king of disease n disease ofking: Gout

1. Gout and Pseudogout
By: Dr Sabir kumar khadka
Jr2,Orthopedics,BPKIHS
2020/06/21
Moderator:Dr Rosan Psd Kalawar1

2. References
• Kelley and Firestein’s Textbook of Rheumatology vol II,10th edition .
• Apley and Solomon’s System of Orthopedics and Trauma , 10th
edition.
• Medscape
2

3. GOUT
• History
• Introduction
• Epidemiology
• Classification
• Etiology
• Purine and Uric acid metabolism
• Pathogenesis
• Pathology
• Clinical Features and stages of Gout
• Laboratory investigations
• Imaging
• Diagnosis
• Treatment 3

4. PSEUDOGOUT
• Crystal deposition diseases
• Pathogenesis
• Clinical Features
• Investigations
• Imaging
• Diagnosis
• Treatment
• Differences between Gout and Pseudogout
4

5. Introduction
• Gout represents a heterogeneous group of disorders of
purine metabolism characterized by :
– Hyperuricemia
– Recurrent attacks of acute arthritis
– Deposition of Monosodium urate monohydrate crystals ( tophi) in
and around the joints
– Renal disease
– Uric acid nephrolithiasis
5

6. Reference range of uric acid
• Men: 2.5 – 8 mg/dl
• Women: 1.9 - 7.5 mg/dl
• Children: 3 – 4 mg/dl
• A serum urate of less than 6mg/dl is the target
of therapy.
6

7. Epidemiology
• Prevalence: 2.6 % – 47.2 %
• Males involved much more ( 2:1 to 7:1)
• Females more commonly affected after menopause
• Age of onset : 35-45 year
7

8. Classification
• Primary ( 95%)
Absence of any obvious cause
– Underexcretion ( 90 %)
– Overproduction ( 10 %)
• Secondary ( 5 %)
– Renal Causes
– Diuretics or Drug induced
– Metabolic
– Myeloproliferative Diseases
8

9. Etiology
• Unknown
• Proposed factors :
1. Genetics :
– Familial incidence : 11 – 80 %
9

10. Etiology
2. Obesity
– Hyperuricemia 3 times more common in people with
bodyweight > 80th percentile
– Hypertriglyceridemia > 80 % of patients with Hyperuricemia
3. Alcohol .
4. Diabetes Mellitus
5. Adrenal Cortex activity .
10

11. Etiology
6. Vascular Changes
7. Disturbed Electrolyte equilibrium
8. Decreased urinary 17 ketosteroids : < 3mg/24 hrs
9. Hypertension and Coronary artery disease :
have predictive relationship with Hyperuricemia
11

12. 12

13. Natural history of gout
• Hyperuricemia – common 2.3-41.4 %,.
• Level of the urate level determines the risk of
the gouty attack – level >9 mg/dl -4.9 % ,7-
8.9mg/dl -0.5%, <7mg/dl -0.1% .
• Second attack –generally 6 months to 2 years
• Chronic tophacious gout –average 11.6 years
,50 % of patient free of obviuos tophi after 10
years ,slowly declines to 28 % in 20 years .
13

14. Clinical Features
• Asymptomatic Hyperuricemia
• Acute Gouty arthritis
• Inter critical gout
• Chronic gouty / tophaceous arthritis
14

15. Asymptomatic Hyperuricemia
• Serum urate levels are high
• > 7mg/dl in males and > 6 mg/dl in females
• No manifestations of gout noted
• Most people with hyperuricemia remain asymptomatic
• Usually sustained for first 10-20 years of illness
• Phase ends with first attack of gout
15

16. Acute Gouty arthritis
• First attack :
– Usually between 40-60 years (males) or >60 (females)
– Monoarticular
– Not associated with many constitutional symptoms
– Usually 1st metatarsophalangeal joint
– Explosive suddenness
– Commonly begins at night
– Joint becomes hot , dusky red , swollen and extremely tender
– May resolve within hrs to days
16

17. Acute Gouty arthritis
17

18. Acute Gouty arthritis
• Later on :
– Skin may desquamate
– More than one site involved
• Other sites :
– Ankle
– Finger joints
– Olecranon
– Heels ,knees , wrists
– Prepatellar /Olecranon bursa
– Ear
18

19. Acute Gouty arthritis
• Precipitating factors :
– Alcohol
– Surgery
– Excess diet
– Glucocorticoid withdrawl
– Trauma
– CVA / MI
– Infection
– Drugs : Antihyperuricemic therapy , Cyclosporine , Heparin ,
Diuretics
19

