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B Y :
D R M E H R U N N I S A U M A R
A S S I S S T A N T P R O F E S O R
D E P A R T M E N T O F M E D I C I N E
CRYSTAL INDUCED
ARTHROPATHIES
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Two main types of crystals:
- Sodium Urate &
- Calcium pyrophosphate crystals
Rarely- Crystals of cholesterol or
- Calcium apatite
cause acute synovitis.
Diffrentiated by their shapes and properties.
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Epidemiology
Affects less than 0.5% of the population
Due to familial disposition, incidence may be as high as80% in families affected by disorder.
Men > Women =10:1
over30 years.
About 90% with Primary gout are men.
In women onset is typically postmenopausal
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Pathogenesis
Hyperuricemia is the major determinant fordeveloping gout.
Uric acid levels depends upon the balance between:- Purine synthesis + ingestion of dietry purines
&
- excretion of uric acid by the kidneys.
Urate saturates in plasma at 7 mg/dLAssuming pH, temp, Na are WNL
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Uric Acid Metabolism
Synthesis:
- Last step in the purine metabolism pathway.
- conversion of :
Hypoxanthine Xanthine - Uric acid- Catalyzed by enzyme Xanthine Oxidase.
Excretion:- Completely filtered by glomerulus
- 98-100% reabsorbed by the proximal tubule.
- 50% is secretted by the distal tubule.
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Causes of Hyperuricemia
Impaired Excretion: (90%)
- Chronic renal disease- Hypertension
- Lead therapy
- Hyperparathroidism
- Hypothyroidism
- Inc. lactic acid production-due to:
- Alcohol - Exercise - Starvation
- Drug therapy:
- Thiazide diuretics - Low dose Aspirin
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Increased production of Uric acid (10%)
- Inc. purine synthesis due to:
- Lesch Nyhan Syndrome
- Phosphoribosyl pyrophosphate synthetase overactivity- G6PD deficiency (inc production +dec excretion)
- Inc. turnover of purines due to:
- Myeloproliferative disorders (Polycythemia Vera)
- Lymphoproliferative disorders (leukemia, lymphoma)- carcinoma
- Severe Psoriasis
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Typical sequence involves progression through:
Asymptomatic hyperuricemia
Acute gouty arthritis
Interval or intercritical gout
Chronic or tophaceous gout
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Types Of Gout
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(diuretics,low dose aspirin,cyclosporin)
Alcohol
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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 arthritis Much greater chance if untreated
Rarely presents as a chronic condition
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Diagnosis
Based on history and physical exam
Confirmed by Arthrocentesis Urate crystals: needle-shaped negatively
birefringent either free floating or withinneutrophils & macrophages.
Uric acid level non specific. 30% may show normal level
24 hrs Urine collection: 800 mg ------- Overproducers
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Microscopic Diagnosis
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Radiology
-Acute Soft tissue swelling
Chronic Chronic tophaceous gouty arthritis,
extensive bony erosions are notedthroughout the carpal bones
Sclerosis and joint-space narrowing are
seen in the first metatarsophalangeal joint,as well as in the fourth interphalangealjoint .
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Treatment
Acute:
NSAIDs anti-inflammatory doses- Naproxen -Indomethacin or- Diclofenac
Colchicine- Started in acute attack.- Stop if no response or side effects.- Causes bone marrow suppression.
Corticosteroids- Intramuscular or- Intra-articular depot methylprednisolone.
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Treatment
Chronic:
Dietry advice:
- Diet will decrease uric acid 1 mg/dL at best
- Dec alcohol intake
- Avoid foods rich in purines such as sea food, Spinach etc.
- Weight loss
Modification of medications
Avoid low dose ASA, diuretics, etc.
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Treatment
Uricosuric drugs: for under-excretors
Probenicid:
Sulfinpyrazone: toxic side effects
Avoid with renal disease
Consider NSAIDs to avoid exacerbation of gout
Should not be started within a month of acute attack
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Treatment
Indications for Allopurinol (xanthine Oxidase inhibitor)
Tophaceous deposites
Uric acid consistently >9
Persistent symptoms with moderate UA levels
Impaired renal function
Prophylaxis for tumor-lysis syndrome
Consider NSAIDs to avoid exacerbation
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Prognosis
Generally good
More severe course when Symptoms present at less
than 30 yrs of age
Up to 50% progress to chronic disease if untreated.
Surgical intervention may be required for tophi.
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PSEUDOGOUT
Characterized by calcium pyrophosphate deposits inhyaline and fibrocartilage.
Leads to chondrocalcinosis
Resembles Gout in presentation
More common in elderly females
Usually effects knee or wrist joints.
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In young people it is associated with:
- Haemochromatosis
- Hyperparathyroidism
-Wilsons disease
- Alkaptonuria
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Diagnosis
Joint Fluid Aspiration:
- Rhomboid shaped, weakly positively
briefringent crystals
Radiology:
- Chondrocalcinosis on X Ray of joints.
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TREATMENT
Aspiration of jointreduces pain.
NSAIDs
Colchicine
Corticosteroidsintra articularAfter exclusion of infection.
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