CASE REPORTJUVENILE RHEUMATOID ARTHRITIS(JRA)by:
Ismafitria Idris
(070100364)
Maal Abrar
(070100374)
Supervisor:
dr. Yazid Dimyati, Sp. A (K)
DEPARTMENT OF PEDIATRICHAJI ADAM MALIK GENERAL HOSPITAL
UNIVERSITY OF SUMATERA UTARA FACULTY OF MEDICINE
MEDAN
2012
PREFACE
First of all, we would like to express our praise and gratitude
to God Almighty that due to Gods grace and blessings this
assignment entitled Juvenile Rheumatoid Arthritis was able to be
finished in time. This assignment was written in order to fulfill
the duties from the Department of Pediatric H. Adam Malik General
Hospital / University of North Sumatera.
We would also like to express our gratitude to dr. Yazid
Dimyati, Sp.A(K) for her valuable advices and guidance throughout
the completion of this assignment. Last but not least, we thank
everyone who have contributed in this assignment.
We are fully aware that this assignment is far from perfect,
therefore, we accept any constructional critics and advice that can
improve this assignment.Medan, 21th May 2012
WritersCONTENTSPREFACE ..ii
CONTENTS iii
CHAPTER I INTRODUCTION1
1.1. Background ................1
1.2. Objective ...................2
CHAPTER II LITERATURE REVIEW3
2.1. Definition ......3
2.2. Epidemiology.................3
2.3. Etiology...................3
2.4. Pathogenesis...4
2.5. Classification8
2.6. Clinical Presentation..9
2.7. Diagnosis...15
2.8. Laboratory Test.16
2.9. Treatments.21
2.10. Prognosis..23
CHAPTER III MEDICAL REPORT25
3.1. Case ...25
3.2. Discussion..27
3.3. Summary....28
REFERENCES........................................................................................29
ATTACHMENTS
CHAPTER I
INTRODUCTION
1 . 1. Background Juvenile rheumatoid arthritis (JRA) is a
generic term for arthritis that has an onset before the age of 16
and persists for more than 6 weeks. The JRA nomenclature represents
an exclusion diagnosis that includes all forms of chronic childhood
arthritis of unknown origin1. Currently, 3 separate classification
systems are used to categorize individuals under 16 years of age
with chronic arthritis. These include the American College of
Rheumatology (ACR), the European League Against Rheumatism (EULAR),
and the International League of Associations for Rheumatology
(ILAR) criteria. Because none of these systems are perfect models,
some JRA patients fulfill criteria for more than one subtype,
whereas others are difficult to classify into any of the specific
subgroups. Both the ACR and EULAR criteria are based solely on the
onset type as it is manifested during the first 6 months of
disease, whereas the ILAR criteria also include the course type
over an unknown period of time thereafter, in order to further
distinguish the group of patients with oligoarticular
disease1.Epidemiological studies of JRA have been hampered by a
lack of standardized criteria and case ascertainment, which has
resulted in wide-ranging results. For instance, the reported
prevalence of JRA ranges from 0.07 to 4.01 per 1,000 children, and
the annual worldwide incidence varies from 0.008 to 0.226 per 1,000
children1. JRA is the most common chronic rheumatic illness in
children and is a significant cause of both short- and longterm
disabilities. The heterogeneity of this disease suggests that
different factors likely contribute to its pathogenesis1. 1 . 2.
Objective
The objective of this case report is to familiarize ourselves
with Juvenile Rheumatoid Arthritis, understand the clinical
presentation, diagnosis, treatment of the disease itself and lastly
to report a case of Juvenile Rheumatoid Arthritis in an 15 years
old boy that was admitted to to the non-infection ward of H Adam
Malik General Hospitals Pediatric Division.
CHAPTER II
LITERATURE REVIEW
2 . 1. Definition JRA is defined as persistent arthritis in 1 or
more joints for at least 6 weeks if certain exclusionary conditions
have been eliminated; disease onset subtype is defined by clinical
symptoms in the first 6 months of disease. The course of JRA is
defined by what happens after the first 6 months2, 3.
2 . 2. Epidemiology
The exact incidence and prevalence of JRA is not known. A recent
meta-analysis of 34 epidemiological studies showed wide variability
in both the reported incidence and prevalence of JRA. Incidence
numbers varied considerably from 0,008 to 0,226/1000 children per
year. Prevalence numbers varied even more widely and ranged from
0,,07 to 4,01/1000 children4.2 . 3. EtiologyJRA is an autoimmune
disease. This means it is the body's own immune system that causes
the damage. The immune system problems may be caused by genetics
and/or environment 3, 5.Various studies seeking epidemiological
evidences for etiology of arthritic manifestation thaw infectious
connection to RA. For obvious reason, triggering immune response
against antigenic determinant is a preparative cascaded reaction in
order to eliminate invaders. There are two principal difficulties
with the hypothesis that infection triggers rheumatoid arthritis:
first proving a causal relation and second the limitation of the
methods of detection of recent or past infection. Past or recent
infection develops onset of polyarthritis persistently associated
with the development of antibody response, giving satisfactory
explanation for infection triggering immune response in rheumatoid
phenomena6.
No particular studies documented persistence of infectious
agents in joint inflammatory site, even though availability of
bacterial products at the site of inflammation and triggered immune
response to earlier infection and its related antibody activities
and particularly of crossreactivity might be given attention in
order to facilitate hypothesis to etiology of rheumatic diseases.
And also from clinical concern, patients with earlier infection
before develops rheumatological criteria may be no longer
infectious giving opportunity to understand its connection and
involvement of such infectious connection to etiopathology. Hence
it could be strengthening the suggestion that rheumatoid arthritic
etiology has satisfactory explanation for infection, and joint
inflammation might have develops soon after or during an infection
elsewhere in the body6.
