guideline of gout

7/22/2019 guideline of gout

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Guideline for gout

management

( A r t h r i t i s )


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Introduction

the deposition of monosodium urate

( MSU ) crystals in the joints and soft

tissues.Incidence: 0.1%


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IntroductionCrystal-Induced Arthritis

Characteristic Gout Pseudogout

Prevalence 1.5 to 2.6 cases per 1000 individuals;

increases with age in men andpostmenopausal women; 15/1000 at

age 58; men:28/1000, women:11/1000

oligoarticular;polyarticular < 30%

Monoarticular > oligoarticular

Most frequently affected joints First MTP joint

initially 50%

eventuall 90%

Ankles, knees, other

Knee, wrist other

Predisposing conditions/risk factors Hyperuricemia*, obesity, hypertension,

hyperlipidemia, alcohol ingestion, leadingeation, hereditary enzyme defect

(rare)

Hypothyroidism, hemochromatosis, OA,

chronic renal insufficiency, diabetes,hyperparathyroidism, hereditary (rare)

Therapeutic options Acute attacks:

NSAIDs, corticosteroids, colchicine

Chronic management

Urate-lowering agents, colchicine

Acute attacks:

NSAIDs, corticosteroids, colchicine

Chronic management

NSAIDs colchicine

*Drugs associated with hyperuricemia include diuretios, low-dose salicylates, nicotinic acid, oyclosporine, ethanol andethambutol.

Adapted from Am J Med 1997; 103 : 68S.


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De novoand salvage pathways in purine metabolism. Phosphoribosyl pyrophosphate amidotransferase (AMPRT) catalyzes the committed step of

de novopurine 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).


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Clinical course

4 clinical phases if untreated:

asymptomatic hyperuricemia,

acute/recurrent gout,

intercritical gout,

chronic tophaceous gout


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symptomatic Hyperuricemiaelevated urate levels without symptoms of gout,nephrolithiasis, or kidney stones.

Hyperuricemiais defined:

>7 mg/dL (0.42mmol/L) in men and postmenopausalwomen

>6 mg/dL (0..36mmol/L) in premenopausal women.

urate =9 mg/dL4.9% annual incidence.the clustering of glucose intolerance, central obesity,dyslipidemia, hypertension, and increased prothromboticand antifihrinolytic factorsin an individual.


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Cause of hyperuricemia

-- decreased renal excretion

Primary

Idiopathic

Familial juvenilegouty nephropathy

Secondary Hypertension

Hyperparathyroidism

Myxoedema

Downs syndrome Increased level of organic level

Lead nephropathy

Sarcoidosis

Bartters syndrome

Beryllium poisoning

Drug: diuretics, B-blocker, ACEI,salicylates (low dose), PEA, EMB,cyclosporin, nicotinic acid

Chronic renal failure

Volume depletion

NDI


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Cause of hyperuricemia

-- increased uric acid productionPrimary

Idiopathic

HPRT def. PPRT overactivity

Ribose-5-phosphate

overproductionAMP-deaminase

def.

Secondary Glycogen storage disease

type II (G6PD), type III, V, VII

Hereditary fructose intolerance

Lymphoproliferative andmyeloproliferative diseases( leukemia, Hodgkins dz,lymphosarcoma, myeloma, PV,Waldenstromsmacroglobulinemia )

Cytotoxic drugs Carcinomatosis

Gauchers disease

Chronic hemolytic anemia

Severe exfoliative psoriasis


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Acute/Recurrent Gout

symptoms: sudden onset of severe pain,inflammation, limited range of motion, andwarmth at the affected joint(s).

slight fever, leukocytosis, elevation ofESR, and elevation of CRP

90% of first attacks are monoarticularwithfirst metatarsophalangeal joint, known aspodagra.

Left untreated, the symptoms are self-limitingbut may take up to 21 week tosubside.


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IntercriticalGoutAfter recovery from an acute goutflare, the patient enters an

asymptomatic phase of the disease.This interval between gout flares: asintercritical or interval gout.

Later, recurrence of acute gout maybecome more frequent andpolyarticular involvement.


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hronicTophaceous GoutTophi are usually present after 10 to 20years of inadequately treated chronic gout.

