Most common rheumatic disease in childhood but prevalence and incidence vary remarkably in different geographic regions •Incidence : 0.8 to 22.6/100,000 children per year •Prevalence : 7 to 401/ 100,000. •Oligoarticular JIA (30-60%): The peak age at onset : Between 2 and 4 yr, F/M: 3:1 Polyarticular (30-35%): Bimodal distribution with peaks at 1-4 yr and 10-14 yr, F/M: RF negative (3 : 1), RF positive (5 : 1) JIA. • Systemic onset (10-20%): peak 1-5 years(No sex predominance) • Enthesitis related arthritis (10-20%):Onset usually after 6 years and M/F: 7:1 • Juvenile psoriatic arthritis (2-5 %): Bimodal distribution 1-4 yr and 10-14 yr 8 Etiopathogenesis • Both immunogenetic susceptibility and an external trigger • Variants in major histocompatibility complex (MHC) class I and class II regions • Non-HLA candidate loci: polymorphisms in the genes encoding protein tyrosine phosphatase nonreceptor 22 (PTPN22), tumor necrosis factor (TNF)-α, macrophage inhibitory factor, interleukin (IL)-6, and IL-1α. • External trigger: bacterial and viral infections, enhanced immune responses to bacterial or mycobacterial heat shock proteins, abnormal reproductive hormone levels, and joint trauma. 9 10 • All these cause inflammatory synovitis, characterized by villous hypertrophy and hyperplasia with hyperemia and edema of synovial tissue. • Vascular endothelial hyperplasia is prominent and is characterized by infiltration of mononuclear and plasma cells with a predominance of T lymphocytes • Advanced and uncontrolled disease leads to pannus formation and progressive erosion of articular cartilage and contiguous bone 11 Genetics • Monozygotic twins : 25% to 40% • Siblings : 15 to 30 fold higher • Role of HLA class I and II alleles HLA B27 Enthesis related arthritis HLA-A2 is associated with early-onset JIA HLA-DRB1*08, 11, and 13 and DPB1*02 :oligoarticular JIA. HLA-DRB1*08 : Rf negative polyarticular JIA. 12 JRA 13 • Age: <16 years & Duration : > 3 months Subtypes (Based on characteristics at onset): JCA • Pauciarticular (1-4 joints) • Polyarticular (≥5 joints) • Presence of RF (2 positive tests at least 3 months apart) • Systemic onset with characteristic features • Juvenile ankylosing spondylitis • Juvenile psoriatic arthritis 14 • Age: <16 years & Duration : > 6 weeks • Systemic onset JIA • Oligoarticular JIA : Persistent and extended • Polyarticular JIA : RF positive and RF negative • Psoriatic arthritis • Enthesitis related arthritis • Undifferentiated arthritis JIA 15 16 Clinical features Symptoms (Arthritis must be present to make a diagnosis of any JIA subtype): Signs: • Early: • Swelling • Warm on palpation • Tenderness but not erythematous • Restricted ROM • Antalgic gait • Late: • Deformities • Growth disturbances • Pain • Swelling • Stiffness following inactivity • Easy fatigability and poor sleep quality 17 Systemic onset JIA Arthritis in ≥1 joint with, or preceded by, fever of at least 2 weeks time.

1. Juvenile Idiopathic Arthritis
Dr. Pratik Silwal
2nd Year Junior Resident
Dept. of Orthopedics, BPKIHS
1

2. References
• Apley’s & Solomon’s system of Orthopedics and Trauma, 10th edition
• Nelson Textbook of Pediatrics, 20th Edition
• Kelley & Firestein’s textbook of Rheumatology, 10th edition
• Turek’s orthopaedics, principles and their appliances, 7th edition
• Campbell’s operative orthopedics, 13th edition
• Online sources
2

3. Contents
• Epidemiology
• Etiopathogenesis
• Criteria for classification of JIA
• ILAR classification
• Clinical manifestations
• Different types of JIA
• Diagnosis
• Complications
• Treatment
• Prognosis
• Summary
3

4. Nomenclature
• Still’s Disease
• JRA
• JCA
• JIA
4

5. Arthritis
• Joint effusion alone or the presence of two or more of the following signs:
1. Limitation of range of motion
2. Tenderness or pain on motion
3. Increased warmth
5

6. Definition
• Per the ILAR criteria, JIA is a diagnosis of exclusion.
• Defined as arthritis of at least one joint with:
1. Manifestations persist for at least six weeks
2. Onset is before 16 years of age
3. Etiology is unknown
6

