Juvenile Rheumatoid Arithritis

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Juvenile Rheumatoid Arithritis ( JRA
) Prepared by Dr. Lami Salah Directed by Dr.
Jareer Halazoon
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• Is one of the most common Rheumatic diseases in
  children and a major cause of chronic disability.
• It is characterized by idiopathic synovitis of
  the peripheral joints, associated with soft
  tissue swelling and effusion.
• In the classification of American collage of
  Rheumatology JRA is regarded not as a single
  disease but as a category of disease with three
  principal types of onset-
• 1- Oligoarithritis or Pauciarticular disease
  (involvement of less than 5 joints)
• 2- Polyarithritis (involvement of more than 5
  joints)
• 3- Systemic onset disease.

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• Etiology
• Exact etiology is unknown although 2 events are
  considered necessary 1- Immunogenetic
  Susiceptibility
• 2- External triggers(environmental)
• eg. -certain viruses as - Parvovirus B19,
• Rubella, EBV.
• -Host Hyper-reactivity to specific self
• antigens as type II collagen.

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• Enhanced T-cell reactivity to bacterial or
  mycobacterial heat shock proteins.

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Epidemiology -Incidence is approximately
14/100000 children per year among children 15
years or younger with an overall prevalence of
113/100000 children. -Different Racial and ethnic
groups appear to have varying frequencies of the
subtypes of JRA, one study reported that black
american children with JRA were
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• Older at presentation.
• Less likely to have elevated ANA titres or
  Uveitis.

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Pathogenesis 1- Inflammation of synovial
membrane synovitis which villous
hypertrophy and edema of subsynovial tissues 2-
There is marked increased in permeability of
blood vessles and the synovial lining layer which
lead to joint effusion that contain lymphocytes
and plasma cells 3- The hyperplastic synovium
spreads from the joint margins onto the cartilage
surface, this Pannus of inflamed synovium
damage the underlying cartilage.
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Cartilage by blocking its normal route of
nutrition and by the direct effects of cytokines
on the chondrocytes. So the cartilage become
thinned making the underlying bone more
susceptible to any minor trauma.
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Clinical Manifestations Initial symptoms
include 1- morning stiffness. 2- easy
fatigability particularly after school in the
early afternoon. 3- joint pain later in the day
and joint swelling. 4- the involved joint often
warm, lacks full range of motion and occasionally
painful on motion but usually not erythematous.
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• In Oligoarithritis (Pauciarticular)
• It predominantly affect joints of lower
  extremities (knees and ankles)
• Involvement of upper extremity large joint is
  also seen but is not characteristic of this type.
• Involvement of hip is almost never a presenting
  sign of this type, although it may occur later
  (particularly in Polyarticular JRA) and is often
  the first sign of deteriorating functional
  course.

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• In Polyarithritis (polyarticular) subtype
• It resembles the adult RA.
• Is generally characterized by involvement of
  large and small joints, as many as 20-40 separate
  joints are often affected.
• Rheumatoid nodules can be found on the extensor
  surfaces of elbows and over the achilles tendon
  and usually associated with more severe course.
• Micrognathia reflects tempromandibular joint
  involvement

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• Cervical spine may be involved too, with risk of
  atlantoaxial sublaxation.

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• In Systemic Onset Disease
• manifested by arithritis and visceral involvement
  including -Hepatosplenomegaly
• -Lymphadenopathy
• -Serositis which may lead to pericardial
• effusion.
• -it is characterized by fever with daily
  temperature spikes to at least 39 C, sometimes
  followed by mildly hypothermic temperature , for
  a minimum of 2 weeks

