GOUT GOUT && PSEUDOGOUTPSEUDOGOUT
OPSC 2018OPSC 2018HOWARD L. FEINBERG, D.O., F.A.C.O.I.., F.A.C.R.HOWARD L. FEINBERG, D.O., F.A.C.O.I.., F.A.C.R.
““Everything in excess Everything in excess is opposed by natureis opposed by nature””
““Eunuchs do not take Eunuchs do not take the gout, nor become the gout, nor become bald.bald.””
GOUTGOUT
Hyperuricemia is not Hyperuricemia is not goutgout
Gout typically follows Gout typically follows years of years of asymptomatic asymptomatic hyperuricemiahyperuricemia
Serum urate Serum urate increased by alcohol, increased by alcohol, height, body weight, height, body weight, age, blood pressure, age, blood pressure, BUN, creatnineBUN, creatnine
13.6/1000 in men13.6/1000 in men
6.4/1000 in women6.4/1000 in women
estrogen causes estrogen causes increased uric acid increased uric acid excretionexcretion
Gout Diagnostic CriteriaGout Diagnostic Criteria
Step 1: Entry CriteriaStep 1: Entry Criteria•• Acute pain and swelling in at least one Acute pain and swelling in at least one
peripheral joint or bursaperipheral joint or bursa
Step 2: Sufficient CriteriaStep 2: Sufficient Criteria•• MSU Crystals in symptomatic joint or tophiMSU Crystals in symptomatic joint or tophi
Step 3: Criteria if Step 2 not metStep 3: Criteria if Step 2 not met
Gout Diagnostic CriteriaGout Diagnostic Criteria
Joint Joint
•• Ankle 1 pointAnkle 1 point
•• MTP 2 pointsMTP 2 points
Redness, CanRedness, Can’’t bear touch, Cant bear touch, Can’’t t walkwalk
•• 1 item 1 point1 item 1 point
•• 2 items 2 points2 items 2 points
•• 3 items 3 points3 items 3 points
Tophus 4 pointsTophus 4 points
Neg. MSU Neg. MSU -- 2 points2 points
ImagingImaging
•• DECT or Ultrasound 4 pointsDECT or Ultrasound 4 points
•• Conventional 4 pointsConventional 4 points
Time to maximal pain <24h, Lasts Time to maximal pain <24h, Lasts less than 14 days, resolves less than 14 days, resolves completely between episodescompletely between episodes
•• 1 episode 1 point1 episode 1 point
•• 2 or more episodes 2 points2 or more episodes 2 points
Serum UrateSerum Urate
•• <4 <4 -- 4 points4 points
•• 66--8 2 points8 2 points
•• 88--10 3 points10 3 points
•• >10 4 points>10 4 points
Gout Diagnostic CriteriaGout Diagnostic Criteria
78% with clinical criteria only78% with clinical criteria only
89% with clinical and x89% with clinical and x--ray criteriaray criteria
Score of 8 required for diagnosisScore of 8 required for diagnosis
Definitive diagnosis Definitive diagnosis –– MSU crystals in MSU crystals in synovial fluid or tophisynovial fluid or tophi
ASSOCIATED CONDITIONSASSOCIATED CONDITIONS
ObesityObesity
EthanolEthanol
Diabetes MellitusDiabetes Mellitus
HypertriglyceridemiaHypertriglyceridemia
HypertensionHypertension
HypothyroidisimHypothyroidisim
AtherosclerosisAtherosclerosis
Syndrome XSyndrome X
PregnancyPregnancy
Acute IllnessAcute Illness
DehydrationDehydration
NEGATIVE ASSOCIATIONSNEGATIVE ASSOCIATIONS
Rheumatoid ArthritisRheumatoid Arthritis
SLESLE
Ankylosing SpondylitisAnkylosing Spondylitis
CLINICALCLINICAL Asymptomatic HyperuricemiaAsymptomatic Hyperuricemia
Acute GoutAcute Gout
Intercurrent PeriodIntercurrent Period
Acute GoutAcute Gout
Chronic GoutChronic Gout
PRESENTATIONPRESENTATION
PATHOLOGYPATHOLOGY
Monosodium Urate Monosodium Urate Crystals are formed Crystals are formed when the bodies when the bodies capacity to store uric capacity to store uric acid is surpassedacid is surpassed
