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Gouty Arthritis
• Chronic heterogeneous disorder of urate metabolism
• Results in deposition of monosodium urate crystals in the joints and soft tissues, with accompanying inflammation and degenerative consequences
• Most common form of inflammatory joint disease in men aged ≥40 years
History• 2640 BC: Podagra first
identified by the Egyptians.
• 5th Century BC: Hippocrates referred to gout as “unwalkable disease” and noted links between gout & lifestyle, demographics & other variables
• The word ‘gout’ is derived from the Latin word ‘gutta’.
• Earlier it was believed that an acute attack of the disease was the result of poison dropping into a joint
• Disease of the ‘KINGS’ (Rich foods have a higher concentration of protein. This could cause major problems for a person afflicted with gout)
The King of Pain• Benjamin Franklin• Thomas Jefferson• Sir Isaac Newton • Charles Darwin• King Henry VIII and other famous leaders
all suffered from gout
Incidence• Persons in USA Affected by Common
Rheumatologic Disorders (As per ACR): Frequent Low Back Pain40.2 million in 2005, projected to increase to 48.6 million in 2025 Osteoarthritis20.7 million in 2005, projected to increase to 28.1 million in 2025 Gout2.6 million in 2005, projected to increase to 3.6 million in 2025 Rheumatoid Arthritis2.1 million in 2005, projected to increase to 2.8 million in 2025
Predisposing Factors• Purine rich foods – meat, kidney, liver, seafood,
anchovies, oatmeal, certain vegetables (peas, beans, lentils, mushrooms, cauliflower, spinach), sweetbreads
• Caffeine• Drugs – Loop diuretics, NSAIDs, corticosteroids,
Niacin, Sinemet, Cyclosporine, Salicylates, Ethambutol, Pyrazinamide
• Trauma• Infection• Other disease – DM, HTN, vascular dx, renal dx,
thyroid dx, sarcoidosis, etc.
Hallmarks of Gout• Group of conditions which
may be characterized by an elevation of serum uric acid (usually)
• Recurrent attacks (flares) of an acute inflammatory arthritis with monosodium urate crystals demonstrated in synovial fluid leukocytes
• Bone and joint destruction in some cases
• Aggregates of uric acid crystals (tophi) in and around joints, soft tissues, and various organs
• Tophus in bone leading to erosions in some cases
• Kidney disease and stones
Hyperuricemia leads to deposit of urates in the joint fluid, triggering an
inflammatory cascade
StagesThis disorder can be progressive through four stages if undertreatedAsymptomatic hyperuricemiaAcute goutIntercritical goutChronic tophaceous gout
Clinical Features
Acute Gout:• Acute gout is a painful
condition that typically affects only one or a few joints.
• The big toe, knee, or ankle joints are most often affected.
• Throbbing, crushing, or excruciating pain
• Joint appears warm and red. Fever may be there.
• The attack may go away in a few days, but may return from time to time.
• Additional attacks often last longer.• After a first gouty attack, half of the people
will have no symptoms. Half of patients have another attack.
Chronic Gout• Signs and symptoms include:• Joint damage• Loss of motion in the joints• Joint pain and other
symptoms most of the time, throughout the day
• Tophi below the skin around joints or in other places (Tophi usually develop only after a patient has had the disease for many years)
Advanced Chronic Tophaceous Gout
• Tophi can be seen clinically, with obvious deformity demonstrated in hands and foot
• Tophi may be associated with bony destruction as seen on the x-ray
• Is characterised by massive deposits of monosodium urate crystals (Tophi) in articular cartilage, subchrondral bone, synovial membrane, capsule, tendon sheaths and peri articular tissues.
• Tophi formation can also occur over eyelids, nasal cartilage, cornea, tongue, vocal cords and penis
• The tophaceous nodules consists of multicentric deposition of urate crystals and intra cellular matrix and foreign body granulomatous reaction.• As they enlarge in size, calcify, they
can cause pressure symptoms.• The tophi are firm yellow in colour
and occasionally discharge a chalky material.
Diagnosis
1977 ACR Criteria for Acute goutThe presence of characteristic urate crystals in the joint fluid, or a tophus proved to contain urate crystals by chemical means or polarized light microscopy, or the presence of 6 of the following 12 clinical, laboratory, and radiographic phenomena:
1. More than one attack of acute arthritis 2. Maximum inflammation developed within 1 day 3. Monoarthritis attack 4. Redness observed over joints
5. First metatarsophalangeal joint painful or swollen 6. Unilateral first metatarsophalangeal joint attack 7. Unilateral tarsal joint attack 8. Tophus (proven or suspected) 9. Hyperuricemia 10. Asymmetric swelling within a joint on x ray/exam 11. Subcortical cysts without erosions on x ray 12. Joint fluid culture negative for organisms during attack
Investigations• Plain radiographs (may be normal)• Serum Uric acid• Synovial fluid analyis (shows uric acid
crystals)• BUN (blood urea nitrogen), Serum
Creatinine• Synovial biopsy• Uric acid – urine
SYNOVIAL FLUID ANALYSIS(Polarized Light Microscopy)
• The Gold standard• Crystals
intracellular during attacks• Needle & rod
shapes• Strong negative
birefringence
BIOCHEMICAL TESTS FOR GOUT:
Differential Diagnosis• Pseudogout: Chondrocalcinosis,
CPPD• Psoriatic Arthritis• Osteoarthritis• Rheumatoid arthritis• Septic arthritis• Cellulitis
Gout vs. CPPD• Similar Acute attacks• Different crystals under Microscope:
Rhomboid, irregular in CPPD
Gout vs RA• Both have polyarticular, symmetric arthritis• Tophi can be mistaken for RA nodules
To be continued..
