2. Definition:
Gout is a clinical disease associated with
hyperuricemia and caused by the deposition of
monosodium urate (MSU) crystals in and
around the tissues, resulting in one or more of
the following manifestations:
I- Acute gouty arthritis
II - Tophaceous gout
III- Gouty nephropathy
IV- Uric acid stones

5. Pathophysiology:

6. Because uric acid has limited
solubility in bodily fluids,
monosodium urate crystal formation
occurs above the solubility threshold
Urate crystals are deposited
preferentially in and around
peripheral joints in the feet, knees,
hands and elbows, especially those
affected by osteoarthritis

7. Metabolism of uric acid and risk
factors for gout:

8. Pathogenesis

9. Pathophysiology:

11. Hyperuricaemia and gout: time for
a new staging system?

12. Diagnosis:

13. Gout tophi :

14. X-ray of Gout:

15. US of Gout:

16. DECT of Gout:

17. The fundamental aims of gout
treatment:
Improve outcomes by
short-term suppression
 long-term elimination of gout flares
 induce durable resolution of tophi
 identify and effectively manage
comorbidities

18. 2012 American College
of Rheumatology
Guidelines for
Management of Gout

19. (A)
Systematic
Nonpharmacologic and
Pharmacologic
Therapeutic Approaches to
Hyperuricemia

21. Systematic Non pharmacologic &
Pharmacologic therapeutic
Approaches to Hyperuricemia:
 Patient education on diet, lifestyle, treatment
objectives,and management of comorbidities
is a recommended core therapeutic measure in
gout.
 Xanthine oxidase inhibitor (XOI) therapy with
either allopurinol or febuxostat is
recommended as the first-line pharmacologic
urate-lowering therapy (ULT).
 The starting dosage of allopurinol should be
no greater than 100 mg/day and less than that
in moderate to severe chronic kidney disease
(CKD), followed by gradual upward titration of
the maintenance dose, which can exceed 300

22. Systematic Non pharmacologic and
Pharmacologic therapeutic
Approaches to Hyperuricemia:
 Probenecid is the first choice among uricosuric
agents for ULT monotherapy.
 Use of agents other than probenecid with clinically
significant uricosuric effects, such as fenofibrate and
losartan, can be therapeutically useful as components
of a comprehensive ULT.
 History of urolithiasis contraindicates first-line
uricosuric urate-lowering monotherapy.
 Combination oral ULT with XOI agent and uricosuric
agent is appropriate when the target has not been
met by appropriate dosing of an XOI.
 Pegloticase is appropriate for patients with severe
gout disease burden and refractoriness to, or

23. Serum urate lowering
agents: Xanthine oxidase inhibitors
 Allopurinol
 Febuxostat
uricosuric agents:
 benzbromarone,
 probenecid
 sulfinpyrazone
Uricase therapies:
 rasburicase, pegloticase

24. Xanthine oxidase inhibitors:
 The usual first-choice ULT, with allopurinol favoured over
febuxostat due to cost considerations and long-term safety data.
 XOIs reduce endogenous production of uric acid by inhibiting the
conversion of hypoxanthine to xanthine and of xanthine to uric acid.

25. Uricosuric drugs:
 Act predominantly on urate anion exchanger 1 (URAT1)
an organic anion transporter to prevent reuptake of uric
acid at the proximal renal tubule and thus increase renal
excretion of uric acid
 The resulting higher concentration of uric acid in the
collecting tubules can predispose to uric acid stone
formation, so the patient should be advised to drink
plenty of fluids and remain well-hydrated
 Three uricosuric drugs are licenced and well-established
as ULT: benzbromarone (50–200 mg daily), probenecid
(250–500 mg twice daily) and sulfinpyrazone (200–800
mg daily)
 Probenecid and sulfinpyrazone are contraindicated in
patients with severe renal impairment or nephrolithiasis.
 The availability of benzbromarone became limited
mainly due to concerns over reports of hepatotoxicity.

