crystal deposition disorders

8/14/2019 Crystal Deposition Disorders

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Introduction

The crystal deposition disorders are a group of conditions characterized bythe presence of crystals in and around joints, bursae and tendons.

Although many different crystals are found, three clinical conditionsin particular are associated with this phenomenon: gout calcium pyrophosphate dihydrate (CPPD) depositiondisease calcium hydroxyapatite (HA) deposition disorders.

Characteristically, in each of the three conditions, crystal deposition has threedistinct consequences:

(1) it may be totally inert and asymptomatic;(2) it may induce an acute inflammatory reaction; or(3) it may result in slow destruction of the affected tissues.


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GOUT

Gout is a disorder of purine metabolism characterizedby hyperuricaemia, deposition of monosodium uratemonohydrate crystals in joints and peri-articular tissues andrecurrent attacks of acute synovitis.Late changes include cartilage degeneration, renal dysfunctionand uric acid urolithiasis.

Although the risk of developing clinical features of goutincreases with increasing levels of serum uric acid, only a

fraction of those with hyperuricaemia develop symptoms.

However, hyperuricaemia and gout are generally regarded aspart and parcel of the same disorder.


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GOUT: Epidemiology

The prevalence of symptomatic gout varies from 1 to over 10 per 1000, depending onthe race, sex and age of the population studied: it is much commoner in Caucasian thanin Negroid peoples; it is more widespread in men than in women (the ratio may be ashigh as 20:1); and it is rarely seen before the menopause in females.

It also corresponds with serum creatinine /BUN levels, body weight, height, age,blood pressure, and alcohol intake.

Body bulk (as estimated by body weight, surface area, or body mass index) hasproved to be one of the most important predictors of hyperuricemia in people ofwidely differing races and cultures.The prevalence of asymptomatic hyperuricemia is 5 to 8%.

Peak incidence in men is in the fifth decade.90% of patients with primary gout are men.

Women rarely develop gout before the menopause, because estrogens are thought to beuricosuric.


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GOUT :Pathology

Nucleic acid and purine metabolism normally proceeds, through complex pathways, to theproduction of hypoxanthine and xanthine; the final breakdown to uric acid is catalysed bythe enzyme xanthine oxidase.

Monosodium urate appears in ionic form in all the body fluids; about 70 per cent is

derived from endogenous purine metabolism and 30 per cent from purine-rich foods in thediet.

It is excreted (as uric acid) mainly by the kidneys and partly in the gut.

Urate is poorly soluble, with a plasma saturation value of only 7 mg/dL (0.42 mmol/L). Thisconcentration is commonly exceeded in normal individuals and epidemiological studieshave identified entire populations (for example the Maoris of New Zealand) who haveunusually high levels of serum uric acid.

The term hyperuricaemia is therefore generally reserved for individuals with a serum urateconcentrationbwhich is significantly higher than that of the population to which they belong(more than two standard deviations above the mean); this is about 0.42 mmol/L for menand 0.35 mmol/L for womenin western Caucasian peoples.

By this definition, about 5 per cent of men and less than 1 per cent of women havehyperuricaemia; the majority suffer no pathological consequences and they remain

asymptomatic throughout life.


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Excretion of Uric Acid

Mechanisms of urate excretionkidney (~66%)

Gut (~33%)

Renal Excretion of Uric Acid- Completely filtered by the glomerulus

- Completely (essentially) reabsorbed in the proximal tubule

- Approximately 50% is secreted back into the tubule in the descendingloop

- Approximately 80% (of the 50% now in the loop) is reabsorbed in theascending loop

- Net excretion = 10% of filtered load


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GOUT : Pathophysiology

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

Urate crystals are deposited in minute clumps in connective tissue, including articular

cartilage; the commonest sites are the small joints of the hands and feet.For months, perhaps years, they remain inert.

Then, possibly as a result of local trauma, the needlelike crystals are dispersed into the

joint and the surrounding tissues where they excite an acute inflammatory reaction.Individual crystals may be phagocytosed by synovial cells and polymorphs or may floatfree in the synovial fluid.

With the passage of time, urate deposits may build up in joints, peri-articular tissues,tendons and bursae; common sites are around the metatarsophalangeal joints of thebig toes, the Achilles tendons, the olecranon bursae and the pinnae of the ears.

These clumps of chalky material, or tophi (L. tophus = porous stone), vary in size fromless than 1 mm to several centimetres in diameter. They may ulcerate through the skinor destroy cartilage and peri-articular bone.


