juvenile idiopathic arthritis........

1. JUVENILE IDIOPATHIC
ARTHRITIS
DR NAZNIN HABIB BARSHA
DR REZWANA
DCH students
Dhaka Medical college hospital,
Dhaka

2. A 10- years- old girl ,presented with pain and swelling of multiple
small and large joints of both upper and lower limbs for last 7 months
,which was symmetrical, non migratory associated with morning
stiffness and irregular low grade fever. She had no h/o rash, oral ulcer,
photosensitivity, chest pain, sore throat, bleeding, breathlessness and
visual problem.

3. She was mildly pale, febrile,
skin survey revealed normal.
Her both knee, elbow and
small joints of hand and feet
were swollen, warm, tender
(grade 3/4) with restricted
movement. Gait was limping.
There was no organomegaly,
lymphadenopathy.

4. • Provisional diagnosis: Polyarticular JIA

5. JUVENILE IDIOPATHIC ARTHRITIS
•Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease
in children.
•Represents a heterogeneous group of disorders all sharing the clinical
manifestation of arthritis.
•The etiology and pathology of JIA are largely unknown.

6. EPIDEMIOLOGY
Incidence: 0.8-22.6/100,000
Prevalence ranges from 7-401/100,000
• Oligoarthritis: 40-50%
• Polyarthritis:
RF negative: 20-35%,
RF positive : <10%
• Systemic JIA: 5-15%
• Psoriatic: 5-10%
• Enthesitis related: 5-10%

7. PEAK AGE OF ONSET (Yr) FEMALE : MALE RATIO
Systemic arthritis 1-5 1 : 1
Oligoarthritis 2-4 3 : 1
Ployarthritis 2-4 and 10-14 3 : 1 and 10 : 1
RF-positive 9-12 9 : 1
Psoriatic arthritis 2-4 and 9-11 2 : 1
Enthesitis-related 9-12 1 : 7
Age and sex predominance

8. Aetiology
• Exact aetiology is unknown
1. Immunogenetic susceptibility
2. External trigger
- virus- parvovirus B19, Rubella, EBV, HIV etc
- immune responses to bacterial/mycobacterial heat shock proteins.
-Joint trauma
-Stress
-Abnormal reproductive hormone

9. 3.Genetic predisposition: HLA association
Early onset oligoarthritis
- HLA DR 5
- HLA DR 8
Oligoarthritis in older children
- HLA B27
Poliarticular JIA (RF +ve)
- HLA DR 4

10. Pathogenesis:
Stimulus
Nonspecific synovial inflammation
Macrophage and mononuclear cell
infiltrate
Production of inflammatory cytokines
IL 1, IL 6, TNFα
Release of metalloproteinase
Tissue destruction
Early changes in joint
Changes in advanced JIA

11. Pathology
• Subsynovial tissue
- Villous hypertrophy and hyperplasia
- Hyperemia and edema
• Vascular endothelium
- Hyperplasia
- Infiltration of mononuclear cell and plasma
cell
• Articular cartilage and contaguous bone
- Progressive erosion
- Pannus formation

15. Criteria for the classification of JIA
• Age at onset <16 yr
• Arthritis in one or more joints
• Duration of disease 6 wk or longer
• Onset type defined by type of articular involvement in first 6 month after
onset :
- Polyarthritis : ≥ 5 inflamed joints
- Oligoarthritis : ≤ 4 inflamed joints
- Systemic disease : arthritis with rash and a characteristic
quotidian fever
• Exclusion of other forms of arthritis

16. Characteristics of the ACR & ILAR classification of childhood chronic arthritis
<16 yr<16 yrAge at onset
≥6 wk≥6 wkMinimum duration
Juvenile idiopathic arthritis
(JIA)
Juvenile rheumatoid
arthritis (JRA)
Term
ILAR (1997)ACR (1977)PARAMETER

17. SystemicSystemicFever, rash, arthritis
Polyarticular RF – negative
Polyarticular RF – positive
Polyarticular>4 joints in 1st 6 mo after
presentation
Oligoarthritis:
A - Persistent: <4 joints for course
of disease
B - Extended: >4 joints after
6 months
Pauciarticular≤4 joints in 1st 6 mo after
presentation
ILAR (1997)ACR (1977)PARAMETER

