Dr. Anupam MahajanDr. Anupam MahajanDept. of OrthopaedicsDept. of OrthopaedicsChristian Medical CollegeChristian Medical College

A group of conditions characterized A group of conditions characterized by the presence of crystals in and by the presence of crystals in and around joints, bursae and tendons.around joints, bursae and tendons.– GoutGout– Calcium pyrophosphate dihydrate Calcium pyrophosphate dihydrate

(CPPD) deposition disease(CPPD) deposition disease– Calcium Hydroxyapatite (HA) deposition Calcium Hydroxyapatite (HA) deposition

disorderdisorder

Crystal Deposition

Inert and Asymptomatic

Acute Inflammatory Reaction

Chronic Destruction

GOUTGOUT

DEFINITIONDEFINITION

A Group of disorders of Purine metabolism A Group of disorders of Purine metabolism characterized bycharacterized by– Hyperuricemia Hyperuricemia – Deposition of monosodium urate monohydrate Deposition of monosodium urate monohydrate

crystals in joints and periarticular tissuescrystals in joints and periarticular tissues– Recurrent attacks of acute synovitis, typically Recurrent attacks of acute synovitis, typically

monoarticularmonoarticular– Chronic destruction of cartilageChronic destruction of cartilage– Interstitial deposition of urate crystals in renal Interstitial deposition of urate crystals in renal

prenchyma – Urate nephropathyprenchyma – Urate nephropathy– UrolithiasisUrolithiasis

Chronic hyperuricemia is Chronic hyperuricemia is necessary but not sufficient necessary but not sufficient for the development of goutfor the development of gout

CLASSIFICATIONCLASSIFICATION Primary gout (95%)

– most commonly due to hyperuricemia due to under-excretion of uric acid (eg. Lesch-Nyhan syndrome, excess PRPP, decreased excretion, G6P deficiency)

Secondary gout (5%)– either defective renal excretion - CRF– overproduction of uric acid (eg.

Myeloproliferative disorders, diuretics, deficiency of HGPRT)

– defective regulation of purine biosynthesis

DISTRIBUTIONDISTRIBUTION Prevalence: 1 – 10/1000 depending on Prevalence: 1 – 10/1000 depending on

age, race and sex of population studied age, race and sex of population studied Gender:Gender:

– Most common in middle age menMost common in middle age men– Seen in up to 10% of malesSeen in up to 10% of males– Common in post menopausal womenCommon in post menopausal women

Geographic:Geographic:– New ZealandersNew Zealanders– MaorisMaoris– Pacific IslandersPacific Islanders

Age: More severe if first experience before Age: More severe if first experience before 30 years old30 years old

Genetic: Runs in familiesGenetic: Runs in families

BIOCHEMISTRYBIOCHEMISTRYGMP Inosinic Acid AMP

PRPP

Guanosine Inosine Adenosine Adenine

PRPP PHOSPHORYLASEHGPRT

Guanine HypoxanthineXanthine oxidase (Allopurinol)

XanthineXanthine oxidase (Allopurinol)

Uric Acid

Urine

AETIOPATHOGENESISAETIOPATHOGENESISOverproduction (5%)Overproduction (5%) Underexcretion Underexcretion

(95%)(95%)

HyperuricemiaHyperuricemia

Predisposing factorsPredisposing factors TriggersTriggers

Urate crystal deposition in joints and connective tissues Urate crystal deposition in joints and connective tissues

Acute inflammatory reactionAcute inflammatory reaction

Chronic inflammation and joint destruction, Chronic inflammation and joint destruction, tophaceous ulcerationstophaceous ulcerations

PREDISPOSITIONPREDISPOSITION Genetic predisposition Cancers and blood disorders Alcohol abuse Obesity Hypothyroidism High intake of purine containing food Lead poisoning (moonshine whisky) Radiation treatment Age Duration of hyperuricemia Starvation Renal failure Pharmacologic agents (thiazides, cyclosporine,

pyrazinamide, ethamburol, nicotinic acid, warfarin, low dose salicylates)