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Acute gout spasm: the inflammation isusually monoarticular, e.g.,metatarsophalangeal joint (podagra), lessfrequently present on feet, ankles, and knees.

Tophaceousgout affecting the hands


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This is the typical gouty type, with hisrubicund face, large olecranon bursae andsmall subcutaneous tophi over the elbows.

Gouty Tophi in the Helix of the Ear


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Factors predisposing to hyperuricaemia

- Older age, male gender

- Genetic enzyme defects, hyperparathyroidism

- Haemolytic disorders, myeloproliferative disorders

- Obesity, diabetes, hypertension- High consumption of red meat, hyperlipidaemia

- Chronic inflammatory diseases

- Long-term use of aspirin or diuretics- Alcohol abuse


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GOUT : Classification

Gout is often classified into primary and secondary forms.

Primary gout (95 per cent) occurs in the absence of any obvious causeand may be due to constitutional under-excretion(the vast majority)or overproductionof urate.

Secondary gout (5 per cent) results from prolonged hyperuricaemiadue to acquired disorders such as myeloproliferative diseases,administration of diuretics or renal failure.

This division is somewhat artificial; people with an initial tendency toprimary hyperuricaemia may develop gout only when secondaryfactors are introduced for example obesity, alcohol abuse, ortreatment with diuretics or salicylates which increase tubularreabsorption of uric acid.


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Causes of decreased renal excretionof URATE

Primary- Idiopathic

- Familial juvenile goutynephropathy

Secondary- Hypertension

- Hyperparathyroidism

- Myxoedema

- Downs syndrome

- Increased level of organic level

- Lead nephropathy

- Sarcoidosis

- Bartters syndrome

- Beryllium poisoning

- Drug: diuretics, B-blocker, ACEI,salicylates (low dose), PEA, EMB,cyclosporin, nicotinic acid

- Chronic renal failure

- Volume depletion


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Causes of increased uric acid production

Primary- Idiopathic

- HPRT deficiency

- PPRT overactivity

- Ribose-5-phosphateoverproduction

- AMP-deaminase deficiency

Secondary- Glycogen storage disease

type II (G6PD), type III, V, VII

- Hereditary fructose intolerance

- Lymphoproliferative andmyeloproliferative diseases

( leukemia, Hodgkins d

z,lymphosarcoma, myeloma, PV,

Waldenstroms macroglobulinemia )

- Cytotoxic drugs

- Carcinomatosis

- Gauchers disease

- Chronic hemolytic anemia

- Severe exfoliative psoriasis


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GOUT : Clinical features

Patients are usually men over the age of 30 years;

women are seldom affected until after the menopause.

Often there is a family history of gout.

The gouty stereotype is obese, rubicund, hypertensiveand fond of alcohol.

However, many patients have none of these attributes

and some are nudged into an attack by theuncontrolled administration of diuretics or aspirin.


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GOUT : THE ACUTE ATTACK

The sudden onset of severe joint pain which lasts for a week or two before resolving completely is typicalof acute gout.

The attack usually comes out of the blue but may beprecipitated by minor local trauma, operation,intercurrent illness, unaccustomed exercise or

alcohol consumption.

The commonest sites are the metatarsophalangeal joint of the big toe, the ankle and finger joints, and theolecranon bursa. Occasionally, more than one site is involved.

The skin looks red and shiny and there is considerable swelling.

The joint feels hot and extremely tender, suggesting a cellulitis or septic arthritis.

Sometimes the only feature is acute pain and tenderness in the heel or the sole.

Hyperuricaemia is present at some stage, though not necessarily during an acute attack. However, while alow serum uric acid makes gout unlikely, hyperuricaemia is not diagnostic and is often seen in normalmiddle-aged men.

The true diagnosis can be established beyond doubt by finding the characteristic negatively birefringenturate crystals in the synovial fluid.A drop of fluid on a glass slide is examined by polarizing microscopy.Crystals may be sparse but if the fluid specimen is centrifuged a concentrated pellet may be obtained forexamination.


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CHRONIC GOUT

Recurrent acute attacks may eventually merge into polyarticular gout.

Joint erosion causes chronic pain, stiffness and deformity; if the fingerjoints are affected, this may be mistaken for rheumatoid arthritis.

Tophi may appear around joints over the olecranon,in the pinna of the ear and less frequently in almost any othertissue.

A large tophus can ulcerate through the skin and discharge its chalkymaterial.

Renal lesions include calculi, due to uric acid precipitationin the urine, and parenchymal disease due to deposition ofmonosodium urate from the blood.