26. Uricase therapies:
Uricase an enzyme that converts uric acid to highly
soluble allantoin.
Pegloticase :
is a pegylated uricase that was recently licenced
(2010 in the USA, 2013 in Europe) for use in
‘treatment-refractory’ gout. This drug is
administered by repeated intravenous infusion (8
mg every 2 weeks )
Pegloticase is extremely effective at rapidly
reducing SUA to very low levels for several weeks.
However it is antigenic, with a risk of anaphylaxis
and infusion reaction, so premedication with
antihistamine and corticosteroids in an
appropriately staffed facility is recommended.
Concerns also remain over cardiovascular risk, and

27. Uricase therapies:
Although pegloticase is seemingly very efficient at
inducing rapid regression of tophi, the number of
patients who are truly refractory to other standard
ULTs is likely to be extremely small, and because of
safety and tolerability concerns, and the cost and
logistics of delivery of this drug, its use is likely to
be very restricted.
Rasburicase: a uricase that has been licenced
for many years for tumour lysis prophylaxis, has
also been used to treat ‘refractory’ gout where
intolerance or renal impairment precludes the use of
other ULTs.
However, although some patients seem to tolerate
repeated doses, rasburicase is unlicenced for gout
and is more antigenic than pegloticase

28. ULTs in development:
Other drugs that are undergoing clinical
investigation as potential ULTs include
RDEA594 (lesinurad), which is a
uricosuric,
BCX4208 (ulodesine), which is a
purine nucleoside phosphorylase
inhibitor.
However, these agents are not yet
available or licenced for use in gout,
either as monotherapy or in
combination with an XOI

29. Asymptomatic hyperuricemia :
 Asymptomatic hyperuricemia is the term
applied to settings in which the serum urate
concentration is elevated but in which
neither symptoms nor signs of urate crystal
deposition (gout) have occurred.
 Although gout may develop in a
hyperuricemic individual at any point, it is
likely that two-thirds or more of
hyperuricemic individuals will remain
asymptomatic
 Antihyperuricemic drug therapy for the great
majority of individuals with asymptomatic
hyperuricemia is not justifiable by
risk/benefit analysis

31. Treatment of Asymptomatic
hyperuricemia :
 Persistent hyperuricemia in the infrequent
patients with sustained serum urate
concentrations greater than 13 mg/dL in
men and 10 mg/dL in women .
 This recommendation does not generally
apply to patients with heart failure who
may develop marked hyperuricemia due
to renal hypoperfusion and to reduced
urate excretion. Such patients typically
have advanced heart failure with limited
life expectancy and are, therefore, at low
risk for chronic urate nephropathy.

32. Treatment of Asymptomatic
hyperuricemia:
 Excretion of urinary uric acid in excess of
1100 mg (6.5 mmol) daily is associated with a
50 percent risk of uric acid calculi.
Management of these individuals should
begin with dietary purine restriction.
Allopurinol should be used if dietary
restriction does not reduce uric acid excretion
to less than 1000 mg/day.
 Patients about to receive radiotherapy or
chemotherapy that is likely to result in
extensive tumor cytolysis should be treated
to prevent acute uric acid nephropathy and
other manifestations of tumor lysis syndrome
. Preventive therapy in patients at risk
includes intravenous hydration and either

33. Diuretic-induced
hyperuricemia&gout :  Hyperuricemia is a relatively common finding in
patients treated with a loop or thiazide diuretic
and may, over a period of time, lead to gouty
arthritis. The degree of urate retention caused
by diuretics is dose dependent .
 Loop and thiazide diuretics decrease urate
excretion by increasing net urate reabsorption;
this can occur either by :
1. A direct effect of diuretics on promoting urate
reabsorption by the proximal tubule.
2. An indirect effect of diuretic-induced volume
depletion on increasing urate reabsorption by
the proximal tubule.

34. Diuretic-induced
hyperuricemia&gout :
 Diuretics may increase the relative risk of gout
by nearly 80 percent; the absolute incidence of
gout in patients taking diuretics may be close
to 3 percent.
 Treatment of diuretic-induced asymptomatic
hyperuricemia is not necessary, even though
the plasma urate concentration may exceed 15
mg/dL particularly in patients with reduced
renal perfusion due to underlying advanced
heart failure . These patients are not at risk of
uric acid nephropathy since the elevation in
the plasma urate level is due to an initial
decrease in the rate of urate excretion.

35. Diuretic-induced
hyperuricemia&gout :
 A diagnosis of gout is not necessarily an
indication for discontinuation of the diuretic,
particularly if diuretic therapy is required for
management of edema. However, if blood
pressure control can be effectively and
affordably achieved with an appropriate
alternative agent, such as an angiotensin
inhibitor or a dihydropyridine calcium channel
blocker, then the diuretic can be stopped.
 Most patients with diuretic-induced gout are
treated with a urate-lowering drug such as
allopurinol.

