Guideline for gout

management
(Arthritis)

高雄長庚醫院風濕過敏免疫科
 Introduction
the deposition of monosodium urate
( MSU ) crystals in the joints and soft
tissues.
Incidence: 0.1%
 Introduction 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
Articular involvement Monoarticular > oligoarticular; Monoarticular > oligoarticular
polyarticular < 30%
Most frequently affected joints First MTP joint Knee, wrist other
　－ initially 50%
　－ eventuall 90%
Ankles, knees, other
Predisposing conditions/risk factors Hyperuricemia*, obesity, hypertension, Hypothyroidism, hemochromatosis, OA,
hyperlipidemia, alcohol ingestion, lead chronic renal insufficiency, diabetes,
ingeation, hereditary enzyme defect (rare) hyperparathyroidism, hereditary (rare)

Therapeutic options Acute attacks: Acute attacks:

　－ NSAIDs, corticosteroids, colchicine 　－ NSAIDs, corticosteroids, colchicine
Chronic management Chronic management
　－ Urate-lowering agents, colchicine 　－ NSAIDs ± colchicine

*Drugs associated with hyperuricemia include diuretios, low-dose salicylates, nicotinic acid, oyclosporine, ethanol and
ethambutol.
De novo and salvage pathways in purine metabolism. Phosphoribosyl pyrophosphate amidotransferase (AMPRT) catalyzes the committed step of
de novo purine nucleotide synthesis. Hypoxanthine phosphoribosyltransferase (HPRT) and adenine phosphoribosyltransferase (APRT) are
responsible for recycling purine bases into nucleotides. 5-phosphoribosyl-1-pyrophosphate (PRPP) levels regulate all of these reactions. Uricase
(UC) prevents the buildup of uric acid in mice, but not in humans. Other important enzymes in the salvage pathway are adenosine deaminase
(ADA), purine nucleoside phosphorylase (PNP), guanase (GA), and xanthine oxidase (XO).
 Clinical course

4 clinical phases if untreated:

 asymptomatic hyperuricemia,
 acute/recurrent gout,
 intercritical gout,
 chronic tophaceous gout
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.
 Cause of hyperuricemia
-- decreased renal excretion
Primary Secondary
 Hypertension
 Idiopathic  Hyperparathyroidism
 Myxoedema
 Familial juvenile  Down’s syndrome
 Increased level of organic level
gouty nephropathy  Lead nephropathy
 Sarcoidosis
 Bartter’s syndrome
 Beryllium poisoning
 Drug: diuretics, B-blocker, ACEI,
salicylates (low dose), PEA, EMB,
cyclosporin, nicotinic acid
 Chronic renal failure
 Volume depletion
 NDI
 Cause of hyperuricemia
-- increased uric acid production
Primary Secondary
 Glycogen storage disease
 Idiopathic type II (G6PD), type III, V, VII
Hereditary fructose intolerance
 HPRT def. 
 Lymphoproliferative and
myeloproliferative diseases
 PPRT overactivity ( leukemia, Hodgkin’s d’z,
lymphosarcoma, myeloma, PV,
 Ribose-5- Waldenstrom’s
macroglobulinemia )
phosphate  Cytotoxic drugs
overproduction  Carcinomatosis
 Gaucher’s disease
 AMP-deaminase  Chronic hemolytic anemia
def.  Severe exfoliative psoriasis
 Acute/Recurrent Gout
symptoms: sudden onset of severe pain,
inflammation, limited range of motion, and warmth
at the affected joint(s).
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.
 Intercritical Gout
After recovery from an acute gout
flare, the patient enters an
asymptomatic phase of the disease.
This interval between gout flares: as
intercritical or interval gout.
Later, recurrence of acute gout may
become more frequent and
polyarticular involvement.
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.
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 or Chronic form can be misdiagnosed
infection as rheumatoid arthritis or
osteoarthritis: acute flare-ups can
be misdiagnosed as cellulitis or
infection
 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
 Criteria for clinical diagnosis
American Rheumatism Association sub-committe on classification criteria for gout 1977

