Documentos de Académico
Documentos de Profesional
Documentos de Cultura
By
Dr: Abd El Hameed Fureeh
MD, Lecturer of Internal Medicine, Mansoura
faculty of Medicine
Diabetes, endocrinology and Metabolism unit
Www.MansFans.coM
What is gout?
▲ Gout is a syndrome caused by the
inflammatory response to tissue
deposition of monosodium urate
crystals (MSU).
▲ Nicknamed the “Disease of Kings”
because it can be caused by rich foods,
alcohol, and royalty often had it.
Prevalence
▲ The prevalence of asymptomatic
hyperuricemia is 5 to 8%.
▲ The prevalence of gout is 13 cases per
1000 men and 6.4 cases per 1000
women.
▲ The higher the uric acid, the higher the
risk to develop gout.
▲ 90% of patients with primary gout are
men.
Www.MansFans.coM
Prevalence
▲ Women rarely develop gout before the
menopause, because estrogens are
thought to be uricosuric.
▲ Peak incidence in men is in the fifth
decade.
▲ Primary gout is associated with: obesity,
hyperlipidemia, diabetes mellitus,
hypertension and atherosclerosis.
Etiology
▲ Hyperuricemia is the common
denominator in gout.
▲ Two-thirds of uric acid are excreted by
the kidney and the rest in the GI tract.
▲ 90% of cases of gout are secondary to
under-excretion.
▲ Overproduction is secondary to defects
in the HGPRT or PRPP.
Etiology
▲ The inflammatory response is
secondary to the response of the
leukocytes to the MSU crystals.
▲ Acute gout is most likely secondary to
the formation of new crystals.
▲ Factors that precipitate gout includes:
surgery, trauma, alcohol, starvation and
medications.
GOUT RISK FACTORS
▲ Male
▲ Postmenopausal
female
▲ Older
▲ Hypertension
▲ Pharmaceuticals:
Diuretics, ASA,
cyclosporine
7
Www.MansFans.coM
8
Www.MansFans.coM
Pathology
▲ The most frequent sites of deposition of
MSU crystals are: cartilage, epiphyseal
bone, periarticular structures and the
kidney.
▲ A tophus is a foreign body reaction that
includes the MSU crystals surrounded
by fibrous tissue.
▲ In the kidney the deposition of MSU
crystals causes interstitial fibrosis and
arteriosclerosis.
Clinical course
4 clinical phases if untreated:
▲ asymptomatic hyperuricemia,
▲ acute/recurrent gout,
▲ intercritical gout,
▲ chronic tophaceous gout
10
Asymptomatic Hyperuricemia
▲ elevated urate levels without symptoms of gout,
nephrolithiasis, or kidney stones.
▲ Hyperuricemia is defined:
>7 mg/dL (0.42mmol/L) in men and postmenopausal
women
>6 mg/dL (0..36mmol/L) in premenopausal women.
▲ urate <7 mg/dL 0.1% annual incidence of gout
urate >=9 mg/dL 4.9% annual incidence.
▲ the clustering of glucose intolerance, central obesity,
dyslipidemia, hypertension, and increased prothrombotic
and antifihrinolytic factors in an individual.
11
Cause of hyperuricemia
-- decreased renal excretion
Primary Secondary
Hypertension
Idiopathic Hyperparathyroidism
Myxoedema
Familial juvenile
Down’s syndrome
12
Www.MansFans.coM
Cause of hyperuricemia
-- increased uric acid production
Primary Secondary
Glycogen storage disease
Idiopathic
type II (G6PD), type III, V, VII
HPRT def. Hereditary fructose intolerance
Lymphoproliferative and
PPRT overactivity myeloproliferative diseases
( leukemia, Hodgkin’s d’z,
Ribose-5- lymphosarcoma, myeloma, PV,
Waldenstrom’s
phosphate macroglobulinemia )
Cytotoxic drugs
overproduction Carcinomatosis
AMP-deaminase Gaucher’s disease
Chronic hemolytic anemia
def. Severe exfoliative psoriasis
13
Acute/Recurrent Gout
symptoms: sudden onset of severe pain,
inflammation, limited range of motion, and
warmth at the affected joint(s).
