Gouty arthritis

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 :2 nd to 4 th 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. 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 C hronic 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. R ecurrent 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 ). 1 st 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 : A cute 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.

23. 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. 24 urine collection for uric acid determination : Assessing the risk of renal stones and planning for therapy.(uric acid stones= nephrolithiasis )

25. 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 .

26. 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

27. Treatment for gout

28. Non pharmacological treatment

29. Non-drug Management: 31 Stop diuretics Dietary changes Stop alcohol weight loss

30. Dietary advices: 32 Fructose Red meat/sea food. Avoid: Beer

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

32. 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 arthritis uricosurics colchicine NSAID Allopurinol Oxypurinol

33. For acute attack Absolute bed rest, Ice packs, Avoidance of alcohol Tab. Colchicine 0.5 mg 3 rd 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

34. 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.

35. 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.

36. ALKAPTONURIC ARTHRITIS OR OCHRONOTIC ARTHRITIS

37. 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

38. Aetiology It is congenital I nherited as recessive triad Often occurring in children of consanguineous parents.

39. Common sites Sclera Ligaments Ear cartilages Nose Intervertebral disc Joints

40. 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

41. Signs and symptoms. The onset occurs in infancy Urine blackens on standing B lack 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

42. 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

43. 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

44. 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.

45. 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.

46. Haemophilic Arthritis

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

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

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

50. 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

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

52. 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.

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

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

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

56. 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.

57. 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.

58. 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

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

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

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

62. 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)

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

64. Treatment Acute Chronic

65. 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

66. 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

67. 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

68. 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

69. 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 .

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

71. Thank you