P. 1
Gout (Www.MansFans.coM)

Gout (Www.MansFans.coM)

4.0

|Views: 839|Likes:
Published by Mans Fans
By
Dr: Abd El Hameed Fureeh
MD, Lecturer of Internal Medicine, Mansoura faculty of Medicine
Diabetes, endocrinology and Metabolism unit
By
Dr: Abd El Hameed Fureeh
MD, Lecturer of Internal Medicine, Mansoura faculty of Medicine
Diabetes, endocrinology and Metabolism unit

More info:

Categories:Topics, Art & Design
Published by: Mans Fans on May 24, 2009
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PPT, PDF, TXT or read online from Scribd
See more
See less

05/11/2014

pdf

text

original

GOUT

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?
v Gout

is a syndrome caused by the inflammatory response to tissue deposition of monosodium urate crystals (MSU). v Nicknamed the “Disease of Kings” because it can be caused by rich foods, alcohol, and royalty often had it.

Prevalence
v The

prevalence of asymptomatic hyperuricemia is 5 to 8%. v The prevalence of gout is 13 cases per 1000 men and 6.4 cases per 1000 women. v The higher the uric acid, the higher the risk to develop gout. v 90% of patients with primary gout are men.

Www.MansFans.coM

Prevalence
v Women

rarely develop gout before the menopause, because estrogens are thought to be uricosuric. v Peak incidence in men is in the fifth decade. v Primary gout is associated with: obesity, hyperlipidemia, diabetes mellitus, hypertension and atherosclerosis.

Etiology
v Hyperuricemia

is the common denominator in gout. v Two-thirds of uric acid are excreted by the kidney and the rest in the GI tract. v 90% of cases of gout are secondary to under-excretion. v Overproduction is secondary to defects in the HGPRT or PRPP.

Etiology
v The

inflammatory response is secondary to the response of the leukocytes to the MSU crystals. v Acute gout is most likely secondary to the formation of new crystals. v Factors that precipitate gout includes: surgery, trauma, alcohol, starvation and medications.

GOUT RISK FACTORS
Male v Postmenopausal female v Older v Hypertension v Pharmaceuticals: Diuretics, ASA, cyclosporine
v

7

Www.MansFans.coM

GOUT RISK FACTORS
v Transplant v Alcohol

intake Highest with beer Not increased with wine v High BMI (obesity) v Diet high in meat & seafood

8

Www.MansFans.coM

Pathology

v The

most frequent sites of deposition of MSU crystals are: cartilage, epiphyseal bone, periarticular structures and the kidney. v A tophus is a foreign body reaction that includes the MSU crystals surrounded by fibrous tissue. v In the kidney the deposition of MSU crystals causes interstitial fibrosis and arteriosclerosis.

Clinical course
4 clinical phases if untreated: v  asymptomatic hyperuricemia, v  acute/recurrent gout, v  intercritical gout, v  chronic tophaceous gout

10

Asymptomatic Hyperuricemia
v v

v

v

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 gouty nephropathy  Increased level of organic level
    

  

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
12

Www.MansFans.coM

Cause of hyperuricemia -- increased uric acid production
Primary  Idiopathic  HPRT def.  PPRT overactivity  Ribose-5phosphate overproduction  AMP-deaminase def. Secondary
  

    

Glycogen storage disease type II (G6PD), type III, V, VII Hereditary fructose intolerance Lymphoproliferative and myeloproliferative diseases ( leukemia, Hodgkin’s d’z, lymphosarcoma, myeloma, PV, Waldenstrom’s macroglobulinemia ) Cytotoxic drugs Carcinomatosis Gaucher’s disease Chronic hemolytic anemia Severe exfoliative psoriasis

13

Acute/Recurrent Gout
symptoms: sudden onset of severe pain,
v

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. v Left untreated, the symptoms are selflimiting but may take up to 21 week to subside.
v
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 Can present at any age, including patients older than 60 years Predominantly men Monarthritis Asymmetric Usually in lower extremity Tophi rare at presentation Acute Can be misdiagnosed as cellulitis or infection Atypical Gout Observed in elderly patients Diagnosed in as many women as men Polyarthritis Symmetric or asymmetric Any joint, upper or lower extremity Tophi common at presentation Chronic but can have acute flareups Chronic form can be misdiagnosed as rheumatoid arthritis or osteoarthritis: acute flare-ups can be misdiagnosed as cellulitis or infection
16

Www.MansFans.coM

ADVANCED GOUT
v Chronic v X-ray v Tophi v Acute

Arthritis

Changes Develop Flares continue
17

ADVANCED GOUT
Chronic Arthritis v Polyarticular acute flares with upper extremities more involved
v

Www.MansFans.coM
18

Www.MansFans.coM

Intercritical Gout
v

It is the asymptomatic period between crises, but MSU crystals can still be recovered if necessary.

v The

duration of this period varies, but untreated patients may have a second episode within two years. v 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. v Visible tophi occur in 12% of patients after 5 years of gout and in 55% of patients after 20 years. v 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.
v
20

Chronic Tophaceous Gout
v Transplant

patients treated with cyclosporine and/or diuretics have an increased risk for tophaceus gout. v The most common sites for tophi are: the olecranon, prepatellar bursa, ulnar surface and Achilles tendon.
Www.MansFans.coM
21

Chronic Tophaceous Gout
v Tophi

in the hands can cause joint destruction. v Tophi can ulcerate the skin and excrete a chalky material composed of MSU crystals. v Tophi progress insidiously with increased stiffness and pain.

