Gout/Pseudogout Flashcards
Gout
general
Metabolic disorder caused by hyperuricemia that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent acute or chronic arthritis
Prevalence is approximately 3% in the United States
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Most common in middle-aged men and postmenopausal women
Presentation before age 30 → severe disease
Risk increases with higher body mass index (BMI)
Condition often runs in families
Gout
Hyperuricemia
Plasma urate level >6.8 mg/dL
Increased intake, overproduction, and/or underexcretion of uric acid
Relationship between hyperuricemia and gout is unclear
The majority (90%) of people with hyperuricemia do not have gout
Normal or low serum UA levels do not rule out gout
The greater the degree and duration → the greater the likelihood that gout develops
Gout
Increased intake of UA
Consumption of purine-rich foods/drinks contribute to hyperuricemia (30%)
Red meat, liver, tuna, scallops, mussels, shrimp, asparagus, mushrooms, carbonated beverages
Ethanol (beer)
Strict low-purine diet lowers serum urate by ~1 mg/dL
Gout
UA Overproduction
Causes of overproduction:
Hereditary
Ethanol is believed to stimulate urate synthesis in the liver
Hematological conditions (leukemia, lymphoma, hemolytic anemia)
Conditions with increased rates of cellular proliferation (psoriasis)
Gout
UA Underexcretion
Most common cause of hyperuricemia
Uric acid is excreted mainly through the kidneys
Causes of decreased renal excretion:
Hereditary
Receiving diuretics or aspirin
High doses of cyclosporine (transplant patients)
Diseases that ↓ glomerular filtration rate (GFR)
Gout
patho
Hyperuricemia→ supersaturation → needle-shaped monosodium urate (MSU) crystals deposition into soft tissue and synovial joints
Can erode the bone and damage other tissues such as tendons and cartilage
Causerecurrent monoarticular arthritis and chronic deforming arthritis
Gout
Risk Factors for Hyperuricemia
Diet:
High purine diet
Beverages containing fructose, alcohol
Obesity
Medical conditions: untreated hypertension, diabetes, metabolic syndrome, heart and kidney diseases
Medications:
Thiazide & furosemide diuretics
Low-dose aspirin
Anti-rejection/immunosuppressive drugs used in organ transplantation (cyclosporine)
Family history of gout
Age and sex:
Middle-aged and older men
Post-menopausal women
Dehydration
Acute Gouty Arthritis
general
Sudden onset of pain (often nocturnal)
Typically monoarticular
Commonly occurs in the lower extremities,most often at the base of the great toe (1st metatarsophalangeal joint) or the knee
Other sites: ankle, wrist, and elbow
Podagra = gouty attack at the 1st MTP joint
Acute gouty arthritis
Pain
Intensely inflammation, causing severe pain, “burning”, redness, warmth, swelling, and disability
Pain peaks within 12–24 hours and resolving within 3–10 days even without treatment
Nocturnal pain
Pain is often described as the joint on fire; weight of a sheet over the area can produce significant pain
Pain is the result of cytokines released from WBCs that enter the joint to remove uric acid
Acute gout flare
Clinical Course
Subsequent flares
Upon resolution of an acute gout flare, patients enter an intercritical (between-flares) period
Most often entirely asymptomatic
Variable in duration
Most patients left untreated will develop a recurrent flare within 2 years
Subsequent flare-ups
Shorter symptom-free intervals between flares
Higher likelihood of being polyarticular
Persist up to 3 weeks if untreated
Chronic Tophaceous Gout
general
Form of gout resulting from chronic inflammation
Palpable tophi develop
Firm yellow or white papules or nodules
Single or multiple
Locations:
Fingers, hands, feet, and around the olecranon or Achilles tendon
Kidneys
Can erupt through the skin, discharging chalky masses of urate crystals
Cause deformities and secondary osteoarthritis
Gout
Dx
Suspected in patients with acute monoarticular arthritis
Diagnosis is established via microscopic analysis of thejoint aspirate, which shows:
Crystals of MSU,which arenegatively birefringent(yellow when parallel to polarizing light) andneedle-shaped
WBC > 2,000/μL with > 50% neutrophils (an acute inflammatory synovial fluid)
X-ray:
Shows no changes early in the disease
Punched-out erosions with an overhanging rim of cortical bone develop with progressive disease
Arthrocentesis and synovial fluid analysis should be done at the initial presentation
Yellow crystals when parallel to the polarizing light and blue when perpendicular
Gout
Blood work may show:
Hyperuricemia (may be normal or low during a flare; best to measure 2 weeks after flare)
Elevated WBC
Elevated erythrocyte sedimentation rate (ESR)
Arthrocentesis
Also referred to as joint aspiration
Clinical procedure of using a syringe to collect synovial fluid from a joint capsule
gout
Gout
General Treatment Measures
Weight loss to achieve BMI < 25
Fluid intake ≥ 3 L/day
Avoid foods high in purines
Avoid certain medications that cause hyperuricemia
Diuretics both increase urate reabsorption and decrease its secretion
Gout
Med Tx
The goal of treatment is to reduce inflammation
Nonsteroidal anti-inflammatory drugs(NSAIDs)
High-dose
Given for several days following the resolution of pain and signs of inflammation to prevent relapse
Contraindicated in active peptic ulcer disease, impaired kidney function, congestive heart failure, and elevated international normalized ratio (INR)
Colchicine
Inhibits WBC migration
Most effective if given within 12-24 hours of an acute flare
Initial dosing 1.2 mg PO, then 0.6 mg PO 1 hour later; continue 0.6-1.2 mg PO daily as the flare resolves
Contraindicated in severe renal or liver disease
Glucocorticoids- if more than one joint involved.
