Basic information about Gout and Gouty arthritis, Hyperuricemia For UnderGraduates and Orthopaedic Surgeons

1. Gout
Dr. Apoorv Jain
D’Ortho, DNB Ortho
drapoorvjain23@gmail.com
+91-9845669975

2. 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

3. 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

4. • 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)

6. The King of Pain
• Benjamin Franklin
• Thomas Jefferson
• Sir Isaac Newton
• Charles Darwin
• King Henry VIII and other famous leaders
all suffered from gout

7. Incidence
• Persons in USA Affected by Common
Rheumatologic Disorders (As per ACR):
 Frequent Low Back Pain
40.2 million in 2005, projected to increase to 48.6 million in 2025
 Osteoarthritis
20.7 million in 2005, projected to increase to 28.1 million in 2025
 Gout
2.6 million in 2005, projected to increase to 3.6 million in 2025
 Rheumatoid Arthritis
2.1 million in 2005, projected to increase to 2.8 million in 2025

8. 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.

9. 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

10. • 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

12. Hyperuricemia leads to deposit of
urates in the joint fluid, triggering an
inflammatory cascade

13. Stages
This disorder can be progressive through
four stages if undertreated
Asymptomatic hyperuricemia
Acute gout
Intercritical gout
Chronic tophaceous gout

14. Clinical
Features

15. 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.

17. • 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.

19. 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)

20. 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

21. • 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

22. • 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.

23. Diagnosis

24. 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

25. 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

26. 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

27. SYNOVIAL FLUID ANALYSIS
(Polarized Light Microscopy)
• The Gold standard
• Crystals
intracellular during
attacks
• Needle & rod
shapes
• Strong negative
birefringence

28. BIOCHEMICAL TESTS FOR GOUT:

29. Differential Diagnosis
• Pseudogout: Chondrocalcinosis,
CPPD
• Psoriatic Arthritis
• Osteoarthritis
• Rheumatoid arthritis
• Septic arthritis
• Cellulitis

30. Gout vs. CPPD
• Similar Acute attacks
• Different crystals under Microscope:
Rhomboid, irregular in CPPD

31. Gout vs RA
• Both have polyarticular, symmetric arthritis
• Tophi can be mistaken for RA nodules

32. To be continued..
Treatment
Gout

33. Drugs Used In Treatment
• NSAIDs
• Colchicine
• Uricosuric agents
• Allopurinol/ Febuxstat

34. NSAIDS:
• Inhibits pain & inflammation.
• Inhibits urate crystal phagocytosis by
decreasing the migration of
granulocytes into the inflammatory
area.
• Indomethacin, Naproxen, Ketorolac.

35. 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.

37. URICOSURIC AGENTS:
• Probenecid & Sulfinpyrazone
• They are weak organic acids .
• Sulfinpyrazone is a metabolite of
phenylbutazone.
• Increase the excretion of Uric acid.

38. Allopurinol/ Febuxstat:
• Inhibits synthesis of uric acid by
inhibiting xanthine oxidase enzyme

39. Uric acid is produced by Xanthine and Hypoxanthine
by Xanthine Oxidase Inhibitor.
Uric Acid is more toxic than either xanthine or
hypoxanthine.

40. 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

41. 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

42. 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

43. 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)
- 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

44. 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

45. 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

46. 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

47. 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

48. 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.

49. 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

50.  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.

52. 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

53. Thank
You