18. YesNoInclusion of psoriatic
arthritis, inflammatory
bowel disease,
ankylosing spondylitis
- Psoriatic arthritis
- Enthesitis-related arthritis
- Undifferentiated:
A - Fits no other category
B - Fits more than one category
Exclusion of
other forms
Other categories
included
ILAR (1997)ACR (1977)PARAMETER

19. CATEGORIES OF DIFFERENT TYPES OF JIA
(ILAR-1997)

20. Defination- Arthritis in ≥1 joints with, or preceded by, fever of at least 2 wk
in duration that is documented to be daily (“quotidian”) for at least 3 days
and accompanied by ≥1 of the following:
1. Evanescent (nonfixed) erythematous rash.
2. Generalized lymph node enlargement.
3. Hepatomegaly or splenomegaly or both.
4. Serositis.
- 5-15%
- Peak age of onset : 1-5 years
- Female : male : 1:1
Systemic onset JIA

21. Athritis pattern -Polyarticular
-affecting knees, wrists ,ankles, fingers
-very distructive. Can include neck, hips, TMJ
Extra articular features : -Daily fever,
-evanescent rash,
-pericarditis,pleuritis
-organomegaly
-MAS etc
Systemic onset JIA

22. Typical spiking fever in systemic JIA

23. Rash in SOJIA
-non fixed
-salmon colored
-Linear/circuler,maculer/maculopapuler
-non pruritic(<5% pruritic)
-migratery
-lasting <1hr
-comes with fever,disappears when fever
subsides
- mostly in trunk and proximal extremities
-Koebner phenomenon often present

26. Definition
Arthritis affecting 1-4 joints during the first 6 months of disease.
Two subcategories are recognized:
1. Persistent – affecting ≤4 joints throughout the disease
course.
2. Extended – affecting >4 joints after the 1st 6 months of
disease.
Oligoarticular JIA

27. • - 40-50 % of all JIA cases (ethnic variation)
• - peak age of onset : 2-4years
• - Female : male : 3:1
Arthritis pattern : knees, ankles, fingers
Extra articular features :
- Uveitis in about 30% of cases
-ANA +ve in about 60%(risk increased)
Oligoarticular JIA

28. Oligo-articular JIA

29. Arthritis affecting ≥5 joints during the 1st 6 months of disease; test for
RF is negative
• 20-35%
• peak age of onset : 2-4 and 10-14 years
• Female : male : 3:1 and 10:1
-Arthritis pattern : small & large joints, cervical spine,TM joint
-Extra articular features : Uveitis (10%)
ANA +ve in 40%
Polyarticular JIA(RF negative)

30. Poly-articular JIA

31. Arthritis affecting ≥5 joints during the 1st 6 months of disease; ≥2 tests for
RF at least 3 month apart during the 1st 6 month of disease are positive
• <10% of all JIA
• Peak age of onset : 9-12 years
• Female : male : 9:1
-Arthritis pattern : aggressive symmetric polyarthritis
- Extra articular features : rheumatoid nodules(10%)
low grade fever
Polyarticular JIA( RF positive)

32. Common sites of
rhematoid nodule

33. Psoriatic arthritis
Definition
Arthritis and psoriasis, or arthritis and at least 2 of the following:
1. Dactylitis.
2. Nail pitting and onycholysis.
3. Psoriasis in a 1st-degree relative.
• Peak age of onset : 2-4, 9-11 years
• Female : male : 2 : 1
• % of all JIA cases : < 5-10

35. Psoriatic arthritis
Arthritis pattern : Asymmetric arthritis of small or medium-sized joints
Extra articular features :
- Uveitis in 10%;
- psoriasis in 50%
- ANA positive in 50%

36. Enthesitis-related arthritis
Definition
Arthritis and enthesitis or arthritis or enthesitis with at least 2 of the following
1. Presence of or a history of sacroiliac joint tenderness or inflammatory
lumbosacral pain or both.
2. Presence of HLA-B27 antigen.
3. Onset of arthritis in a male > 6 yr old.
4. Acute (symptomatic) anterior uveitis.
5. History of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with
inflammatory bowel disease, Reiter syndrome, or acute anterior uveitis in
1st-degree relative

