DR .

ARIF K S Associate Professor Yenepoya Medical College

CLASSIFICATION :

MONOSODIUM URATE CRYSTAL ARTHROPATHY GOUT CALCIUM PYROPHOSPHATE DIHYDRATE CRYSTALS ARTHROPATHY PSEUDOGOUT

 CALCIUM HYDROXYAPATITE CRYSTALS AND OTHER BASIC CALCIUM PHOSPHATE CRYSTALS ARTHROPATHY ASSOCIATED WITH CALCIFIC TENDINITIS, ACUTE CLACIFIC PERIARTHRITIS, MILWAUKEE SHOULDER SYNDROME MISCELLANEOUS .

GOUT
Gout -latin word Gutta means a drop Gout is a term representing a group of diseases found exclusively in human species that include An elevated serum uric acid concentration (Hyperuricemia) Recurrent attacks of acute arthritis in which monosodium urate monohydrate crystals are demonstrable in synovial fluid leukocytes.

 Aggregates of Sodium urate monohydrate crystals (tophi) deposited chiefly in and around joints which sometimes lead to deformity. Renal disease including glomerular, tubular and interstitial tissues . Uric acid urolithiasis.

Normal values
Uric acid (serum)
Males 3-7 mg/dl Females 3-6 mg/dl Children 3-4 mg/dl.

Etiology of gout

Primary Secondary

Primary
Unidentified molecular defects

Partial HGPRT defeciency

(Hypoxanthine guanine phosphoribosyl transferase)

PRPP Synthetase increased activity

(Phosphoribosyl pyrophosphate)

Secondary

Underexcretion of uric acid(10%) Overproduction of uric acid(90%)

Underexcretion of uric acid

Renal diseases polycystic kidney disease, Lead nephropathy. Diuretic therapy Accumulation of organic acids alcoholic ketosis, starvation , diabetic ketoacidosis.

Overproduction of uric acid

Glucose -6- phosphatase deficiency

Lesch-Nyhan syndrome.(complete hypoxanthine guanine phosphoribosyl transferase defeciency)

Fructose-1-phosphate aldolase deficiency

Overproduction of uric acid

Increased nucleic acid turnover myeloproliferative and lymphoproliferative disorders. Excess ATP degradation Acutely ill patients eg. status epilepticus , excess alcohol consumption

Drug induced
Diuretic therapy Cyclosporine Lead intoxication IV Heparin

Pathogenesis

Tophi
They are the pathognomonic hallmark of gout. They are formed by large aggregation of uric acid crystals surrounded by an inflammatory reaction of macrophages, lymphocytes and large foreign body giant cells, which may have completely or partially engulfed the masses of crystals

Acute arthritis
Characterised by dense neutrophilic infiltrate. Monosodium urate crystals in the synovium. Synovium edematous and congested and contains scattered lymphocytes, plasma cells, macrophages.

Chronic arthritis
Due to repetitive precipitation of urate crystals during acute attacks. The urates form visible deposits in the synovium. The synovium becomes hyperplastic and thickened by inflammatory cells and forms pannus that destroys the underlying cartilage leading to bone erosions.

Clinical features

Acute
Sudden onset.

Affected joint hot, red, swollen, extremely tender.

Single joint involved (85-90%)

1. First metatarsophalangeal joint. 2. Ankle

3. Knees
4. Wrist

 Mild attack may subside in several hours. Severe attack may last for weeks.

Intercritical gout
Interval between gouty attacks
Complete recovery Interval between first two attacks may vary from 6 months to several years(5-10years).

CHRONIC
Polyarticular. Marked limitation of joint movements. The crystals may assume large globular shapes, distending the overlying skin and rupturing to form a chronically discharging sinus.

Spine involvement
Facetal joints will be involved Cause of chronic back pain Usually no neurological involvement

Associated conditions
Hypertension Atherosclerosis Pregnancy Acute illness Hypothyroidism

Renal parenchymal disease

Precipitation of uric acid crystals in
Collecting ducts Ureters Urolithiasis.

Diagnosis
Family history of gouty arthritis Repeated attacks with interval of freedom from pain Renal disturbance such as renal calculi Hyperuricemia Satisfactory response to adequate doses of colchine.

Investigations

 Serum uric acid levels will be elevated

Systemic signs leukocytosis, elevated ESR.

 Synovial fluid Cloudy Increased cell count (2000-60000) Microscopic examination Crystals which show negative birefringence when viewed under polarizing microscope.

Murexide test

Suspected substance containing uric acid + nitric acid mixture evoporated to dryness . Ammonia added to the mixture purple colour indicates presence of uric acid.

Radiological appearance
Joint effusion. Periarticular soft tissue swelling. Preservation of joint space. Absence of periarticular demineralization. Overhanging bony edges. Sclerosis of bone margins.

