1. Presented by-
Dr. Ashutosh Kumar
AP Dept. of Orthopaedics
Rohilkhand medical collage and hospital,
Bareilly.
GOUT
2. Definition
• Gout is a disorder that manifests as a spectrum of clinical and pathologic features
built on a foundation of an excess body burden of uric acid, manifested in part by
hyperuricemia, which is variably defined as a serum urate level greater than
360µmol/l (6.8mg%)
• Chronic heterogeneous disorder of urate metabolism.
• Most common form of inflammatory joint disease in men aged ≥40 years
3. Definition
The term gout is derived from the latin word 'guta' meaning a drop, and originally may
have referred to a drop of poison or evil humor.
a group of diseases characterized by
hyperuricaemia and uric acid crystal
formation.
4. Stages
This disorder can be progressive through four
stages if undertreated
Asymptomatic hyperuricemia
Acute gout
Intercritical gout
Chronic tophaceous gout
5. Who May Be the Patient With Hyperuricemia and Gout?
Demographics
• Advanced age
• Male
• Postmenopausal women
Commonly Used Medications
• Diuretics
• Low-dose aspirin (eg, <325 mg)
• Cyclosporine
• Niacin
• Salicylates, Ethambutol, Pyrazinamide
• Comorbidities
• Cardiovascular disease, HTN, CKD
• DM, Dyslipidemia, metabolic syndrome
• Lifestyle
• Obesity (high BMI)
• Purine rich food- meat, kidney, liver, seafood, anchovies,
oatmeal, certain vegetables (peas, beans, lentils, mushrooms,
cauliflower, spinach), sweetbreads,
• High alcohol intake
• Frequent consumption of high-fructose corn syrup
6.
7. Hyperuricemia leads to deposit of urates in the joint fluid, triggering
an inflammatory cascade
8.
9. • 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
10.
11. 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.
12.
13.
14. 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)
15. 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
16. • 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.
21. 1977 ACR Criteria for Acute gout
The 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
23. Radiographic Hallmarks of Gout
Overhanging edges
Punched out lesions with sclerotic borders.
Preservation of joint space (till late)
Degenerative changes
24. SYNOVIAL FLUID ANALYSIS
(Polarized Light Microscopy)
• The Gold standard
• Crystals intracellular during attacks
• Needle & rod shapes
• Strong negative birefringence
30. TREATMENT GOALS
1. Rapidly end acute flares
2. Protect against future flares
3. Reduce chance of crystal induced inflammation
4. Prevent disease progression
5. Lower serum urate to deplete total body urate pool
6. Correct metabolic cause
31. Acute Flares Treatment
NSAI
DS
Colchicine
Corticosteroids
• Not as effective “late” in flare
• Contraindicated in dialysis patients
• Cautious use in :
• Renal or liver dysfunction
• Active infection
• Age > 70
• Worse glycemic control
• May need to use mod-high doses
• Interaction with
warfarin
• Contraindicated in:
• Renal
disease
• PUD
• GI bleeders
32. 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
33. Acute Gout - Rx
NSAIDs (unless CRI, CHF, PUD, etc.)
Corticosteroids (Intra-articular if one
joint, systemic if multiple joints)
Colchicine (adjust dose in patients w/
renal insufficiency)
-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.
-Indomethacin 50mg tid
-Naproxen 825mg once, then 275 q8hr
-Sulindac 200mg bid
-20-30mg/day if systemic used
34. 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
35. 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.
36. FDA-Approved
Urate-LoweringAgents
Dose RangeDrug Action
First-Line (Uricostatic)
S
Allopurinol
Febuxostat
Xanthine Oxidase
inhibitor
Xanthine Oxidase
inhibitor
100-800 mg daily (decrease
dose in renal impairment)
40-80 mg daily
econd-Line (Uricostatic)
Probenecid URAT1 and GLUT9 500-2000 mg daily (carefully
inhibitor adjust dose to 3000 mg maximum)
For Severe, Treatment-Refractory Disease (Uricostatic)
Pregloticase IV Recombinant, 8 mg IV every 2 weeks PEGylated
uricase
37. Uric acid is produced by Xanthine and Hypoxanthine by Xanthine Oxidase Inhibitor.
Uric Acid is more toxic than either xanthineor hypoxanthine.
40. Prevent Disease Progression
• Lower urate to < 6 mg/dl :
• Depletes
Total body urate pool Deposited
crystals
• Treatment is lifelong & continuous
• Drug choices : Uricosuric agents
Xanthine oxidase inhibitor
41. 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
42. 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.
43. PREVENTION
Maintain the concentration of Uric Acid level within the normal range.
Drinking Plenty of Water.
Balance your weight with proper diet and exercise
Avoid purine rich foods
Reducing alcohol consumption
Avoid Diuretic Drugs.
44. 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.
45.
46. Newer Drugs
URICASE 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