20. Acute Gouty arthritis
• When to label the condition as acute gout :
1. Triad of
1. Acute monoarticular arthritis
2. Hyperuricemia
3. Dramatic response to colchicine therapy
2. Criteria for classification of Acute gouty arthritis
1. Presence of characteristic urate crystals in the joint fluid
OR
2. Tophus proved to contain urate crystals by chemical or polarised
light OR
20

21. Acute Gouty arthritis
• When to label the condition as acute gout :
3. Presence of atleast 6 of the following:
– More than one attack of acute arthritis
– Maximum inflammation within 1 day
– Attack of monoarticular arthritis
– Joint redness
– 1st MTP joint swollen/inflammed
– Unilateral attack involving 1st MTP joint
– Unilateral attack involving tarsal joint
– Suspected tophus contd …
21

22. Acute Gouty arthritis
• When to label the condition as acute gout :
3. Presence of atleast 6 of the following:
– Hyperuricemia .
– Asymmetric swelling within a joint ( XRay)
– Subcortical cyst without erosion ( XRay)
– Negative culture of joint fluid for micro-organism during attack
of acute inflammation
22

23. Inter-critical Gout ( Interval Gout)
• Some patients never have a second attack
• Second attack usually follow 6 months to 2 years later
• Frequency of attack increases with time
• Later attacks have a
– Less explosive onset
– Polyarticular
– More severe
– Last longer
– Take longer to subside
23

24. Inter-critical Gout ( Interval Gout)
• X ray changes may occur in between without evidence of
tophi in intervals
• Diagnosis tests on joint aspiration only
24

25. Chronic Tophaceous Gout
• No pain free intercritical periods
• Interval between 1st attack and chronic gout may last
from 3 – 42 years
• Rate of formation of tophi depends on both intensity and
duration of hyperuricemia
• Irregular asymmetric moderately discrete tumescence of
fingers , hands , knees or feet
• Usually painless but may be accompanied by periods of
painful inflammation
25

26. Chronic Tophaceous Gout
26

27. Chronic Tophaceous Gout
• Other sites include :
– Ulnar surfaces of forearm
– Antihelix of ear
– Fusiform enlargement of Achilles tendon
– Saccular distensions of olecranon bursa
• Eventually extensive destruction of joint occurs
• Deformities and progressive crippling
• Tense shiny thin skin over tophi may ulcerate
• White, chalky or pasty material extruded
27

28. Chronic Tophaceous Gout
• May lead to marked limitation of joint by :
– Involvement of joint directly
– Involvement of tendon
• Acute gouty spondylitis rare
• Nerve / spinal cord compression rare
28

29. Chronic Tophaceous Gout
29

30. Chronic Tophaceous Gout
30

31. Chronic Tophaceous Gout
31

32. Chronic Tophaceous Gout
32

33. Investigations
• Asymptomatic Hyperuricemia :
– Serum urate levels high
• Acute Gouty Arthritis :
– Aspiration of joint and identification of intracellular needle
shaped crystals
– Crystals have negative birefringence on polarized microscopy
– Crystals : rod shaped , blunt ended and digested by uricase
– Serum urate levels high
33

34. • Definitive diagnosis only
possible by aspirating and
inspecting synovial fluid or
tophaceous material and
demonstrating MSU crystals
• Polarized microscopy, the
crystals appear as bright
birefringent crystals that are
yellow (negatively
birefringent)
34

35. Investigations
• Murexide Test :
– Few drops of nitric acid are added to substance and mixture
evaporated to dryness. Ammonium hydroxide added. If uric acid
present : purple colour occurs
35

36. Synovial Fluid Findings
• Needle shaped crystals
of monosodium urate
monohydrate that have
been engulfed by
neutrophils
36

37. Imaging
• Acute attacks : only soft tissue swelling
• Chronic :
– Joint space narrowing
– Juxta articular osteoporosis
– Secondary Osteoarthritis
– Tophi : punched out cysts or deep erosions in para-articular
bone ends ( Martel’s Sign)
– Erosions with sclerotic margins and overhanging margins
37

38. Imaging
A large tophus is replacing
much of the fifth left
metatarsal
Classical ‘punched-out’ para-articular
erosion with a sclerotic margin of the
proximal phalanx 38

39. Imaging
39

40. Imaging
40

41. Imaging
41

42. Diagnosis
• Family history of gouty arthritis
• Repeated attacks with intervals of freedom from pain
• Renal disturbance or urate calculus
• Hyperuricemia
• Response to colchicine
42

