Juvenile idiopathic arthritis, diagnosis and treatment

1. Juvenile Idiopathic Arthritis
Ireska Tsaniya Afifa
Allergy Immunology Rotation

2. Juvenile idiopathic arthritis
Chronic joint swelling, with functional limitation
for at least 6 weeks of unknown cause
that starts before 16 years of age
Uknown
etiology
At least
6 weeks
Onset
before
16 y.o.

3. Juvenile idiopathic arthritis
• Juvenile idiopathic arthritis (JIA) is a chronic idiopathic inflammatory disorder
primarily involving joints
• The most common rheumatic disease in children
• Heterogeneous group of disorders
• The etiology and pathogenesis of JIA are largely unknown, and the genetic
component is complex, making clear distinction among various subtypes difficult

4. Juvenile idiopathic arthritis
• JIA were previously termed as:
• Juvenile rheumatoid arthritis (JRA) – mainly in the US
• Juvenile chronic arthritis (JCA) – mainly in Europe

5. Epidemiology
• Worldwide incidence of JIA ranges from 0.8 to 22.6 per 100,000 children per year
• Prevalence ranges from 7 to 401 per 100,000
• This number is estimated because the variations in diagnostic criteria and difficulty in
case ascertainment
• Oligoarthritis is the most common subtype (40-50%), followed by polyarthritis (25-30%)
and systemic JIA (5-15%)
• More girls than boys are affected in both oligoarticular (3:1) and polyarticular (5:1) JIA
• Peak onset:
• Oligoarticular disease: 2-4 years for
• Polyarthritis: 2-4 years and 10-14 years (bimodal onset)
• sJIA: throughout childhood with a peak between 1 and 5 year

6. Etiology
• The etiology and pathogenesis of JIA are not completely understood,
• Both immunogenetic susceptibility and an external trigger are necessary
• Variants in major histocompatibility complex (MHC) class I and class II regions
have been associated with different JIA subtypes
• Possible nongenetic triggers include bacterial and viral infections, enhanced
immune responses to bacterial or mycobacterial heat shock proteins, abnormal
reproductive hormone levels, and joint trauma.

7. Pathogenesis
• Pathogenesis and etiology of JIA are unclear
• Interaction among: genetic factors, immune mechanisms, environmental
exposures
• Genetic predisposition: related to MHC loci and HLA genes
• Potential environmental influences that may improve or worsen disease include
infection, antibiotic use, breastfeeding, maternal smoking, and vitamin D/sun
exposure

10. Classification
according to Intl League of Associations for Rheumatology of JIA
• Systemic
• Oligoarthritis
• Polyarthritis
• RF Negative
• RF Positive
• Psoriatic arthritis
• Enthesitis-related arthritis
• Undifferentiated arthritis

12. Signs and symptoms
Articular
• Arthritis, defined as intraarticular swelling
of two or more of the following signs:
• limitation of ROM
• tenderness
• pain on motion
• warmth
• Morning stiffness
• Limp or felling after inactivity
• Involved joints are usually swollen, with
reduced ROM, warm but not erythematous
Extra-articular
• General
• Growth disturbances
• Arthritis in large joints accelerates the
linear growth and resulted in length
discrepancy
• Continued inflammation stimulates rapid
closure of the growth plate and resulted
in shortened bones
• Skin
• Others
• Enthesitis

13. Signs and symptoms: extra-articular
• General
• Fever, pallor, anorexia, weight loss
• Growth disturbances
• Arthritis in large joints accelerates the
linear growth and resulted in length
discrepancy
• Continued inflammation stimulates
rapid closure of the growth plate and
resulted in shortened bones
• Skin
• Subcutaneous nodules
• Rash
• Others
• Hepatosplenomegaly,
lymphadenopathy
• Serositis, muscle weakness
• Uveitis
• Enthesitis

15. Oligoarthritis
• JIA involving ≤4 joints within the 1st 6 mo of disease onset, and often only a single joint is involved.
• Most oligoarticular arthritis occurs in 50-60% of young people with JIA; the most common type of JIA
• 2 types:
• Oligoarticular-persistent JIA
• Oligoarticular-extended JIA
• Positive ANA increased risk for uveitis; and also can be correlated with younger onset, female sex,
asymmetric arthritis, and lower number of involved joints overtime.
Subtypes Age at onset Diagnostic
• Persistent
• Extended
< 6 years old • Affects ≤ joints throughout course of disease
• Affects >4 joints after the 1st 6 months of disease

17. Polyarthritis JIA
• Second most common type of JIA
• Is characterized by inflammation of ≥5 joints in both upper and lower extremities
• Rheumatoid factor (RF)–positive polyarthritis resembles the characteristic symmetric
presentation of adult rheumatoid arthritis, affect both small and large joints symmetrically
• Rheumatoid nodules on the extensor surfaces of the elbows, spine, and over the Achilles
tendons, are associated with a more severe course and usually occur in RF-positive
individuals
Subtypes Age at onset Diagnostic
• RF (-)
• RF (+)
6-7 years
9-12 years
• Affects ≥ 5 joints in 1st to 6th mo of disease, with negative RF
• Affects ≥ 5 joints in 1st to 6th mo of disease, with ≥2 positive RF tested
at least 3 mo apart

