crystal deposition diseases

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Crystal deposition diseasesCrystal deposition diseases

Prof. Dr. Abdel Samad El Hewala

Professor of Rheumatology and Rehabilitation

Faculty of Medicine- Zagazig University


This group of diseases include:This group of diseases include: GoutGout: the responsible crystals are

monosodium urate crystals. PseudogoutPseudogout: the responsible crystals are

calcium pyrophosphate crystals. Apatite crystal diseaseApatite crystal disease: the responsible

crystals are hydroxiapatite crystals.


In this group of diseases the metabolic product may cause arthropathy in one of two ways:

The crystals enter the joint space to The crystals enter the joint space to provoke an acute crystal synovitis, orprovoke an acute crystal synovitis, or

The presence of this crystalline The presence of this crystalline material within the articular cartilage material within the articular cartilage leads to chronic degenerative changes. leads to chronic degenerative changes.

GoutGout

Gout is the deposition of monosodium urate crystals in the joints and other connective tissues. This deposition is the result of hyperuricaemia.

By Royal Authority” by George Cruickshank. A gout sufferer helped onto his horse.

“The Gout” by James Gilray, 1799. Gout depicted as an evil demon attacking a toe

Purine metabolism:Uric acid is produced by the degradation of the

purine bases, adenine and guanine “constituents

of nucleic acid and nucleotides” according to the

following scheme:

Adenine Guanine

Hypoxanthine Xanthine Xanthine oxidase

Uric acid

Purine metabolism:

In lower mammals this sequence is carried a stage further by the enzyme uricase converting uric acid to allantoinallantoin which is then rapidly eliminated through the kidneys.

In man, there is no uricase enzyme and uric acid is the end product of purine metabolism.

Etiology of Hyperuricemia

Increased uric acid in the serum can

result from over production or under

excretion of uric acid.


Break down of body constituents; purines

(endogenous)

Break down of ingested dietary; purines

(exogenous)

Urate in plasma

Excretion

Renal Gut Effective therapy Progressive gout


The three important variables determining the plasma uric acid level are:

1.The rate of endogenous purine breakdown

2.The amount of purines in the diet

3.The rate of renal clearance of urate

The normal range of plasma uric acid level:

In male 4-7 mg/100ml

In female 4-6 mg/100ml

Hyper uricaemia may be:

Primary hyper uricaemia which is the

result of multiple interacting factors as

genetic and environmental factors.

Hyper uricaemia may be: Secondary hyper uricaemia, which is due mainly to a single well, defined cause: Increased turnover of purines such as myeloproliferative disorders or neoplastic disease. Reduced renal urate excretion. Low dose aspirin. Chronic administration of thiazide diuretics. Cyclo sporne. Acidosis.

Pathogenesis of Gout

Monosodium urate crystals can cause

acute or chronic inflammation by

stimulation of chemotactic factors and

other mediator of inflammation.

Pathogenesis of Gout

Urate crystals can also be deposited around tendons and subcutaneous tissues

as tophitophi, in the renal which may be associated with nephropathy and excess urate excretion in kidneys can result in urate stones formation which are radiolucent.

Clinical Aspects

Gout can take several forms:

Asymptomatic hyperuricaemia is not strictly considered gout, as by no means all patients with hyperuricaemia will develop signs of gout.

Acute arthritis:

The acute arthritis of gout is the most common early clinical manifestation.The metatarsophalangeal joint of the first toe is involved most often (75%), the ankle, tarsal joints, and the knee are also commonly involved.A wrist or finger joint is less often involved during early attacks.

Acute arthritis:

The first episode of acute gouty arthritis may begin abruptly in a single joint, often during the nightthe night, so that the patient awakes with dramatic unexplained joint painpain and swelling.swelling.

Acute arthritis:

Affected joints are usually worm, red, worm, red, tender and drytender and dry (contrasting with the moist skin over the acute rheumatic fever).

Acute attacks may be triggered by specific events such as, trauma, alcohol, drugs, swings, in uric levels, surgical stress, or acute medical illness.

Intercritical gout:

The intervals between attacks constitute the intercritical stage of gout. This stage is asymptomatic and diagnosis can made by aspiration of aspiration of monosodium urate crystals from monosodium urate crystals from previously involved joints.previously involved joints.

Chronic gouty arthritis: Deforming can develop as a result of

the erosion of cartilage and subcondral bone caused by crystal deposition and chronic inflammatory reactions.

Chronic gouty arthritis can mimic rheumatoid arthritis although it tends to be less symmetric than typical rheumatoid arthritis.

Tophi:

Clinically evident monosodium urate crystal containing tophi occur only in fairly advanced gout.

Gouty tophi involving the proximal interphalangeal joint with erythema of the overlying skin.

Tophi at helix of ear.

Urate stones:

Urate urolithiasis occurs in about 20% of gouty subjects. The formation of urate stones is favored by:

- High urinary urate output.

- Concentrated urine.

- Highly acidic urine.

Pure urate calculi are radiolucent on x-ray in contrast to calcium containing stones.

Gouty nephropathy is characterized by: - Proteinuria.

- Impaired conc.

- Decreased clearance volume.

- Hypertension.

N.B: Renal disease is most important cause of death in gouty subjects.

Investigations

The value of serum uric acid level in the diagnosis of acute attack is limited, serum uric acid levels can be normal at the time of acute gouty arthritis.

In almost all patients, serum uric acid levels will be elevated at some time.

Serum urate measurements are important in following treatment.

Investigations

Some people without gout may have elevated serum uric acid due to drugs or other causes.

Diagnosis of gout is confirmed by demonstration of monosodium urate crystal within synovial fluid by polarized microscope.

Course and prognosis

Initial acute attacks subside

spontaneously over days to a week.

If gout is inadequately treated,

episodes become more frequent and

chronic tophaceous gout can develop.

Differential diagnosis

Acute gout from causes of acute monoarthritis.

Chronic gout from causes of chronic polyarthritis.

Treatment

Acute gout: Rest to the acutely inflamed joint.Non-steroidal anti-inflammatory

drugs. (NSAID) in dose near maximum recommended dose is the most common recommended regimen.

(e.g. indomethacin 150 mg/day, Diclophenac 150 mg/day).

Acute gout:

Colchicine is used less often, one tablet (0.5 mg) every hour until 8 tablets or intolerance.

( Side effects such as nausea, vomiting or diarrhea are common.)

Acute gout: Because many patients with gout have

contraindications to NSAIDs or colchicines, or have sever attacks that are less responsive, ACTH have been used increasing by (40-80 IU subcauteneously).

If only 1-2 joints are involver, depot corticosteroids can be injected, intra-articulary once infection has been excluded.

Prophylaxis between the attacks: Colchicine in doses of 0.5 to 1 mg

daily reduces the frequency of acute attacks.

Reduction of plasma uric acid level: If patients have recurrent attacks or

tophi, plans must be made for long-term treatment with urate lowering agents such as:

Uricosuric drugs probencid 1-2 g/d.

Allopurinol is as inhibitor for the enzyme xanthine oxidase, and so reduce the production of urate (300-600 mg/d).

crystal deposition diseases

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