▲ The joints are red, hot, and exquisitely tender;
even a bed sheet on the swollen joint is
uncomfortable, slight fever, leukocytosis,
elevation of ESR, and elevation of CRP
▲ 90% of first attacks are monoarticular with
first metatarsophalangeal joint, known as
podagra.
▲ Left untreated, the symptoms are self-
limiting but may take up to 21 week to
subside.
14
90% of gout patients eventually have
podagra : 1st MTP joint
Www.MansFans.coM
15
Table. Characteristics of Classic Gout vs Atypical Gout
Classic Gout Atypical Gout
Can present at any age, including Observed in elderly patients
patients older than 60 years
Predominantly men Diagnosed in as many women as
men
Monarthritis Polyarthritis
Asymmetric Symmetric or asymmetric
Usually in lower extremity Any joint, upper or lower extremity
Tophi rare at presentation Tophi common at presentation
Acute Chronic but can have acute flare-
ups
Can be misdiagnosed as cellulitis Chronic form can be
or infection misdiagnosed as rheumatoid
arthritis or osteoarthritis: acute
flare-ups can be misdiagnosed as
cellulitis or infection
16
Www.MansFans.coM
ADVANCED GOUT
▲ Chronic Arthritis
▲ X-ray Changes
▲ Tophi Develop
17
ADVANCED GOUT
▲ Chronic Arthritis
▲ Polyarticular acute
flares with upper
extremities more
involved
Www.MansFans.coM
18
Www.MansFans.coM
Intercritical Gout
▲ It is the asymptomatic period between
crises, but MSU crystals can still be
recovered if necessary.
▲ The duration of this period varies,
but untreated patients may have a
second episode within two years.
▲ Some patients evolve to chronic
polyarticular gout without pain free
intercritical episodes.
19
Chronic Tophaceous Gout
▲ Tophi are usually present after 10 to 20
years of inadequately treated chronic
gout.
▲ Visible tophi occur in 12% of patients after
5 years of gout and in 55% of patients after
20 years.
▲ most common sites of tophaceous gout:
olecranon bursae (elbow) and the joints of
the hand and feet.
Other sites: the helix of the ear, the
Achilles tendons, and the knees.
20
Chronic Tophaceous Gout
▲ Transplant patients treated with
cyclosporine and/or diuretics have an
increased risk for tophaceus gout.
▲ The most common sites for tophi are:
the olecranon, prepatellar bursa, ulnar
surface and Achilles tendon.
Www.MansFans.coM
21
Chronic Tophaceous Gout
▲ Tophi in the hands can cause joint
destruction.
▲ Tophi can ulcerate the skin and excrete
a chalky material composed of MSU
crystals.
▲ Tophi progress insidiously with
increased stiffness and pain.
22
Www.MansFans.coM
TOPHI
▲ Solid urate deposits
in tissues
Www.MansFans.coM
23
TOPHI
▲ Irregular &
destructive
Www.MansFans.coM
24
TOPHI RISK FACTORS
Www.MansFans.coM
25
Www.MansFans.coM
Renal disease
▲ Urolithiasis,
▲ Urate nephropathy (deposition of MSU
crystals in the interstitium), and
▲ Uric nephropathy ( deposition of MSU
crystals in the collecting tubes).
▲ The prevalence of urolithiasis is 22% in
primary gout and 42% in secondary
gout.
26
Nephrolithiasis
▲ The prevalence of nephrolithiasis
correlates with the serum and urinary
uric acid levels.
▲ Serum urate levels 13 mg/dl
▲ Urinary uric acid excretion > 1100 mg/d
Www.MansFans.coM
27
Urate Nephropathy
▲ Deposits of monosodium urate crystals
surrounded by a giant cell inflammatory
reaction in the medullary intrerstitium
and pyramids.
▲ Clinically: silent or cause proteinuria,
hypertension and renal insufficiency.
Www.MansFans.coM
28
Uric acid nephropaty
▲ Precipitation in renal tubules and collecting
ducts cause obstruction to urine flow.