7. Epidemiology
• Most common rheumatic disease in childhood but prevalence
and incidence vary remarkably in different geographic regions
• Incidence : 0.8 to 22.6/100,000 children per year
• Prevalence : 7 to 401/ 100,000.
• Oligoarticular JIA (30-60%): The peak age at onset : Between 2
and 4 yr, F/M: 3:1
7

8. • Polyarticular (30-35%): Bimodal distribution with peaks at 1-4 yr
and 10-14 yr, F/M: RF negative (3 : 1), RF positive (5 : 1) JIA.
• Systemic onset (10-20%): peak 1-5 years(No sex predominance)
• Enthesitis related arthritis (10-20%):Onset usually after 6 years
and M/F: 7:1
• Juvenile psoriatic arthritis (2-5 %): Bimodal distribution 1-4 yr
and 10-14 yr
8

9. Etiopathogenesis
• Both immunogenetic susceptibility and an external trigger
• Variants in major histocompatibility complex (MHC) class I and class II
regions
• Non-HLA candidate loci: polymorphisms in the genes encoding
protein tyrosine phosphatase nonreceptor 22 (PTPN22), tumor
necrosis factor (TNF)-α, macrophage inhibitory factor, interleukin (IL)-
6, and IL-1α.
• External trigger: bacterial and viral infections, enhanced immune
responses to bacterial or mycobacterial heat shock proteins,
abnormal reproductive hormone levels, and joint trauma.
9

10. 10

11. • All these cause inflammatory synovitis,
characterized by villous hypertrophy and
hyperplasia with hyperemia and edema
of synovial tissue.
• Vascular endothelial hyperplasia is
prominent and is characterized by
infiltration of mononuclear and plasma
cells with a predominance of T
lymphocytes
• Advanced and uncontrolled disease leads
to pannus formation and progressive
erosion of articular cartilage and
contiguous bone
11

12. Genetics
• Monozygotic twins : 25% to 40%
• Siblings : 15 to 30 fold higher
• Role of HLA class I and II alleles
HLA B27 Enthesis related arthritis
HLA-A2 is associated with early-onset JIA
HLA-DRB1*08, 11, and 13 and DPB1*02 :oligoarticular JIA.
HLA-DRB1*08 : Rf negative polyarticular JIA.
12

13. JRA
13

14. • Age: <16 years & Duration : > 3 months
Subtypes (Based on characteristics at onset):
• Pauciarticular (1-4 joints)
• Polyarticular (≥5 joints)
• Presence of RF (2 positive tests at least 3 months apart)
• Systemic onset with characteristic features
• Juvenile ankylosing spondylitis
• Juvenile psoriatic arthritis
JCA
14

15. • Age: <16 years & Duration : > 6 weeks
• Systemic onset JIA
• Oligoarticular JIA : Persistent and extended
• Polyarticular JIA : RF positive and RF negative
• Psoriatic arthritis
• Enthesitis related arthritis
• Undifferentiated arthritis
JIA
15

16. 16

17. Clinical features
Symptoms (Arthritis must be
present to make a diagnosis of
any JIA subtype):
• Pain
• Swelling
• Stiffness following inactivity
• Easy fatigability and poor sleep quality
Signs:
• Early:
• Swelling
• Warm on palpation
• Tenderness but not erythematous
• Restricted ROM
• Antalgic gait
• Late:
• Deformities
• Growth disturbances
17

18. Systemic onset JIA
Arthritis in ≥1 joint with, or preceded by, fever of at least 2 weeks 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
18

19. • Exclusions:
a) Psoriasis or a history of psoriasis in the patient or a 1st-degree
relative
b) Arthritis in an HLA-B27–positive boy beginning after the 6th
birthday
c) Ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with
inflammatory bowel disease, Reiter syndrome, or acute anterior
uveitis, or a history of one of these disorders in a 1st-degree relative
d) Presence of immunoglobulin M RF on at least 2 occasions at least 3
months apart
19

20. Rash:
• Evanescent, non-pruritic
• Salmon-colored linear or circular macular rash on
upper trunk and extremities
• Positive Kobner’s phenomenon
• Accompanies febrile periods
20

21. Oligoarticular JIA
Arthritis involving 1- 4 joints within 6 months of disease onset
• Knees>ankle>subtalar>wrist (usually asymmetric)
1. Persistent oligoarthritis: affecting ≤4 joints throughout the disease
course
2. Extended oligoarthritis: affecting > 4 joints after first 6 months of
disease
21

22. • Less systemic features
• ANA positive
• Female, young age of disease onset <7 years, asymmetric arthritis
• Uveitis: In female with ANA +
Non-granulomatous, chronic and anterior uveitis
22