Visible tophi occur in 12% of patients after5 years of gout and in 55% of patientsafter 20 years.

most common sites of tophaceous gout:

olecranon bursae (elbow) and the joints ofthe hand and feet.

Other sites: the helix of the ear, theAchilles tendons, and the knees.


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Table. Characteristics of Classic Gout vs Atypical Gout

Classic Gout Atypical Gout

Can present at any age, including

patients older than 60 years

Observed in elderly patients

Predominantly men Diagnosed in as many women as

men

Monarthritis Polyarthritis

Asymmetric Symmetric or asymmetricUsually in lower extremity Any joint, upper or lower extremity

Tophi rare at presentation Tophi common at presentation

Acute Chronic but can have acute flare-

upsCan be misdiagnosed as cellulitis

or infection

Chronic form can be misdiagnosed

as rheumatoid arthritis or

osteoarthritis: acute flare-ups can

be misdiagnosed as cellulitis or

infection


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Complication of gout

Joint: destruction

Soft tissue

nerve entrapment syndrome: CTS,tarsal tunnel syndromes

kidney: uric acid calculi(10-15%),

chronic urate nephropathy, andacute uric acid nephropathy

Heart: ischemic heart disease


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Criteria for clinical diagnosisAmerican 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 lightmicroscopic study

If none of above, diagnosis is 6/12 clinical, radiographic, andlaboratory 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


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Differential diagnosis

Acute Infective arthritis

Bursitis, cellulitis, tenosynovitis

Other crystal arthropathy

( pseudogout, apatite orbrushite arthritis or periarthritis )

Traumatic arthritis

Hemoarthrosis

RA with palindromic onset

Reactive arthritis

Spondarthritis with peripheralinvolvement

Psoriatic arthritis

Sarcoid arthritis

Rheumatic fever

Chronic

Nodular rheumatoidarthritis

Psoriatic arthritisOsteoarthritis with

Heberdens andBouchards nodes

Sarcoid arthritis

xanthomatosis


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History taking

Age of onset

Involving joints

Frequency of attackFamily hx

Previous treatment and other medication

Associated medical hx: 4H ( hypetension,hyperglycemia, hyperlipidemia, and

hyperuricemia )


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Events provoking acute

gouty arthritisTrauma

unusual physical exercise

Surgery

Severe systemic illness

Severe dieting

Dietary excess

Alcohol

Drugs ( diuretics, initiation of uricosuric or allopurinoltherapy, initiation of B12 therapy in perniciousanemia, cytotoxic drug therapy )


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Physical examination

Vital sign

Body weight and body height

General appearance: Cushingnoid

ConsciousnessHEENT

Chest ( CV )

Abdomen

Extremity

-- PE of joint: appearance, joint effusion, ROM-- location of tophi

-- sign of neuropathy

-- muscle power, DTR


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Diagnostic evaluation

CBC/DC

Glucose, Na/K, Ca/P, uric acid, AST/ALT/ALP,

HDL-cholesterol electrophoresisU/A, 24hr uric acid(U)

Synovial study

Special investigation-- EKG, CXR, joint radiography

-- skeleto-muscular ultrasound examination


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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


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Indications for Antihyperuricemic Therapy in Gout

Frequent and disabling attacks of acute gouty arthritis

Clinical or radiographic signs of chronic gouty joint diseaseThe presence of tophaceous deposits in soft tissues or

subchondral bone

Gout with renal insufficiencyRecurrent nephrolithiasis

Serum urate levels persistently in excess of 13 mg/dL in menor 10 mg/dL in women

Urinary uric acid excretion exceeding 1100 mg/day

Impending cytotoxic chemotherapy or radiotherapy forlymphoma or leukemia


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Table III. Main medications used in the treatment and prophyaxis of gout.1-8,13,81

Agent Adverse Events Contraindications Regimen

Acute therapy/

prophylaxis

NSAIDs

Dose-dependent gastropathy,

nephropathy, liver

dysfunction, central nervous

system dysfunction. May

cause fluid overload in

patients with congestive

heart failure.