TRIGGERSTRIGGERS Injury

Surgery

Consumption of large quantities of alcohol

Consumption of large quantities of purine rich foods

Fatigue

Emotional stress

Illness

SIGNS AND SYMPTOMSSIGNS AND SYMPTOMS

Usually men over 30 yrs of ageUsually men over 30 yrs of age Family history +Family history + Stereotype - Obese, rubicund, Stereotype - Obese, rubicund,

hypertensive and fond of alcoholhypertensive and fond of alcohol Uncontrolled use of diuretics or Uncontrolled use of diuretics or

aspirinaspirin

SIGNS AND SYMPTOMSSIGNS AND SYMPTOMS 1-2 joints affected at a time

Cooler joints affect more commonly because urate crystals form at cool temperatures

Podagra, or pain in the first metatarsophalangeal joint, is the classic presentation

Common Joints: Ball of big toeFeet AnklesWrist Elbow

Rare Joints: Spine HipsShoulders

CLINICAL PRESENTATIONCLINICAL PRESENTATION Asymptomatic hyperuricemia:

– Uric acid levels >8mg/dl in men; >7mg/dl in women– Not actively treated

Acute Gouty arthritis: – Painful attack in single joint– Uric acid levels normal in 30% of pts– If elevated uric acid, do not initially manipulate

Chronic Gouty arthritis:– Joint deformity– Lower Uric acid levels if frequent arthritic attacks, renal

damage or consistent elevated levels

ACUTE:– Suddenly appears in 12-24 hour,

lasts for a week or two and resolves completely

– Usually occurs overnight (bc metabolic changes)

– Skin: red-purplish, tight and shiny– Joint: painful, swelling, warm– Recurrent attacks develop– Fever– Chills– General sick feeling– Rapid heartbeat

CHRONIC: – Progressive joint damage– More frequent attacks– Crippling deformity– Disability– Restricted joint motion– Hard lumps of urate crystals (tophi) in:

Synovium Bone – olecranon Skin around joint pinna Kidney Achilles tendon Elbows

* Tophi may shrink slowly with decreasing uric acid levels

* Large tophi may be surgically removed

CHRONIC PRESENTATION:

Tophi

Podagra

RENAL RENAL MANIFESTATIONSMANIFESTATIONS

NEPHROLITHIASISNEPHROLITHIASIS– Related directly to the serum and urinary uric acid levels Related directly to the serum and urinary uric acid levels

– 50% in UA > 13 mg/dl– 50% in UA > 13 mg/dl– Not all stones are of uric acid only. oxalates, phosphates Not all stones are of uric acid only. oxalates, phosphates

and combinations can occurand combinations can occur– Can be the only manifestationCan be the only manifestation

URATE NEPHROPATHYURATE NEPHROPATHY– Late manifestation of severe goutLate manifestation of severe gout– Deposition of urate crystals in medulla and pyramids – Deposition of urate crystals in medulla and pyramids –

CRFCRF URIC ACID NEPHROPATHYURIC ACID NEPHROPATHY

– Reversible cause of acute renal failure Reversible cause of acute renal failure – Due to precipitation of uric acid in renal tubules and Due to precipitation of uric acid in renal tubules and

collecting ducts – obstruction of urinecollecting ducts – obstruction of urine– 24 hr urinary Uric acid : creatinine > 1 24 hr urinary Uric acid : creatinine > 1

DIAGNOSISDIAGNOSIS Distinctive symptoms Examination of the joint Laboratory results:

– High serum uric acid levels (may be NL w/acute attack)

– Increased serum white blood cells– High 24 hour urinary uric acid

Joint aspiration (tophus or fluid):– Negatively birefringent needle-shaped urate

crystals X-ray:

– Joint damage – Tophi that displaces the bone and produces

cysts

Crystals of sodium urate that can be visualized under polarized light and seen as intensely birefringent needle-like crystals intra- and extracellularly.

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 across the direction of polarization (ie, they exhibit negative birefringence).

Imaging StudiesImaging Studies RadiographsRadiographs

– Patients with new onset Patients with new onset of acute gout usually of acute gout usually have no radiographic have no radiographic findings.findings.

– Radiographic lesions of Radiographic lesions of chronic gout may chronic gout may appear as rat-bitten, appear as rat-bitten, sclerotic regions on the sclerotic regions on the joint surfaces, with joint surfaces, with overhanging marginsoverhanging margins

Gout in handGout in hand

Bone scan reveals increased Bone scan reveals increased nuclide nuclide

concentration at affected sites.concentration at affected sites.