Can be given via IV, IM, oral, orintra-articularroutes
Rule out septic arthritisbefore giving corticosteroids
Gout
Lowering serum urate levels
Tx indications
Target serum UA
Indications for urate-lowering therapy
Tophaceous deposit
Frequent or disabling flares (>2 flares/year) of gouty arthritis
Urolithiasis- kidney stones
Infrequent flares, but serum uric acid is > 9 mg/dL
Multiple comorbidities that are relative contraindications to NSAIDs or corticosteroids
Tophaceous deposits are resorbed by lowering serum urate
Target serum urate level of < 6 mg/dL
Colchine, NSAIDs, and corticosteroids do not retard the progressive joint damage caused by tophi
Usuallycontraindicated/not recommended in an acute attackas they may cause the disease to flare up
Gout
Allopurinol
Drug class: xanthine oxidase inhibitor
Works by reducing the production of uric acid in the body
Inhibits xanthine oxidase, an enzyme in the purine catabolism pathway
FDA approved for:
Treatment of gout
Prevention of recurrent nephrolithiasis in patients with hyperuricosuria
Dosing: 50-100 mg PO daily
Increased slowly to a maximum dose of 800mg PO daily
Adverse effects: gastrointestinal discomfort and rash
Metabolized in the liver
Metabolites are excreted in the urine
Most commonly prescribed and preferred initial urate-lowering therapy
Pseudogout
general
Also known as calcium pyrophosphate dihydrate or chondrocalcinosis
Arthritis involving intra-articular and/or extra-articular deposition of calcium pyrophosphate dihydrate (CPPD) crystals
Commonly seen in patients ≥ 50 years
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Gout
Febuxostat
Drug class: xanthine oxidase inhibitor
Works by reducing the production of uric acid in the body
Inhibits xanthine oxidase, an enzyme in the purine catabolism pathway
FDA approved for:
Chronic management of hyperuricemia in patients diagnosed with gout
Dosing: 40 mg PO daily; maximum dose 80 mg daily
An increase in gout flares frequently occurs after the initiation
Give NSAIDs or colchicine concurrently to prevent acute flares
Metabolized in the liver
Metabolites are excreted in the urine and feces
Gout
Probenecid
Drug class: uricosuric
Works by inhibiting active transport sites of the proximal tubules → reuptake of uric acid is blocked and increased amounts are excreted
FDA approved for:
Treatment of hyperuricemia associated with gout and gouty arthritis
Dosing: 250 mg PO twice daily, with doses increased as needed; maximum of 1 g PO 3x daily
Exacerbation of gout following therapy may occur
Give NSAIDs or colchicine concurrently to prevent acute flares
Metabolized in the liver
Metabolites are excreted in the urine
Pseudogout
patho/etiology
Etiology is unknown
Associated with conditions that result in ↑ PTH, ↑ iron, ↓ phosphate, or ↓ magnesium
Pathogenesis
Increased pyrophosphate production → calcium pyrophosphate supersaturation → formation of CPPD crystals in joints and tissues → inflammation
pseudogout
Clinical Presentation
Acute – similar to gout
Sudden, monoarticular joint pain
less intense than gout
Joint will be swollen, warm, and tender to touch
Overlying skin may be erythematous
Most common joints: knee and wrist
Less common joints: shoulders, ankle, elbows
Chronic – similar with rheumatoid arthritis and osteoarthritis
Persistent pain and stiffness in multiple joints
Rarely develop large deposits of crystals (tophi)
Pseduogout
Dx
Suspected in patients with acute monoarticular arthritis
Diagnosis is established via microscopic analysis of thejoint aspirate, which shows:
Crystal of CPPD, which are weakly positively birefringent (blue when parallel to polarizing light) and rhomboid or rod-shaped
X-ray
Indicated if synovial fluid cannot be obtained
Multiple linear or punctate calcifications in articular cartilage
Pseudo gout
Pseudogout
Tx
Nonsteroidal anti-inflammatory drugs(NSAIDs)
High-dose
Colchicine
Most effective if given within 12-24 hours of an acute flare
Initial dosing 1.2 mg PO, then 0.6 mg PO 1 hour later; continue 0.6-1.2 mg PO daily as the flare resolves
Contraindicated in severe renal or liver disease
Also used for prophylaxis
Glucocorticoids
Synovial fluid drainage and instillation of triamcinolone 40 mg into the joint space
No available long-term control medications
Podagra
Acute gouty arthritis of an MTP
