CRYSTAL ASSOCIATED DISEASE 10/8/20151Dr. Alka Stoelinga.

CRYSTAL ASSOCIATED DISEASE

04/21/23 1Dr. Alka Stoelinga

CRYSTAL ASSOCIATED DISEASESCRYSTAL ASSOCIATIONCOMMON• Monosodium urate monohydrate

• Calcium pyrophosphate dihydrate

•Basic calcium phosphates

• Acute gout• Chronic tophaceous gout• Acute pseudogout• Chronic arthropathy• Chondrocalcinosis• Calcific periarthritis• Calcinosis

UNCOMMON• Cholesterol

• Calcium oxalate

• Extrinsic crystals/ semi-crystalline particles• Synthetic crystals• Plant thorns/ sea urchin spines

• Chronic effusions in rheumatoid arthritis• Acute arthritis in Dialysis patient

• Acute synovitis• Chronic monoarthritis, tenosynovitis

04/21/23 Dr. Alka Stoelinga 2

GOUT


GOUTAlso known as podagra when it involves the big toe Is medical condition usually characterized by recurrent attacks of acute

inflammatory arthritisGout is an abnormality of uric acid metabolism that results in the

deposition of Monosodium urate Monohydrate crystals It is caused by elevated levels of uric acid in the blood which crystallize and

are deposited in joints, tendons, and surrounding tissues.The metatarsal- phalangeal joint at the base of the big toe is the most

commonly affected Results in pathological reaction in:1. Joints: Gouty arthritis2. Soft tissue: Tophi and Tenosynovitis3. Urinary tract: Urate stones/ Urate nephropathy. M:F=10:1 Prevalence rate increase with: --Age --Serum uric acid concentration


• Hyperuricemia is the underlying cause of gout.• Hyperuricemia is defined as

– A plasma urate level• > 420 μmol/L (7.0 mg/dL) in males and • > 360 μmol/L (6.0 mg/dL) in females.

• This can occur for a number of reasons, including– Diet– Genetic predisposition– Underexcretion of urate, the salts of uric acid

• Renal underexcretion of uric acid is the primary cause of hyperuricemia in about 90% of cases

– Overproduction is the cause in less than 10%• About 10% of people with hyperuricemia develop gout at some point

in their lifetimes• The risk varies depending on the degree of hyperuricemia.

– When levels are between 415 and 530 μmol/L (7 and 8.9 mg/dL), the risk is 0.5% per year

– In those with a level greater than 535 μmol/L (9 mg/dL), the risk is 4.5% per year


04/21/23 Dr. Alka Stoelinga 6PATHOPHYSIOLOGY

Pathophysiology• Disorder of purine metabolism• Final metabolite uric acid• Crystallizes in the form of monosodium urate, precipitates in joints, on

tendons, and in the surrounding tissues.• These crystals then trigger a local immune-mediated inflammatory

reaction with interleukin 1β• An evolutionary loss of uricase (breaks down uric acid)• Uric acid crystallizes as levels increase• Other factors triggering an acute episode of arthritis include

– cool temperatures, rapid changes in uric acid levels, acidosis, articular hydration, and extracellular matrix proteins, such as proteoglycans, collagens, and chondroitin sulfate.

• Rapid changes in uric acid may occur due to a number of factors, including – trauma, surgery, chemotherapy, diuretics, and stopping or starting

allopurinol.


Types:

1. Primary Gout:• Exclusively in male• Common cause of inflammatory arthritis in

men>40 years2. Secondary Gout:• Due to renal impairment• Drugs


Predisposing factors for Hyperuricemia:

1. Diminished renal excretion of uric acid Inherited isolated renal tubular defect Renal failure Drugs: Diuretics, Pyrazinamide, Low dose of aspirin Lead poisoning Hyperparathyroidism Myxedema Down’s syndrome Lactic Acidosis: Alcohol, Exercise, Starvation,

Vomiting, Toxemia of pregnancy


Predisposing factors for Hyperuricemia:

2. Increased production of Uric acid:Increased turnover of Purines--Chronic Myeloproliferative disorders e.g. Polycythaemia

Vera--Chronic Lymphoproliferative disorders e.g. CLL--Psoriasis

Increased purine synthesis de novo--Unidentified abnormality--Specific enzyme defect--HGPRT deficiency--PRP deficiency


Predisposing factors for Hyperuricemia:MSUM crystal deposition:1.Around synovial joints2.Initially lower limb joints3.Especially 1st Metatarsophalangeal joint4.Small joints of feet and hand

Crystal induces:1.Inflammation of the joints/Periarticular tissue2.Pressure effect3.Secondary osteoarthritis


Gout with Tophi on elbow and knee.


