State of Art

goutBY:

Abdallah Allam MSc Assistant Lecturer. Department of Physical Medicine,

Rheumatology and Rehabilitation

Faculty of Medicine, Tanta University. Egypt

What is the function of uric acid

And purines ?

What is the normal ?

Rees, F. et al. (2014) Optimizing current treatment of goutNat. Rev. Rheumatol. doi:10.1038/nrrheum.2014.32

Reginato, A. M. et al. (2012) The genetics of hyperuricaemia and gout Nat. Rev. Rheumatol. doi:10.10.38/nrrheum.2012.144

24 hs urine uric acid excretion

600-800 mg

Metabolic pathway

Serum urate level greater than approximately

6.8 mg/dL, the saturation point of urate in

biological fluids, is the underlying cause of gout.

Why gout doesn’t affect animals?

Diet and gout

Cherries as one-half cup, or 10 to 12 cherries.==>1- DECREASES SERUM URIC ACID2- Prevents flares3- Reduces pain and inflammation

Epidemiology

BMJ VOLUME 332 3 JUNE 2006

Etiology

Over production(5-10%)

Genetic

Acquired

Genetic - HGPRT deficiency X linked,

*partial Kelly Seeg Miller

*complete Lish Nyhan- G6PD deficiency ( LACTIC )- Over PR1P synthetase

( sensory neural hearing loss).

Acquired- Diet- Obesity - Tumors- Chemotherapy- Alcohol(Lactate, ATP,

Purine guanosine)- Vigorous exercise.- Psoriasis.

Under excretion(90-95%)

Genetic

Acquired

Genetic - Down.- PCD.

Acquired *Decreased exc.- RF- KETO ACIDOSIS - LACTIC ACIDOSIS- HYPERTRIGLYCERIDEMIA

*increased Abs.- Dehydration- Starvation - Insulin R- Drugs

Associated with:Obesity,

Hypertension,

Diabetes (Bell shaped curve),

Sleep Apnea Syndrome.

Hyperlipidaemia.

Pathogenesis

Why gout doesn’t always hurt?

Why MSU precipitates in the periphery ?

· MSU precipitates at the periphery of the body, where

lower body temperatures may reduce the solubility of

MSU.

· Albumin levels decrease, which causes decreased

urate solubility

· Change in ion concentration & decreases of PH

enhance urate deposition

· Trauma promotes urate crystal precipitation

Mechanism of acute attack

OA and Gout

Gouty tophus and erosions

How does acute attack subside alone?

Rheumatology 2005;44:1090–1096

Heat

Stress steroid release

C/P

1 -Early onset.

2 -Classic.

3 -Late onset.

4 -NSAIDs masked.

1 -Early onset.

HPRT

2 -Classic.

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 75 • SUPPLEMENT 5 JULY 2008

Normal serum uric acid during attack

3 -Late onset.

Perioperative goutNSAID MASKED GOUTORGAN TRANSPLANTATION

Diagnostic work up

1 -Laboratory investigations

-Plain x-ray

-MSK U/S -DECT

2 -Imaging

3 -Arthrocentesis

Laboratory investigations

24 hs urine collection (not done

during attack)

>800mg / d over producers

<400 mg / d under excretors

Imaging

Plain X-ray

Soft tissue swelling.

Dorsoplantar radiograph

shows mild soft tissue

swelling medial to the first

metarsophalangeal joint .

Dorsopalmar radiograph

shows soft tissue masses

around the fourth proximal

interphalangeal joint and

radial to the fifth

metacarpophalangeal joint.

The joint spaces are normal.

MSK U/S

DECT

Dual-energy CT imaging of tophi in patients with gout

Arthrocentesis

Gold standard

(A) Monosodium urate crystals of gout appear as fine yellow needlelike crystals that are negatively birefringent under compensated polarized light.

(B) In contrast, crystals of calcium pyrophosphate dihydrate (CPPD) crystal deposition disease are rhomboid in shape and weakly positively birefringent under compensated polarized light ABC

Criteria for Diagnosis

DD

Procalcitonin ???

Medications

ProbenicidSulfinpyrazone

FebuxostateLosartan

Fenofibrate Vit C

LeflunomideLisinopril

AllopurinolFebuxostate

Pegloticase Rasburicase

Colchicine

Rees, F. et al. (2014) Optimizing current treatment of goutNat. Rev. Rheumatol. doi:10.1038/nrrheum.2014.32

Colchicine Creatinine clml/min

Dose >50 0.6 mg twice daily

35-49 0.6 mg once daily

10-34 0.6 every 2 or 3 days

<10 stop

Avoided in RT TTT by cyclosporine

neuromyotoxicity myopathy (proximal + increased

creatinine + EMG STOP FOR 3 WEEKS CURE

Treat to Target• < 6 mg/dl

• < 5 mg/dl

• < 4 mg/dl ( tophaceous gout)

Rees, F. et al. (2014) Optimizing current treatment of gout Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2014.32

XOI

Allopurinol GFRml/min

Dose N 300 mg/d

60 200mg/d

30 50-100 mg/d

ALLOPURINOL HYPERSENSITIVITY SYNDROME

• 5- 10%

• Morbidity and mortality: 20-30%

• MAJOR RISKS:

R I 75%

Diuretic TTT 50%

• ONSET 2-4 WKS

C/P: skin rash , esinophilia, fever, hepatic necrosis, leucocytosis and ↓ RF

TTT: - Steroids - Renal dialysis

Pegloticase pegilated uricase

• 8 mg in 250 cc N or half normal saline over 2 hours.

• Every 2 weeks.

• Pre ttt by hydrocortisone iv, acetaminophen 500 -1000 mg

iv & antihistaminics.

• Monitor serum uric acid before each dose ( Auto Abs).

• Colchicine for 3 mos at least.

• Flare of acute attack, Nephrolithiasis, Arthralgia, Nausea,

Dyspepsia, Diarrhea, Rash, Back pain.

CI : G6PD

Rasburicase recombinant uricase

• 0.2mg/kg iv over 30 min qd * 5 days

• Every 2 weeks.

• Leukemia , lymphoma , chemotherapy

ACR 2012 Guidelines

(CAN’T LEAP)1-Cyclosporine2. Alcohola. Associated with lactic acid productioni. Reduces renal excretion of urateb. Increases synthesis of urate by accelerating the degradation ofATPc. Beer contains a lot of purine guanosine

3. Nicotinic acid4. Thiazidesa. Interferes with urate excretion at the proximal convoluted tubule5. Lasix6. Ethambutol7. Aspirina. Low dose <2 g/day8. Pyrazinamide

Rees, F. et al. (2014) Optimizing current treatment of goutNat. Rev. Rheumatol. doi:10.1038/nrrheum.2014.32

Thank you