Uric acid is a Uric acid is a byproduct of purine byproduct of purine metabolismmetabolism
Serum saturation Serum saturation 6.7mg/dl 6.7mg/dl
TOPHITOPHI
RADIOGRAPHIC FINDINGSRADIOGRAPHIC FINDINGS
GOUT ULTRASOUNDGOUT ULTRASOUND
DECT (DUAL ENERGY CT SCAN)DECT (DUAL ENERGY CT SCAN)
Primary HyperuricemiaPrimary Hyperuricemia
Underexcretion Underexcretion -- 90%90%•• IdiopathicIdiopathic
Overproduction Overproduction -- 10%10%•• HGPRT deficiency HGPRT deficiency
(hypoxanthine Guanine (hypoxanthine Guanine Phosphoribosyltransferase Phosphoribosyltransferase Deficiency)Deficiency)
•• PRPP Synthetase PRPP Synthetase SuperactivitySuperactivity
•• GG--66--PP--D DeficiencyD Deficiency
•• FructoseFructose--11--Phosphate Phosphate Aldolase DeficiencyAldolase Deficiency
SECONDARY HYPERURICEMIASECONDARY HYPERURICEMIA
Hyperuricemia which occurs as a result of Hyperuricemia which occurs as a result of a drug effect or is secondary to another a drug effect or is secondary to another diseasedisease
OVERPRODUCTIONOVERPRODUCTION
DietDiet
Myeloproliferative Myeloproliferative DisordersDisorders
Lymphoproliferative Lymphoproliferative DisordersDisorders
Accelerated ATP Accelerated ATP DegradationDegradation
Glycogen Storage Glycogen Storage Disease (type I, III, V, Disease (type I, III, V, VII)VII)
Severe Muscle Severe Muscle ExertionExertion
Hemolytic DiseaseHemolytic Disease
PsoriasisPsoriasis
GG--66--PD DeficiencyPD Deficiency
FructoseFructose--11--Phosphate Phosphate Aldolase DeficiencyAldolase Deficiency
HGPRT DeficiencyHGPRT Deficiency
Under ExcretionUnder ExcretionKnown MechanismKnown Mechanism
•• inhibition of tubular inhibition of tubular urate secretion (DKA, urate secretion (DKA, lactic acidosis, Maple lactic acidosis, Maple Syrup Urine Disease, Syrup Urine Disease, Alcoholic Ketosis)Alcoholic Ketosis)
•• enhanced tubular enhanced tubular reabsorbtion reabsorbtion (dehydration, (dehydration, diuretics)diuretics)
Unknown MechanismUnknown Mechanism•• HypertensionHypertension
•• LeadLead
•• HyperparathyroidHyperparathyroid
•• DrugsDrugs–– CyclosporineCyclosporine
–– ASAASA
–– EthambutolEthambutol
–– PyrazidamidePyrazidamide
–– EthanolEthanol
–– Nicotinic AcidNicotinic Acid
Combined Overproduction Combined Overproduction & Underexcretion& Underexcretion Glucose Glucose -- 66-- Phosphatase DeficiencyPhosphatase Deficiency
Fructose Fructose --11--phosphate aldolase deficiencyphosphate aldolase deficiency
INDICATIONS FOR TREATMENTINDICATIONS FOR TREATMENT
Acute GoutAcute Gout
TophiTophi
Uric Acid StonesUric Acid Stones
Uric Acid NephropathyUric Acid Nephropathy
Interstitial NephritisInterstitial Nephritis
TREATMENT GOALSTREATMENT GOALS Stop acute attacksStop acute attacks
Resolve TophiResolve Tophi
Prevent joint damagePrevent joint damage
Decrease uric acid below 6.0Decrease uric acid below 6.0
TREATMENTTREATMENT
AcuteAcute•• colchicinecolchicine
•• IndomethacinIndomethacin
•• Other NSAIDOther NSAID
•• SteroidSteroid
•• Pain MedicationPain Medication
•• ACTHACTH
•• Joint InjectionJoint Injection
Chronic Chronic •• AllopurinolAllopurinol
•• Febuxostat (Uloric)Febuxostat (Uloric)
•• ProbenecidProbenecid
•• SulfinpyrazoneSulfinpyrazone
•• NSAIDNSAID
•• ColchicineColchicine
•• Pegloticase Pegloticase
(Krystexxa)(Krystexxa)
CALCIUM PYROPHOSPHATECALCIUM PYROPHOSPHATE
Common name PseudogoutCommon name Pseudogout
Occurs exclusively in and around jointsOccurs exclusively in and around joints
May be asymptomatic or cause diseaseMay be asymptomatic or cause disease