37. Enthesitis-related arthritis

38. Enthesitis-related arthritis
• peak age of onset : 9-12 years
• Female : male : 1 : 7
• % of all JIA cases : 5-10
- Arthritis pattern : Predominantly lower limb joints affected; sometimes axial
skeleton (but less than in adult, ankylosing spondylitis)
- Extra articular features :- Acute anterior uveitis,
- association with reactive arthritis and IBD
- 80% of patients +ve for HLA-B27

39. Undifferentiated arthritis
Arthritis that fulfills criteria in no category or in ≥ 2 of the above
categories.

43. Complications
Articular Extra articular SOJIA
Flexion contracture Uveitis Macrophage activation
syndrome(MAS)
Leg length discrepancy Growth retardation Amyloidosis
TM joint involvement Psychosocial deprivation
Cervical spine involvement osteoporosis
Swan neck deformity
Popliteal cyst

44. Swan neck deformity Leg length discrepancy
Popliteal cyst

45. Ocular problem in JIA
• Iridocyclitis
-Acute
-Chronic
• Posterior synechiae
• Cataract
• Secondary glaucoma
• Permanent blindness
Iridocyclitis: irregular pupil
Cataract ,band keratopathy
Uveitis

46. Differential Diagnoses
1. Infection
• Septic arthritis
• Osteomyelitis
• TB arthritis
2. Reactive
• Post streptococcal
• Post viral
• Post enteric
• ARF

47. 3. Other rheumatic disease
• SLE
• Juvenile Dermatomyositis
4. Systemic vasculitis
- HSP
- Kawasaki Disease
5. Malignancy
- Leukemia

48. 6. Hematological
- Hemophilia
7. Arthritis associated with IBS
8. Trauma

49. Diagnosis
Diagnosis is done by excluding the differentials through
• Thorough history taking
• Meticulous clinical examination
• Appropriate investigations

50. Approach to a patient with joint manifestation
History to be taken
1 . Age and sex of the child
2. Presenting complaints
3. Onset and Duration of illness
4. Number of joint involvement
5. Symmetrical or not
6. - Morning stiffness
7. Migratory or intermittent
8. Presence of fever, rash,
constitutional symptoms
9. Presence of eye
complaints(redness,pain)
10. Respiratory difficulty, chestpain

51. Systemic enquiry:
1. H/O trauma(septic arthritis)
2. Dysuria, haematuria,abdominal pain(Reactive arthritis, HSP)
3. Photosensitivity, Oral ulceration, Malar rash and other skin rash(SLE)
4. H/O sore throat(Rheumatic fever)
5. H/O contact with TB patient(TB arthritis)
6. H/O bleeding manifestation(ALL,Hemophilia)

52. • Treatment received during period of illness:
• Drug history
• Immunization H/O
• Personal H/O- Daily living activities dressup, Bathing, toilet, combing,
climbing stairs,Sports,school performance
• Family history: psoriasis, autoimmune disease

53. Clinical examination
• General examination
-appearance
- Pallor
- Clubbing
- Oedema
- Conjunctivitis
- Lymphadenopathy
- Bony tenderness
- Skin rash, BCG mark
- Nail pitting
- Alopecia
- Anthropoemetry
- Slit lamp examination
- BSUA
- Vitals

54. • Respiratory
- Pleuritis
• Nervous system
- Psychosis
- Convulsion
- Chorea
- Neuropathies
• CVS - Pericarditis
- Myocarditis
- Murmur
• Alimentary system
- Mouth ulcer
- Dry, fissured lips
- Strawberry tongue
- Hepatoslplenomegaly
testis??

55. • Locomotor system
1 . pGALS -pediatric gait arm and leg
Screening tool actively done by patent
2. local examination –Look, Feel, Move
Passively done by doctor

56. pGALS

57. pGALS

58. Inspection(look)-1. Swelling
2 . Redness
3.deformity or contracture
4.muscle wasting
5.Leg length discrepancy
Palpation(feel)- 1.temperature
2. tenderness
3.fluctuation test
4.patellar tap
5. bulging test
Move- Range of movement of the joints.
Gait- antalgic/limping
Some special test- Schobers test
Thomas test