TREATMENT OF ACUTE GOUT

REST

Immobilization of the affected limb and icepack to reduce pain.

 Diet restriction Food rich in purine should be avoided eg mussels, yeast, sardines, sweetbread, liver, turkey, goose.

Drugs
Colchicine Orally 0.5 to 0.6 mg tablet is given every hour until 1. Pain is reduced and toxic features subsided. 2. omiting and diarrhea develops or a maximum of 10 doses is taken. Intravenously 1-2 mg is given as an initial dose followed by an additional 1mg after 6 hours.

 Mechanism of action Inhibits migration of

inflammatory cells into the joint.

Toxic effects nausea, vomiting, diarrhea, abdominal pain, bone marrow suppresion, renal complication(proteinuria,hematuria)

NSAIDS
Indomethacin 25 mg given 4 times a day followed by 50 mg every 6 to 8 hours. Other NSAID used are naproxen, sulindac, piroxicam, ketoprofen, fenoprofen, ibuprofen.

Drugs used in chronic gout

Allopurinol.

Uricosuric agents.

ALLOPURINOL
Dose Initial daily dose of 100 mg. Most patients are maintained at 300 mg/day. Those with more severe gout may require 400-600 mg/day.

Mechanism of action Xanthine oxidase inhibitor. Adverse effects 1. Hypersensitivity reactions 2. Fever, myalgia 3. Hepatomegaly

Uricosuric agents
Probenecid 250 mg twice daily increased over 1-2 weeks to 500 to 1000 mg twice daily. Mechanism of action Increases urinary excretion of uric acid by inhibiting reabsorption. Adverse effects 1. Nausea 2. Vomiting

 Sulfinpyrazone 100 200 mg twice daily.

Mechanism of action Inhibits renal tubular reabsorption of uric acid.

Adverse effects Nausea , vomiting.

Newer drugs :
FEBUXOSTAT, orally administered, non purine, selective inhibitor of xanthine oxidase, indicated in chronic hyperuricemia MOA : inhibition of xanthine oxidase Dose : 80 or 120mg orally once daily for atleast 6 month Adverse effects : liver function test abnormalities, diarrhea, headache, rashs

Managament of nephrolithiasis
Increased fluid intake to maintain large urinary volume .
The treatment of choice in nephrolithiasis is allopurinol because it lowers both urinary and serum uric acid values.

Surgical management
1. 2. 3. 4. Indications Pain Interference with movement of joint or tendon Discharging sinus Cosmetic Surgical intervention mainly involves excision of the lesion.

INTRODUCTION
Calcium pyrophosphate dihydrate
disease (CPPD) is a disorder due to

precipitation of calcium pyrophosphate

dihydrate crystals in the connective

tissues.

PSEUDOGOUT
Adams-1850- First case of CPPD

ACUTE ARTHRITIS caused by release of

CPPD crystals into joint space

Monoarticular
Takes a more slower clinical progression when compared to gout

OTHER NAMES
CHONDROCALCINOSIS ARTICULARIS
PYROPHOSPHATE ARTHROPATHY

CPPD
CALCIUM PYROPHOSPHATE GOUT

PATHOGENESIS

PATHOGENESIS
The exact pathology of CPPD is unknown, Increased Adenosine Triphosphate BREAKDOWN

A CHROMOSOME T(2;10) has been described in one

case involving the temporomandibular joint.

 CPPD crystals are

PHAGOCYTOSED by
neutrophils This results in release of LYSOSOMAL ENZYMES and

chemotactic factors

CPPD: ASSOCIATED DISEASES

DEFINITELY ASSOCIATED
HYPERPARATHYROIDISM HYPOPHOSPHATEMIA HYPOMAGNESEMIA

HEMOCHROMATOSIS
WILSONS DISEASE

CPPD: ASSOCIATED DISEASES

POSSIBLY ASSOCIATED
HYPOTHYROIDISM GOUT OCHRONOSIS

PATHOLOGY IN ACUTE FORM

Pyrophosphate deposit usually occur in the

MIDZONE OF HYALINE CARTILAGE

Rarely seen in tendons and bursae

Synovial CHALKY WHITE DEPOSITS

Chondrometaplasia

PATHOLOGY IN CHRONIC FORM

Synovium with increased FIBROSIS
Mononuclear cell INFILTRATES

GIANT CELL surrounding crystalline deposits

Foreign body GRANULOMA

Deposits occur OUTSIDE the chondrocytes

CLINICAL PRESENTATION

COMMON SITES

KNEE> WRIST> MCPS>

CLINICAL
CPPD has the capacity to mimic ANY TYPE OF
ARTHIRITIS

ASYMPTOMATIC DISEASE Most joints with radiographic evidence of CPPD

deposition have mild to no symptoms of disease

CLINICAL
Acute pseudogout PSEUDO - rheumatoid pattern

PSEUDO - osteoarthritis
Chondrocalcinosis

Neuropathic joint

PSEUDOGOUT

MONOARTHRITIS Commonly
Signs of severe acute INFLAMMATION Occurrence of CLUSTER ATTACKS Resembles gout

