Gouty Arthritis

dr Putra Hendra SpPd

UNIBA

Gout

Disorder of urate metabolism, results in deposition of monosodium urate (MSU) crystals in joints and soft tissues. 1st described 5th century BC Hippocrates described gout as the king of diseases and the disease of kings Burden: In 1981, 37 million lost work days in US*

2003 Kim et al estimates the annaul cost of Acute Gout is $27,378,494 in the USA (underestimate: women excluded & not all indirect and intangible costs included)

NHANES III 1988-94

(5.6%)
National

(2.7%)

Health Intv Survey (&PE) = 17,030 men/women

Prevalence of Gout
Age (years)

20-29
30-39 40-49 50-59 60-69 70-79 >80

Men 3.4 Million Population % 0.2 2.1 2.2 5.7 9.1 10.8 8.6

Women 1.7 Mill Population % 0.6 0.1 0.6 2.3 3.5 4.7 5.6

NHANES

III 1988-94

What is Gouty Arthritis

Purines

are not properly processed in our body

Excreted

through kidneys and urine

Hyperuricemia-

build-up of uric acid in body and joint fluid

Gout

Impaired excretion or overproduction of uric acid Uric acid crystals precipitate into joints (Gouty Arthritis), kidneys, ureters (stones) Lead impairs uric acid excretion lead poisoning from pewter drinking goblets

Fall of Roman Empire?

Xanthine oxidase inhibitors inhibit production of uric acid, and treat gout Allopurinol treatment hypoxanthine analog that binds to Xanthine Oxidase to decrease uric acid production

CRYSTAL ARTHRITIS

GOUT (monosodium urate) PSEUDOGOUT (calcium pyrophosphate) HYDROXYAPATITE

PSEUDOGOUT

HYPERPARATHYROIDISM HEMOCHROMATOSIS HYPOTHYROIDISM HYPOMAGNESIEMIA HYPERCALCEMIA HYPOPHOPHATASIA

Pathophysiology

Urate saturates in plasma at 7 mg/dL

Assuming pH, temp, Na are WNL

MSU deposits in less vascular tissue

Cartilage Tendons/ligaments

There is a predilection for peripheral joint/tissue

Pathophysiology

Primary gout:
Overproducers: 10% Under-excretors: 90%

Secondary gout:
Excess nucleoprotein turnover (lymphoma, leukemia) Increased cell proliferation/death (psoriasis) Rare genetic disorder Lesch-Nyan Syndrome pharmaceuticals

Products of Intracellular or dietary/intestinal degradation can be recycled via salvage pathways 1 and 2 (red)

Nucleobase

Purine

biodegradation in humans leads to uric acid

Gout

Precipitation and deposition of uric acid causes arthritic pain and kidney stones Causes: impaired excretion of uric acid and deficiencies in HGPRT (Lesch-Nyhan Syndrome)

The Four Stages of Gout

Asymptomatic Acute Intercritical Chronic

SYMPTOMS

Joint pain
Affects one or more joints : hip, knee, ankle, foot, shoulder, elbow,wrist, hand, or other joints Great toe, ankle and knee are most common

Swelling of Joint
Stiffness Warm and red Possible fever

Skin lump which may drain chalky material

Gout

Acute: intermittent/recurrent, LE, ascending, inflammatory mono/oligoarthritis, Podagra Intercritical gout: between attacks Tophaceous gout: chronic, accumulation of MSU crystals as tophi (may look like RA) Asymptomatic hyperuricema: elevated uric acid without evidence of gout, nephrolithiasis. Higher levels increase risk of these diseases Renal: nephrolithiasis, gouty nephropathy, uric acid nephropathy

Acute (Classic) Gout

Acute, severe onset of pain, warmth, inflammation, Limited motion cant walk, cant put sheet on it. Podagra (50-90%): pain, swelling warmth in 1st MTP Joints: MTP, tarsus, ankle, knee Associated with fever, leukocytosis, high ESR or Creactive protein levels. Precipitants: stress, trauma, excess alcohol, infection, surgery, drugs, makanan Chronology: untreated attacks last 7-14 days. Acute gout risk of repeat attack estimated to be 78% w/in 2 yrs

ACUTE

Sever and sudden onset Involve one or a few joints Frequently starts nocturnally Joint is warm, red, and tender

INTERCRITICAL

More concentration of uric acid crystals Typically no need for drug intervention at the time.

CHRONIC

Continuous or persistent over a long period of time Treatment required Not easily or quickly resolved

CHRONIC GOUT

Diagnosis

Based on history and physical Confirmed by arthrocentesis

Urate crystals: needle-shaped negatively birefringent either free floating or within neutrophils & macrophages.

Laboratorium Radiografi

Acute Gout

Laboratory Findings
40-49% will have normal uric acid levels Leukocytosis common ESR and CRP elevated No indices of chronic inflammatory disease (alb, Hgb) Measureable elevations in IL-6 and IL-1

Radiographic findings
Soft tissue swelling (Opacities = tophi) Normal Joint space and Normal ossification Erosions: nonarticular, punched out, Sclerotic margins, overhanging edge

X-ray
Acute

Soft tissue swelling

Chronic chronic tophaceous gouty arthritis, extensive bony erosions are noted throughout the carpal bones Sclerosis and joint-space narrowing are seen in the first metatarsophalangeal joint, as well as in the fourth interphalangeal joint .

Treatment

Acute:
NSAIDs anti-inflammatory doses Colchicine 0.5 mg po q2 hours, may require 6 mg.

Stop with response or side effect Can be used for chronic disease, increased risk for BM suppression

Aspirate followed by administration of corticosteroids Prednisone ACTH 40-80 IM/IV or Solumedrol Opiates and Tylenol Alopurinol kontraindikasi

Treatment

Chronic:
Diet will decrease uric acid 1 mg/dL at best Weight loss Limit ETOH Modification of medications Avoid low dose ASA, diuretics, etc.

Treatment

Chronic
Indications for Allopurinol Tophaceous deposites Uric acid consistently >9 Impaired renal function Prophylaxis for tumor-lysis syndrome Consider NSAIDs to avoid exacerbation

Uric Acid Lowering Therapy

Lifestyle, dietary modification Diet high in vegetables, dairy, water beneficial Initiate uric acid lowering therapy after 1(?) or 2 episodes of acute gouty arthritis Always prophylaxis for first 6 months with low dose steroids, NSAIDs, or colchicine

Rich

foods have a higher concentration of protein. This could cause major problems for a person afflicted with gout.

Disease of Kings

ORGAN MEATS WILD GAME SEAFOOD LENTILS PEAS ASPARAGUS YEAST BEER

URICOSURICS

Uricosurics
probenecid 1-3 grams / day sulfinpyrazone 200-400 mg / day Benzbromarone 100-200 mg / day (not available)

URICOSURICS

Contraindications
Tophi CRI (GFR >35ml/min) H/O urolithiasis Intolerance Rapid cell turnover states

25% failure rate mild CRI Interact with ASA, NSAIDs, PCN, captopril Watch for rash , GI,HA, dyscrasias,nephrosis

Uricostatic Drugs

Allopurinol - developed 1957

Reduce annual gout attacks 4.4 to .06 / yr Gradual resolution of tophi w/ uric acid < 6 Titrate dose up to 600 mg /day Uncreased toxicity with Allopurinol hypersensitivity rare but can be fatal Multiple interactions imuran, 6MP, warfarin, theophylline, ampiciliin, diuretics Treatment is lifelong

Prognosis

Generally good More severe course when Sx present < 30 y/o Up to 50% progress to chronic disease if untreated. Surgical intervention may be required for tophi.