59. Schobers test

61. Investigation
To established diagnosis:
• Complete blood count-
Hb- low (7-10 g/dl)
TC WBC- Raised
Platelet-Raised
• PBF - Microcytic anemia
• ESR-Raised
• CRP - Elevated

62. Serological tests
• ANA titer –Raised in 40-85% in Oligoarticular or polyarticular
JIA, rare in SJIA
• RF factor- Positive in 5-15% patient with Polyarticular JIA.
• Anti CCP Ab
• HLA marker

63. Radiography :
• Xray :
Stages of radiological progression in rhematoid arthritis
Stage I : no change, only soft tissue swelling
Stage ll : periarticular osteoporosis, effusion
Stage lll : loss of articular cartilage
Stage lv : erosion
Stage v : subluxation & ankylosis
• MRI
• Ultrasonography.

64. For exclusions of other disease (in suspected cases):
-ASO Titre
-ECG
-ECHO
-Mantoux test
-PBF
-Bone marrow study
-S.C3, S.C4
Before starting DMARDs
- S. ALT
- S. creatinine

65. Early change Late change

66. MRI with gadolinium contrast showing dense white signal in the symvium near the
distal femur, proximal tibia, and patella reflects inflammation.

67. X-ray cervical spine showing fusion of the neural arch between joints
C2 and C3

68. CT scan of the temporomandibular joint in JIA.

70. A multi-disciplinary approach is essential
Paediatrician
Paediatric Rheumatologist
Ophthalmologist
Orthopedic Surgeon
Occupational therapist
Psychologist
Physiotherapist

71. Treatment of oligoarthritis
• Initially NSAIDS.
• Intra-articular steroid injections:
• The very young
• Marked persistent joint swelling
• Synovial cysts causing limitation of movement.
• Prolonged disease or extension to polyarticular disease- MTX .
Etanercept, in cases unresponsive to MTX.
• Uveitis -corticosteroid eye drops and mydriatics.Severe disease oral
prednisolone.

72. Treatment
Oligoarthritis NSAID No or partial response within
4-6 week,who have functional limitation injection of intra
articular corticosteroid. DMRD (MTX) Biological agent
(anti TNF alfa)

74. Polyarticular JIA
• Initially a trial of an NSAID for 4-8 weeks.
• In non-responders to NSAIDs, intra-articular steroid injections.
• DMARDs should also be introduced for at least 3 months.
• Methotrexate is the first-line drug. Sulfasalazine used if there are
features of spondyloarthropathy.
• Etanercept is used for patients intolerant of or unresponsive to,
methotrexate.

75. Treatment
Children with Polyarthritis
NSAID, DMARD (Methotrexate)
No response in 6-12 weeks
Addition of biologic DMARD Such as TNF α antagonist
children with poor prognostic factor and severe disease.

77. Systemic arthritis
• NSAIDS alone rarely induce remission in children with SoJIA.
• DMARDS currently available for adjunctive therapy.
• Failure of MTX monotherapy along with bDMARD show excellent
disease control.
• Early and aggressive treatment with TNFα inhihibitor show excellent
outcome.
• When systemic symptoms dominates initiation of interleukin 1 receptor
antagonist therapy induces a dramatic and rapid response.

78. Drugs used in JIA

79. Nonsteroidal anti inflammatory drugs
Medication Dose Subtype
Naproxen 15mg/kg/day Polyarthritis,systemic,
Oligoarthritis
Ibuprofen 40mg/kg/day Same
Meloxicam 0.125mg/kg/day Same

80. Cont…
Disease modifying antirheumatic drugs
Methotrexate 10-30mg/m2 PO or
S/C wkly
Polyarthritis,systemic,
Oligoarthritis
Salfasalazine Initial 12.5mg/kg daily
Maintenance 40-
50mg/kg
Polyarthritis
Leflunomide 10-20mg daily Polyarthritis

81. MTX
Folic Acid Antagonist
Mode of action of MTX in JIA:
I. ↓ pro-inflammatory cellular signaling
II. Immunosuppressive & lymphotoxic effects
III. ↓ metalloproteinase & collaginase enzymes
IV. ↓ of leucocytic prolifeation

82. MTX
How to use
Dose: 10-20/mg/m2/wk
Route: oral – empty stomach
- with clear liquids
- or 1 hr before BF
Parenteral – SC, IM , IV
Availability –Tablets,Injections

