Calcium containing crystalsCalcium containing crystals
Major manifestationsMajor manifestationsAcute periarthritisAcute periarthritisDestructive arthropathyDestructive arthropathyTissue deposits mimicking tumor like massesTissue deposits mimicking tumor like masses
Types of crystalsTypes of crystalsCalcium pyrophosphate dihydrateCalcium pyrophosphate dihydrateBasic calcium phosphateBasic calcium phosphate
CPPDCPPD
Chondrocalcinosis Chondrocalcinosis Pyrophosphate arthropathy Pyrophosphate arthropathy
CPPDCPPD
Precipitation of crystals of calcium Precipitation of crystals of calcium pyrophosphate dihydrate (CPPD) in pyrophosphate dihydrate (CPPD) in connective tissuesconnective tissues
Ca2P207.2H20Ca2P207.2H20CPPD formation appears restricted CPPD formation appears restricted
principally to fibro- and hyaline cartilage, principally to fibro- and hyaline cartilage, less commonly capsule or tendon less commonly capsule or tendon
EPIDEMIOLOGY EPIDEMIOLOGY
Chondrocalcinosis increases with age Chondrocalcinosis increases with age from the from the 6th decade6th decade and shows and shows femalefemale preponderance . preponderance .
The strong association with The strong association with osteoarthritis (OA)osteoarthritis (OA) and and Joint traumaJoint trauma and and agingaging
PREVALENCEPREVALENCE
65 to 74 years old— 15 percent 65 to 74 years old— 15 percent 75 to 84 years old — 36 percent 75 to 84 years old — 36 percent >84 years old— almost 50 percent >84 years old— almost 50 percent
NTPPPH = Nucleoside triphosphate NTPPPH = Nucleoside triphosphate pyrophosphohydrolasepyrophosphohydrolase
NTPase = ( one kind of NTPPPH) is a NTPase = ( one kind of NTPPPH) is a ectoenzymeectoenzyme
NTP PPi CCPD NTP PPi CCPD productionproduction
(ATP)
NTPaseNTPPPH supersaturation
Metabolism of PPi and formation of CPPD crystals in haemochromatosis (1) and hypomagnesaemia (2).
Wright G D , Doherty M Ann Rheum Dis 1997;56:586-588
©1997 by BMJ Publishing Group Ltd and European League Against Rheumatism
Crystal formationCrystal formation Crystal formation may reflect elevated levels of Crystal formation may reflect elevated levels of
either either calciumcalcium or or pyrophosphatpyrophosphatee (PPi), (PPi), matrixmatrix changeschanges that enhance local CaPPi that enhance local CaPPi supersaturation, supersaturation, NTPPPH overactivityNTPPPH overactivity or a or a combination of these factors. combination of these factors.
A close association is reported with hypertrophic A close association is reported with hypertrophic or metaplastic chondrocytes, the surrounding or metaplastic chondrocytes, the surrounding matrixmatrix often being proteoglycan depleted and often being proteoglycan depleted and degenerative. degenerative.