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Diagnosis

Clinical:In men , initial attack monoarticular 1stMTP joint(50% of cases)Other jts involved instep/knees/wrists/ olecranon bursa.Often begins at night. Usually abrupt , severely painful.Later attacks polyarticular , associated with systemic signs., most ofteninitial presenting complaint in women. (hands/tarsal jts/knees)Precipitants Minor trauma , ethanol, diuretics , Surgery, severe medical

illness, hypouricemic drugs.Tophi Classically , helix/ antihelix ,but rare ; more common , hands, feet,olecranon bursa.Complications : ulceration/infection.Laboratory:- GOLD STANDARDSynovial Fluid Analysis WBC count 2000-100 000/ml

MSU crystals- needle shaped , negatively birefringent.Serum Uric acid level important in monitoring treatment .(42% - normallevels)24 hr uric acid collection useful in young patients with gout/ + familyhistory


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Diagnosis : CONT.

X-raysDuring the acute attack x-rays show only soft-tissue swelling.Chronic gout may result in joint space narrowing and secondaryosteoarthritis.Tophi appear as characteristicpunched-out cysts or deep erosions in

the para-articular bone ends; these excavations are larger and slightlyfurther from the joint margin than the typical rheumatoid erosions.Occasionally, bone destruction is more marked and may resembleneoplastic disease.

Radiographic Hallmarks of Gout

- Overhanging edges- Punched out lesions with sclerotic borders.- Preservation of joint space (till late)- Degenerative changes


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American College of Rheumatology (ACR)Diagnostic Criteria Of Gout

Criteria for a definitive gout diagnosis from the American College of Rheumatology (ACR) are asfollows:

A. Presence of characteristic urate crystals in the joint fluid, orB. Presence of a tophus proven to contain urate crystals by chemical means or polarized lightmicroscopy, orC. Presence of six of the following clinical, laboratory, and radiographic phenomena:1- More than one attack of acute arthritis.

2- Development of maximal inflammation within 1 day.3- Attack of monarticular arthritis.4- Observation of joint redness.5- Pain or swelling in first metatarsophalangeal joint.6- Unilateral attack involving first metatarsophalangeal joint.7- Unilateral attack involving tarsal joint.8- Suspected tophus.

9- Hyperuricemia.10- Asymmetric swelling within a joint on x-ray.11- Subcortical cysts without erosions on x-ray.12- Negative culture of joint fluid for microorganisms during attack of joint inflammation.


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Exacerbation of a chronic gout process in the hand: the fingers are deformed, thejoints of the phalanges are swollen, with tight, hot, and dark-red skin, frequentlyaccompanied by some general symptoms (fever, higher sedimentationrate, increased number of white blood cells) (a).The radiograph of the same patient presents the characteristics of chronic gouty

arthropathy, narrowed joint spaces, and typical punched-out periarticular lyticlesions (b)


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Late stage of gout: numerous subcutaneoustophi are present in the palmar region (a).

These tophaceus gouty deposits are alsovisible in the radiograph around thesmall joints of the hand (b)


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Deposits of urate crystals may occur in the synovium (a) and in the cartilage ofthe knee joint (b) as visualized by arthroscopy


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Acute gout spasm of theleft knee

Bursitis olecrani due to the massive

tophaceus deposit of urate crystals


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The intraoperative picture demonstrates the encapsulated yellow chalky mass ofgouty tophi (a). The cut surface of a gouty tophus (b)


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Gout x-rays

The typical picture is of large periarticularexcavations tophi consisting of uric aciddeposits.

Arthropathy of the left ankle joint in a patientsuffering from gout for a long time.

Note the narrowed joint space and the depositsaround the joint, visible on the radiograph


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Gout x-rays

Late stage of goutwith extensivedestruction of the

elbow joint andtophaceus goutydeposits around it aredemonstrated on theanteriorposterior(a)and lateral (b)

radiographs


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Sodium urate crystal image

Sodium urate crystal image on polarizationmicroscope: characteristic negative double

refraction

The electron microscope image of sodiumurate crystals (magnifi cation: 6,600).


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Differential diagnosis

AcuteInfective arthritisBursitis, cellulitis, tenosynovitisOther crystal arthropathy( pseudogout, apatite or brushite

arthritis or periarthritis )Traumatic arthritisHemoarthrosisRA with palindromic onsetReactive arthritisSpondarthritis with peripheral

involvementPsoriatic arthritisSarcoid arthritisRheumatic fever

ChronicNodular rheumatoid arthritis

Psoriatic arthritis

Osteoarthritis with Heberdens and

Bouchards nodesSarcoid arthritis

xanthomatosis


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Treatment

The acute attack The acute attack should be treatedby resting the joint, applying ice packs if pain is severe,

and giving full doses of a non-steroidal anti-inflammatory

drug (NSAID).