Clinical features:ACUTE GOUTY ARTHRITIS:Peak age of onset in men is 45 yearsUsually after 20-30 years of sustained HyperuricemiaUsually single joint involvement at first, common is 1st

Metatarsophalangeal joint of great toe.Other joints : Ankle, Midfoot, Knee, small joints of

hands and wristSevere pain and extreme tendernessThe joint is red, hot, swollen with shiny overlying skin

and dilated veinsFever, malaisePruritis, desquamationInitial attacks are usually self limited over 5-14 days


Interictal period: More than 50% of patients experience recurrent

arthritis within 1 year of first attack, subsequently frequency increases, attacks will be more prolonged and severe and involve multiple joints.

Precipitating factors:1. Dietary excess2. Alcohol3. Starvation4. Diuretics5. Trauma, unusual physical exercise6. Systemic infection


Acute gouty arthritis on the big toe of an elderly man.


CHRONIC TOPHACEOUS GOUT:Recurrent attacks are followed by chronic gout in

which there is progressive cartilage and bone erosions in association with deposition of Tophi and secondary degenerative changes

They appear 10-15 years after initial attackTophi is firm, painless, irregular nodules, due to

deposition of large MSUM crystalsFound around extensor surfaces of joints and

their presence cause immobility of joints and severe joint deformities

Usual sites: Fingers, hand, forearm, elbow, Achilles tendon, cartilage of ear.

May ulcerate, discharge of white gritty material04/21/23 16Dr. Alka Stoelinga

Severe gout in the fingers resulting in large, hard deposits of crystals of uric acid. These deposits are

called Tophi04/21/23 17Dr. Alka Stoelinga


OTHER MANIFESTATIONS:• Synovitis• Deformity of joints• Urolithiasis: Uric acid Calculi• Chronic urate nephropathy


INVESTIGATIONS:1. Synovial fluid examination• A definitive diagnosis of gout is based upon the identification of monosodium urate

(MSU) crystals in synovial fluid or a tophus• Under polarized light microscopy, they have a needle-like morphology and strong

negative birefringence.• The fluid must also be examined relatively quickly after aspiration, as temperature and

pH affect their solubility.• Increased cells: Neutrophils• Turbid 2. Blood tests• Hyperuricemia is a classic feature of gout• However, Gout occurs nearly half of the time without hyperuricemia, and most people

with raised uric acid levels never develop gout.• Other blood tests commonly performed are

– White blood cell count– Electrolytes– Renal function test– Liver function test– Erythrocyte sedimentation rate (ESR).

• Both the white blood cells and ESR may be elevated due to gout in the absence of infection

3. Joint X-ray/ KUB4. Dual-energy CT scanning (DECT)


Using a sterile syringe and needle, fluid is withdrawn from the inflamed joint and then analyzed for uric acid crystals


Fluid obtained from crystal deposits in a patient with gout


A purulent knee aspirate from a person with presumed gout


Needle-shaped urate crystals diagnostic of gout from an acutely inflamed joint (left) as seen under polarized

microscopy and unpolarized microscopy (right)


Gouty Tophi


MANAGEMENT

Treatment of Acute attack:• NSAIDS • Indomethacin and Naproxen• Colchicine• Joint aspiration• Intra-articular steroids• Analgesics: Opioids may be required for pain and

aspirin should be avoided• Bed rest for 24 hours


Long term therapy:

Long term therapy should be started when acute attack has settled.

Indications of Hypourecemic drug:1.Recurrent attack of acute gout2.Presence of Tophi3.Increased uric acid level4.Evidence of bone or joint damage5.Associated with renal disease


Drug therapy:1.Allopurinol: --Indicated In overproduction of uric acidsXanthine oxidase inhibitorCan precipitate acute attackStart with low dose/combine with ColchicineNot to be used during acute attack

2. Uricosurics:--Indicated in undersecretors of uric acid--when increased frequency or severity of acute Gout.ProbenecidSulfinpyrazone04/21/23 28Dr. Alka Stoelinga


LIFE STYLE MODIFICATION:Weight reductionReduction of alcohol intakeAvoidance of foods containing high levels of

Purine E.g. Meat, organ meat, seafood, beans, spinach, alcohol

Adequate fluid intakeWithdrawal of drugs such as Diuretics and

salicyclates.


Relationship of Hyperuricemia with other diseases:

Patients with Hyperurecemia and Gout have and increased incidence of:

1.Hypertension2.Renal disease (Nephrosclerosis, Tophi,

Pyelonephritis)3.Diabetes mellitus4.Hypertriglyceridemia5.Atherosclerosis



CRYSTAL ASSOCIATED DISEASE 10/8/20151Dr. Alka Stoelinga.

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