presence of characteristic urate crystals in the joint fluid

Tophus proved to contain urate crystals by negative polarized light
microscopic study
If none of above, diagnosis is 6/12 clinical, radiographic, and laboratory
criteria include:
1. more than one attack of acute arthritis
2. Maximum inflammation within 24 hours
3. Attack of monoaricular arthritis
4. Joint redness observed
5. first MTP joint painful or swollen
6. Unilateral attack involving first MTP
7. Unilateral attack involving tarsal joint
8. Suspected tophus
9. Hyperuricemia
10. Asymmetric swelling within a joint ( roentgenogram )
11. Subcortical bone cysts without erosions ( roentgenogram )
12. Negative synovial culture during attack of joint inflammation
 Differential diagnosis
Acute Chronic
 Infective arthritis
 Bursitis, cellulitis, tenosynovitis
 Nodular rheumatoid
 Other crystal arthropathy
( pseudogout, apatite or brushite
arthritis
arthritis or periarthritis )  Psoriatic arthritis
 Traumatic arthritis
 Hemoarthrosis  Osteoarthritis with


RA with palindromic onset
Reactive arthritis
Heberden’s and
 Spondarthritis with peripheral Bouchard’s nodes
involvement
 Psoriatic arthritis
 Sarcoid arthritis
 Sarcoid arthritis  xanthomatosis
 Rheumatic fever
 History taking
Age of onset
Involving joints
Frequency of attack
Family hx
Previous treatment and other medication
Associated medical hx: 4H ( hypetension,
hyperglycemia, hyperlipidemia, and
hyperuricemia )
 Events provoking acute
gouty arthritis
Trauma
unusual physical exercise
Surgery
Severe systemic illness
Severe dieting
Dietary excess
Alcohol
Drugs ( diuretics, initiation of uricosuric or allopurinol
therapy, initiation of B12 therapy in pernicious
anemia, cytotoxic drug therapy )
 Physical examination
Vital sign
Body weight and body height
General appearance: Cushingnoid …
Consciousness
HEENT
Chest ( CV )
Abdomen
Extremity
-- PE of joint: appearance, joint effusion, ROM
-- location of tophi
-- sign of neuropathy
-- muscle power, DTR…
 Diagnostic evaluation
CBC/DC
Glucose, Na/K, Ca/P, uric acid, AST/ALT/ALP,
HDL-cholesterol electrophoresis
U/A, 24hr uric acid(U)
Synovial study
Special investigation
-- EKG, CXR, joint radiography
-- skeleto-muscular ultrasound examination
 Long-term treatment
Indication:
1. Recurrent attacks
2. Evidence of tophi or chronic gouty arthritis
3. Associated renal disease
4. Patient is young with high serum UA and FH of
renal or heart disease
5. Normal serum UA cannot be achieved by life-style
modifications
Medication:
1. Allopurinol
2. Uricosuric agents: probenecid or sulfinpyrazone
3. benzbromarone
Indications for Antihyperuricemic Therapy in Gout

•Frequent and disabling attacks of acute gouty arthritis

•Clinical or radiographic signs of chronic gouty joint disease
•The presence of tophaceous deposits in soft tissues or
　 subchondral bone
•Gout with renal insufficiency
•Recurrent nephrolithiasis
•Serum urate levels persistently in excess of 13 mg/dL in men
　 or 10 mg/dL in women
•Urinary uric acid excretion exceeding 1100 mg/day
•Impending cytotoxic chemotherapy or radiotherapy for
　 lymphoma or leukemia
 Table III. Main medications used in the treatment and prophyaxis of gout.1-8,13,81
Agent Adverse Events Contraindications Regimen
Acute therapy/ Dose-dependent gastropathy, Peptic ulcer disease or bleeding Indomethaction 50mg TID for 2 to
prophylaxis nephropathy, liver dysfunction, ASA- Or NSAID-induced asthma, 3 days, then tapered over 5 to 7
NSAIDs central nervous system urticaria, or allergic-type reactions. days; naproxen 750 mg, followed
dysfunction. May cause fluid by 250mg TID, then tapered over
overload in patients with 5 to 7 days, sulindac 200mg BID,
congestive heart failure. then tapered over 5 to 7 days.
Prophylaxis low daily doses.

Cox-2 selective inhibitors Less GI toxicity than Cautious use in patients with Etoricoxise 120 mg/d (available
(etoricoxib) conventional NASIDs renal advanced renal disease, history of outside the United States)
effecect similar to conventional ischemic heart disease, or history
NSAIDs of NSAID-induced asthma.

Colchicine Dose-dependent GI symptoms, Use cautiously in renal or hepatic 1.2mg initially then 0.6mg every 1
neuromyopathy; improve IV dysfunction. to 2 hours until pain relief or
dosing can cause bone narrow abdominal discomfort/diarrhea
suppression, renal failure, develops (do not exceed 4 mg/d).
paralysis, and death. Prophylaxis 0.6 to 1.2 mg/d.