43. Differential Diagnosis
• Trauma
• Infections
– septic arthritis, gonococcal arthritis, cellulitis
• Inflammatory
– Rheumatic arthritis, Reiter’s syndrome, Psoriatic
arthritis
• Metabolic
– pseudogout
• Miscellaneous
– Osteoarthrtis
43

44. Treatment
• Therapeutic Aims :
– Terminate attack of acute gout promptly and gently
– Prevent recurrence of acute gouty arthritis
– Prevent or reverse complications of disease resulting from
deposition of urate
– Prevent or Reverse associated illness like obesity , hypertension ,
hypertriglyceridemia
44

45. Treatment :
Asymptomatic Hyperuricemia
• Hyperuricemia alone not an indication of starting anti
hyperuricemic therapy
• Cause of hyperuricemia if any to be found
• Therapy to be started only if metabolic/ inherited causes
• Obesity , Hypertension , Hypertriglyceridemia need
attention
• Lifestyle modifications
45

46. Treatment :
Acute Gout
• Termination of attack may require
– NSAIDs (sure diagnosis)
– Colchicine ( unconfirmed diagnosis)
– Glucocorticoid preparation ( elderly )
– Ice packs
• Colchicine :
– Oral : 0.5 /0.6 mg tablet started ,taken every hour till :
• Nausea , vomiting or diarrhea occurs
• Joint symptoms eased
• Maximum 10 doses taken
46

47. Treatment :
Acute Gout
• Colchicine :
– Side effects :
• Increased peristalsis
• Cramping abdominal pain
• Diarrhea , nausea , vomiting
– The 2012 ACR guidelines recommend starting 1.2mg, followed by
0.6mg 1 hr later, and then 0.6 mg every 12 hrs until the attack has
subsided.
– The regimen can then be followed by 0.6mg once or twice daily for
prophylaxis as needed.
– For severe renal insufficiency:0.3mg/day
47

48. Treatment :
Acute Gout
• Colchicine :
– Acts by inhibiting E selectin mediated adhesiveness for neutrophils
– Decreases
• neutrophil L selectin expression
• Random motility of neutrophils
• Chemotaxis
• PLA 2 acivation
• IL 1 expression
• Mast cell histamine release
• Endothelial cell ICAM 1 expression
– Downregulates TNFα receptors on macrophages
48

49. Treatment :
Acute Gout
• Non Steroidal anti-inflammatory drugs :
– Effective in 90% of patients and the resolution of signs and
symptoms usually occurs in 5 to 7 days
– Indomethacin : NSAID of choice
– 50-75 mg is initial dose followed by 50 mg every 6 to 8 hrs
– With a maximum of 200mg in 1st 24 hrs
– Taper by 50 mg every 8 hrs for next 2 days
– Steady dose of 50 – 75 mg /day
– Ibuprofen : 800 mg tid or Diclofenac 50 mg tid
– Naproxen : very good results
– Sulindac , Piroxicam , Ketoprofen , COX 2 inhibitors
49

50. Treatment :
Acute Gout
• Glucocorticoids :
– Intra – articular glucocorticoids useful in treatment of single
joint or bursa
– A single intravenous dose of methylprednisolone or
– 7 mg of betametasone or
– 20 to 40 mg of intraarticular triamcinolone acetonide
– ACTH as an intramuscular injection of 25 to 80 IU in a single
dose or every 12 h for 1 to 2 days is effective in patients with
acute polyarticular refractory gout or with a contraindication for
using colchicine or NSAIDs
– Oral glucocorticoids such as prednisone, 20 to 60 mg/d as the
initial dose and tapered over 5 to 7 days equally effective
50

51. :
IL-1 inhibition
• Canakinumab
• single s/c injection 150mg
• For NSAID’s,colchine contraindicated patient
51

52. Recommendations for low purine
diet
• Beverages: carbonated drinks, fruit juice
• Dairy products: milk, cream,butter,cheese
• Cereals: all grains, bread, pasta , cakes
• Vegetables: lettuce, tomatos, vegetables
except peas, beans, lentils and spinach
• Fruite all kind, cherries
• Nuts: all kind
• Eggs, vitamin C
52

53. Foods to be avoided
• Tea, coffee and chocolate, high fructose corn
syrup
• Animal based proteins: meats, poultry, sea
foods, meat extracts, liver, kidney, heart,
gizzard, sweet breads
• Vegetables: peas, beans, spinach, lentils
• Beverages: alcohol, beer and beer products
53

54. Treatment :
Interval Gout
54

55. Treatment :
Interval Gout
55

56. prophylaxis
• Continued till serum uric acid normal and no
acute attacks for 3 to 6 months.
• 2012 ACR guidelines recommend prophylaxis
for 6 months, or 3months after achieving
target serum urate for patients w/o tophi or
• 6 months after acheving target serum urate
with resolution of tophi.
56