23. Polyarticular JIA
≥ 5 joints during 1st 6 months of disease in both upper and lower extremities
Types of polyarthritis:
• Rheumatoid factor positive polyarticular JIA: Presence of a rheumatoid factor
antibody in the blood ≥ 2 RF are positive at least 3 months apart
• Rheumatoid factor negative polyarticular JIA: No rheumatoid factor antibody in
the blood.
23

24. RF positive:
• Arthritis similar to adult RA
• Aggressive, symmetric, small
joint involvement of both the
hands and feet and the cervical
spine and TMJ may be involved.
24

25. • Radiologic
changes tend to
take place early
resulting from
bony erosions
and joint
destruction
especially in
hands and feet
25

26. • Hip involvement is common and
debilitating.
• Rheumatoid nodules
26

27. • RF negative: two clinical subgroups based on ANA
1. ANA+ form: resembles oligoarticular JIA, young girls aged 6 years or
less, asymmetric arthritis > 4 joints and high risk of uveitis, and
2. ANA− form: similar to adult-onset RF− rheumatoid arthritis (RA),
older patients, symmetric synovitis of large and small joints, a
greater cumulative number of affected joints, and less uveitis.
27

28. Complications
• Anemia of chronic disease
• Growth disturbances
• Uveitis
28

29. Juvenile Spondyloarthritis/Enthesis related
arthritis
1. Arthritis and enthesitis, or
2. Arthritis or enthesitis, with at least 2 of the following:
• Presence or H/O SI joint tenderness and/or LS pain or both
• HLA B27 antigen
• Onset of arthritis in a male > 6 years old
• Acute anterior uveitis
• History of Ankylosing Spondylitis, Enthesitis-related arthritis, Sacroiliitis with
inflammatory bowel disease, Reiter syndrome, or Acute anterior uveitis in a 1st-
degree relative
29

30. • Pain, stiffness, and loss of mobility of the
lower back
• Can present with arthritis in lower extremity
joint
• SI joint can be involved
• Acute iritis, erythematous conjunctiva,
photophobia and pain.
30

31. Psoriatic arthritis
1. Arthritis and psoriasis, or
2. Arthritis and at least 2 of the following:
a. Dactylitis
b. Nail pitting (minimum of 2 pits on ≥1 nails at any
time) and onycholysis
c. Psoriasis in a first degree relative
31

32. • 2 onset groups:
a. Younger-onset: more likely ANA+, female, and have chronic
uveitis,
b. Older-onset: more likely to have HLA-B27 positivity, enthesitis
and axial disease
32

33. Diagnosis
• Clinical and exclusion of other conditions
• Tests: Supportive or Prognostic
1) Full blood count and peripheral blood film
2) Acute phase reactants
3) Antinuclear antibody , Rheumatoid factor, ACCP antibody, HLA B27
4) Others: Ferritin, Tg, LDH, FDPs, LFT
5) Synovial fluid analysis
6) Radiological investigations
33

34. Plain radiographs
• Early features:
Soft tissue swelling,
Periarticular osteopenia
Periosteal new-bone apposition
around affected joints
Increased joint space
34

35. • Late features:
Symmetric loss of joint space
Marginal/ subchondral erosions
Growth disturbances (epiphyseal overgrowth or "ballooning")
Joint subluxation, deformities & ankylosis.
35

36. • Cervical spine
radiographs may
demonstrate:
Atlantoaxial subluxation
Odontoid erosions
Ankylosis, especially of the
facet joints
• USG:
Cartilage thickness, bony
erosions, synovial
hypertrophy and effusion of
joints.
36

37. MRI:
• MRI may show synovial hypertrophy, joint effusions and rice bodies,
as well as osseous and cartilaginous erosions.
37

38. Synovial fluid analysis
Parameters Normal JIA
Color Straw Yellow to greenish
Transparency Transparent Turbid
Viscosity Normal Decreased
Mucin clot Good Poor
WBC count <200 1000-60,000
PMNs <20% 55%
Glucose 20mg/dl >30mg/dl
Proteins 1.8g/dl 4.1g/dl
38

39. Complications
Medical
• Anemia
• Malnutrition
• Uveitis
• MAS
• Secondary amyloidosis and its complications
Orthopaedic
• Growth disturbances: Limb length discrepancy, short stature
• Ankylosis, S/L and D/L
• Deformities
• Neurological deficit
• Osteopenia and osteoporosis and fractures 39

40. MAS (Macrophage activation syndrome)
• Rare but fatal complication of sJIA
• Secondary hemophagocytic syndrome(HPS) or hemophagocytic
lymphohistiocytosis (HLH)
• Acute onset high grade fever, lymphadenopathy, hepatosplenomegaly &
encephalopathy.
• Purpura and mucosal bleeding
40