Www.MansFans.coM
29
Complication of gout
▲ Joint: destruction
▲ Soft tissue
▲ nerve entrapment syndrome: CTS,
tarsal tunnel syndromes
▲ kidney: uric acid calculi(10-15%),
chronic urate nephropathy, and
acute uric acid nephropathy
▲ Heart: ischemic heart disease
30
Www.MansFans.coM
31
Www.MansFans.coM
32
Www.MansFans.coM
33
GOUTY ARTHRITIS & TOPHI
34
Www.MansFans.coM
Diagnosis of gout
▲ Clinicaldiagnosis: Triad of
1- hyperurecemia
2- Acute monoarticular arthritis
3- Response to colchicine
▲ Laboratory diagnosis
▲ Differential diagnosis
35
Criteria for clinical diagnosis
American Rheumatism Association sub-committe on classification criteria for gout 1977
Www.MansFans.coM
36
Www.MansFans.coM
Laboratory Diagnosis
▲ Even the clinical appearance strongly
suggests gout. The diagnosis should be
confirmed by needle aspiration of acute or
chronically inflamed joints or tophaceous
deposits.
▲ Acute septic arthritis several of the other
crystalline – associated arthropathies, and
psoriatic arthritis may present with similar
clinical features.
37
SYNOVIAL FLUID ANALYSIS
(Polarized Light Microscopy)
▲ The Gold standard
38
Www.MansFans.coM
SYNOVIAL FLUID
39
SYNOVIAL FLUID
▲ Presence of MSU crystals do not
exclude the possibility of septic arthritis,
for this reason it is also recommended
to request a Gram smear.
40
SYNOVIAL FLUID
- Cloudy due to leukocytes and a large
amounts crystals ocassionally produce a
thick pasty or chalky joint fluid.
-Increased leukocytes: >15,000/cc WBCs,
primarily PMNs
Www.MansFans.coM
41
42
SERUM URATIC ACID LEVELS
▲ This is the most misused test in the diagnosis
of gout.
▲ Not reliable
43
Serum uric acid
-Normal range:
male 3-8 mg/dl
female 1.5-6 mg/dl
children 3-4 mg/dl
("normal" values may vary between laboratories)
-False elevation by:
levodopa if colorimetric method used
44
Uric acid in 24-hour urine sample
▲ 24 urine collection for uric acid
determination is useful in assessing the
risk of renal stones and planning for
therapy.
▲ Urinary levels above 750 mg/dl in 24h
in gout or > 1100 mg/dl in asymptomatic
hyperuricemia indicates urate
overproduction.
45
Radiographic Features
▲ Cystic changes, well-defined erosions
described as punched-out lytic lesion.
▲ Soft tissue calcified masses (chronic
tophaceous gout)
▲ Is helpful to exclude other kinds of
arthritis.
46
Www.MansFans.coM
RADIOLOGIC SIGNS
47
48
Blood chemistry
▲ Renal function before deciding on therapy
▲ Plasma glucose: Patients with gout are at an increased
risk of developing diabetes mellitus.
▲ Abnormal liver function tests need to be considered
when therapy is selected.
▲ CBC count: The WBC count may be elevated in patients
during the acute gouty attack, particularly if it is
polyarticular.
▲ Lipids: Hypertriglyceridemia and low high-density
lipoproteins are associated with gout.