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-each febrile episode is often accompanied by
a faint, erythematous, macular Salmon colored
rash which may be linear or circular from 2-5 mm
distributed most commonly over the trunk and
proximal extremities. -Koebner phenomena it is
cutaneous hypersensitivity to superficial trauma
, is elicited by lightly running the edge of the
examiners fingernail along the uninvolved skin,
and is usually suggestive of Systemic Onset
disease
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Note Some children will have persistent
arthralgia despite repeated normal physical
examination, although those children dont
fulfill the diagnostic criteria for JRA
initially, the diagnosis of JRA may sometimes be
established as long as 2 years after initial
presentation
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Diagnosis is usually clinical and supported with
the lab findings Clinical Criteria for diagnosis
include 1-Age of onset less than 16
years. 2-Arithritis(swelling or effusion) , or
presence of two or more of the following signs in
one or more joints -limitation of full range
of movement -tenderness or pain on
motion. -increase heat. 3-Duration of disease
of 6 weeks or longer
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4-Onset type is defined by type of disease in
first 6 months. Polyarithritis 5 or more
inflamed joints. Oligoarithritis less than 5
joints involved Systemic onset arithritis with
characteristic fever 5-Exclusion of other forms
of juvenile arithritis.
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Finding which may support the diagnosis 1-
Inflammatory reflectors as Raised CRP,Serum
Ig, leukocytosis, thrombocytosis and
ESR. NOTE ESR could be normal propably when
most activated lymphocytes responsible for
disease have shifted from blood stream and
entered the synovium.
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2- Hematological abnormalities - anemia of
chronic disease. - raised platelets count. -
raised WBCs count. 3- Elevated ANA titres in 40
to 85 of children with Pauciarticular or
Polyarticular JRA but unusual in Systemic Onset
disease. Detectable ANA are usually associated
with increased risk for the development of
chronic Uveitis.
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4- Positive Rhuematoid Factor (RF) - These are
circulating auto-antibodies which have the Fc
portion of IgG as their antigen. - The nature of
the antigen means that they self aggregate into
immune complexes and thus activate complement
system and stimulate inflammation, causing
chronic synovitis. -Transient production of RFs
is an essential part of bodys normal mechanism
for removing immune complexes, but in JRA they
show much higher affinity and their production is
persistent and occurs in the joint.
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-These RFs can be of any Ig subclass (IgM, IgG,
IgA) but the most common tests employed
clinically detect the IgM RF. -The term
sero-negative RA is used for patients in whom the
standard tests for IgM RF are persistently
negative, those tend to have more limited pattern
of synovitis. -IgM RF is not diagnostic of JRA,
nor its absence rule the diagnosis out , but is
useful predictor of prognosis. -For example a
persistently high titre of RFs in early disease
implies more persistently active synovitis , more
joint damage and greater disability
eventually. -Other causes for elevated RF and ANA
in childhood is viral infection as EBV.
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5- Bone mineral metabolism is often abnormal is
children with JRA and predominantly affects
appendicular cortical bones. a- Early
radiographic changes include -Soft tissue
swelling. -Osteoparosis. -Periostitis about
the affected joints. b- Regional epiphyseal
closure maybe accelerated. c- Continued disease
may lead to subchondral erosions and narrowing of
cartilage space with varying degrees of bony
destruction and fusion.
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d-Late radiographic changes are seen in the hands
and cervical spine most frequently at the level
of C2-C3.
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Differential Diagnosis 1- Any rheumatic disease
as -SLE -Juvenile dermatomyositis -Sarcoidosis
-Vasculitis 2- Trauma 3- Infection 4- Rheumatic
fever
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5- Autoimmune hepatitis. Less Commonly 1-
Leukemia 2- DM 3- Cystic Fibrosis 4- Glycogen
Storage disease
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Treatment -the long term treatment of children
with JRA is initiated and subsequently modified
according to Disease subtype, Severity, and
Response to therapy. -Aim of treatment is to
establish the child in a pattern of adaptation
that is as normal as possible and to accomplish
this goal with minimal risk of adverse effects.
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For example -Most Children with Oligoarticular
JRA respond to NSAIDs alone as a first line of
treatment. -Most Polyarticular patients and some
oligoarticular patients with aggressive disease
require additional medications as a second line
of treatment. -There is whats called Therapeutic
Pyramid in which we start with NSAIDs as a
first line of treatment then precedes through the
Sulfasalazine, Methotrexate and
immunosuppressives (azathioprine,
Cyclophosphamide) and experimental drugs.
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-Glucocotricoids are used for the management
of- 1- overwhelming inflammatory or systemic
illness. 2- in lower doses as for bridge therapy
for children who did not respond, in addition to
another drug such as methotrexate. 3- for ocular
and intra-articular use. -Are very powerful
anti-inflammatory drugs, but they maybe
associated with tachyphylaxis and impose upon
child the risk of severe toxicities as Cushing
Syndrome , Growth retardation.
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• Methotrexate is considered the safest most
  effective and least toxic of currently available
  second line agents.
• It can be given -Orally
• -SC once weekly
• Other aspects of management
• Routine slit lamp eye examination for early
  detection of uveitis.
• Dietary evaluation to ensure adequate Ca intake.

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• Prognosis
• Although the course of JRA is unpredictable ,
  some general statement can be made concerning
  onset type and outcome.

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Onset type Course type Subsequent clinical manifestations Outcome
1-Polyarthritis RF ve Female Older age Hand/wrist Erosions Nodules Unremitting Poor
1-Polyarthritis ANA ve Female Young age Good
1-Polyarthritis Sero -ve Variable
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Onset type Course type Subsequent clinical manifestations Outcome
2-oligoarthritis ANA ve Female Young age Chronic anterior uveitis (iridocyclitis) Excellent except eye
2-oligoarthritis RF ve Erosions Unremitting Poor
2-oligoarthritis HLA-B27 ve Male Older age Good
2-oligoarthritis Sero ve Good
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Onset type Course type Subsequent clinical manifestations Outcome
3-Systemic onset Oligoarthritis Good
3-Systemic onset Polyarthritis Erosions Poor
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• Complications
• 1-Anemia
• -usually unresponsive to iron therapy and maybe
  exacerbated by GI bleeding due to the use of
  NSAIDs.
• 2- SLE
• in children with polyarticular JRA particularly
  when they develop high titres of ANA
• 3- Orthopedic Complication
• -bone deformity as leg discrepancy, secondary
  scoliosis, flexion contractures.

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4- Psychological Trauma -As problems in school
attendance and socialization.
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