GOUTY ARTHRITIS,ALKAPTONURIC ARTHRITIS HAEMOPHILIC ARTHRITIS

Moderator:Proff.Dr.A.E.MANOHARAN

GOUT

Defenition

• Gout is a hereditary condition of disturbed uric acid

metabolism in which urate salts gets deposited in articular,

periarticular and subcutaneous tissues.

• Clinically it is characterised by reccurring attacks of

acute arthritis by interval of freedom from pain &

• In late stages by deforming arthritis, nephritis,

urinary calculi.

Predisposing factors:

• Alcohol abuse

• High consumption of Red meat

&Beans

• Obesity

• Diabetes

• Hypertension

• Hyperlipidemia

• Chronic inflammatory diseases

• Long term use of diuretics or aspirin

• Hyper parathyroidism

• Myeloprolifrative disorders

Etiology

• Idiopathic

• Hereditory :family members have hyperuricemia without

gout .

• Race : Whites> Blacks

• Sex : Males >Females

• Age :2nd to 4th decade common at 40 years.

• Adrenal cortex isufficiency: an adequate amount of

coticosteroids counteracts the gouty attack.

• Disturbed electrolyte equilibrium: Marked diuresis that

preceeds acute attacks of gout.

Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS7

Purine nucleotides

hypoxanthine

xanthine

Uric acidXanthine oxidase

Alimentary excretion

Urinary excretion

Tissue deposition in excess

Urate crystal microtophi

Phagocytosis with acute inflammation and arthritis

Pathology

• Sodium urate is deposited as crystals on the

surface of articular cartilage.

• Then articular cartilage is eroded

• The subchondral bone is replaced by

crystaline deposit.(tophii)

• A pannus of granulation tissue grows over the

articular surface, invades and replaces the

cartilage .

• Then granulation tissue bridges the joint to the

opposite articular surface and producing

fibrous ankylosis

Microscopically

The deposites are

surronded by an

inflamatory

reaction,fibrous tissue

and giant cells

Common sitesSmaller joints: First metatarsophalyngeal

jointsInterphalyngeal joints of footInterphalyngeal joints of

the hands Knee jointElbow joint

Classification

• Primary gout (95%)

• Secondary gout (5%)

Primary gout

• Common type (95%)• Idiopathic • Due to under excretion or overproduction of

monosodium urate (MSU).

Secondary gout

• Comprises 5%• Prolonged hyperuricaemia• Administration of diuretics• Renal failure.

Gout staging

• Typical sequence involves progression

through:

– Asymptomatic Hyperuricemia

– Acute gouty arthritis

– Interval or Intercritical gout

– Chronic or tophaceous gout

Hyperuricaemia⇩

May be asymptomatic⇩

Deposition of monosodium urate crystals in synovial tissue

(contain various Ig’s, complement, fibrinogen, fibronectin)

⇩Complement activated

⇩Neutrophils phagocytose & lyse crystals

⇩Release chemical mediators (e.g. TNF-α; IL-1)

⇩ACUTE GOUTY ARTHRITIS

⇩May resolve & become asymptomatic

(INTERCRITICAL GOUT)

pathogenesis

Recurrent episodes of Gout⇩

Large deposits of chalky white urate tophi⇩

Chronic granulomatous inflammatory condition⇩

Fibrosis of synovium ⇩

Erosion of articular cartilage ⇩

CHRONIC TOPHACEOUS ARTHRITIS

⇩ankylosis

⇩Tophi may be deposited in soft tissue

⇩Can ulcerate if sub-cutaneous

Clinical featuresAcute gout: Precipitated by local trauma

unaccustomed excercise and alcohol consumption

Acute arthritis is the most common manifestation

Excruciating pain over hours frequently nocturnal

Swelling, redness and tenderness Monoarticular and lower

extremities(MetatarsoPhalyngeal joint, ankle and knee).

• 1st MTP classic presentation• May affect knees, wrist, elbow, and

rarely SI and hips.

Pain appears last, disappears first

Mimic septic arthritis, cellulitis or thromboplebitis

Nocturnal attacks are common.

• Attacks subside in 3 to 10 days.

• Recurrent attacks involve more joints and usually persist longer.

• Systemic reaction like malaise,fever.

Intercritical gout:• Asymptomatic period

between crises• Duration varies, but

untreated patients may have a second episode within two years.

• Some patients evolve to chronic polyarticular gout without pain free intercritical episodes.

Chronic tophaceus Gout:

• The clinical characteristic is the

deposition of solid urate in the

connective tissue.

• It is associated with early age of

onset

• long duration of untreated disease

• upper extremity involvement

• polyarticular disease and elevated

serum uric acid

• Cyclosporine and/or diuretics

increased risk for tophaceus gout

Most common sites for tophi

• olecranon,

• prepatellar bursa,

• ulnar surface

• Achilles tendon.