TreatmentGout
Drugs Used In Treatment
• NSAIDs• Colchicine • Uricosuric agents• Allopurinol/ Febuxstat
NSAIDS:
• Inhibits pain & inflammation.• Inhibits urate crystal phagocytosis by
decreasing the migration of granulocytes into the inflammatory area.• Indomethacin, Naproxen, Ketorolac.
COLCHICINE:
• Produces its anti-inflammatory effects by binding to the intracellular protein tubulin, preventing its polymerization leading to the inhibition of leukocyte migration into affected area.• Inhibits the synthesis & release of
leukotrienes.
URICOSURIC AGENTS:
• Probenecid & Sulfinpyrazone• They are weak organic acids .• Sulfinpyrazone is a metabolite of
phenylbutazone.• Increase the excretion of Uric acid.
Allopurinol/ Febuxstat:• Inhibits synthesis of uric acid by
inhibiting xanthine oxidase enzyme
Uric acid is produced by Xanthine and Hypoxanthine by Xanthine Oxidase Inhibitor.Uric Acid is more toxic than either xanthine or hypoxanthine.
TREATMENT GOALS1. Rapidly end acute flares2. Protect against future flares3. Reduce chance of crystal induced
inflammation4. Prevent disease progression5. Lower serum urate to deplete total
body urate pool6. Correct metabolic cause
ENDING ACUTE FLARES
• Control inflammation & pain to resolve the flare• Not a cure• Crystals remain in joints• Don’t try to lower serum urate
during a flare
Acute Flares Treatment• Interaction with warfarin• Contraindicated in:
• Renal disease• PUD• GI bleeders
NSAIDS• Not as effective “late” in flare• Contraindicated in dialysis patients• Cautious use in :
• Renal or liver dysfunction• Active infection• Age > 70
Colchicine
• Worse glycemic control• May need to use mod-high
doses
Corticosteroids
Acute Gout - RxNSAIDs (unless CRI, CHF, PUD, etc.)
Corticosteroids (Intra-articular if one joint, systemic if multiple joints)
Colchicine (adjust dose in patients w/ renal insufficiency)
- Indomethacin 50mg tid- Naproxen 825mg once, then 275 q8hr- Sulindac 200mg bid
- Most beneficial in first 12-36 hours of an attack
- 1mg initially, then 0.5mg qhr until either symptoms relieved or GI side fx (N/V/diarrhea) or 7mg total given
- Renal dosing:- If Cr clearance < 50, dec. dose 50%- If Cr clearance < 10, contraindicated.
- 20-30mg/day if systemic used
Protection Against Future Flares• Colchicine : 0.5-1.0 mg/day• Low-dose NSAIDS• Both decrease frequency & severity of
flares• Prevent flares with start of urate-
lowering drugs• Best with 6 months of concomitant
treatment
Intercritical Gout - Rx
Probenecid if:- Recurrent attacks and 24hr urine uric acid < 800mg/dL
Allopurinol therapy if:- Recurrent attacks despite diet chg/etc.- Hx of nephrolithiasis- Serum creatinine > 2.0- Serum uric acid > 11.0- 24 hr urine uric acid > 800mg/dL- Tophi present
Education, Lifestyle/Diet modification, Pharmacotherapy modification
Allopurinol toxicity?
Colchicine
Prevent Disease Progression• Lower urate to < 6 mg/dl :• Depletes
Total body urate poolDeposited crystals
• Treatment is lifelong & continuous• Drug choices :
Uricosuric agentsXanthine oxidase inhibitor
Asymptomatic Hyperuricemia• Indications for Rx include: 24hr Urinary Uric Acid Excretion > 1100mg Serum uric acid: Men > 13mg/dL, Women > 10mg/dL Nephrolithiasis Any hx of symptoms of gout, especially w/ worsening
renal function Presence of gouty tophi in bone or soft tissues Radiographic signs of gouty arthritis Impending chemotherapy or radiotherapy for leukemia
or lymphoma
Which Drug to use?• Base choice on above considerations &
whether patient is an overproducer or underexcretor.
• Need to get a 24-hr. urine for urate excretion:
< 700 --- underexcretor (uricosuric)
> 700 --- overproducer (allopurinol)
• 90% of the patients are underexcretors.
PREVENTION
Avoid purine rich foods
Reducing alcohol consumption
Avoid Diuretic Drugs.
Maintain the concentration of Uric Acid level within the normal range.
Drinking Plenty of Water.
Balance your weight with proper diet and exercise
Foods known to decrease the occurrence of gout include dairy, foods high in potassium, black cherry juice, blueberries and lemon juice.
Immediately treating gout will not allow it worse.
Newer DrugsURICASE ENZYMES:• Catabolize urate to allantoin:
More soluble, excretable form• Currently approved for hyperuricemia in
tumor lysis syndrome• Some concerns: fatal immunogenicity &
unknown long-term effects
Thank You