Magnetic resonance imagingMagnetic resonance imaging

– Magnetic resonance imaging (MRI) Magnetic resonance imaging (MRI) is capable of detecting deposits of is capable of detecting deposits of crystals .crystals .

– Is very useful in determining the Is very useful in determining the extent of the disease extent of the disease

– It is recommended that MRI It is recommended that MRI studies be done with gadolinium studies be done with gadolinium to evaluate any tendon sheath to evaluate any tendon sheath involvement and to evaluate for involvement and to evaluate for osteomyelitis in the differential.osteomyelitis in the differential.

– Large deposits of crystals may Large deposits of crystals may be seen in bursae or ligaments. be seen in bursae or ligaments. Tophi usually are low or Tophi usually are low or intermediate signal intensity on intermediate signal intensity on T1-weighted images.T1-weighted images.

Diagnostic CriteriaDiagnostic Criteria††

Acute Gout StudyAcute Gout StudyA)The presence of characteristic urate crystals in the

joint fluid (if at past attack then C1 and C4 also)

Or

B) A tophus proved to contain urate crystals by chemical or polarized light microscope and C1 and C4.

Or

C) Presence of 6 of the following 12 clinical, laboratory, and X-ray phenomenon:

1) Maximum inflammation developed 1) Maximum inflammation developed within 1 daywithin 1 day

2) More than 1 attack of acute arthritis2) More than 1 attack of acute arthritis

3) Presents with monoarticular 3) Presents with monoarticular arthritisarthritis

4) Redness is observed over the 4) Redness is observed over the affected joint(s)affected joint(s)

5) First metatarsophalangeal pain or 5) First metatarsophalangeal pain or swelling swelling

6) Unilateral first metatarsophalangeal 6) Unilateral first metatarsophalangeal joint attackjoint attack

7) Unilateral tarsal joint attack7) Unilateral tarsal joint attack

8) Tophus is suspected8) Tophus is suspected

9) Hyperuricemia9) Hyperuricemia

10) Asymmetric swelling within a 10) Asymmetric swelling within a jointjoint

11) Subcortical cysts without 11) Subcortical cysts without erosions on X-rayerosions on X-ray

12) Joint fluid culture negative for 12) Joint fluid culture negative for organismsorganisms

TREATMENTTREATMENT Diet: Reduce foods high in purines

Decrease alcohol intakeIncrease water consumption

Weight loss

Adjust current medications (eg. HTN meds)

Add gout medications (take them even if feeling worse):Acute: NSAIDs (eg. indomethacin, celecoxib)

Glucocorticoids (eg. prednisone)Colchicine

Chronic: AllopurinolUricosuric drugs (eg. probenecid,

sulfinpyrazone)

Drug MOA DosingPurpose

NSAIDS anti-cox-2 taper dose 2-8 days prophylaxis

(indomethacin, anti-prostaglandins 12-24 hrs response pain prevention phenylbutazon, (in bone, pmns, macro) Tt acute attackcoxibs)

*low tox, hi na/k, bleeding, giCORTICOSTEROIDS

anti-T cl prolif dose to response when NSAIDS ineff(glucocorticoids, anti-IL-1,2,6, INF-a/g then taper rapid dramatic reliefprednisone) anti-PAF, LTN, PGs

*gi, osteoporosis, dec immunity, cushingoid habitusANTI-GOUT

anti-mitotic agent w/in 1st 12-24hr prophylaxis(colchicine) anti-tubulin polymer of attack suppress symptoms

anti-leukocyte migration relief 6-12 hrs dec pain of arthritisblocks lipoxygenase

*gi toxicity, bm supress, skin irrit

Drug MOA DosingPurpose

ALLOPURINOLanti-xanthine oxidase adj dose for hepat & prophylaxisdec synthesis of uric acid renal pts

primary dec purine synthesis no use w/uricosuricshyperuricemia of gout &

2nd to cancer therapy

long term lowers serum

uric acidremoves

crystals from kidney

*hypersensitivity, gi, leukopenia, hepat/renal tox

URICOSURICSincrexcretion of uric acid adj dose for renal

prophylaxis(Probenecid, blocks reabs of uric acid dec excr pcn, ind

long term sulphinpyrazole) alkalinizes urine sulfonurea lowers

serum no use w/salicy luric acidnot for hi uric acid level=stone

*ha, nausea, nephrolithiasis

PROGNOSISPROGNOSIS Without treatment:

Gouty symptoms subside within few days - weeks Remission can be for months or years Increased frequency of onset, duration & severity of

pain Tophi can burst and discharge chalky masses of

urate crystals through the skin

With treatment: Decreased frequency and severity of attacks Decreased uric acid levels

*1/5 pts with gout also develop urolithiasis (uric acid kidney stones

FOODS RICH IN FOODS RICH IN PURINESPURINESAnchovies AsparagusBeans BrothsConsomme Fish roeHerring LentilsMeat gravies MushroomsMussels PeasSardines ScallopsShellfish SweetbreadsBrewers Yeast Bakers YeastOrgan meats (liver, kidney, tongue, Tripe)

NATUROPATHIC NATUROPATHIC TREATMENTTREATMENT

Drink Water: % of body weight (eg.150lb pt =75oz H2O/day

96oz during attack; 64oz regularly daily30% more than expel

Supplements:Quercetin Inhibits uric acid productionBromelain Anti-inflammatoryVitamin EFlaxseed oil

*Avoid Vitamin C and Niacin (vit B3) bc increase uric acid levels

Eat:Unsweetened cherries Lowers uric acid

levelsBlueberries, blackberries, dark pigmented berries

SECONDARY GOUTSECONDARY GOUT ETIOLOGY: Defective renal excretion or overproduction

Excretion: Intrinsic renal dz Diuretic therapyLow dose aspirin Nicotinic acidCyclosporine Ethanol abuse

Hyperuricemia: Starvation Lactic acidosisDehydration PreeclampsiaDiabetic ketoacidosis

Overproduction: Myeloprolif dz Hemolytic anemia

Lymphoprolif dzPolycythemia

Cyanotic congenital heart dz

TREATMENT: Underlying cause and Allopurinol

DIFFERENTIALSDIFFERENTIALS Ankle Injury, Soft TissueAnkle Injury, Soft Tissue

Arthritis, Rheumatoid Arthritis, Rheumatoid

Bursitis Bursitis

Cellulitis Cellulitis

Dislocations, Interphalangeal Dislocations, Interphalangeal

Fractures, Foot Fractures, Foot

Hyperparathyroidism Hyperparathyroidism

Knee Injury, Soft Tissue Knee Injury, Soft Tissue

Osteomyelitis Osteomyelitis

Paronychia Paronychia

Reiter SyndromeReiter Syndrome

TenosynovitisTenosynovitis

Toenails, Ingrown Toenails, Ingrown

PSEUDOGOUTPSEUDOGOUT

STAGESSTAGES CHONDROCALCINOSIS CHONDROCALCINOSIS

appearance of calcific material in articular appearance of calcific material in articular cartilage and meniscicartilage and menisci

PSEUDOGOUTPSEUDOGOUT

crystal induced synovitiscrystal induced synovitis

CHRONIC PYROPHOSPHATE ARTHROPATHYCHRONIC PYROPHOSPHATE ARTHROPATHY

degenerative joint diseasedegenerative joint disease

PATHOLOGYPATHOLOGYPyrophosphate is probably generated in abnormal Pyrophosphate is probably generated in abnormal cartilage by enzyme activity at chondrocyte cartilage by enzyme activity at chondrocyte surfacesurface

Combines with calcium ions in the matrix to form Combines with calcium ions in the matrix to form crystal nucleuscrystal nucleus

Stage of propagationStage of propagation inflammation inflammation and and hypertrophic hypertrophic

reactionreaction*most pronounced in *most pronounced in fibrocartilagenous structures fibrocartilagenous structures

– Menisci of kneeMenisci of knee– Triangular ligament of the wristTriangular ligament of the wrist– Pubic symphysisPubic symphysis– Intervertebral discsIntervertebral discs

Hyaline articular cartilage, tendons & peri Hyaline articular cartilage, tendons & peri articular soft tissuesarticular soft tissues

