Dr-Abdulameer Majeed Abunailah

Rheumatologist
Canadian Specialist Hospital
Gout
 a disease recognized since antiquity, has increased in
prevalence in recent years and the clinical profile of
this disease has become increasingly complex, owing
to large numbers of cases with iatrogenic factors,
multiple comorbidities, advanced age, and
hyperuricemia and arthritis refractory to treatment.
 The prevalence is 2.7%.
Gout
Is characterized
biochemically
by extracellular fluid urate
saturation, which is defined as
urate levels > 6.8 mg/dl ,
The clinical manifestations
include one or more of the following:
 Recurrent attacks of acute inflammatory arthritis
 Chronic arthropathy .
 Accumulation of urate crystals in the form of tophaceous deposits .
 Uric acid nephrolithiasis .
 A chronic nephropathy that in gouty patients is most often due to
comorbid states.
Classification
Persistent hyperuricemia can be divided into
two categories;

•Primary hyperuricemia, which usually lasts indefinitely,

describes urate saturation arising in the absence of
coexisting diseases or drugs that alter uric acid
production or excretion.
•Secondary hyperuricemia refers to excessive urate
production or diminished renal clearance that is the
result of another disease, drug, dietary product, or toxin.
Clinical associations
 Renal disease: chronic urate nephropathy , acute uric
acid nephropathy and uric acid nephrolithiasis .
 Hypertension: present in 25%-50% of people with
gout, 2-14% of people with hypertension have gout.
 Obesity: individuals with gout commonly are
overweight.
 Hyperlipidemia: serum triglycerides are elevated in
80% of gouty patients.
CLINICAL
SYNDROMES
 Acute gouty arthritis.

 Intercritical (or interval).

 Chronic recurrent and tophaceous gout.

With current effective therapies, progression of gout to the

chronic tophaceous stage is now less frequent among the
majority of compliant patients with primary gout, and most
patients with secondary gout.
ACUTE GOUTY ARTHRITIS
•Severe pain, redness, swelling, and disability. Maximal
severity of the attack is usually reached within 12 to 24
hours. that typically involves a single joint(80%), but can
affect multiple joints(20%).
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 Lower extremity involvement. At least 80 percent of
initial attacks involve a single joint, most often at the
base of the great toe (first metatarsophalangeal joint,
known as podagra), or the knee.
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 Involvement in an ankle or instep, or in a wrist, finger
or olecranon bursa can occur initially, but is more
common in a recurrent episode of gouty arthritis.
 Other potential sites of involvement include other
bursas, shoulders, hips, sterno-clavicular joints, spine
and sacroiliac joints.
Predisposing factors
•Trauma, surgery, starvation,
fatty foods and other dietary
overindulgence
(High levels of meat and seafood consumption) ,
dehydration, and ingestion of drugs affecting serum
urate concentrations as Thiazide , low dose aspirin .
Criteria for classification of Acute
Gout
MSU microcrystals in joint fluid or tophus proved to contain urate
Or the presence of 6 of the following 12 criteria:

 More than 1 attack of acute arthritis

 Maximum inflammation developing within 1 day
 Monoarthritis attack
 Redness observed over joints
 First metatarsophalangeal joint painful or swollen
 Unilateral first metatarsophalangeal joint attack
 Unilateral tarsal joint attack
 Tophus (suspected)
 Hyperuricemia
 Asymmetric swelling within a joint on x-ray
 Subcortical cysts without erosions on x-ray
 Joint fluid culture negative for organisms during attacks.
Diagnosis of
acute gout
 Polarizing microscopy :
Synovial fluid obtained
from joints or bursas .
 Laboratory tests: hyperuricemia,elevated ESR & CRP.
 Subcortical bone cysts apparent on plain radiograph,
ultrasound examination displaying typical features of
synovial tophaceous deposits, or magnetic resonance
imaging (MRI) examination identifying gouty
erosions. Changes are not usually detectable at the
time of the first acute attack of gouty arthritis.
Treatment of acute gout
 The goal of therapy :
is prompt and safe termination of pain and disability.
 Without therapy, acute gouty arthritis usually resolves
within a few days to several weeks. However,
symptoms improve more quickly with administration
of any of a broad array of anti-inflammatory drugs.
 Symptom resolution is more prompt and complete
with early initiation of therapy.
Treatment
A number of drugs have been used for the treatment of
acute gout:
 Nonsteroidal antiinflammatory drugs
 Colchicine
 Intraarticular or systemic glucocorticoids
 Interleukin 1 beta inhibition .
Management of acute gout 
NSAIDS/COX-2 INHIBITORS
 Complete or nearly complete resolution of pain and
disability typically occurs within several days to one
week.
 A number of randomized trials have compared
different NSAIDs with each other, without any
apparent differences in efficacy.
 Etoricoxib 120 mg once daily provides rapid and
effective treatment for acute gouty arthritis
comparable to indometacin 50 mg three times daily.
Etoricoxib was generally safe and well tolerated,
Arthritis Rheum. 2004;50(2):598.
NSAIDs
 Unless contraindicated, we suggest administration of a
potent oral non-selective NSAID (such as naproxen or
indomethacin) for reduction of acute gouty
inflammation, especially if treatment is initiated
within 24 hours of the onset of symptoms. A typical
starting dose for naproxen is 500 mg twice daily and
for Indomethacin 150 mg/day given in three divided
doses.
NSAIDs
 In view of the frequent gastrointestinal intolerance
associated with NSAIDs, the dose should be reduced
by one-half as soon as objective and subjective
improvement is noted, often within three days.
Further dose reductions and withdrawal over several
more days is safe and practical. Most patients are on
NSAIDs until the attack has completely resolved; this
may be a total of seven to ten days.
NSAIDs
 In an attack of several days duration a longer course of
treatment may be necessary and an anti-inflammatory
agent with fewer gastro-duodenal side effects (such as
a selective COX-2 inhibitor) may be preferred. In
patients at high risk of gastric ulcer or gastrointestinal
bleeding addition of an antiulcer medication to a non-
selective NSAID may be helpful.
COLCHICINE
 Oral Colchicine can be effective for the treatment of
acute gouty arthritis, and side effects are less likely
when a low-dose regimen is used at the onset of
symptoms of flare.
 The regimen recommended by the FDA for
administration of this agent is a low-dose course
consisting of 1.2 mg at the first dose followed one hour
later by 0.6 mg, to give a total dose of 1.8 mg on the
first day of colchicine treatment
Colchicine
 The EULAR guideline recommended colchicine 0.5
mg three times daily.
 Low-dose colchicine may have similar efficacy to that
of a higher dose regimen.

 the GI toxicity of the high-dose regimen substantially

reduces the benefit to risk ratio of treatment. In
contrast, toxicity of low-dose treatment was not
discernibly different from that of placebo, supporting
recommendations for low-dose colchicine treatment
in acute gout rather than higher-dose treatment.
Colchicine
 Low-dose colchicine yielded both maximum plasma
concentration and early gout flare efficacy comparable with
that of high-dose colchicine, with a safety profile
indistinguishable from that of placebo ,Arthritis Rheum.
2010;62(4):1060.