Colchicine, one of the oldest of medications, is less effective andmay cause diarrhoea, nausea and vomiting.

A tense joint effusion may require aspiration and intra-articularinjection of corticosteroids.

Oral corticosteroids are sometimes used for patients who cannottolerate NSAIDs or in whom NSAIDs are contraindicated.

The sooner treatment is started the sooner is the attack likely toend.


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Treatment : CONT.

Interval therapy Between attacks, attention should be given to simplemeasures such as losing weight, cutting out alcohol and eliminating diuretics.

Urate-lowering drug therapy is indicated if acute attacks recur at frequentintervals, if there are tophi or if renal function is impaired. It should also beconsidered for asymptomatic hyperuricaemia if the plasma urate

concentration is persistently above 6 mg/dL (0.36 mmol/L).

However, one must remember that this starts a life-long commitment andmany clinicians feel that people who have never had an attack of gout and arefree of tophi or urinary calculi do not need treatment.

Uricosuric drugs (probenecid or sulfinpyrazone) can be used if renal functionis normal. However, allopurinol, a xanthine oxidase inhibitor, is usuallypreferred, and for patients with renal complications or chronic tophaceousgout allopurinol is definitely the drug of choice.


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Treatment : CONT.

Urate-lowering drugs should never be started before the acute attack hascompletely subsided, and they should always be covered by an anti-inflammatory preparation or colchicine, otherwise they may actually

prolong or precipitate an acute attack.

Patients who suffer an acute attack of gout while already on a constant dose of

urate-lowering treatment should be advised to continue taking the drug at theusual dosage while the acute episode is being treated.SurgeryWith prolonged urate-lowering therapy, adjusted to maintain anormal serum uric acid level (less than 0.36 mmol/L), tophi may graduallydissolve.

However, ulcerating tophi that fail to heal with conservative treatment can beevacuated by curettage; the wound is left open and dressings are applied untilit heals.


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Indications for Antihyperuricemic Therapy

in Gout

1- Frequent and disabling attacks of acute gouty arthritis

2- Clinical or radiographic signs of chronic gouty joint disease

3-The presence of tophaceous deposits in soft tissues orsubchondral bone

4- Gout with renal insufficiency

5- Recurrent nephrolithiasis

6- Serum urate levels persistently in excess of 13 mg/dL in menor 10 mg/dL in women

7- Urinary uric acid excretion exceeding 1100 mg/day

8- Impending cytotoxic chemotherapy or radiotherapy forlymphoma or leukemia


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Therapy

- Patients taking uricosuric agents are at risk for urolithiasis. This can bedecreased by ensuring high urinary output and by adding sodium bicarbonate1 gram TID.- The available agents include: probenecid (1-2 g/day) and sulfinpyrazone(50-400 mg BID).- Dose should be increased to decrease uric acid < 6.0 mg/ml

- Allopurinol decreases uric acid in overproducers and under- excreters; it isalso indicated in patients with a history of urolithiasis, tophaceus gout, renalinsufficiency and in prophylaxis of tumor lysis syndrome.

- Allopurinol: usual dose is 300 mg/day. Maximal recommended dose is 800

mg/day.- In renal insufficiency dose should be decreased to 200 mg/day for creatinineclearance < 60ml/min and to 100 mg/day if clearance < 30 ml/min).


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Therapy

- Start with small doses of allopurinol to reduce the risk ofprecipitating an acute gout attack.

- Most common side effects are rash (2% of patients) but rarelypatients can develop exfoliative dermatitis that can be lethal.

-Chronic use of colchicine (0.6-1.2 mg/day) is used asprophylaxis for acute attacks.

1.2 mg followed by 0.6 mg 2 hrs later.

-Loadingdose same in renal insufficiency.

- Maintenance (preventive) dose 0.6 mg qd or bid.

- 0.3 mg 2-3 times per week in dialysis patients (preventive).


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Therapy :Febuxostat

- Non-xanthine inhibitor of XO and XD.- Better tolerated than allopurinol.

- Lower uric acid levels than allopurinol (53% vs. 21% met target of 6.0mg/dl).

-Better dissolution of tophi.