83. Contraindication of MTX
 White cell count < 3500/cmm
Neutrophil count <1500× /cmm
Platelet count <150000/cmm
ALT level >2 times of upper level
 Immunodeficiency state,
 Child coming in contact with chicken pox, Measles or develops chicken pox
 Liver or Renal Failure

84. Adverse effect of MTX
 Bone marrow suppression, leukopenia
 GI intolerance
 Hepatic insufficiency
 Mucositis, Somatitis
 Renal impairment

85. Monitoring of Treatment
Baseline- CBC with ESR,
-CRP
-LFT
After starting MTX- Initially monthly for 3 months then every 8-12 weeks

86. Cont…
Biologic agents
Anti tumor necrosis factor α Etanercept,Infiximab,Adalimumab
Anticytotoxic T lymphocyte
associated Ag 4 Immunoglobulin
Abatacept
Anti CD 20 Rituximab
Interlukin 1 inhibitors Anakinra, Canakinumab
Interlukin 6 receptor antagonist Tocilizumab

87. Central Role of TNFa in JIA

88. Mechanisms of Action
Etanercept
Recombinant soluble TNF α receptor blocker. Prevents TNF α from binding its
receptor.
Infliximab
Monoclonal Ab against soluble and transmembrane TNFα.
Adalimumab
Humanized monoclonal Ab against TNF α Preventing its binding to its receptor.

89. TNF-α inhibitors
• Monotherapy and Combination
• With methotrexate
• Improved quality of life
• Decreased joint tenderness and swelling
• Improved radiographic changes

90. Other Issues in the management
• Physical and occupational therapy: Maintain and improve range of
motion, muscle strengths and daily activities skills.
• Splints: prevention of contractures/ improve range of motion.
• Arthroplasty: lengthening of tendons or tenotomy might be needed.
• No role of Tractions.

91. Contd:
• Nutritional support : monitoring of growth and pubertal status
• Appropriate calcium intake with vitamin D along with physical activities
for prevention of low bone mineral density
• Use of folic acid
Vaccination but not live vaccines

92. Contd:
• Counseling of the family (most important)
• Attention to the psychological well-being
• Parents and if possible child be educated about current knowledge of
management and outcome.
• Adolescent patient: Discussion about transition to adult health care
service

93. Follow up
• At each visit, evaluation for subjective and objective evidence of active
disease:
1. Degree of joint pain (By visual analog scale).
2. Duration of morning stiffness.
3. Duration of fatigue.
4. Limitation of function (Functional grade).
5. Presence of actively inflamed joints (Tender and swollen joint counts).

94. Follow up
Periodical evaluation for disease progression
1. Evidence of disease progression on physical
examination -
Loss of function, Instability,
Malalignment, Deformity
2. ESR or CRP elevation.
3. Progression of radiographic damage.
4. Slit lamp examination.

95. Eye Screening: (AAP)
Types Examination
frequency
High risk OJIA or Poly,<7 yrs at onset of arthritis,
and ANA test positive
3–4 months
Medium risk I) OJIA or POJIA onset, <7 years at onset of arthritis, and
ANA test negative
II) OJIA or poly , >7 years at onset of arthritis, and ANA
test positive or negative
6 months
Low risk SJIA 12 months

96. Clinical Remission
Clinical remission on medication (CRM)
Inactive disease for a period of 6 months on medication.
Clinical remission off medication (CR)
Inactive disease for a period of 12 months after discontinuation of
medication.

97. Complete remission
• Complete remission is defined as the absence of at least 5 of the
followings for 2 consecutive months.
- Symptoms of active inflammatory joint pain.
- Morning stiffness.
- Fatigue.
- Synovitis on joint examination.
- Progression of radiographic damage.
- Elevation of ESR or CRP levels.

98. Conclusion:
• In spite of development in the management, JIA remains an important
cause of chronic pain and disability in children.
• Early diagnosis with classification is important.
• Early, Effective & Aggressive treatment of this disease - better disease
control and achieve inactive disease

99. Conclusion (Contd)
And
• Better quality of life allowing children to become adult leading normal
or near normal lives.
• So, Increasing awareness for early diagnosis and proper management is
crucial for the JIA patients for providing them better quality of life