated at some time in almost all patients. However it is NOT DIAGNOSTIC. 4. Urine uric acid >750 to 1000 mg/day suggests overproduction of uric acid. 5. May have leukocytosis, high ESR, increased Creactive protein during acute attack.

If synovial fluid is aspirated from a patient with gout, the fluid can be examined for the presence of sodium urate crystals, which are seen here to be needle shaped.

Differential Diagnosis Septic Arthritis

Septic and gouty arthritis present with many of the same signs and symptoms
fever and monoarthritis

Beware: both septic and gouty arthritis may present in the same joint

What are the typical radiographic findings in gout?

1. Soft tissue swelling during

acute attack.
2. Soft tissue density if tophi

are present.
3. Oval bone erosions with overhanging edge is classic abnormality.

Chronic gout leads to deposion of urates into a chalky mass known as a "tophus". Such tophi can destroy the joint and adjacent bone as seen in these sequential radiographs of the same foot.

Treatment

Acute Gout
(1) Nonsteroidal antiinflammatory drugs (2) Corticosteroids if resistant to NSAID and colchicine, of if they are contraindicated (3) Colchicine generally outmoded for acute attack. Often used as maintenance antiinflammatory agent (4)Allopurinol and uricosuric drugs are of no benefit in acute gout and may make acute attack more difficult to control.

Treatment of Acute gouty arthritis

Colchicine-- inhibits neutrophil activation, effective, less frequently because of its side effects. Colchicine -- 0.5-mg dose every hour until : improvement, GI adverse effects (abdominal pain, diarrhea, and nausea), or a total of 10 doses without relief.

Treatment of Acute gouty arthritis

Indomethacin and other NSAID -- drugs of choice NSAIDs -a 7-10 day course or until 3-4 days after all signs of inflammation have resolved. Use NSAIDs with caution -- in edematous states, such as heart failure, peptic ulcer disease or renal insufficiency.

Treatment of Chronic Gouty Arthritis

The choice of urate-lowering medications: uricosuric drugs (which promote uric acid excretion) xanthine oxidase inhibitors (which inhibit uric acid production).

Treatment of Chronic Gouty Arthritis

uricosuric drug Probenecid, benzbromazone inhibits the tubular reabsorption of filtered and secreted urate, thereby increasing urate excretion.

Treatment of Chronic Gouty Arthritis

Allopurinol is competitive inhibitors of the enzyme xanthine oxidase Treatment principle: lower the plasma urate concentration to such a degree, as to allow urate to be resorbed from the surface of the tophi.

Treatment of Chronic Gouty Arthritis

The ideal candidates for allopurinol treatment are uric acid overproducers renal insufficiency nephrolithiasis tophaceous gout at risk for developing uric acid nephropathy

Treatment of Chronic Gouty Arthritis

allopurinol can be used in almost any hyperuricemic state the usual maintenance dose for adults is between 200 and 300 mg/d long half-life of oxypurinol makes once daily dosing possible.

Treatment of Chronic Gouty Arthritis

skin rash may proceed into severe hypersensitivity reactions patients who develop a skin rash should discontinue allopurinol. hepatotoxicity, bone marrow depression, and interstitial nephritis are rare but serious adverse effects of allopurinol.

Treatment of Tophi
Colchicine and most NSAIDs, while controlling acute attacks, will not prevent the formation of tophi and may, by preventing the inflammatory response, actually increase the development of tophi unless hyperuricemia is controlled at the same time.

Treatment of Tophi
allopurinol is the treatment of choice. dose of allopurinol serum uric acid response checked after 3 months adjust the dose (allopurinol 300mg tablet) treatment will be life-long at the start of therapy acute attacks may occur

Treatment of Tophi
The concomittant use of a NSAID or a prophylactic dose of colchicine for the first month of treatment with allopurinol is therefore recommended allopurinol should likewise not be started within 1 month of an acute attack of gout, as it may precipitate another attack

Treatment of Tophi
The activity of allopurinol and uricosurics is additive when administered concomitantly, smaller doses of each drug can be used Combined use of the 2 types of drugs is especially effective in the presence of tophaceous deposits.

Treatment of Tophi
Dose of allopurinol adult dose: initially 100mg daily in a single dose maintenance: 100-300mg daily is usually adequate maximum 900 mg/day in divided doses renal impairment: low dose of allopurinol (50mg daily)

Treatment of Tophi
Surgery is rarely used to treat gout. Surgical indication: draining, infected, or are interfering with the movement of your joints It is sometimes necessary to replace joints.

Treatment of Tophi
non-drug methods encourage controlled weight loss avoidance of alcohol, salicylates and food which may trigger an acute attack

Prognosis of Gout
Current therapy permits most patients to live a normal life if the disease is diagnosed early and medical advice is followed. Complications include urolithiasis, urinary tract obstruction and infection, with secondary tubulointerstitial disease.