Adverse ReactionsNauseaGout flare (must be on prophylaxis!)Elevated ALT, AST (3% > 3xULN)Elevated CRPRash

Elevated CK

USES:

- Allopurinol failures- Renal insufficiency- Tophaceous gout

T bl III M i di ti d i th t t t d h i f t 1 8 13 81


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Table III. Main medications used in the treatment and prophyaxis of gout.1-8,13,81

Agent Adverse Events Contraindications Regimen

Acute therapy/

prophylaxis

NSAIDs

Dose-dependent gastropathy,

nephropathy, liver

dysfunction, central nervous

system dysfunction. May

cause fluid overload inpatients with congestive

heart failure.

Peptic ulcer disease or bleeding

ASA- Or NSAID-induced asthma,

urticaria, or allergic-type

reactions.

Indomethaction 50mg TID for 2

to 3 days, then tapered over 5

to 7 days; naproxen 750 mg,

followed by 250mg TID, then

tapered over 5 to 7 days,sulindac 200mg BID, then

tapered over 5 to 7 days.

Prophylaxis low daily doses.

Cox-2 selective inhibitors

(etoricoxib)

Less GI toxicity than

conventional NASIDs renal

effecect similar to

conventional NSAIDs

Cautious use in patients with

advanced renal disease, history

of ischemic heart disease, or

history of NSAID-induced

asthma.

Etoricoxise 120 mg/d

(available outside the United

States)

Colchicine Dose-dependent GI

symptoms, neuromyopathy;

improve IV dosing can cause

bone narrow suppression,

renal failure, paralysis, and

death.

Use cautiously in renal or

hepatic dysfunction.

1.2mg initially then 0.6mg

every 1 to 2 hours until pain

relief or abdominal

discomfort/diarrhea develops

(do not exceed 4 mg/d).

Prophylaxis 0.6 to 1.2 mg/d.

Corticosteroids Fluid detention, impairedWound healing, psychosis

Hyperglycemia

hypothalamus

Pituitary axis suppression

Osteoporosis, potential for

Rebound inflammation.

Intra-articular;methylprednisolone 10 to

20mg for a small joint; 20 to

10 mg for large joint. IM:

triamcinolone acetonide 60mg

repeat after 24 hours if

necessary. PO: prednisone 30

to 60mg QD, then tapered over

7 to 10 days.


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Table III. (Continued)

Agent Adverse Events Contraindications Regimen

ACTH Fluid retention, hypokalemia relapse

of gout, worse diabetes control

40 to 80 IU IM, repeat every

12 hours as necessary.

Orate-lowering therapy

Allopuriol Rash, GI symptoms, headache,

urticaria, and intestinal nephritis;

rare potentially fatal hypersensitivity

syndrome, reduces orate levels in

over producers and underexcretors.

Probenecid Rash, headache, and GI symptoms;

rare nephritic syndrome, hepaticnecrosis, aplastic anemia and

hemolytic anemia. Reduced orate

levels in underexcretors.Potential for

numerous drug interactions because

of interference with excretion of

many medications.

Renal dysfunction (CrCI


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Low Purine Diet

On a strict low purine diet, protein is derived principally from

eggs and cheese. Grains, most vegetables, fruits and nutsare acceptable.

The following should be AVOIDED

Animal-based proteinsMeats, poultry, seafood,Liver, kidney, heart, gizzard,

sweetbreads,

Meat extracts, yeast extract.

Vegetables Peas, beans, spinach, lentils.

Beverages Alcohol, beer, and beer products.

CALCIUM PYROPHOSPHATE DIHYDRATE


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CALCIUM PYROPHOSPHATE DIHYDRATEARTHROPATHY (PSEUDOGOUT)

CPPD deposition encompasses three overlapping conditions:(1) chondrocalcinosis the appearance of calcific material in articular cartilage andmenisci;(2)pseudogout a crystal-induced synovitis; and(3)chronic pyrophosphate arthropathy a type of degenerative joint disease.

Any one of these conditions may occur on its own or in any combination with theothers.

In contrast to classic gout, serum biochemistry shows no consistent abnormality.CPPD crystal deposition is known to occur in certain metabolic disorders (e.g.hyperparathyroidism and haemochromatosis) that cause a critical change in ioniccalcium and pyrophosphate equilibrium in cartilage. The rare familial forms ofchondrocalcinosisare probably due to a similar biochemical defect.

However, in the vast majority of cases chondrocalcinosis follows some local change inthe cartilage due to ageing, degeneration, enzymatic degradation or trauma.


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CPPD deposition

Demographics:

- It is predominantly a disease of the elderly, peak age 65 to75 years old. It has female predominance (F:M, 2-7:1).

- Prevalence of chondrocalcinosis is 5 to 8% in the generalpopulation.