▲ Urinalysis: Patients with gout are at an increased risk of
renal stones
49
Differential diagnosis
Acute Chronic
Infective arthritis Nodular rheumatoid
Bursitis, cellulitis, tenosynovitis
Other crystal arthropathy arthritis
( pseudogout, apatite or Psoriatic arthritis
brushite arthritis or periarthritis )
Traumatic arthritis Osteoarthritis with
Hemoarthrosis
RA with palindromic onset
Heberden’s and
Reactive arthritis Bouchard’s nodes
Spondarthritis with peripheral Sarcoid arthritis
involvement
Psoriatic arthritis xanthomatosis
Sarcoid arthritis
Rheumatic fever
50
Gout vs. CPPD
51
Www.MansFans.coM
Gout vs CPPD
52
Crystal-Induced Arthritis
Characteristic Gout Pseudogout
Prevalence 1.5 to 2.6 cases per 1000 individuals; <1 case per 1000 individuals; increases
increases with age in men and with age
postmenopausal women; 15/1000 at
age 58; men:28/1000, women:11/1000
Crystals
Chemistry Monosodium urate Calcium pyrophosphate dihydrate
Appearance Negatively birefringent; needle-shaped Weakly positively birefringent; linear or
rhomboidal
Most frequently affected joints First MTP joint Knee, wrist other
- initially 50%
- eventuall 90%
Ankles, knees, other
54
RA vs Gout
55
Treatment of gout
Www.MansFans.coM
56
TREATMENT GOALS
▲ Rapid and safe pain relieve (end
acute flares)
▲ Protect against future flares
▲ Prevent disease progression
▲ Correct metabolic cause
57
ENDING ACUTE FLARES
▲ Control inflammation & pain & resolve
the flare
▲ Not a cure
▲ Crystals remain in joints
▲ Don’t try to lower serum urate during a
flare
▲ Choice of med not as critical as alacrity
& duration
58
Acute Flare Med Choices
▲ NSAIDS
▲ Colchicine
▲ Corticosteroids
59
Colchicine
1. Mechanism of action
-decreases inflammatory response through binding of
microtubular proteins which interferes with granulocyte
mobility
2. Efficacy: somewhat diagnostic for gout because
-90% respond to colchicine if treatment is initiated
within a few hours after onset, response rates decline if
acute attack is >24hrs old
-colchicine is relatively specific therapy for acute gout
60
Colchecine
Dosing:
-colchicine has a narrow therapeutic index
-doses should be decreased in renal and
hepatic
dysfunction, but there are no standard
guidelines
-PO: 1.2mg stat, then 0.6mg every hour until:
response is achieved, or gastrointestinal
toxicity (diarrhea, abd. pain), or maximum
dose of 12 tablets is taken
61
Www.MansFans.coM
Colchecine
-IV: 2mg in 20cc NS infused slowly, may repeat with 1mg
after 6hrs but no more than 4mg in 24hours
-Decrease total dose to 2mg/24hrs in elderly patients
or patients who have been on colchicine maintenance
-Give only to patients who cannot tolerate the oral
tablets
-Avoid extravasation because it causes soft tissue
necrosis
62
Colchecine
Adverse reactions
-Gastrointestinal: diarrhea, nausea, vomiting, hemorrhagic
colitis, occurs in 70-80% of patients on oral therapy, less
frequent with IV therapy but may see with high doses
-Bone marrow depression: cumulative toxicity
-Renal dysfunction: toxic side effect seen after large doses,
hematuria, oliguria
-Necrosis of soft tissue after extravasation: do not give
IM/SC
63
Www.MansFans.coM
NSAID
Mechanism of action:
-anti-inflammatory effects through
inhibition of prostaglandin
synthesis and inhibition of motility of
PMNs
-not specific for gout—adequate doses
will relieve inflammation from any
cause
64
NSAID
Agents and Dosing
-Indomethacin: 75mg stat, 25-50mg q6hr, taper as
symptoms resolve
-avoid in elderly
-Any non-salicylate NSAID should be effective if
given in anti-inflammatory doses
-avoid salicylates because of effect on uric acid
elimination
65
NSAIDS
▲ NSAIDS :
Interaction with
warfarin
Contraindicated in:
Renal disease
PUD
GI bleeders
ASA-induced RAD
66
Intra-articular Steroids
-Effective anti-inflammatory agents
-Reserve for patients who cannot tolerate oral
colchicine or NSAID therapy and who are not
candidates for IV colchicine
-Limited to 4 injections per joint per year
Can use:
-Methylprednisolone (Depomedrol)
-Triamcinolone hexocetanide
67
Syst. Corticosteroids
68
PROTECTION VS. FUTURE
FLARES
▲ Colchicine : 0.5-1.0 mg/day
▲ Low-dose NSAIDS
69
Www.MansFans.coM
PREVENT DISEASE
PROGRESSION
▲ Lower urate to < 6 mg/dl : Depletes
Total body urate pool
Deposited crystals
▲ RX is lifelong & continuous
▲ MED choices :
Uricosuric agents
Xanthine oxidase inhibitor
70
PREVENT THIS
71
Www.MansFans.coM
Uricosuric agents
▲ Indicated in patients with normal renal
function, under-excretion and no
evidence of tophi.