36.  Among patients with hypertension, the concurrent
administration of an ACE inhibitor or ARB can minimize
the diuretic-induced rise in plasma urate concentration
. This has been thought to be mediated by reversal of
the stimulatory effect of angiotensin II on proximal
sodium and urate reabsorption.
 In addition, losartan may have a more direct uricosuric
effect, thereby inhibiting urate reabsorption and
lowering the plasma urate concentration.
 The combination of losartan or an ACE inhibitor with a
thiazide has the added advantages of a more potent
antihypertensive effect than seen with either drug
alone and of minimizing other metabolic effects of the
diuretic, such as hypokalemia and hyperlipidemia.

37. (B)
Therapy and anti-inflammatory
Prophylaxis
of Acute Gouty Arthritis

41. NSAID:
 An oral NSAID is by far the most commonly used
treatment for acute gout in general practice.
 Because of the severity of pain experienced in
acute gout, the NSAID should be commenced at its
maximum dose, rather than titrating upwards
from the lower end of the dose range.
 Although some doctors still hold the traditional
belief that indomethacin is more effective than
other NSAIDs, studies comparing different quick-acting
NSAIDs demonstrate their equal efficacy in
acute gout.
 Selective (COX)-2 inhibitors compare favourably
with nonselective NSAIDs for the treatment of
acute gout in terms of similar efficacy but lower
incidence of serious gastrointestinal events.

42. Colchicine:

43. Colchicine:
 oral NSAIDs+ oral colchicine is recommended as a first-line
treatment for acute gout attacks.
 current EULAR guidelines recommend a maximum dose of 0.5
mg colchicine three times a day
 ACR guidelines recommend a regimen involving a loading dose
of 1.2 mg then 0.6 mg 1 h later, followed after a further 12 h
by 0.6 mg once or twice daily. Such low doses seem to be
effective and well-tolerated in clinical practice. Even lower
doses (0.5 mg once or twice daily) can be tried in patients with
persistent adverse effects and in those with moderate to severe
CKD.
 Colchicine is considered to work best when commenced within
24 h of first symptoms of an acute attack
 ACR guidelines recommend that colchicine is not initiated more
than 36 h after symptom onset. Treatment is usually continued
until the acute attack has subsided.

44. Corticosteroids :
Intra-articular corticosteroids
Aspiration of an affected joint followed by injection of
corticosteroids is ideal for treatment of acute gout attacks,
particularly in a hospital setting where first-line use of this
intervention can provide prompt relief with minimal adverse
effects. This treatment is a particularly useful option where
colchicine, NSAIDs or oral corticosteroids are
contraindicated.
Oral corticosteroids :
Oral prednisolone can be used where colchicine or NSAIDs are
contraindicated or have failed to provide sufficient relief, this
method of delivery of corticosteroids is the one most commonly
used in general practice.
Intramuscular corticosteroids:
single injection but, but there is no consensus on dose.

45. Biologic agents :
 Available biologic agents that inhibit IL-1 and
which have been assessed in treatment of acute
attacks of gout specifically anakinra, canakinumab
and rilonacept have either had no comparator or
have been compared to a possibly suboptimal
dose of triamcinolone (40 mg intramuscularly)
rather than a more commonly used short course
of oral prednisolone (for example, 30–35 mg
prednisolone daily).
 Modest advantages of biologic agents have been
reported, but these treatments remain
comparatively very expensive, and as yet are
largely unlicenced for acute gout in most
countries (canakinumab is now licenced for use in
europe, but not in the UK or USA).

46. Long-term management:
 The aim of long-term therapy is to ‘cure’ gout
by lowering SUA levels to below the saturation
point for urate that is, to at least below (6
mg/dl)thus promoting crystal dissolution and
preventing formation of new crystals.
 The most effective method of achieving this
SUA level is the use of urate-lowering therapy
(ULT).
 Indications for ULT include recurrent attacks
of gout, clinically detectable tophi, joint
damage or nephrolithiasis in other words,
well-established and relatively severe gout.

47. References:
New Gout Management Guidelines: A Quick
and Easy Guide Bret S. Stetka, MD; Jonathan
Kay, November 19, 2012.
 Optimizing current treatment of gout Rees, F.
et al. Nat. Rev. Rheumatol. 10, 271–283 (2014)

48. Thank You