Disease Associations: hyperthyroidsm, hypocalciuria,

hypercalcemia, hemochromatosis, hemosiderosis,hypophosphatasia, hypomagnesemia, hypothyroidsm,gout, neuropathic joints, amyloidosis, trauma and OA.


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CPPD deposition : Pathology

The incidence of CPPD arthropathy rises with increasing age; women are moreaffected and in some cases the disease runs in families .Pyrophosphate is probably generated in abnormal cartilage by enzyme activity atchondrocyte surfaces; it combines with calcium ions in the matrix where crystalnucleation occurs on collagen fibres. The crystals grow into microscopic tophi, whichappear as nests of amorphous material in the cartilage matrix.

Chondrocalcinosis is most pronounced in fibrocartilaginous structures(e.g. themenisci of the knee, triangular ligament of the wrist, pubic symphysis andintervertebral discs) but may also occur in hyaline articular cartilage, tendons and peri-articular soft tissues.From time to time CPPD crystals are extruded into the joint where they excite aninflammatory reaction similar to gout. The longstanding presence of CPPD crystals

also appears to influence the development of osteoarthritis in joints not usually proneto this condition (e.g. shoulders, elbows and ankles).Characteristically, there is a hypertrophic reaction with marked osteophyte formation.

Synovitis is more obvious than in ordinary osteoarthritis.


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CPPD deposition : Clinical features

The clinical disorder takes several forms, all of them appearingwith increasing frequency in relation to age.Asymptomatic chondrocalcinosisCalcification of the menisci is common in elderly people and is

usually asymptomatic. When it is seen in association withosteoarthritis, this does not necessarily imply cause and effect.Both are common in elderly people and they are bound to beseen together in some patients; x-rays may revealchondrocalcinosis in other, asymptomatic, joints.

Chondrocalcinosis in patients under 50 years of age shouldsuggest the possibility of an underlying metabolic disease or afamilial disorder.


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Acute synovitis (pseudogout)The patient, typically a middle-aged woman, complains of acute pain and swelling inone of the larger joints usually the knee.Sometimes the attack is precipitated by a minor illness or operation.The joint is tense and inflamed, though usually not as acutely as in gout. Untreated thecondition lasts for a few weeks and then subsides spontaneously.

X-rays may show signs of chondrocalcinosis, and the diagnosis can be confirmed by

findingpositively birefringent crystals in the synovial fluid.Chronic pyrophosphate arthropathyThe patient, usually an elderly woman, presents with polyarticular osteoarthritisaffecting the larger joints (hips, knees) and more helpfully unusual joints, such asthe ankles, shoulders, elbows and wristswhere osteoarthritis is seldom seen.There are the usual features of pain, stiffness, swelling, joint crepitus and loss ofmovement.It is often diagnosed, simply, as generalized osteoarthritis, but the x-ray features aredistinctive.Sometimes alternating bouts of acute synovitis and chronic arthritis may mimicrheumatoid disease.


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X-raysThe characteristic x-ray features arise from a combination of(1)intra-articular and peri-articular calcification,and (2) degenerative arthritis in distinctive sites.

Calcificationis usually seen in and around the knees, wrists, shoulders, hips, pubicsymphysis and intervertebral discs; it is often bilateral and symmetrical.In articular cartilage it appears as a thin line parallel to the joint. In thefibrocartilaginous menisci and discs it produces cloudy, irregular opacities.Less common sites are the joint synovium, capsule, ligaments, tendons and bursae.

Degenerative changes are similar to those of straightforward osteoarthritis butnotably involving unusual sites such as the non-weightbearing joints, the isolated

patellofemoral compartment in the knee and the talonavicular joint in the foot. Inadvanced cases joint destruction may be marked, with the formation of loose bodies.


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GOUT AND PSEUDOGOUT


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CPPD deposition : Diagnosis

Synovial fluid examinationCPPD crystals (Compensated polarised microscopy)

In pseudogout, CPP crystals appear shorter and often rhomboidal.

Positive birefringent

In gout, crystals of MSU appear as needle-shaped intracellular and extracellularcrystals. When examined with a polarizing filter, they are yellow when aligned

parallel to the axis of the red compensator, but they turn blue when aligned acrossthe direction of polarization (ie, they exhibit negative birefringence)

Turbid fluid

Blood stained

Radiographs

Chondrocalcinosis in hyaline and fibrocartilage (Occasionally capsule or ligament)with/ without structural changes of osteoarthritis


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Metabolic screening

For patients with

Early-onset CPPD deposition;


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THE ACUTE ATTACKPseudogout must be distinguished from other acute inflammatory disorders.

