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