41. 41

42. • Diagnosed by bone marrow biopsy.
• Treatment of MAS
• High dose IV methylprednisolone
• Cyclosporine
• Anakinra (1-2 mg/kg S.C. daily)
42

43. Treatment
• Primary goals of treatment:
Disease remission
Prevent or halt joint damage and normalize joint function
Preserve normal growth and development
• Children with JIA need individualized treatment plans, and
management is tailored according to:
Disease subtype and severity
Presence of poor prognostic indicators
Response to medications
43

44. Pharmacotherapy
• NSAIDS
• Corticosteroids
• DMARDS
Conventional
Biologicals
44

45. NSAIDs
• Decrease both pain and acute and chronic inflammation
• Not disease modifying
• 4-6 weeks for anti-inflammatory effect
• CBC ,RFT, LFT, urinalysis every 6-12 monthly
• 40-60% of JIA arthritis improve with NSAIDs therapy
45

46. Drug Dose Side effect
Naproxen (Polyarthritis,
Systemic)
15 mg/kg/day PO divided
bid
(maximum dose 500 mg
bid)
Gastritis,
renal and hepatic toxicity
Ibuprofen 40 mg/kg/day PO divided
tid
(maximum dose 800 mg
tid)
Meloxicam 0.125 mg/kg PO once daily
(maximum
dose 15 mg daily)
46

47. Non Biologic DMARDs
Methotrexate
• Sustained effectiveness and low toxicity
• Folic acid given as adjunct to minimize side effects
• CBC and LFT every 4 week for 3 months then every 8-12 week
• Lymphoproliferative disorders have been reported in association with EBV
47

48. Drug Dose Side effect
Methotrexate 0.5-1 mg/kg PO or SC
weekly
(maximum dose 25
mg/wk)
Nausea, vomiting, oral ulcerations,
hepatic toxicity, blood count dyscrasias,
immunosuppression, teratogenicity
Sulfasalazine Initial 12.5 mg/kg PO
daily; increase by
10 mg/kg/day
Maintenance: 40-50
mg/kg divided bid
(maximum dose 2 g/day)
GI upset, allergic reaction, pancytopenia,
renal and hepatic toxicity, Stevens-
Johnson syndrome
Leflunomide 10-20 mg PO daily GI upset, hepatic toxicity, allergic rash,
alopecia (reversible), teratogenicity
(needs washout with cholestyramine)
48

49. Glucocorticoids
Oral
• Short term and low doses
• For bridge therapy during wait for therapeutic response to a DMARD
49

50. Intravenous
• Systemic symptoms in sJIA
• Severe polyarthritis
Methylprednisolone, 10-30 mg/kg/dose up to a maximum of 1 g, given over 1
hr daily for 1-5 days
50

51. Ocular:
• As ophthalmologic drops or injections into the soft tissue
surrounding the globe (sub–tenon capsule injection) for active
uveitis
Intra-articular:
• Initial therapy for children with increasing frequency as initial
therapy with oligoarticular JIA
• As bridge therapy while awaiting response from a DMARD in
polyarticular disease
51

52. Biologics
Drug Dose Side effect
TNF alfa inhibitors
Etanercept 0.8 mg/kg SC weekly or 0.4 mg/kg SC
twice weekly (maximum dose 50 mg/wk)
Immunosuppressant,
concern for
malignancy, demyelinating
disease,
lupus-like reaction,
injection site reaction
Infliximab
Adalimumab
3-10 mg/kg IV q4-8 wk
10 to <15 kg: 10 mg SC every other week
15 to <30 kg: 20 mg SC every other week
>30 kg: 40 mg SC every other week
Infusion reaction
Same as above
Proteins that have been engineered to target and modulate specific
components of the immune system
52

53. Drug Dose Side effect
Anticytotoxic T-Lymphocyte–Associated Antigen-4 Immunoglobulin
Abatacept <75 kg: 10 mg/kg/dose IV q4wk
75-100 kg: 750 mg/dose IV q4wk
>100 kg: 1,000 mg/dose IV q4wk
SC once weekly:
10 to <25 kg: 50 mg
≥25 to <50 kg: 87.5 mg
≥50 kg: 125 mg
Immunosuppressant,
concern for
malignancy, infusion
reaction
Drug Dose Side effect
Anti-CD20
Rituximab 750 mg/m2 IV 2 wk × 2 (maximum dose
1,000 mg)
Polyarthritis
Immunosuppressant,
infusion reaction,
progressive multifocal
encephalopathy
53