Peptic ulcer disease or bleeding

ASA- Or NSAID-induced asthma,

urticaria, or allergic-type

reactions.

Indomethaction 50mg TID for 2

to 3 days, then tapered over 5

to 7 days; naproxen 750 mg,

followed by 250mg TID, then

tapered over 5 to 7 days,

sulindac 200mg BID, then

tapered over 5 to 7 days.

Prophylaxis low daily doses.

Cox-2 selective inhibitors

(etoricoxib)

Less GI toxicity than

conventional NASIDs renal

effecect similar to

conventional NSAIDs

Cautious use in patients with

advanced renal disease, history

of ischemic heart disease, or

history of NSAID-induced

asthma.

Etoricoxise 120 mg/d

(available outside the United

States)

Colchicine Dose-dependent GI

symptoms, neuromyopathy;

improve IV dosing can cause

bone narrow suppression,

renal failure, paralysis, and

death.

Use cautiously in renal or

hepatic dysfunction.

1.2mg initially then 0.6mg

every 1 to 2 hours until pain

relief or abdominal

discomfort/diarrhea develops

(do not exceed 4 mg/d).

Prophylaxis 0.6 to 1.2 mg/d.

Corticosteroids Fluid detention, impairedWound healing, psychosis

Hyperglycemia

hypothalamus

Pituitary axis suppression

Osteoporosis, potential for

Rebound inflammation.

Intra-articular;methylprednisolone 10 to

20mg for a small joint; 20 to

10 mg for large joint. IM:

triamcinolone acetonide 60mg

repeat after 24 hours if

necessary. PO: prednisone 30

to 60mg QD, then tapered over

7 to 10 days.


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Table III. (Continued)

Agent Adverse Events Contraindications Regimen

ACTH Fluid retention, hypokalemia relapse

of gout, worse diabetes control

40 to 80 IU IM, repeat every

12 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;

rare nephritic syndrome, hepaticnecrosis, aplastic anemia and

hemolytic anemia. Reduced orate

levels in underexcretors.Potential for

numerous drug interactions because

of interference with excretion of

many medications.

Renal dysfunction (CrCI


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HyperuricemicSymptoms

Asymptomatic

y

ObesityEthanolDrugs

Salicylates(low dose)DiureticsPyrazinamideEthambutol

Nicotinic acidLaxative abuse(alkalosis)Cyclosporine

Renal insufficiencyPolycystic kidney diseaseLead nephropathyHypothyroidismHyperparathyroidismDiabetic ketoacidosisLactic acidosisStarvationDehydration

Salt restrictionDiabetes insipidusBartters syndromeSarcoidosisDowns syndromeToxemia of pregnancyHypoxemiaChronic beryllium disease

If positiveIf negative

Correct underlying cause ifpossible and / or appropriate

Consider secondary causes of hyperuricemiaassociated with elevated uric acid production

TreatRoutine medical

management

Myeloproliferative diseasesLymphoproliferative diseasesMyeloproliferative diseasesLymphoproliferativeHemolytic anemiasPolycythemia veraObesityEthanolFructose (large doses)Tissue necrosisExerciseConvulsionsDrugs

Cytotoxic agentsB12 (patients with pernicious anemia)Pancreatic extract

If positive and clinical setting for acuteuric acid nephropathy; Myelo-or

lymphoproliferative disorder, solidtumor with anticipated cytotoxic and/

or radiation therapy, inherited disorderswith overproduction of uric cid, or

rhabdomyolysis

It positive and patient isasymptomatic and not in

clinical setting for acute uricacid nephropathy

24-hour urine uric acid

>1100 mg/day


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Cause of hyperuricemia is not discermible

Symptomatic Asymptomatic

Serum urate>11 mg/dl

Serum urate1100 mg/day


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Low Purine Diet

On a strict low purine diet, protein is derived principally from

eggs and cheese. Grains, most vegetables, fruits and nutsare acceptable.

The following should be AVOIDED

Animal-based proteinsMeats, poultry, seafood,

Liver, kidney, heart, gizzard,

sweetbreads,

Meat extracts, yeast extract.

Vegetables Peas, beans, spinach, lentils.

Beverages Alcohol, beer, and beer products.

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