Corticosteroids Fluid detention, impaired Intra-articular;

Wound healing, psychosis methylprednisolone 10 to 20mg
Hyperglycemia hypothalamus for a small joint; 20 to 10 mg for
Pituitary axis suppression large joint. IM: triamcinolone
acetonide 60mg repeat after 24
Osteoporosis, potential for hours if necessary. PO:
Rebound inflammation. prednisone 30 to 60mg QD, then
tapered over 7 to 10 days.
 Table III. (Continued)
Agent Adverse Events Contraindications Regimen
ACTH Fluid retention, hypokalemia relapse of 40 to 80 IU IM, repeat every 12
gout, worse diabetes control hours as necessary.

Orate-lowering therapy
Allopuriol Rash, GI symptoms, headache,
urticaria, and intestinal nephritis; rare
potentially fatal hypersensitivity
syndrome, reduces orate levels in over
producers and underexcretors.

Probenecid Rash, headache, and GI symptoms; Renal dysfunction (CrCI 250mg BID for 1 to 2 weeks↑
rare nephritic syndrome, hepatic <50mL/min) or renal calculi ny500mg increments every 1
necrosis, aplastic anemia and to 2 weeks until satisfactory
hemolytic anemia. Reduced orate control is achieved or maximal
levels in underexcretors.Potential for dose 3 g.
numerous drug interactions because of
interference with excretion of many
medications.

Sulfinpyrazone Rash, headache, and GI symptoms, Renal dysfunction (CrCI 50mg BID;↑ to 300 to 400
bone narrow suppression, minor <50mL/min) or renal calculi mg/d in 2 to 3 divided doses
hypersensitive. Possesses inherent maximum dose 800 mg/d.
antiplatelet activity.
 Consider acquired causes of hyperuricemia associated with
normal urinary acid excretion

Obesity Renal insufficiency Salt restriction

Ethanol Polycystic kidney disease Diabetes insipidus
Drugs Lead nephropathy Bartter’s syndrome
　 Salicylates(low dose) Hypothyroidism Sarcoidosis
　 Diuretics Hyperparathyroidism Down’s syndrome
　 Pyrazinamide Diabetic ketoacidosis Toxemia of pregnancy
　 Ethambutol Lactic acidosis Hypoxemia
　 Nicotinic acid Starvation Chronic beryllium disease
　 Laxative abuse(alkalosis) Dehydration
　 Cyclosporine
If negative
If positive
Correct underlying cause if Consider secondary causes of hyperuricemia
possible and / or appropriate associated with elevated uric acid production

Hyperuricemic Asymptomatic Myeloproliferative diseases

Symptoms Lymphoproliferative diseases
Myeloproliferative diseases
Routine medical Lymphoproliferative
Treat management Hemolytic anemias
Polycythemia vera
Obesity
Ethanol
Fructose (large doses)
Tissue necrosis
Exercise
Convulsions
Drugs
　 Cytotoxic agents
　 B12 (patients with pernicious anemia)
　 Pancreatic extract
If positive and If positive and clinical setting for acute It positive and patient is
hyperuricemic uric acid nephropathy; Myelo-or asymptomatic and not in
symptoms lymphoproliferative disorder, solid clinical setting for acute uric
tumor with anticipated cytotoxic and/ acid nephropathy
Treat or radiation therapy, inherited disorders
with overproduction of uric cid, or
rhabdomyolysis 24-hour urine uric acid

>1100 mg/day <1100 mg/day

Treat
Close follow-up of Routine medical
renal function management
 Cause of hyperuricemia is not discermible

Symptomatic Asymptomatic

Treat Serum urate Serum urate

>11 mg/dl <11 mg/dl

24-hour urine Routine medical

uric acid management

>1100 mg/day <1100 mg/day

Follow renal Routine medical

Function closely management
 Low Purine Diet
On a strict low purine diet, protein is derived principally from
eggs and cheese. Grains, most vegetables, fruits and nuts
are acceptable.
The following should be AVOIDED ：

Animal-based proteins ： Meats, poultry, seafood,

Liver, kidney, heart, gizzard,
sweetbreads,
Meat extracts, yeast extract.
Vegetables Peas, beans, spinach, lentils.

Beverages Alcohol, beer, and beer products.