Site of crystal formationSite of crystal formation
CPPD crystals form in peri-cellular sites,in CPPD crystals form in peri-cellular sites,in the mid-zone of fibro- and hyaline the mid-zone of fibro- and hyaline cartilagecartilage
Inhibitor of CPPD depositionInhibitor of CPPD deposition
Local MgLocal MgProteoglycanProteoglycanAlkalinphosphatase Alkalinphosphatase 5´ nucleotidase5´ nucleotidase
Promoting factor for crystal Promoting factor for crystal formationformation
IronIronCalciumCalciumPhospholipidPhospholipidCopperCopperPTH promotion of PP synthtesisPTH promotion of PP synthtesisOther crystalsOther crystals
Metabolic diseases predisposing to Metabolic diseases predisposing to CPPDCPPD
DefiniteDefinite HyperparathyroidismHyperparathyroidism Haemochromatosis Haemochromatosis HypophosphatasiaHypophosphatasia HypomagnesaemiaHypomagnesaemia Wilson's diseaseWilson's disease HypothyroidismHypothyroidism
ProbableProbable GoutGout Ochronosis Ochronosis joint injection of joint injection of
hyaluronate hyaluronate X-linked X-linked
hypophosphatemic hypophosphatemic ricketsrickets
familial hypocalciuric familial hypocalciuric hypercalcemia hypercalcemia
Clinical manifestationsClinical manifestations
Acute pseudo-goutAcute pseudo-goutMay rarely present asMay rarely present as
Pseudo-rheumatoidPseudo-rheumatoidPseudo-ankylosing spondylitisPseudo-ankylosing spondylitisPseudo-neuropathic arthropathyPseudo-neuropathic arthropathy
Secondary osteoarthritisSecondary osteoarthritisChondrocalcinosisChondrocalcinosisTenosynovitisTenosynovitis
Acute peudogoutAcute peudogout
CPPD crystal induced synovitis – clinically CPPD crystal induced synovitis – clinically resembles goutresembles gout
Precipitated by trauma, surgery or severe Precipitated by trauma, surgery or severe medical illnessmedical illness
Acute attacks are usually self-limiting and Acute attacks are usually self-limiting and resolve within one to three weeks resolve within one to three weeks
Fever is common, mildly confusedFever is common, mildly confused Knee – most common jointKnee – most common joint Coexistence of urate and CPPD crystals in a Coexistence of urate and CPPD crystals in a
single inflammatory effusion is not uncommonsingle inflammatory effusion is not uncommon
Acute CPPDAcute CPPD
Acute pseudogout Acute pseudogout
CPPD crystalsCPPD crystals
Detected by compensated polarized light Detected by compensated polarized light microscopymicroscopyPositively (but weakly) birefringentPositively (but weakly) birefringentRhomboid shapedRhomboid shapedMore difficult to detectMore difficult to detectSmaller and more polymorphicSmaller and more polymorphic
A faintly yellow, positively birefringent, rhomboidal, intracellular crystal characteristic of calcium pyrophosphate dihydrate (CPPD) is seen in the
synovial fluid of a patient with pseudogout, when viewed with compensated, polarized microscopy.
CPPD crystal CPPD crystal
triggers of acute pseudogouttriggers of acute pseudogout
TraumaTrauma Intercurrent medical illnessIntercurrent medical illnessSurgerySurgeryBlood transfusion/parenteral fluid Blood transfusion/parenteral fluid
administrationadministration
AutoremissionAutoremission
PhagocytosisPhagocytosis and dissolution of crystals and dissolution of crystals may play a role. may play a role.
Adhesion of components of Adhesion of components of extracellular extracellular fluid or plasma to crystals may decrease fluid or plasma to crystals may decrease their inflammatory potential. their inflammatory potential.
Familial ChondrocalcinosisFamilial Chondrocalcinosis
Autosomal dominant diseaseAutosomal dominant disease
Clinical disease occurs early in lifeClinical disease occurs early in life
Associated with ANKH gene mutationAssociated with ANKH gene mutationTransmembrane protein involved in Transmembrane protein involved in
pyrophosphate transportpyrophosphate transport
Chronic pyrophosphate arthropathyChronic pyrophosphate arthropathy elderly and female.elderly and female. Asymptomatic radiographic finding of Asymptomatic radiographic finding of
calcification of articular or fibrocartilage.calcification of articular or fibrocartilage.