22

Www.MansFans.coM

TOPHI
v

Solid urate deposits in tissues

Www.MansFans.coM

23

TOPHI
v

Irregular & destructive

Www.MansFans.coM

24

TOPHI RISK FACTORS
v Long

duration of hyperuricemia serum urate

v Higher v Long

periods of active, untreated gout

Www.MansFans.coM
25

Www.MansFans.coM

Renal disease
v Urolithiasis, v Urate

nephropathy (deposition of MSU crystals in the interstitium), and v Uric nephropathy ( deposition of MSU crystals in the collecting tubes). v The prevalence of urolithiasis is 22% in primary gout and 42% in secondary gout.
26

Nephrolithiasis
v The

prevalence of nephrolithiasis correlates with the serum and urinary uric acid levels. v Serum urate levels 13 mg/dl v Urinary uric acid excretion > 1100 mg/d

Www.MansFans.coM
27

Urate Nephropathy
v Deposits

of monosodium urate crystals surrounded by a giant cell inflammatory reaction in the medullary intrerstitium and pyramids. v Clinically: silent or cause proteinuria, hypertension and renal insufficiency.
Www.MansFans.coM
28

Uric acid nephropaty
v

Precipitation in renal tubules and collecting ducts cause obstruction to urine flow. Following sudden urate overproduction and marked hyperuricaciduria:
x x x

v

Dehydration and acidosis Lymphoma Cytolytic therapy

Www.MansFans.coM
29

Complication of gout
v Joint:

destruction v Soft tissue v nerve entrapment syndrome: CTS, tarsal tunnel syndromes v kidney: uric acid calculi(10-15%), chronic urate nephropathy, and acute uric acid nephropathy v 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
v Clinical

diagnosis: Triad of 1- hyperurecemia 2- Acute monoarticular arthritis 3- Response to colchicine v Laboratory diagnosis v Differential diagnosis

35

Criteria for clinical diagnosis
American Rheumatism Association sub-committe on classification criteria for gout 1977 v v v

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
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. v Acute septic arthritis several of the other crystalline – associated arthropathies, and psoriatic arthritis may present with similar clinical features.
v
37

SYNOVIAL FLUID ANALYSIS (Polarized Light Microscopy)
v v v v

The Gold standard Crystals intracellular during attacks Needle & rod shapes Strong negative birefringence meaning that the crystals are yellow when aligned parallel to the slow ray of the compensator and that they are blue when they are perpendicular.
38

Www.MansFans.coM

SYNOVIAL FLUID

39

SYNOVIAL FLUID
v 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
v

This is the most misused test in the diagnosis

of gout. v Not reliable
v

May be normal with flares May be high with joint Sx from other causes

v

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
v 24

urine collection for uric acid determination is useful in assessing the risk of renal stones and planning for therapy. v Urinary levels above 750 mg/dl in 24h in gout or > 1100 mg/dl in asymptomatic hyperuricemia indicates urate overproduction.
45

Radiographic Features
v Cystic

changes, well-defined erosions described as punched-out lytic lesion. v Soft tissue calcified masses (chronic tophaceous gout) v Is helpful to exclude other kinds of arthritis.

46

Www.MansFans.coM

RADIOLOGIC SIGNS

47

48

Blood chemistry
v v v v

v v

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
  

       

Infective arthritis Bursitis, cellulitis, tenosynovitis Other crystal arthropathy ( pseudogout, apatite or brushite arthritis or periarthritis ) Traumatic arthritis Hemoarthrosis RA with palindromic onset Reactive arthritis Spondarthritis with peripheral involvement Psoriatic arthritis Sarcoid arthritis Rheumatic fever

Chronic  Nodular rheumatoid arthritis  Psoriatic arthritis  Osteoarthritis with Heberden’s and Bouchard’s nodes  Sarcoid arthritis  xanthomatosis

50

Gout vs. CPPD
Similar Acute attacks v Different crystals under Micro;
v

Rhomboid, irregular in CPPD Pseudogout crystals are positively birefringent. Pragmatically, this means that their colors are opposite those of gout. Thus, pseudogout crystals are blue when aligned parallel to the slow ray of the compensator and yellow when they are perpendicular.

