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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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