57. Treatment : Intercritcial Gout
• Prophylaxis :
– 0.6 mg of Cochicine once to thrice daily to prevent attacks
– May produce axonal neuromyopathy
– Indomethacin 25 mg TDS also effective
• Antihyperuricemic therapy :
– Usually started after 1st attack in a patient of hyperuricemia
– Need definite if existent hypertension
– Lifelong continuation usually required
57

58. Anti hyperuricemic therapy
1. Xanthine oxidase inhibitor ( Allopurinol)
2. Uricosurics
• Lower the serum uric acid level , faster the reduction in
its deposition
• Should never be given during an acute attack
• Target to reduce Serum uric acid to < 6 mg/dl
• Helpful in prevention of renal deterioration
58

59. Anti hyperuricemic therapy
Xanthine oxidase inhibitor ( Allopurinol, febuxostat )
• Indications :
1. Hyperuricemia with increased uric acid production :
– Urinary uric acid excretion of > 1000 mg / 24 hrs
– Hyperuricemia with HPRT deficiency or PRPP synthetase
hyperactivity
– Uric acid nephropathy
– Nephrolithiasis
– Prophylaxis before cytolytic therapy
59

60. Anti hyperuricemic therapy
Xanthine oxidase inhibitor ( Allopurinol , febuxostat)
• Indications :
2. Intolerance or reduced efficacy of uricosurics :
– Gout with renal insufficiency ( GFR < 60 ml/min )
– Allergy to uricosurics
60

61. Anti hyperuricemic therapy
Xanthine oxidase inhibitor ( Allopurinol)
• Substrate for Xanthine oxidase which oxidises to Oxypurinol which
inhibits Xanthine oxidase
• The starting dose is usually 100mg/day but 50 mg or even 50mg on
alternate day for elderly or with renal impairment.
• 4 weeks before starting Allopurinol , NSAID or Colchicine should be
started
• Most important side effect :
Allpurinol Hypersensitivity syndrome : skin rash , fever , esophilia ,
hepatitis , renal impairment
• Others : GI intolerance , TEN , Alopecia , Rashes , Bone marrow
suppression
61

62. Anti hyperuricemic therapy
Uricosurics :
• Increase the rate of uric acid excretion
• Uricosuric drugs present in the lumen and competitively inhibit
urate for the transporter
• Probenecid , Sulfinpyrazone , Benzbromarone, lesinurad )
• Probenecid :
– Maintaince dose of 500 mg – 3gm /day in 2 or 3 divided doses
– High drug interaction
62

63. Anti hyperuricemic therapy
63

64. Anti hyperuricemic therapy
Uricosurics :
• Ideal candidate :
– < 60 years
– Normal renal function
– Uric acid excretion of < 800 mg /24 hrs
– No history of renal caliculi
– Not taking inflammatory doses of salicylates
64

65. Newer Therapies
• Uricase
– Enzyme that oxidizes uric acid to a more soluble form
– Natural Uricase from Aspergillus flavus and Candida utilis under investigation
– Pegloticase for refractory tophaceous gout.
• Febuxostat
– New class of Xanthine Oxidase inhibitor
– More selective than allopurinol
– Little dependence on renal excretion
– Initial dose: 40 mg po od, can be increased upto 80mg
• Losartan
• Fenofibrate
– Studies note when used in combo with Allopurinol produced additional
lowering of the urate
65

66. Surgical Procedures
• Immobilization of joint will lessen the degree of
destruction
• Large tophi that interfere with joint movement may need
removal
• Surgery requires following precautions :
– Avoidance of local anesthesia
– Incision parallel with course of blood vessels
– Sharp dissection
– Loose suturing to allow escape of liquefied deposits
– Pressure dressing
– Avoidance of prolonged splintage
66

67. Other Crystal Deposition disorders
Calcium Pyrophosphate dehydrate deposition :
• Chondrocalcinosis
• Pseudogout
• Chronic pyrophosphate arthropathy
Calcium hydroxyapatite deposition disorders
( Basic Calcium phosphate deposition disorders)
67

68. Associations of CPPD
• Ageing
• Disease-associated
• Primary hyperparathyroidism
• Hemochromatosis
• Hypophosphatasia
• Hypomagnesemia
• Chronic tophaceous gout
• Postmeniscectomy
• Epiphyseal dysplasias
• Hereditary
• Wilson’s Syndrome
68