Daignosis• Arthrocentesis:Polarising Microscopy showing

Monosodium urate (MSU) : needle-shaped

negatively birefringent either free floating

or within neutrophils & macrophages.Joint Fluid analysis: Acute gout=• Inflammatory (>2000 cells/ml);• Monosodium urate (MSU) crystals do not

exclude the possibility of septic arthritis, for this reason it is also recommended to request a Gram smear.

Serum Uric Acid:• Normal = 4.0 to 8.6 mg/dl in men = 3.0 to 5.9 mg/dl in women. • Urinary levels are normal below 750 mg/ 24h. • Urinary levels above 750 mg/dl in 24h in gout • > 1100 mg/dl in asymptomatic hyperuricemia

(indicates urate overproduction.)

24 urine collection for uric acid determination :

• Assessing the risk of renal stones and planning for therapy.(uric acid stones=nephrolithiasis)

Radiological examination• To exclude other kinds

of arthritis.• Tophi• Normal mineralization• Asymmetric polyarticular

distribution• Juxta-articular bony erosion

associated with periarticular tophi

• subchondral erosions with overhanging bony edges .

Differential Diagnosis of gout Acute Gout:

• Septic arthritis.

• Pseudogout (calcium pyrophosphate crystals)

• Reactive arthritis.

• Acute rheumatic fever

• Other crystalline arthropathies.

Chronic tophaceus gout:

• Rheumatoid Arthritis

• Pseudogout

Treatment for gout

Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS

Non pharmacological treatment

Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS

Non-drug Management:

31

Stop diureticsDietary changes

Stop alcohol weight loss

Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS

Dietary advices:

32

Fructose Red meat/sea food.

Avoid:

Beer

Pharmacotherapy

• Non steroidal anti inflamatory drugs (NSAID’S)

• Colchicine,• Corticosteroids

Uricosurics• Probenecid, • Sulfinpyrazone.

Synthesis inhibitor• Allopurinol,• Febuxostat .

Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS34

Purine nucleotides

hypoxanthine

xanthine

Uric acid

Xanthine oxidase

Alimentary excretion

Urinary excretion

Tissue deposition in excess

Urate crystal microtophi

Phagocytosis with acute inflammation and arthritis

uricosurics

colchicine NSAID

Allopurinol

Oxypurinol

For acute attack

• Absolute bed rest,

• Ice packs,

• Avoidance of alcohol

• Tab. Colchicine 0.5 mg 3rd hrly followed by maintenance dose of

0.5 – 1 mg/day. It has significant GI toxicity and delayed onset of

action.

• Tab.Phenylbutazone 200mg TDS for colchicine resistant patient

• Alternatively oral Prednisolone 20-40mg/day is also effective

For chronic gout,Allopurinol The first choice of drug in chronic gout started

with 100mg OD and gradually increased upto 300mg/day,

Febuxostat It is a recently introduced nonpurine xanthain

oxidase inhibitor dosage is 40-80mg/day, it has hepatotoxic side effect hence pt followed up with liver function test.

• Intra-articular corticosteroids.

• Surgical treatmentExcision of gout trophy.

Arthrodesis of the joint in functional position,

Removal of lesion adjacent to the joint preserves joint

function.

ALKAPTONURIC ARTHRITISOR

OCHRONOTIC ARTHRITIS

DEFENITION

Alkaptonuric arthritis is result from inherited defect

in metabolism of phenylalanine and tyrosin results

in accumulation of homogentisic acid which

deposits in cartilage and other connective tissue

results in arthritis

Aetiology

• It is congenital • Inherited as recessive triad • Often occurring in children of consanguineous

parents.

Common sites

• Sclera• Ligaments • Ear cartilages• Nose • Intervertebral disc• Joints

Pathophysiology • Homogentisic acid is a strong reducing agent that when

oxidised converted to dark pigment.

• It deposits particularly over tendons, ligaments cartilages

intervertebral discs& become darkened with pigment.

• These tissues loses its elasticity become brittle and has

poor resistance to mechanical strain cracks easily and

produce symptoms

Signs and symptoms.• The onset occurs in infancy

• Urine blackens on standing

• Black staining on diapers

• Brownish stain over sclera and cutaneous

tissues.

• Joint symptoms occurs after 40 yrs of age,

• Spine and large joints are commonly affected

• Entire thoracic and lumbar spine are rigid

• Increase rounding of thoracic spine and

flattening of lumbar spine

A 57 yr old man at the time of total knee arthroplasty, the color of the knee joint cartilage was black throughout and involved the full thickness of the cartilage. The tendons and meniscus showed scattered pigmentation, but the subchondral bone was normal.(JBJS Case Connect, 2013 Jun 26; 3 (2)

Ear wax of a person with ochronosis will also be dark in color

X – ray findings• X-ray spine are

characteristic• Disc appears as

elliptical, thin, calcified wafers

• Apposing vertebral bodies are sclerotic spurred

• Sacroilitis may be present

Diagnosis.