▲ Patients taking uricosuric agents are at
risk for urolithiasis. This can be
decreased by ensuring high urinary
output and by adding sodium
bicarbonate 1 gram TID.
72
Uricosuric agents
▲ The available agents include:
probenecid (1-2 g/day) and
sulfinpyrazone (50-400 mg BID).
▲ Dose should be increased to decrease
uric acid < 6.0 mg/ml
73
Sulfinpyrazone (Anturane)
Uricosuric: has Increased potency vs probenecid
Has antiplatelet effect at doses of 600-800mg/day
Dosing: 50mg bid-400mg/day, may go up to
800mg/day
Adverse reactions:
-Hypersensitivity reactions (uncommon): rash, may
cause bronchoconstriction in patients with ASA
intolerance, contraindicated in patients allergic to
phenylbutazone/pyrazoles
-Gastrointestinal irritation: take with food or milk
74
XANTHINE OXIDASE
INHIBITOR
75
Allopurinol
▲ Blocks conversion of hypoxanthine to
uric acid
▲ Decreases uric acid in overproducers
and underexcreters; it is also indicated
in patients with a history of urolithiasis,
tophaceus gout, renal insufficiency and
in prophylaxis of tumor lysis syndrome.
76
Allopurinol
▲ usual dose is 300 mg/day. Maximal
recommended dose is 800 mg/day.
▲ In renal insufficiency dose should be
decreased to 200 mg/day for creatinine
clearance < 60ml/min and to 100
mg/day if clearance < 30 ml/min).
77
Allopurinol
▲ Start with small doses of allopurinol to
reduce the risk of precipitating an acute
gout attack.
▲ Most common side effects are rash (2%
of patients) but rarely patients can
develop exfoliative dermatitis that can
be lethal.
▲ Chronic use of colchicine (0.6-1.2
mg/day) is used as prophylaxis for
acute attacks.
78
Allopurinol Dosing
-Start at 100mg per day, increase weekly as
needed
-70% of patients will be controlled on
300mg/day
-May give up to 1200mg/day if necessary
-May be given once daily because of long
half life of active metabolite, but divided
doses recommended if total daily dose
>300mg
-Renal disease requires dose adjustment
79
Www.MansFans.coM
80
Febuxostat
▲ Potentnew xanthine oxidase inhibitor
▲ Metabolized by the liver (used in RI)
▲ No hypersensitivity reaction
▲ Dose: 80-120 mg/d
81
WHICH AGENT
▲ Base choice on above considerations &
whether pt is an overproducer or
underexcretor : Need to get a 24-hr.
urine for urate excretion:
< 700 --- underexcretor
(uricosuric)
> 700 --- overproducer
(allopurinol)
82
Www.MansFans.coM
Purine nucleotides
hypoxanthine Allopurinol
xanthine Xanthine
oxidase
Oxypurinol
Uric acid
84
URICASE ENZYMES
(Stay Tuned)
85
Treating the Asymptomatic
Hyperuricemic Patient:
Controversial, no set guidelines, but consider
in the following patient groups:
A. Develops symptoms
B. Excretes >900mg of uric acid/24hr: risk for
kidney stones
C. Serum uric acid >12mg/dl,
D. Patient with malignancy using
chemotherapy
86
Diet
▲ Usually impractical, ineffective and
rarely adhered to in clinical practice.
▲ Indications for pharmacological therapy
includes: inability to reverse secondary
causes, tophaceus gout, recurrent
acute gout and nephrolithiasis.
87
Www.MansFans.coM
88
Prophylaxis A. When to treat
2. Tophi: indicator of long-standing
disease, will regress/disappear with
uric acid lowering therapy, patients
with tophi should be treated e even if
gout attacks are not frequent
3. Uric acid nephrolithiasis: treatment
will prevent further stones (and
development of renal dysfunction due
to gouty nephropathy?)
89
Www.MansFans.coM
QUESTIONS
90
91