69. Clinical features (CPPD)
• > 60 years
• Asymptomatic Chondrocalcinosis :
– Calcification of the menisci asymptomatic
– Hemarthrosis
• Acute Synovitis ( Pseudo gout )
– Typically involve one large joint
– Most often knee ; 1st MTP involved very rarely
– Sudden onset
– Excruciatingly painful
69

70. Clinical features (CPPD)
• Acute Synovitis ( Pseudogout )
– Periarticular swelling, warmth and edema
– Attacks last for 7 -10 days usually
– Associated with fever and chills
– Leukocytosis
• Chronic pyrophosphate arthropathy :
– Mimics osteoarthritis
– Pain , stiffness , swelling , crepitus , loss of movement
– Seen in shoulders , hips , knees , wrists
70

71. Clinical Features ( CPPD )
71

72. Clinical Features (CPPD)
• Provocative factors :
– Direct trauma to joint
– Intercurrent medical illness
– Surgery ( especially parathyroidectomy)
– Blood transfusion
– Thyroxine replacement therapy
– Joint lavage
– Arthroscopy
– Hyaluronic acid injection
72

73. Clinical Features ( HA )
• Acute / Subacute Periarthritis :
– Commonest form of HA crystal deposition
– Adult between 30-50 yrs
– Pain near one of the larger joints : eg. knee /shoulder
– Seen most commonly in rotator cuff lesions of shoulder
– Preceded usually by minor trauma
– Symptoms subside themselves within few weeks
– May reveal tense globule of creamy material oozing from
between frayed fibres of tendon /ligament
73

74. Clinical Features ( HA )
• Chronic Destructive arthritis :
– Shoulder ( Milwaukee Shoulder ) : bilateral , worse on the side of
dominant hand
– Synovial fluid is blood stained
– May also involve knee
74

75. Investigations
• Leukocytosis ( > 20,000 /mm3)
• ESR increased
• Presence of CPPD crystals in synovial fluid
• Crystals are weakly birefringent , rhomboid
• HA crystals : nonbirefringent globular clumps
• HA crystals stain with Alizarin red
75

76. Imaging
• Calcification seen in and around :
– Knees , wrists , shoulder , hips , Pubic symphysis
• Heavy punctate and linear calcification
• Radiocarpal or patellofemoral joint space narrowing
• Patella wrapped around femur
• Scaphoid lunate widening
• Femoral cortical erosion superior to patella
• Metacarpal squaring with beak like osteophytes and subchondral
cyst
• Tendon calcification
76

77. Imaging
77

78. Imaging
78

79. Imaging
79

80. Imaging
80

81. Imaging (Hydroxyapatite)
• Calcification seen in tendons and ligaments close to joints
• Most commonly calcification in shoulder
• No calcification in fibrocartilagenous structures
• Loose bodies seen in synovial joints
• Loss of articular space
• Little / No sclerosis or osteophyte formation
• Subchondral bone eroded in later stages
81

82. Diagnosis of CPPD
Criteria :
1. Demonstration of CPPD crystals obtained by biopsy or aspirated
synovial fluid
2. Identification of monoclinic or triclinic crystals showing weakly
positive birefringence by polarized light microscopy
3. Presence of typical calcifications in radiographs , punctate and
linear calcifications , especially if bilaterally symmetrical
4. Acute arthritis especially of knee or other large joints
5. Chronic arthritis accompanied by acute exacerbations of elbow ,
shoulder , MCP joints
82

83. Diagnosis of CPPD
Diagnostic Categories :
• Definite : Criteria 1 or 2
• Probable : Criteria 2 or 3
• Possible : Criteria 4 or 5
83

84. Treatment
• Rest
• High dosage NSAIDs
• Joint aspiration
• Intra-articular glucocorticoid therapy
• Low dose colchicine orally only for prophylaxis
• Possible benefits of Magnesium , Hydroxy chloroquine
• Colchicine intravenously not recommended
84

85. Treatment ( Hydroxyapatite)
• NSAIDs especially COX 2 inhibitors
• Local Corticosteroid injection
• Local irrigation
• Surgical removal of calcific deposits
85

86. GOUT and PSEUDOGOUT
GOUT PSEUDOGOUT
Mainly involves 40-60 yrs > 60 yrs
Smaller joints involved ( esp 1st
MTP )
Larger joints involved ( esp knee)
Pain is intense Pain moderate
Joint inflamed Joint swollen
Hyperuricemia Chondrocalcinosis
Negatively birefringent crystals ,
rod shaped
Positively birefringent crystals ,
rhomboid shaped
Crystals digested by uricase Not digestable by uricase
XRay : No calcification , erosion
characteristic
Calcification seen , erosion
degenerative 86

87. 87