20. Systemic JIA
• Is less common and only affects 10-15% of children and adolescent
with JIA ; Boys = girls
• Joint symptoms begin 6 mo after fever onset
Subtypes Age at
onset
Diagnostic
• Systemic 2-4 years Affects ≥ 1 joint with or preceded by fever (≥39oC) of at
least 2 weeks duration, plus 1 or more of the following:
• Evanescent rash on trunk and proximal extremities
• Enlarged lymph nodes
• Hepatomegaly / Splenomegaly
• Pericarditis / pleuritis / peritonitis
• Koebner phenomenon, cutaneous hypersensitivity in
which classic lesions are brought on by superficial
trauma, or by heat
• Anemia

21. Complication of sJIA
• In patients with sJIA, macrophage activation
syndrome can happen and usually are severe
• Onset of spiking fever, lymphadenopathy,
hepatosplenomegaly, encephalopathy
• Thrombocytopenia, leukopenia, elevated liver
enzymes, LDH, ferritin, triglycerides
• Elevated fibrin products, prolonged PT APTT
• Hypofibrinogenemia

23. Enthesis arthritis
• Enthesis-related arthritis involves inflammation in both the joints and the
entheses, the spots where tendons and ligaments attach to bonea
Subtypes Age at onset Diagnostic
• Enthesis related 9-12 years 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 a 1st-
degree relative

25. Enthesitis arthritis
• Male > female
• Often lasts into adulthood
• Usually involves just a few joints in the
legs; hips often affected
• Knee, heel, and foot pain are common
• Can cause sausage toes called dactylitis

26. Psoriatic arthritis
• Patients with psoriasis can develop arthritis  called psoriatic arthritis
• Psoriasis may starts before arthritis, of arthritis begins before psoriasis
• Can occur at any age, male = female
• Involve hips and back, with moderate risk for uveitis
Subtypes Age at onset Diagnostic
• Psoriatic 7-10 years
old
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

28. Diagnosis of JIA
• Mainly clinical diagnosis without any diagnostic laboratory tests
• Should exclude other diseases first because it often mimics other disease
• Laboratory study are mainly supportive or prognostic
• Peripheral blood count  anemia, leukocytosis, thnrombocytopenia
• ESR & CRP  raised in inflammation
• X-ray of affected joints  signs of inflammation and look for malignancy
• Antinuclear antibody  risk for uveitis
• Rheumatoid factor  assess for prognosis in polyarthritis JIA
• Others: LFT, complement, ASTO, synovial fluid aspiration, imaging

29. Diagnosis of JIA
Radiography is important to exclude other diseases. Basic radiographic changes in JIA include the following:
• Soft tissue swelling
• Osteopenia or osteoporosis
• Joint-space narrowing
• Bony erosions
• Intra-articular bony ankylosis
• Periosteitis
• Growth disturbances
• Epiphyseal compression fracture
• Joint subluxation
• Synovial cysts

31. Treatment
• Goal of treatment are:
• Disease remission
• Prevent or halt joint damage
• Prevent loss of function
• Decrease pain
• Normal growth and development in children and adolescents

32. Determining disease activity
2011 ACR Juvenile Arthritis Treatment Recommendations
• Low disease activity is defined by the as meeting all of the following criteria: ≤1
active joint, normal inflammatory markers ( ESR or CRP), physician global
disease activity assessment of <3 (0 to 10 scale), and patient/parent global
assessment of overall well-being of less than <2 (0 to 10 scale).
• High disease activity is defined as meeting at least three of the following criteria:
≥2 active joints, inflammatory markers greater than twice the upper limit of
normal, physician global disease activity assessment ≥7 (0 to 10 scale), and
patient/parent overall well-being assessment ≥4 (0 to 10 scale).
• Moderate disease activity does not satisfy criteria for low or high disease
activity

33. Pharmacological treatment
• NSAID have traditionally been the mainstay of therapy in all forms of JIA, and a
first line therapy now
• Not disease modifying
• Merely symptomatic
• Usually can relieve symptoms in 2 weeks
• Several NSAID were approved for pediatrics: naproxen, ibuprofen, indomethacin,
naproxen, tolmetin, meloxicam, celecoxib.

35. Pharmacological treatment
• In patients who respond with NSAIDs, treatment are continued until there has been a
minimum of six months of disease inactivity
• Those who have no or partial response after 4-6 wk of treatment with NSAIDs or who
have functional limitations, such as joint contracture or leg-length discrepancy, may
benefit from injection of intraarticular corticosteroids
• Intraarticular glucocorticoid injection should improve arthritis for at least four months.
• Patients who have persistent symptoms despite treatment with NSAIDs and
intraarticular glucocorticoids should be treated with methotrexate.
• It may take 6-12 wk to see the effects of methotrexate. Failure of methotrexate
monotherapy warrants the addition of a biologic DMARD.

39. Non-pharmacological intervention
• Physiotherapy and occupational therapy
• To keep or restore joint function and alignment as much as possible
• To achieve a normal pattern of mobility
• Use of orthostatic if needed
• Surgical approach to irreversible joint contractures, dislocations, or joint replacement may be
indicated, although the role of orthopedic surgery in JIA is much more limited
• Periodic ophthalmologic examination for uveitis
• Dietary approach: appropriate calcium, vitamin D, protein, and calorie intake
• Physical activity: non-weight bearing (swimming, cycling)