54. Drug Dose Side effects
Interleukin-1 Inhibitors
Anakinra 1-2 mg/kg SC daily (maximum dose
100 mg/day)
Immunosuppressant, GI upset,
injection site reaction
Canakinumab 15-40 kg: 2 mg/kg/dose SC q8wk
>40 kg: 150 mg SC q8wk
Immunosuppressant,
headache, GI upset,
injection site reaction
Rilonacept 2.2 mg/kg/dose SC weekly
(maximum
dose 160 mg)
Immunosuppressant, allergic
reaction,
dyslipidemia, injection site
reaction
54

55. Drug Dose Side effects
Interleukin-6 Inhibitors
Tocilizumab IV q2 wk:
<30 kg: 12 mg/kg/dose q2wk
>30 kg: 8 mg/kg/dose q2wk (maximum
dose 800 mg)
SC:
<30 kg: 162 mg/dose q3wk
≥30 kg: 162 mg/dose q2wk
Immunosuppressant,
hepatic toxicity,
dyslipidemia, cytopenias,
GI upset,
infusion reaction
55

56. 56

57. 57

58. 58

59. Supportive
Physiotherapy
• Avoid prolonged immobilization
• Strengthens muscles, improves and maintain range of movement
• Maintain nutrition of cartilage
• Improves balance and cardiovascular fitness
Ophthalmologist
• All patients must be referred to the ophthalmologist for uveitis
screening and have regular follow-up.
59

60. Nutritional Therapy
• Calcium intake
• Calcium + vitamin D is advised in patients on corticosteroids
• Ensure appropriate protein and calorie intake
Orthosis or plaster cast
• To rest acutely inflamed joint or to prevent or to correct deformity
Heat
• Stiffness & painful muscle spasm
60

61. Surgical Treatment
61

62. • Contractures release: soft tissue release, capsulotomy, tenotomy
• Osteotomy: to correct severely fixed flexion or valgus deformity of
knee or fixed flexion- adduction deformity of hip
• Arthrodesis: reserved for joints that are severely damaged & no other
surgical procedure are likely to be successful, C1 C2 subluxation, wrist,
fingers, ankle.
• Arthroplasty: surgery performed after full growth is attained.
• Problems in surgery: osteoporosis, poor development of acetabulum,
femur, arthrodesis, poor skin healing, increased risk of infections,
anesthetic problems. 62

63. American College of Rheumatology (ACR)
criteria for complete remission
• No inflammatory joint pain
• No morning stiffness
• No fatigue
• No synovitis
• No progression of damage, as determined in sequential radiographic
examinations
• No elevation of the erythrocyte sedimentation rate (ESR) and C-
reactive protein (CRP) levels
63

64. Frequency of Ophthalmologic Examination
in Patients With Juvenile Idiopathic Arthritis
64

65. 65

66. Prognosis
• 50% patient with JIA have active disease persisting into early adulthood with
severe limitations of physical function
• Persistent Oligoatricular disease: majority achieve remission
• Oligoarthritis in girls with ANA positive with onset < 6 years: risk of chronic uveitis
66

67. • Poor prognosis in Polyarticular JIA
Young age at onset and RF seropositivity
Presence of Anti-CCP antibody
Many affected joints
Involvement of hip and hand/wrist
• Poor prognosis in Systemic JIA
Polyarticular
Fever lasting > 3 months
Increased inflammatory markers> 6 months
67

68. Summary
ILAR subtype Peak age
at onset
F:M % of all
cases
Arthritis pattern Extraarticular features
Systemic
arthritis
1-5 1:1 5-15 Polyarthritis, knees,
wrist, ankles, fingers,
neck hips
Fever, rash, pericarditis,
pleuritis
Oligoarthritis 2-4 3:1 40-50 Knees++, ankles,
fingers+
Uveitis in 30%
Polyarthritis
RF negative
2-4 and
10-14
3:1
and
10:1
20-35 Symmetric or
asymmetric, small &
large joints, cervical
spine, TMJ
Uveitis 10%
Polyarthritis
RF positive
9-12 9:1 <10 Aggressive symmetric
polyarthritis
Rheumatoid nodules in
10% low grade fever
Psoriatic 2-4 and
9-11
2:1 5-10 Asymmetric arthritis
of small and medium
sized joints
Uveitis in 10 %
Psoriasis in 50 %
Enhthesis
related
9-12 1:7 5-10 Predominant LL
joints, axial skeleton
Acute anterior uveitis ,
association with Reactive
arthritis and IBD 68

69. THANK YOU
69