Acute gout usually occurs in men, and typically in smaller joints or in the olecranonbursa. The final word often lies with joint aspiration and identification of thecharacteristic crystals.

Post-traumatic haemarthrosis can be misleading; pseudogout is often precipitated by

trauma. A clear history and aspiration of blood-stained fluid will solve the problem.Septic arthritis must not be missed; a delay of 24 hours can mean the differencebetween successful and unsuccessful treatment. Systemic features are moreevident, but blood tests and joint aspiration are essential to clinch the diagnosis; jointfluid should be submitted with a request for both crystal analysis and bacteriologicalculture.

Reiters disease can start in a single large joint; always enquire about (and look for)signs of conjunctivitis, urethritis and colitis.


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CHRONIC CPPD ARTHROPATHYChronic pyrophosphate arthropathy usually affects multiple joints and it has to bedistinguished from other types of polyarticular arthritis.

Osteoarthritis and joint calcification are both common in older people; the twotogether do not necessarily make it a CPPD arthropathy.The distinctive x-ray features, and especially the involvement of unusual joints (the

elbow, wrist and ankle), point to a CPPD disorder rather than a simple concurrence oftwo common conditions.

Inflammatory polyarthritis usually involves the smaller joints as well, and systemicfeatures of inflammation are more marked.

Metabolic disorders such as hyperparathyroidism, haemochromatosis andalkaptonuria may be associated with calcification of articular cartilage andfibro cartilage as well as joint symptoms. It is important to exclude such generalizeddisorders before labelling a patient as just another case of chondrocalcinosis


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CPPD deposition : Treatment

The treatment ofpseudogout is the same as that of acutegout: rest and high-dosage anti-inflammatory therapy.

In elderly patients, joint aspiration and intra-articularcorticosteroid injection is the treatment of choice as thesepatients are more vulnerable to the side effects of non-steroidal anti-inflammatory drugs.

Chronic chondrocalcinosis appears to be irreversible.

Fortunately it usually causes few symptoms and littledisability. When it is associated withprogressive jointdegeneration the treatment is essentially that of advancedosteoarthritis.

BASIC CALCIUM PHOSPHATE


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BASIC CALCIUM PHOSPHATECRYSTAL DEPOSITION DISEASE

Basic calcium phosphate (BCP) is a normal component of bonemineral, in the form of calcium hydroxyapatite crystals. It also occursabnormally in dead or damaged tissue.Minute deposits in joints and periarticular tissues can give rise toeither an acute reaction (synovitis or tendinitis) or a chronic,destructive arthropathy.

Prolonged hypercalcaemia or hyperphosphataemia, of whatevercause, may result in widespread metastatic calcification.

However, by far the most common cause of BCP crystal deposition in

and around joints is local tissue damage strained or torn ligaments,tendon attrition and cartilage damage or degeneration.


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Basic calcium phosphate crystals

Types of crytals- Hydroxyapatite

- Tricalcium phosphate

- Octacalcium phosphate

Identification of crystals

- Very difficult to detect secondary to small size

- Non-birefringent chunks

- Stain positive with Alizarin red stain


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BCP DEPOSITION DISEASE: Pathology

The minute (less than 1 mm) BCP crystals are deposited around chondrocytes inarticular cartilageand in relatively avascular or damaged parts of tendons and ligaments most notablyaround the shoulder and knee.The deposits grow by crystal accretion and eventually may be detectable by x-ray in theperiarticular tendons or ligaments. Calcification of the posterior longitudinal ligamentof the cervical spine may also be associated with BCP crystal deposition.

Sometimes the calcific deposit has a creamy consistency but in longstanding cases it ismore like chalk.The mini-tophus may be completely inert, but in symptomatic cases it is surrounded byan acute vascular reaction and inflammation.Crystal shedding into joints may give rise to synovitis. More rarely this is complicated

by the development of a rapidly destructive, erosive arthritis.

Bits of articular cartilage and bone or fragments of a meniscus may be found in thesynovial cavity.


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BCP DEPOSITION DISEASE: Clinical features

Two clinical syndromes are associated with BCP crystal deposition:(1) an acute or subacute peri-arthritis; and(2) a chronic rapidly destructive arthritis.