DIFFERENTIATE from gout

SLOWER IN PROGRESSION compared to gout

PSEUDO-RHEUMATOID ARTHRITIS
5% 10%- positive RA factor

Polyarthritis
Symptoms lasting for months

Symptoms include significant morning stiffness, fatigue,

synovial thickening, localized edema, and restricted

joint motion

PSEUDO-OSTEOARTHRITIS
50 % The joints most commonly affected include the knees, followed by the wrists, MCPs, hips, shoulders, elbows,

and spine DIFFERENTIATE from primary osteoarthritis

More likely to affect the lateral compartment knee Patellofemoral arthritis Uncommon site

DIAGNOSIS

SYNOVIAL FLUID ANALYSIS

CLOUDY HIGH CELL COUNT INTRACELLULAR AND EXTRACELLULAR CRYSTALS

DIAGNOSIS
Synovial fluid
POSITIVELY BIREFRINGENT rhomboid crystals During acute pseudogout attacks phagocytosed crystals within PMNs ARE FOUND

Negative Birefringence

CPPD-Arthroscopic View

RADIOGRAPHIC FEATURES
CHONDROCALCINOSIS
Punctate and linear radiodensities in fibrocartilage and articular cartilage

RADIOGRAPHIC FEATURES
General similarities to osteoarthritis Chondrocalcinosis--calcification of cartilage
MENISCI of knees CARTILAGE of wrists SYMPHYSIS PUBIS

RADIOGRAPHIC FEATURES
Other sites demonstrating calcification
Bursae Joint capsule Synovium

Tendon

Diagnosis

Chondrocalcinosis of knee joint

WRAP AROUND appearance of patella

DIAGNOSTIC CRITERIA
Definitive diagnosis of CPPD deposition requires

Demonstration of CPPD crystals in synovial fluid by x-ray diffraction,

or
POSITIVELY BIREFRINGENT CRYSTALS seen by
compensated polarized light microscopy

DIAGNOSTIC CRITERIA BY MC CARTY

1. Demonstration of CPPD crystals obtained by

joint aspiration or biopsy by infrared spectroscopy 2. (a) Identification of positive birefringence by

compensated polarized light microscopy

(b) Presence of typical calcifications of fibrocartilage and hyaline cartilage on radiographs

3.(a) Acute arthritis, especially of knees or other large

joints (b) Chronic arthropathy, especially of knees, hips, wrists, carpus, elbows, shoulders, and metacarpophalangeal joints

 Definite diagnosis: Criterion I or IIa Probable diagnosis: Criterion IIa or IIb Possible diagnosis: Criterion IIIa or IIIb

TREATMENT OPTIONS
Joint aspiration

NSAIDs
Colchicine (not as effective as for gout) Steroids (not as effective as for gout)

oral
intra-articular Analgesics

Surgery if necessary to preserve function

TREATMENT
Acute Pseudogout Removal of crystals by joint aspiration Administration of NSAIDs or colchicine

Intraarticular injection of steroids

Joint immobilization

TREATMENT
Colchicine
Blocks release of chemotactic factors for

neutrophils and mononuclear cells and inhibits

neutrophil-endothelial cell binding

PROGNOSIS
ANKYLOSIS
CARPAL TUNNEL SYNDROME DEFORMITIES DEMINERALIZATION STRESS FRACTURES

CALCIUM PHOSPHATE APATITE CRYSTAL DEPOSITION DISEASE

Carbonate substituted apatite Octacalcium phosphate Tricalcium phosphate dihydrate Dicalcium phosphate dihydrate

PRESENTATION
Clinically similar to cppd and gout

Calcific tendinitis bursitis Acute arthritis Joint Destruction

PRESENTATION
They are below the limits of resolution of
ordinary optic microscope

Aggregate as irregular glossy clumps

Do not show any chracteristic crystalline shape

DIFFERENTIAL DIAGNOSIS

MONOARTHRITIS
Infection Transient synovitis of the hip Metastatic carcinoma Pigmented villonodular

Rheumatoid arthritis
Gout Pseudogout

synovitis

Apatite-related arthropathy Hemarthrosis Reactive arthritis SLE Sickle cell disease . Neuropathic arthropathy

Osteoarthritis
Intra-articular injury

DIFFERENTIAL DIAGNOSIS FOR CHONDROCALCINOSIS

Systemic sclerosis
Dermatomyositis

Polymyositis
Systemic lupus erythromatosis Hemodialysis Heterotrophic calcification

Thank you