Charactristic site of CPPD depositionCharactristic site of CPPD deposition
¤ Lateral & medial meninscus in knee jointLateral & medial meninscus in knee joint
((most commonmost common))
¤ Acetabular labrum in hipAcetabular labrum in hip
¤ Fibrocartilageinous Symphysis pubisFibrocartilageinous Symphysis pubis
¤ articular disc of wristarticular disc of wrist
¤ Anulus fibrous of intervertebral discsAnulus fibrous of intervertebral discs
X Ray findingX Ray finding
Normal wristNormal wrist
Axial presentations Axial presentations
'pseudo-ankylosing spondylitis' 'pseudo-ankylosing spondylitis' acute self-limiting meningitic episodes may acute self-limiting meningitic episodes may
relate to CPPD deposition in degenerative relate to CPPD deposition in degenerative ligamenta flava and cervical discsligamenta flava and cervical discs
SpineSpine
Crowned dens syndrome Crowned dens syndrome
Odontoid erosion Odontoid erosion
Pseudo - osteoarthritisPseudo - osteoarthritis
Consider CPPD Consider CPPD disease when O.A disease when O.A occurs in joints not occurs in joints not commonly affected in commonly affected in primary O.Aprimary O.A
Wrist, MCP joints, Wrist, MCP joints, shoulders and elbowsshoulders and elbows
CPPDCPPD
CPPDCPPD
Chronic pyrophosphate arthropathy Chronic pyrophosphate arthropathy DD with OADD with OA
the site of predominant involvement the site of predominant involvement (wrists, shoulders, ankles and elbows are (wrists, shoulders, ankles and elbows are uncommonly affected in OA) uncommonly affected in OA)
the often marked inflammatory component the often marked inflammatory component superimposition of acute attacks superimposition of acute attacks
CPPD disease treatmentCPPD disease treatment
Acute pseudo-goutAcute pseudo-goutNSAIDs , colchicine, I.A steroid injectionNSAIDs , colchicine, I.A steroid injectionProphylaxis with colchicine 0.6mg P.O bidProphylaxis with colchicine 0.6mg P.O bid
Chronic and progressive CPPD crystal Chronic and progressive CPPD crystal depositiondepositionNo effective treatmentNo effective treatmentProbenecid is being investigatedProbenecid is being investigated
Basic calcium phosphate Basic calcium phosphate crystalscrystals
Types of crytalsTypes of crytals HydroxyapatiteHydroxyapatite Tricalcium phosphateTricalcium phosphate Octacalcium phosphateOctacalcium phosphate
Identification of crystalsIdentification of crystals Very difficult to detect secondary to small sizeVery difficult to detect secondary to small size Non-birefringent chunksNon-birefringent chunks Stain positive with Alizarin red stainStain positive with Alizarin red stain
BCP crystal deposition diseaseBCP crystal deposition disease
Acute calcific periarthritisAcute calcific periarthritisDestructive arthropathyDestructive arthropathyOsteoarthritisOsteoarthritisSoft tissue calcificationSoft tissue calcification
Acute calcific periarthritisAcute calcific periarthritis
Hydroxyapatite Hydroxyapatite
Hydroxyapatite Hydroxyapatite
HydroxyapatiteHydroxyapatite
Hydroxyapatite Hydroxyapatite
Destructive arthropathyDestructive arthropathy
Milwaukee shoulder syndromeMilwaukee shoulder syndromeBCP crystal associated joint degenerationBCP crystal associated joint degenerationMassive joint effusions – usually bloodyMassive joint effusions – usually bloodyMay effect other joints – knees, hips and May effect other joints – knees, hips and
elbowselbows
Milwaukee shoulder Milwaukee shoulder
BCP crystals and OABCP crystals and OA
Calcium crystals are very common in O.A Calcium crystals are very common in O.A joints ( in contrast rarely found in R.A )joints ( in contrast rarely found in R.A )
Data support a causative roleData support a causative rolePresence correlates strongly with severity of Presence correlates strongly with severity of
radiographic O.Aradiographic O.A
BCP crystal deposition in other BCP crystal deposition in other diseasedisease
AtherosclerosisAtherosclerosisHydroxyapatite is the major constituentHydroxyapatite is the major constituentPositive correlation between coronary artery Positive correlation between coronary artery
calcification and cardiovascular eventscalcification and cardiovascular eventsBreast cancerBreast cancer
Mammary microcalcifications is a diagnostic Mammary microcalcifications is a diagnostic marker of breast cancermarker of breast cancer
BCP crystals augment mitogenesis in breast BCP crystals augment mitogenesis in breast cancer cell linescancer cell lines
Potential treatment optionsPotential treatment options
PhosphocitratePhosphocitrate Inhibits BCP and CPPD crystal formationInhibits BCP and CPPD crystal formationBlocks degeneration promoting effects of Blocks degeneration promoting effects of
crystalscrystalsBisphosphonateBisphosphonate
High dose etidronateHigh dose etidronate