Gouty Gouty ArthritisArthritis

Calvin DamanikDepartemen Penyakit Dalam

FK Universitas Methodist Indonesia Medan

Epidemiology

men womenmean age of onset 49 60incidence (age 32-64) 2.8% 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

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

Gout: Pathophysiology

• Uric acid: overproduction vs. underexcretion

• Mechanisms of urate “production”– cellular nucleoproteins/nucleotides (~ 66%)– diet (~33%)

• Mechanisms of urate excretion– kidney (~66%)– gut (~33%)

Renal Excretion of Uric Acid

• Completely filtered by the glomerulus• Completely (essentially) reabsorbed in the

proximal tubule• Approximately 50% is secreted back into the

tubule in the descending loop• Approximately 80% (of the 50% now in the

loop) is reabsorbed in the ascending loop• Net excretion = 10% of filtered load

Urate Excretion

• hOAT3- human renal organic anion transporter

• hUAT1• hUAT2• URAT 1

OAT

• OAT– URAT1-

• mutations implicated in familial renal hypouricemia

• Proximal tubule• Suppressed by

uricosurics and losartan, high dose salicylate

• Lasix may increase its fxn

Bieber JD et al. Gout-On the Brink of Novel Therapeutic Options for an Ancient Disease. 50 (8). August 2004, p2400-2414.

Diet

• 12 year prospective study of 47,150 men with no h/o gout

• 730 new cases of gout• Conclusions:

– High levels of meat and seafood increased risk– High levels of dairy decreased the risk– Moderate intake of purine-rich vegetable or protein

not associated with increase risk of gout

Choi HK, et al. Purine-Rich Foods, Dairy and Protein Intake, and the Risk of Gout in Men. NEJM 350(11). March 2004. 10931103.

Asymptomatic Hyperuricemia

• Hyperuricemia alone does NOT make a diagnosis of gout-only a subset of people with hyperuricemia

will develop gout-probability of gout increases with higher uric

acid levels

• Asymptomatic hyperuricemia generally requires no treatment

Conditions AssociatedWith Hyperuricemia

• Lymphomas (esp. Hodgkin’s disease)• Myeloproliferative disorders• Diabetes• Psoriasis• Sarcoid• Glycogen storage disease

Acute Gouty Arthritis:Clinical Features

• Acute onset (hours) of severe arthritis• Usually monarticular

– almost any joint can be affected– 1st MTP joint (podagra) most common (50%)– Other joints (in decreasing frequency): midfoot,

ankle, heel, knee, wrist, fingers, elbow

• Associated findings: fever, WBC, ESR• Typically resolves over days or weeks,

regardless of treatment

Acute Gouty Arthritis

Acute Gouty Arthritis:Precipitating Factors

• Surgery• Alcohol• Fluctuation of uric acid level

– initiation of therapy to lower uric acid level– diuretics (esp. hydrochlorothiazide)– aspirin

• low doses raise uric acid levels• high doses lower uric acid levels

Acute Gouty Arthritis:Diagnosis

• Observation of monosodium urate crystals in synovial fluid leukocytes

• Monosodium urate crystals are – needle-shaped– negatively birefringent

Manifestations of Hyperuricemia

• subcutaneous tophaceous deposits• urolithiasis• nephrolithiasis• renal diseases involving the

tubules, interstitium, or glomeruli

Treatment

• NSAIDs• colchcine• allopurinol• steroids• to prevent recurrent attacks,

serum urate levels should be kept < 6 mg/dl

Intercritical Gout

• Symptom-free period between attacks (may be months or years)

• If untreated, episodes of acute gouty arthritis become more frequent, last longer, and often involve more joints (polyarticular)

Chronic Tophaceous Gout:Clinical Features

• Tophi are deposits of urate crystals in tissue

• Common sites:– synovium– subchondral bone– olecranon bursae– infrapatellar– Achilles tendon

Chronic Tophaceous Gout:Clinical Features

• Frequent attacks of acute gouty arthritis

• Bone destruction and degenerative arthritis are common in advanced cases

Chronic Tophaceous Gout

Chronic Tophaceous Gout

Chronic Tophaceous Gout

Chronic Gout-Radiographic Features

Chronic Tophaceous Gout:Treatment Options

• Control and prevent acute gouty arthritis– Non-steroidal antiinflammatory drugs– Colchicine– Steroids– Analgesics

• Reduce serum uric acid levels (< 4.0 mg/dL)– decrease uric acid production (inhibit xanthine

oxidase)– increase uric acid excretion (uricosuric drugs)

Xanthine Oxidase Inhibition:Allopurinol

• Blocks conversion of hypoxanthine to xanthine, and xanthine to uric acid

• Accumulation of hypoxanthine inhibits de novo purine biosynthesis (negative feedback)

• DO NOT USE allopurinol with azathioprine or 6-mercaptopurine

Uricosuric Agents:Probenecid

• Blocks renal tubular resorption of uric acid

• Most effective when urine pH basic and flow relatively high

• Used less frequently than allopurinol

Differential Diagnosispseudogout

• Goutnegative birefringent needle-shaped intraleukocytic crystals– yellow when parallel– blue when perpendicular

• Pseudogoutrod- or rhomboid-shaped crystals with opposite refractive properties

Differential DiagnosisSeptic 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

Differential Diagnosissynovial fluid analysis

gout septicWBC > 50 k 15 k (5 to 80k)PMNs > 90% ~70%