Alkaptonuric arthritis and haemophilic arthritis

1. GOUTY ARTHRITIS,
ALKAPTONURIC ARTHRITIS
HAEMOPHILIC ARTHRITIS
Moderator:Proff.Dr.A.E.MANOHARAN

2. GOUT
Defenition
• Gout is a hereditary condition of disturbed uric acid
metabolism in which urate salts gets deposited in articular,
periarticular and subcutaneous tissues.

3. • 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.

4. 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

5. Etiology
• Idiopathic
• Hereditory :family members have hyperuricemia without
gout .
• Race : Whites> Blacks
• Sex : Males >Females
• Age :2nd to 4th decade common at 40 years.

6. • Adrenal cortex isufficiency: an adequate amount of
coticosteroids counteracts the gouty attack.
• Disturbed electrolyte equilibrium: Marked diuresis that
preceeds acute attacks of gout.

7. Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS
7
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

8. 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

9. Microscopically
The deposites are
surronded by an
inflamatory
reaction,fibrous tissue
and giant cells

10. Common sites
Smaller joints:
First metatarsophalyngeal
joints
Interphalyngeal joints of
foot
Interphalyngeal joints of
the hands
Knee joint
Elbow joint

11. Classification
• Primary gout (95%)
• Secondary gout (5%)

12. Primary gout
• Common type (95%)
• Idiopathic
• Due to under excretion or overproduction of
monosodium urate (MSU).

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

14. Gout staging
• Typical sequence involves progression
through:
– Asymptomatic Hyperuricemia
– Acute gouty arthritis
– Interval or Intercritical gout
– Chronic or tophaceous gout

15. 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

16. 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

17. Clinical features
Acute 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.

18.  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.

19. 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.

20. 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

21. Most common sites for tophi
• olecranon,
• prepatellar bursa,
• ulnar surface
• Achilles tendon.

22. 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.

24. 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.)

25. 24 urine collection for uric acid determination :
• Assessing the risk of renal stones and planning
for therapy.(uric acid stones=nephrolithiasis)

26. 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 .

28. 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

29. Treatment for gout

30. Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS
Non pharmacological treatment

31. Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS
Non-drug Management:
31
Stop diuretics
Dietary changes
Stop alcohol weight loss

32. Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS
Dietary advices:
32
Fructose
Red meat/sea food.
Avoid:
Beer

33. Pharmacotherapy
• Non steroidal anti
inflamatory drugs
(NSAID’S)
• Colchicine,
• Corticosteroids
Uricosurics
• Probenecid,
• Sulfinpyrazone.
Synthesis inhibitor
• Allopurinol,
• Febuxostat .

34. Dr.Sandeep Agrawal,Agrasen Hospital,Gondia MS
34
Purine nucleotides
hypoxanthine
xanthine
Uric acid
Xanthine
oxidase
Alimentary
excretion
Urinary
excretion
Tissue deposition in
excess
Urate crystal microtophi
Phagocytosis
with acute
inflammation
and
uricosurics
colchicine NSAID
Allopurinol
Oxypurinol

35. 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

37. 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.

38. • Intra-articular corticosteroids.
• Surgical treatment
Excision of gout trophy.
Arthrodesis of the joint in functional position,
Removal of lesion adjacent to the joint preserves joint
function.

39. ALKAPTONURIC ARTHRITIS
OR
OCHRONOTIC ARTHRITIS

40. 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

41. Aetiology
• It is congenital
• Inherited as recessive triad
• Often occurring in children of consanguineous
parents.

42. Common sites
• Sclera
• Ligaments
• Ear cartilages
• Nose
• Intervertebral disc
• Joints

43. 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

44. 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

45. 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

46. 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

47. 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.

48. 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.

49. Haemophilic Arthritis

50. • Defenition
It is a heriditory coagulatory disorder charecterised
by the occurance of haemorrhages that appear
spontaneously or as a result of insignificant trauma.

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

52. Etiology :
• Genetically determined
• Due to the defeciency of factors VII to XI
• Sex linked recessive transmission

54. • 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

55. Common sites
• Haemophilic arthropathy is often monoarticular or
oligoarticular.
• Large joints are most commonly involved
• knee
• elbow
• ankle
• hip
• shoulder

56. 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.

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

58. Severity of haemophilia
• Severe haemophilia : spontaneous bleeding
with out any injury
• Moderate haemophilia : following minor
trauma
• Mild haemophilia : uncontrolled bleeding post
surgical, major trauma

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

60. 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.

61. 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.

63. Classification of haemophilic Arthritis
Arnold 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

64. Clinical features
• Acute Haemarthrosis
–Pain
–Warmth
–Boggy swelling
–Limitation of
movement
–Tendency to hold
the limb in flexion
•Common site : knee, elbow, hip, ankle

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

66. Investigations
• X-Ray :
– osteoporosis
– Narrowing of joint space
– Articular surface erosion
– Subchondral cyst
•Ultra sonogram of the joint

67. 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)

68. Differential diagnosis
• Von Willebrand Disease
• Thrombocytopenia(Idiopathic
Thrombocytopenia Purpura )
• Vitamin C deficency

69. Treatment
• Acute
• Chronic

70. 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

71. • 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

72. 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

73. 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

74. • 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.

75. Concentrates used
• Fresh frozen or freeze dried plasma
• Cryoprecipitate
• Recombinant concentrate