CLINICAL PRESENTATIONSCLINICAL PRESENTATIONS
AcuteAcute•• similar to goutsimilar to gout
•• may have fever, leukocytosis, elevated ESRmay have fever, leukocytosis, elevated ESR
ChronicChronic•• similar to OAsimilar to OA
•• symmetricalsymmetrical
•• mainly in knees, wrists, hipsmainly in knees, wrists, hips
•• isolated patellofemoral diseaseisolated patellofemoral disease
CLINICAL PRESENTATIONSCLINICAL PRESENTATIONS
PolyarticularPolyarticular--may mimic Rheumatoid may mimic Rheumatoid ArthritisArthritis
OligoarticularOligoarticular--usually elderlyusually elderly
Pyrophosphate ArthropathyPyrophosphate Arthropathy•• EarlyEarly--mimics Osteoarthritismimics Osteoarthritis
•• LateLate--Charcot JointCharcot Joint
Precocious OsteoarthritisPrecocious Osteoarthritis
CHONDROCALCINOSISCHONDROCALCINOSIS
Rheumatoid 5%Rheumatoid 5%•• 10% RF positive10% RF positive
Gout 25%Gout 25%
OA 50%OA 50%
Asymptomatic 20%Asymptomatic 20%
Present inPresent in•• 4% of adult population4% of adult population
•• 50% over age 9050% over age 90
EPIDEMIOLOGYEPIDEMIOLOGY Hereditary Hereditary --
autosomal autosomal dominantdominant
Post TraumaticPost Traumatic
SporadicSporadic--rare rare under age 40under age 40
OsteochondroOsteochondro-- dysplasiadysplasia
22o o To Metabolic To Metabolic DiseaseDisease
•• hemachromatosishemachromatosis
•• hyperparathyroidhyperparathyroid
•• hypothyroidhypothyroid
•• amyloidamyloid
•• hypomagnesemiahypomagnesemia
•• hypophosphatemiahypophosphatemia
•• RicketsRickets
•• Familial hypocalcuric Familial hypocalcuric hypocalcemiahypocalcemia
RADIOGRAPHIC FINDINGSRADIOGRAPHIC FINDINGS
ChondrocalcinosisChondrocalcinosis
Crowned DensCrowned Dens•• neck pain due to neck pain due to
crystal deposits crystal deposits surrounding denssurrounding dens
Cord compressionCord compression Wrap Around PatellaWrap Around Patella
Erosive OAErosive OA
DIAGNOSISDIAGNOSISDefiniteDefinite
•• Calcium pyrophosphate crystals in jointCalcium pyrophosphate crystals in joint
ProbableProbable•• Other calcium crystals in jointOther calcium crystals in joint
PossiblePossible•• Diagnostic CriteriaDiagnostic Criteria
CALCIUM PYROPHOSPHATECALCIUM PYROPHOSPHATE
PATHOLOGYPATHOLOGY
Normal serum phosphateNormal serum phosphate
Normal phosphate excretionNormal phosphate excretion
Elevated levels of inorganic Elevated levels of inorganic phosphate in synovial fluidphosphate in synovial fluid
Cause Cause -- NTPPPHaseNTPPPHase (Nucleoside (Nucleoside triphosphatetriphosphate pyrophosphohydrolasepyrophosphohydrolase))
TREATMENTTREATMENT
NSAIDNSAID
ColchicineColchicine
Steroids Steroids
Physical TherapyPhysical Therapy
SurgerySurgery
Joint InjectionsJoint Injections
APATITE APATITE --LIKE CRYSTALSLIKE CRYSTALS
Carbonate substituted apatiteCarbonate substituted apatite
OctacalciumOctacalcium Phosphate (OCP)Phosphate (OCP)
TricalciumTricalcium phosphate (TCP)phosphate (TCP)
DicalciumDicalcium phosphate phosphate dihydratedihydrate ((brushitebrushite))
APATITE APATITE -- LIKE DISEASELIKE DISEASE
BursitisBursitis
TendonitisTendonitis
ArthritisArthritis
Renal FailureRenal Failure
epiphysealepiphyseal dysplasiadysplasia
destructive OAdestructive OA
Crystals not visible Crystals not visible on microscopyon microscopy
AlizarenAlizaren RedRed--stain stain redred
von von KossaKossa--stain stain blackblack
precise ID requires precise ID requires xx--ray diffractionray diffraction
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