Gout

Gout
Gout is defined as a peripheral arthritis resulting from the deposition of sodium urate crystals in one or more joints.

Gout
Gout encompasses a group of disorders that occur alone or in combination and include (1) hyperuricemia, (2) attacks of acute, typically monarticular, inflammatory arthritis, (3) tophaceous deposition of urate crystals in and around joints, (4) interstitial deposition of urate crystals in renal parenchyma, and (5) urolithiasis
Copyright 1998 McGraw-Hill. All rights reserved.

Gout
Affects less than 0.5% of the population Due to familial disposition, incidence may be as high as 80% in families affected by disorder.

Stoffey et al, Emed 2002

Gout
Typical sequence involves progression through:
asymptomatic hyperuricemia acute gouty arthritis interval or intercritical gout chronic or tophaceous gout

Pathophysiology
Urate saturates in plasma at 7 mg/dL
Assuming pH, temp, Na are WNL

MSU deposits in less vascular tissue

Cartilage Tendons/ligaments

There is a predilection for peripheral joint/tissue

Pathophysiology
Primary gout:
Overproducers: 10% Under-excretors: 90%

Secondary gout:
Excess nucleoprotein turnover (lymphoma, leukemia) Increased cell proliferation/death (psoriasis) Rare genetic disorder Lesch-Nyan Syndrome pharmaceuticals

Signs and Symptoms

Acute attack:
Over hours frequently nocturnal Excruciating pain Swelling, redness and tenderness Podagra: 1st MTP classic presentation May effect knees, wrist, elbow, and rarely SI and hips.

Chronic:
Destructive tophacous Much greater chance if untreated Rarely presents as a chronic

Signs and Symptoms

Renal lithiasis Uric acid nephropathy Urate nephropathy

Diagnosis
Based on history and physical Confirmed by arthrocentesis
Urate crystals: needle-shaped negatively birefringent either free floating or within neutrophils & macrophages.

Uric acid level non specific.

30% may show normal level

Urine collection:
<800 mg underexcertor(<600 purine-free diet)

Microscopic Diagnosis

Gout Arthritis
Gout can also occur as a result of overproduction of uric acid Gout is an attack of uric acid deposits in joints Usually found in joints of feet and legs

What is Gout Arthritis

Purines are not properly processed in our body Excreted through kidneys and urine Hyperuricemia- buildup of uric acid in body and joint fluid

The Four Stages of Gout

Asymptomatic Acute Intercritical Chronic

ASYMPTOMATIC
A- meaning without indicates that there are no symptoms associated Patient will be unaware of what is happening Gout can only be determined with the help of a physician

ACUTE
Sever and sudden onset Involve one or a few joints Frequently starts nocturnally Joint is warm, red, and tender

INTERCRITICAL
More concentration of uric acid crystals Typically no need for drug intervention at the time.

CHRONIC
Continuous or persistent over a long period of time Treatment required Not easily or quickly resolved

SYMPTOMS
Joint pain
Affects one or more joints : hip, knee, ankle, foot, shoulder, elbow,wrist, hand, or other joints Great toe, ankle and knee are most common

Swelling of Joint
Stiffness Warm and red Possible fever

Skin lump which may drain chalky material

Diagnosing Gout
X-rays Arthrocentesisextraction of joint fluid Examination of joint Patient medical history

Epidemiology
Prevalence of hyperuricemia
2.3 41.4% in various populations. Corresponds with serum creatinine /BUN levels, body weight, height, age, blood pressure, and alcohol intake. (Taiwan) Body bulk (as estimated by body weight, surface area, or body mass index) has proved to be one of the most important predictors of hyperuricemia in people of widely differing races and cultures.

Incidence of Gout
Varies depending on population studied 1.8 /1000 3.2/1000 RR for blacks slightly higher (1.3)

1977 ACR criteria for acute gout

The presence of characteristic urate crystals in the joint fluid, or a tophus proved to contain urate crystals by chemical means or polarized light microscopy, or the presence of 6 of the following 12 clinical, laboratory, and radiographic phenomena: 1. More than one attack of acute arthritis 2. Maximum inflammation developed within 1 day 3. Monoarthritis attack 4. Redness observed over joints 5. First metatarsophalangeal joint painful or swollen 6. Unilateral first metatarsophalangeal joint attack 7. Unilateral tarsal joint attack 8. Tophus (proven or suspected) 9. Hyperuricemia 10. Asymmetric swelling within a joint on x ray/exam 11. Subcortical cysts without erosions on x ray 12. Monosodium urate monohydrate microcrystals in joint fluid during attack 13. Joint fluid culture negative for organisms during attack

Classification of Hyperuricemia and Gout

Primary Hyperuricemia and Gout with No Associated Condition Uric acid undersecretion(80%90%)
Idiopathic

Urate overproduction (10%20%)