51

Www.MansFans.coM

Gout

vs

CPPD

52

Crystal-Induced Arthritis Characteristic
Prevalence

Gout
1.5 to 2.6 cases per 1000 individuals; increases with age in men and postmenopausal women; 15/1000 at age 58; men:28/1000, women:11/1000

Pseudogout
<1 case per 1000 individuals; increases with age

Crystals   Chemistry   Appearance Articular involvement Most frequently affected joints Monosodium urate Negatively birefringent; needle-shaped Monoarticular > oligoarticular; polyarticular < 30% First MTP joint  - initially 50%  - eventuall 90% Ankles, knees, other Hyperuricemia*, obesity, hypertension, hyperlipidemia, alcohol ingestion, lead ingeation, hereditary enzyme defect (rare) Calcium pyrophosphate dihydrate Weakly positively birefringent; linear or rhomboidal Monoarticular > oligoarticular Knee, wrist other

Predisposing conditions/risk factors

Hypothyroidism, hemochromatosis, OA, chronic renal insufficiency, diabetes, hyperparathyroidism, hereditary (rare)

Therapeutic options

Acute attacks: Acute attacks:  - NSAIDs, corticosteroids,  - NSAIDs, corticosteroids, colchicine 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. Adapted from Am J Med 1997; 103 : 68S. 53

RA vs Gout
v Both

have polyarticular, symmetric arthritis can be mistaken for RA nodules

v Tophi

54

RA

vs Gout

55

Treatment of gout

Www.MansFans.coM

56

TREATMENT GOALS
v Rapid

and safe pain relieve (end acute flares) v Protect against future flares v Prevent disease progression v Correct metabolic cause

57

ENDING ACUTE FLARES
v Control

inflammation & pain & resolve the flare v Not a cure v Crystals remain in joints v Don’t try to lower serum urate during a flare v Choice of med not as critical as alacrity & duration
58

Acute Flare Med Choices
v

NSAIDS Colchicine Corticosteroids

v

v

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

NSAID
Mechanism of action:

Www.MansFans.coM

-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
v

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
-IM injection of depot corticosteroid product (e.g. DepoMedrol ) or ACTH -Tapering effect of depot product prevents rebound gout attacks -Efficacy comparable to NSAID in studies -Limited toxicity due to short term use

- Worse glycemic control May need to use mod-high doses

68

PROTECTION VS. FUTURE FLARES
v v

Colchicine : 0.5-1.0 mg/day Low-dose NSAIDS Both decrease freq & severity of flares Prevent flares with start of urate-lowering RX Best with 6 mos of concommitant RX

v v

EBM
v

Won’t stop destructive aspects of gout

69

PREVENT DISEASE PROGRESSION
v Lower

Www.MansFans.coM

urate to < 6 mg/dl : Depletes Total body urate pool Deposited crystals v RX is lifelong & continuous v MED choices : Uricosuric agents Xanthine oxidase inhibitor
70

PREVENT THIS

71

Www.MansFans.coM

Uricosuric agents
v Indicated

in patients with normal renal function, under-excretion and no evidence of tophi. v 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
v The

available agents include: probenecid (1-2 g/day) and sulfinpyrazone (50-400 mg BID). v 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
v Blocks

conversion of hypoxanthine to uric acid v 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
v usual

dose is 300 mg/day. Maximal recommended dose is 800 mg/day. v 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
v Start

with small doses of allopurinol to reduce the risk of precipitating an acute gout attack. v Most common side effects are rash (2% of patients) but rarely patients can develop exfoliative dermatitis that can be lethal. v 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

Allopurinol Adverse Reactions
Hypersensitivity rash: maculopapular/purpuric: usually occurs within 1st5weeks , resolves with drug DC . rechallenge cautiously, may cause fatal reactions severe hypersensitivity more common in pts with impaired renal function & ampicillin treatment Gastrointestinal: nausea, vomiting,abdominal pain, hepatomegaly.

80

Febuxostat
v Potent

new xanthine oxidase inhibitor v Metabolized by the liver (used in RI) v No hypersensitivity reaction v Dose: 80-120 mg/d

81

WHICH AGENT
v 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

Purine nucleotides hypoxanthine xanthine Uric acid Urinary excretion uricosurics colchicine Alimentary excretion Allopurinol

Www.MansFans.coM

Oxypurinol

Xanthine oxidase

Tissue deposition in excess Urate crystal Phagocytosis with acute inflammation and arthritis microtophi

NSAID
83

NEW AGENTS
v RX

gaps : v Can’t always get urate < 6 v Allergies v Drug interactions v Allopurinol intolerance v Worse Renal disease

84

URICASE ENZYMES
(Stay Tuned)
v

Catabolize urate to allantoin: More soluble, excretable form Currently approved for hypoeruricemia in tumor lysis syndrome Some concerns: fatal immunogenicity & unknown long-term effects
85

v

v

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
v Usually

impractical, ineffective and rarely adhered to in clinical practice. v Indications for pharmacological therapy includes: inability to reverse secondary causes, tophaceus gout, recurrent acute gout and nephrolithiasis.

87

Www.MansFans.coM

Prophylaxis A. When to treat
1. Recurrent attacks: choice of treatment will depend on the frequency of the attacks. Attacks once yearly may be better treated with colchicine/NSAID acutely rather than exposing the patient to yearlong therapy. Frequency of attacks >1-2/year are a good indication for prophylactic or uric acid lowering therapy.
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

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->