ACUTE OR SUBACUTE PERI-ARTHRITISThis is by far the commonest form of BCP crystal deposition disorder affecting joints.The patient, usually an adult between 30 and 50 years, complains of pain close to oneof the larger joints most commonly the shoulder or the knee.Symptoms may start suddenly, perhaps after minor trauma, and rise to a crescendoduring which the tissues around the joint are swollen, warm and exquisitely tender

but tender near the joint in relation to a tendon or ligament, rather than in the joint.At other times the onset is more gradual and it is easier to localize the area oftenderness to one of the periarticular structures.Both forms of the condition are seen most commonly in rotator cuff lesions of theshoulder. Symptoms usually subside after a few weeks or months; sometimes they areaborted only when the calcific deposit is removed or the surrounding tissuesare decompressed.


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BCP DEPOSITION DISEASE: Clinical features

CHRONIC DESTRUCTIVE ARTHRITISBCP crystals are sometimes found in association with a chronicerosive arthritis; whether they cause the arthritis or modify a pre-existing disorder remains uncertain.

A more dramatic type of rapidly destructive arthritis of the shoulder isoccasionally seen in elderly patients with rotator cuff lesions.This was described in 1981 by McCarty and his colleagues fromMilwaukee and acquired the sobriquet Milwaukee shoulder.

Similar conditions affect the hip and knee. They have been attributedto BCP crystal (or mixed BCP and CPPD crystal) shedding into the

joint.


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Syndromes Associated with Hydroxyapatite

- Acute monoarthritis (pseudopseudogout)

- Acute calcific tendinitis, bursitis

- Scleroderma, dermatomyositis

- Heterotopic calcification- Milwaukee shoulder

- Crowned Dens Syndrome.

Acute Apatite Monoarthritis


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Acute Apatite Monoarthritis(Pseudopseudogout)

- Is usually aperi-arthritis.

- Intense inflammation (looks septic)

- Synovial fluid often non-inflammatory.

- Often causes podagra (especially in youngerwomen).

- Look for the tell-tale calcifications on

radiographs.


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Crowned Dens Syndrome

- Headache- Pain with head rotation

- Shoulder myalgias

-Very elevated sedimentation rate


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Milwaukee Shoulder

- Severe, destructive shoulder arthropathy.

- Seen in elderly females with DJD of shoulder.

- High-riding humeral head on radiographs (large

rotator cuff tear).- Non-inflammatory fluid with BCP crystals.- May effect other joints knees, hips and elbows


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BCP DEPOSITION DISEASE: X-rays

With peri-arthritis, calcification may be seen in tendons or ligamentsclose to the joint, most commonly in the rotator cuff around theshoulder.

Articular cartilage and fibrocartilaginous menisci and discs nevershow the type of calcification seen in CPPD deposition disease, but

loose bodies may be seen in synovial joints.

Erosive arthritis causes loss of the articular space, with little or nosclerosis or osteophyte formation.The typical picture of rapidly destructive arthritis is one of severe

erosion and destruction of subchondral bone.

In advanced cases the joint may become unstable and, eventually,dislocated.


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i i


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BCP DEPOSITION DISEASE: Investigations

There is little help from special investigations.Serum biochemistry is usually normal, except in thosepatients with hypercalcaemia or hyperphosphataemia.

Synovial fluid examination may reveal high counts ofpolymorphonuclear leucocytes, but this hardly servesto distinguish the condition from other types of subacutesynovitis.

BCP crystals are too small to be seen by light microscopybut can be identified by electron probe or transmissionelectron microscopy.

O O


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BCP DEPOSITION DISEASE: Treatment

Acute peri-arthritis should be treated by rest and nonsteroidal anti-inflammatory drugs.Resistant cases may respond to local injection of corticosteroids; thistreatment should be used only to weather the acute storm repeatedinjections for lesser pain may dampen the repair process in damagedtendons or ligaments and thus predispose to recurrent attacks.

Persistent pain and tenderness may call for operative removal of thecalcific deposit or decompression of the affected tendon or ligament.

Erosive arthritis is treated like osteoarthritis. However, rapidly

progressive bone destruction calls for early operation: in the case ofthe shoulder, synovectomy and soft-tissue repair; for the hip, usuallytotal joint replacement.

S id C l A h i i


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Steroid Crystal Arthritis

- Iatrogenic crystal arthritis.- Starts several hours after intra-articular steroidinjection.

- Septic arthritis usually takes longer.- Usually short-lived.

- Ice it; may drain it, but dont operate on it.

R f


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References

ApleysSystem of Orthopaedics and Fractures 9thEdition Color Atlas of Clinical Orthopedics by Mikls Szendri & FranklinH. Sim

Moritz and Dave DycksRounds

Web Sites:

American College of Rheumatology

://www.thegoutacademy.comhttp

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Wikipedia
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