 Intravenous — Because of the potential for life-threatening

adverse effects, the United States Food and Drug
Administration in February 2008 asked that intravenous
preparations containing colchicine no longer be
manufactured or shipped in the USA. Although existing
intravenous preparations were not recalled, this cessation
of supply severely limits, and effectively ends, the use of
colchicine by the intravenous route in the USA.
Colchicine
 Intravenous colchicine is a consideration in
hospitalized patients who are unable to take oral
medications. However, its use is limited by serious
systemic reactions, including bone marrow
suppression, hepatic necrosis, acute renal failure,
disseminated intravascular coagulation, seizures, and
even death. Severe sclerotic tissue reactions can occur
in the event of colchicine extravasation, so secure
intravenous access is essential.
GLUCOCORTICOIDS
 Intraarticular glucocorticoids are a reasonable option
in patients with only one or two actively inflamed
joints, although evidence of their benefit has been
limited to small, open label trials .
 in one uncontrolled trial, all 19 patients receiving
intra-articular depot corticosteroid injections
improved within 48 h.
Glucocoticoids
 Systemic glucocorticoids may be administered orally
in patients who cannot take NSAIDs or colchicine and
who are not candidates for intraarticular
glucocorticoid injection because of polyarticular
disease.
 The use of oral prednisolone (35 mg daily) has recently
been shown to be comparably effective to Naproxen
500 mg twice daily in a randomised trial .
ACTH
 In addition to stimulating release of corticosteroids,
ACTH may act on melanocortin type 3 receptors on
cells involved in gouty inflammation.
 In one retrospective report, virtually all acute attacks
resolved within 5.5 days of ACTH administration with
few significant adverse effects(mild hypokalemia,
hyperglycemia, fluid retention and rebound arthritis
occurred as adverse effects ).
ACTH
 Various ACTH dosing regimens have been advocated.
We have used 40 to 80 USP units, administered twice
daily for two days and then once daily for several
succeeding days as needed.
Interleukin-1 inhibition
Interleukin-1 (IL-1) is an important mediator of
inflammation which is released by monocytes and
synovial mononuclear cells .
 Anakinra : a recombinant human interleukin-1
receptor antagonist .
 Canakinumab :a fully humanized monoclonal
antibody that blocks IL-1β signaling.
Treatment of acute gout with IL-1 inhibition remains off-
label and cannot currently be recommended.
IL-1 inhibition
 An uncontrolled trial of IL-1 inhibition with anakinra
was effective in the treatment of acute gout in 10
patients and may also have a role in treatment-
resistant inflammation associated with tophaceous
gout.
 IL-1 inhibitory agent, rilonacept, has also been shown
to be effective at suppressing flares of gouty arthritis
and C-reactive protein (CRP) levels.
SPECIAL CIRCUMSTANCES
 Hospitalized patients : often postoperative
Treatment options in this setting include:
 Intraarticular glucocorticoids
 Intravenous glucocorticoids
 Intramuscular or subcutaneous ACTH.
Diuretic-induced hyperuricemia
and 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 .
 Treatment is not necessary.
 Gouty arthritis is not common in this setting,
occurring primarily in patients with a personal or
family history of the disease.
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 The concurrent administration of an angiotensin
converting enzyme inhibitor or an angiotensin II
receptor blocker can minimize the diuretic-induced
rise in plasma urate concentration .
End-stage renal disease
 advanced chronic kidney disease or end-stage renal
disease requiring maintenance dialysis may be at lesser
risk of symptomatic disease . Such patients can be
safely treated with intraarticular or oral
glucocorticoids .
Hyperuricemia and gout in renal
transplant recipients
 Reduced uric acid excretion can occur after renal
transplant, particularly in patients receiving
cyclosporine to prevent graft rejection.
 Pharmacologic treatment and prevention of gout is
not without risk in the transplant recipient .
 colchicine administration should be limited to a single
oral dose of 0.6 mg and not repeated for at least three
days. For gout flare prophylaxis, a colchicine dose of
0.3 mg daily or every other day (depending on renal
functional status) can be given.
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 short-term NSAID use and supplementation of the
baseline corticosteroid dose most transplant recipients
receive. Slow (over 10 to 14 days) rather than rapid
tapering of corticosteroids to the baseline dose is
recommended to avoid rebound gout flares.
 The xanthine oxidase inhibitors should be avoided in
patients treated with azathioprine.
PATIENTS TAKING
ANTIHYPERURICEMIC THERAPY
 In patients who have had recurrent attacks of acute
gouty arthritis, antihyperuricemic therapy (eg,
allopurinol, febuxostat, probenecid, pegloticase) is
used for long-term prophylaxis but has no role in the
treatment of active gouty inflammation. However,
once treatment with an antihyperuricemic agent has
been initiated, should not be interrupted during an
acute attack.
Education of patient
 patient education regarding lifestyle in the plan for
prevention of subsequent flares. Patients should be
encouraged to lose weight and counselled to avoid
excessive consumption of animal purines, high-
fructose sweeteners and alcohol.
 However, the maximum serum urate reduction
achieved by diet alone is typically only ~1 mg/dl or up
to 15%, which renders pharmacologic options
necessary for most patients with gout.
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