Risk factors:Older age OA

Gout HeredityHyperpthism HemochromatosisDM HypothyroidismHypomagnesemia Neuropathic

joint

Triggers: Dehydration Acute illnessSurgery

CLINICAL FEATURESCLINICAL FEATURES Typically occurs in women over 60 years of ageTypically occurs in women over 60 years of age

Generally same clinical features as gout Generally same clinical features as gout

Acute monoarthritis, oligioarthritis or chronic Acute monoarthritis, oligioarthritis or chronic polyarthritis (often confused with Charcots joints)polyarthritis (often confused with Charcots joints)

More common in knee, wrist and shoulderMore common in knee, wrist and shoulder

Usually No tophiUsually No tophi

* Chondrocalcinosis in patients under 50 years of * Chondrocalcinosis in patients under 50 years of age should suggest the possibility of an age should suggest the possibility of an underlying metabolic or familial disorderunderlying metabolic or familial disorder

Laboratory findings: ESR: usually elevated Elevated: Calcium, PTH, Iron Decreased: Magnesium

RADIOGRAPHIC FINDINGSRADIOGRAPHIC FINDINGS

– Calcifications in the menisci, soft Calcifications in the menisci, soft tissues, tendons, or bursae.tissues, tendons, or bursae.

– Bilateral and symmetrical Bilateral and symmetrical involvementinvolvement

– Degenerative joint changes – similar Degenerative joint changes – similar to OA but unusual sites like non to OA but unusual sites like non weight bearing joints, TN, isolated weight bearing joints, TN, isolated PF in kneePF in knee

o In pseudogout, CPP In pseudogout, CPP crystals appear crystals appear shorter and often shorter and often rhomboidal. rhomboidal.

o Under a polarizing Under a polarizing filter, CPP crystals do filter, CPP crystals do not change color not change color depending upon their depending upon their alignment relative to alignment relative to the direction of the the direction of the red compensator.red compensator.

DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS ACUTE ACUTE

– Acute GoutAcute Gout– Post traumatic hemarthrosisPost traumatic hemarthrosis– Septic arthritisSeptic arthritis– Reiter’s diseaseReiter’s disease

CHRONICCHRONIC– OA – typical hypertrophy in pseudo, with unusual joint OA – typical hypertrophy in pseudo, with unusual joint

invinv– Inflammatory polyarthritis (RA) – absence of small joint Inflammatory polyarthritis (RA) – absence of small joint

invinv– Metabolic disorders Metabolic disorders

Hemachromatosis – bronze diabetes, cirrhosis, MCP joint invHemachromatosis – bronze diabetes, cirrhosis, MCP joint inv Alkaptonuria – spine inv first then larger joints, dark urineAlkaptonuria – spine inv first then larger joints, dark urine hyperparathyroidismhyperparathyroidism

TREATMENTTREATMENT

Initially NSAIDs (brief high dose)Oral corticosteroidsColchicineAspiration of fluidIntra-articular injection of glucocorticoidPhysical therapy (ROM, strengthening)

Allopurinol and Uricosuric agents have no therapeutic role

APATITE DISEASEAPATITE DISEASE Hydroxyapatite is a normal component of Hydroxyapatite is a normal component of

bone mineralbone mineral

CalcificationCalcification

MetastaticMetastatic DystrophicDystrophic

Prolonged hypercalcemia or Prolonged hypercalcemia or Hyperphospatemia of any cause can cause Hyperphospatemia of any cause can cause metastatic calcificationmetastatic calcification

Most commonly due to local tissue damage Most commonly due to local tissue damage in and around joints – torn ligaments, in and around joints – torn ligaments, tendon attrition, cartilage damagetendon attrition, cartilage damage

Minute HA cystals (< 1 micro) depositedMinute HA cystals (< 1 micro) deposited

Around jointsAround joints in jointsin joints

Acute or subacuteAcute or subacute chronic chronic periarthritisperiarthritis destructive destructive arthritisarthritis

Most commonly involves the shoulder and Most commonly involves the shoulder and the kneethe knee

No crystals present in synovial fluid (Hydroxyapatite complexes and basic calcium phosphate complexes seen by EM and MS.)

Treatment– Periarthritis

Acute – rest, NSAIDS, local corticosteroids Chronic – operative removal, or

decompression

– Erosive arthritis – treated like OA

Questions ……….. ?Questions ……….. ?