• Presence of homogentisic acid in urine is the diagnostic criteria

• When urine exposed to air the colour changes to black.

• This can be tested by addition of diluted ferric chloride to the urine which turns the urine into bluish green colour.

Treatment

• There is no known treatment for ocronotic arthritis.

• Rest to the affected joint.

• Avoidance of food containing phenylalanine and

tyrosine will postpone the onset of symptoms.

• Vitamin C supplementation: reduces the excretion of

homogentisicacid but no effect on the progress of

disease.

Haemophilic Arthritis

• Defenition It is a heriditory coagulatory disorder charecterised

by the occurance of haemorrhages that appear spontaneously or as a result of insignificant trauma.

• Commonest inherited bleeding disorder• X linked recessive disorder • manifesting in males but carried by females.• Incidence is 1 in 10000 male births

Etiology :

• Genetically determined

• Due to the defeciency of factors VII to XI

• Sex linked recessive transmission

• Types:– •Haemophilia A – deficiency of Factor VIII– •Haemophilia B – deficiency of Factor IX– •Haemophilia C – deficiency of Factor XI

– 80% have haemophilia A– 15% have haemophilia B

Common sites• Haemophilic arthropathy is often monoarticular or

oligoarticular.•  Large joints are most commonly involved• knee• elbow• ankle• hip• shoulder

Severity of haemophilia

• 1ml of normal plasma contains 1 unit(U) of each factor.

• 100ml plasma contains 100U/dl(100%activity) • Haemostatic level of factor VIII : 30-40U/dl.• Haemostatic level of factor IX : 25-30U/dl.

Severity of haemophilia

• Severity depends on factor level in blood • Severe haemophilia : <1U/dl(%)• Moderate haemophilia : 1-5U/dl(%)• Mild haemophilia : 5-30U/dl(%)

Severity of haemophilia

• Severe haemophilia : spontaneous bleeding with out any injury

• Moderate haemophilia : following minor trauma

• Mild haemophilia : uncontrolled bleeding post surgical, major trauma

Bleeding in Haemophilia

• Acute Haemarthrosis• Chronic haemophilic arthropathy• Bleeding into muscles• Haemophilic pseudotumour-cysts• Haematuria• Gastrointestinal bleeding• Intracranial bleeding

Pathology

• Haemorrhage in to the joint causes synovial irritation, inflammation and synovial fibrosis.

• Haemosiderin appears in the synovial cells and macrophages.

• After repeated bleeds the synovium becomes thick and heavily pigmented.

Pathology

• A vascular pannus creeps over the articular surface and cartilage is gradually eroded

• The sub chondral bone may get exposed and penetrated ,large cysts may develop.

• These changes are attributed to cartilage degrading enzymes.

Classification of haemophilic ArthritisArnold and hilgartner• Stage 1 – soft tissue swelling• Stage 2 – osteoporosis and epiphyseal overgrowth• Stage 3 – joint space narrowing• Stage 4 – marked narrowing of joint space• Stage 5 – joint disintegration

Clinical features

• Acute Haemarthrosis– Pain– Warmth– Boggy swelling– Limitation of

movement– Tendency to hold

the limb in flexion

•Common site : knee, elbow, hip, ankle

• Chronic haemophilic arthropathy – there is stiffness of joint– Cartilage erosion– Subchondral cyst– Flexion deformity– Muscle wasting– Joint instability in some cases

Investigations

• X-Ray :– osteoporosis– Narrowing of joint space – Articular surface erosion– Subchondral cyst

•Ultra sonogram of the joint

Lab investigations

• Plasma levels of individual clotting factors are calculated

• This helps in the mainstay of treatment.• Complete blood count (CBC)• Bleeding time, Clotting time (BT/CT)• Erythrocyte sedementation rate(ESR)

Differential diagnosis• Von Willebrand Disease• Thrombocytopenia(

Idiopathic Thrombocytopenia Purpura )• Vitamin C deficency

Treatment

• Acute• Chronic

Acute cases

• Immediate clotting factor replacement• Analgesics are given for pain• Limb is immobilised with splint for a day or

two, movement is encouraged after that

• Aspiration is usually avoided• Done is sever cases of distention or if there is

strong suspicion of infection• Done under the cover of factor concentrate

replacement

Chronic cases

• The aim is prevent joint contracture, stiffness, and muscle weakness.

• Under the cover of clotting factors patient is given physiotherapy and intermittent splintage

Surgical management

• Clotting factor concentrates are administered before surgery

• Plasma concentration raised above 25% for factor VIII deficiency

• And above 15% for factor IX deficiency• These levels are maintained through out the

post operative period

• Tendon lengthening to correct contracture• Osteotomy for established deformity• Arthodesis for painful joint destruction • Arthoplasty can be done after considering the

risks and its usefulness to the patient but meticulous haemostasis should be achieved.

Concentrates used

• Fresh frozen or freeze dried plasma• Cryoprecipitate• Recombinant concentrate

Thank you