Idiopathic HGPRT deficiency PRPP synthetase overactivity

Secondary Hyperuricemia and Gout with Identifiable Associated Condition Uric acid undersecretion Renal insufficiency Polycystic kidney disease Lead nephropathy Drugs(Diuretics,Salicylates (low dose), Pyrazinamide, Ethambutol,Niacin, C yclosporine, Didanosine ) Urate overproduction Myeloproliferative/ Lymphoproliferative diseases / Hemolytic anemias/ Polycythemia vera/Other malignancies Psoriasis/Glycogen storage disease Dual mechanism Obesity, ETOH,Hypoxemia and hypoperfusion

Outcomes in Gout
Clinical outcomes
60% of untreated gout have attacks within 1 yr , 78% have recurrence in 2 yrs, only 7% have no attacks in 10 yrs. Chronic tophaceous gout develops after 10 -20 yrs of untreated gout. Incidence decreased from 14% in 1949 > 3% in 1972.(Oduffy et al)-----colchicine effect Hyperuricemia control superior to self medication alone.

Humanistic outcomes
Treatment outcomes decrease QOL in pts with gout. Adherence to allopurinol only 56%. (Riedel et al , managed care study)

Economic outcomes
Direct burden annually is 27.4 million USD. (men only) Patients with acute gout miss 3-5 days of work annually. Average cost-effectiveness ratio for patients using urate-lowering drugs is $487 to $983 compared with a cost of $5070 to $6571 for those not using these agents.

Diagnosis

Clinical :
In men , initial attack monoarticular 1st MTP joint(50% of cases) Other jts involved instep/knees/wrists/ olecranon bursa. Often begins at night. Usually abrupt , severely painful. Later attacks polyarticular , assoc with systemic signs., most often initial presenting complaint in women. (hands/tarsal jts/knees) Precipitants Minor trauma , ETOH, diuretic Rx, Surgery, severe medical illness, hypouricemic Rx. Tophi Classically , helix/ antihelix ,but rare ; more common , hands, feet, olecranon bursa. Complications : ulceration/infection.

Laboratory:- GOLD STANDARD

SF Analysis WBC ct 2000-100 000/ml MSU crystals- needle shaped , negatively birefringent. Serum Uric acid level important in monitoring treatment .(42% - normal levels) 24 hr uric acid collection useful in young pts with gout/ + fam h/o

Diagnosis
Radiologic X RAY : Punched out erosions only 45% of pts have them, takes 6 yrs to develop Martels sign CT/MRI/US/Bone scan
Sensitive , non specific

Treatment
Acute gouty arthritis:
Anti- inflammatory drugs ( if s.creat < 2mg/dl, no PUD) Colchicine preferred in pts without confirmed diagnosis of gout.
Endpoints improvement in jt symptoms/ GI symptoms/ 10 doses taken.

NSAIDs if diagnosis confirmed. Any NSAID can be used .

Newer agents Etoricoxcib 120 OD comparable to indomethacin 50 TID.

In c/o renal failure /PUD - IM ACTH , oral /iv prednisone. Avoid adjusting dosage of urate lowering agents.

Prophylaxis :
Only indicated if patient is started on urate lowering Rx. Colchicine( 1-3 pills a day)/ NSAID( in colchicine intolerant). Does not alter crystal deposition and development of tophi. Continue till serum urate levels stabilize and no attacks for 3 6 mths. If long term prophylactic colchicine given, check CBC ,CK every 6 mths.

Treatment (contd)
Control of hyperuricemia
Differing opinions regarding initiation esp. around 1st attack. Clear evidence if erosions + on X-ray / chronic tophaceous gout/ >2 gout attacks per year. Goal : s. urate levels < 6 mg%. Serial s. uric acid at least once every 6 mths upon initiation. Choice of agents : Xanthine oxidase inhibitor Uricosuric agents. Equal efficacy in pts with normal renal function and who excrete < 800 mg/day of uric acid.

Treatment (contd)
Xanthine oxidase inhibitors
Allopurinol- only prescription drug available. Renally excreted, therefore adjust dose if s.creat > 2mg% or CrCl <50 Usually DOC in most patients. S/E GI / rash / sarcoid like reaction/Allopurinol hypersensitivity syndrome Drug interaction esp. with 6 MP/azathioprine/ warfarin/theophylline. Desensitization protocols exist. Oxypurinol possible option Indications no h/o renal calculi , pts <60 yrs, U.A excretion < 800 mg/d CI - + nephrolithiasis, renal insufficiency Limit ASA to 81 mg/day Probenecid/ Benzbromarone

Uricosuric agents

Treatment (contd)
Adjuvant Rx
Control obesity ,ETOH intake, hyperlipidemia ,HTN Losartan / fenofibrate weakly uricosuric Diet moderation in purine intake. Makes a difference of up to 1mg % in s. uric acid.
Beer, other alcoholic beverages. Anchovies, sardines in oil, fish roes, herring. Yeast. Organ meat (liver, kidneys, sweetbreads) Legumes (dried beans, peas) Meat extracts, consomm, gravies. Mushrooms, spinach, asparagus, cauliflower

Treatment (contd)
Newer agents PEG- uricase Febuxostat Asymptomatic hyperuricemia Investigate cause No recommendations for Rx.