2 . 4. Pathogenesis Associations of human leukocyte antigen
(HLA) and non-HLA molecules in JRA
The genetic basis of JRA is complex, but it has been estimated
that the sibling recurrence risk of developing the disease is
around 15. To date, only 2 genetic risk factors, HLA and protein
tyrosine phosphatase non-receptor 22 (PTPN22) genes, have been
unequivocally confirmed as JRA susceptibility genes in multiple
populations. The most well-established genetic factors for JRA are
the HLA genes. Because the main function of HLA molecules is
presenting antigenic peptides to T cells, HLA associations with JRA
imply that this disease may be caused by an unidentified
arthritogenic antigen1, 7.However, both the strength of these
associations and the associated alleles vary between the JRA
subtypes. Specifically, oligoarthritis has been consistently
associated with HLA-A2, HLA-DRB1*11, and HLA-DRB1*08. Rheumatoid
factor (RF)-positive polyarthritis is reportedly associated with
HLADR4 in children, similarly to in adults. Moreover, the presence
of HLA-B27 confers an increased risk of enthesitis-related
arthritis. PTPN22 encodes a lymphoid-specific phosphatase (Lyp). A
variant in the coding region of this gene, which is reportedly
associated with a number of autoimmune diseases, has also been
identified as a susceptibility locus for JRA. The effect size of
PTPN22 varies somewhat between JRA subtypes but, in general, is
more consistent than that of HLA genes. A few other genes,
including macrophage inhibitory factor, interleukin (IL)-6, IL-10,
and tumor necrosis factor (TNF)-, have also been associated with
JRA in different populations and subtypes. However, these discussed
genes may collectively account for only a small proportion of the
total genetic contribution to disease1, 7.
Inflammatory mediators of joint damage
Synovial membranes of JRA patients contain activated T and B
cells, plasma cells, and activated macrophages that are recruited
via an intense neovascularization process. Host tissue cells,
including activated synovial fibroblasts, chondrocytes, and
osteoclasts, mediate cartilage and bone destruction. It has been
established that the recruitment, activation, and effector function
of each of these contributor lineages are directed principally by a
network of cytokines.
Figure 1. Cytokine signaling pathways involved in JRA.
Interactions among macrophages, T cells, B cells, and
non-hematopoietic cells including fibroblasts are important in the
pathogenesis of JRA. These interactions are facilitated by the
actions of cytokines that induce the production of other
proinflammatory cytokines1.
Antigen-specific T cells appear to play a central role in the
pathogenesis of arthritis subtypes within JRA. T-cell infiltrates
are composed predominantly of T helper 1 (Th1) cells, which express
an activated memory phenotype and high concentrations of chemokine
receptors. Th1 cells stimulate B cells, monocytes, macrophages, and
synovial fibroblasts to produce immunoglobulins and inflammatory
mediators. Activated B cells produce immunoglobulins, including RF
and antinuclear antibodies (ANAs). The precise pathogenic role of
RF remains unknown, but it may involve the activation of complement
through the formation of immune complexes. ANAs, which are mainly
associated with early-onset oligoarthritis, have been reported to
react against different nuclear targets, none of which are specific
for JRA. Activated macrophages, lymphocytes, and fibroblasts, as
well as their products including vascular endothelial growth factor
(VEGF) and osteopontin, can stimulate angiogenesis. VEGF is highly
expressed in synovial tissue, whereas osteopontin is raised in
synovial fluid and tissue, and correlates with new
vascularisation1.
TNF- and IL-1 produced by activated monocytes, macrophages, and
synovial fibroblasts likely have primary roles in the pathogenesis
of JRA. These cytokines are detected in synovial fluids or tissues
in a majority of JRA patients, and are known to stimulate
mesenchymal cells, such as synovial fibroblasts, osteoclasts, and
chondrocytes, to release tissue-destroying matrix
metalloproteinases. TNF- and IL-1 also inhibit synovial fibroblasts
from producing tissue inhibitors of metalloproteinases.
Collectively, these dual actions seem to lead to joint damage.
Indeed, data from animal models strongly suggest TNF- and IL-1 play
roles in JRA. For instance, transgenic mice that expressed a
deregulated human TNF- gene spontaneously developed an inflammatory
and destructive polyarthritis similar to JRA. Moreover, blocking
TNF- with either a soluble TNF-receptor fusion protein ormonoclonal
antibodies also ameliorated disease activity in mice with type II
collagen-induced arthritis. Injection of IL-1 into the knee joints
of rabbits has been demonstrated to result in the degradation of
cartilage, whereas the injection of antibodies against IL-1
ameliorated collagen-induced arthritis in mice and decreased the
damage to cartilage1.IL-6 is a multifunction cytokine that has a
wide range of biological activities in various target cells and
regulates immune responses, acute phase reactions, hematopoiesis,
and bone metabolism. Circulating levels of IL-6 are markedly
elevated in patients with JRA, and are associated with laboratory
and clinical variables of disease activity. IL-6 stimulates
hepatocytes and induces the production of several acute-phase
proteins, such as C-reactive protein (CRP)33). Thus, elevated
levels of IL-6 in serum correlate with CRP levels in JRA patients
with active disease. IL-17 is produced by Th17 cells, and induces a
massive tissue reaction due to the broad distribution of the
receptors to this cytokine. Recent evidence suggests that
IL-17-producing Th17 cells have a crucial role in autoimmune
inflammation. In particular, IL-17 promotes a proinflammatory
cytokine environment in the joint, stimulating macrophage
production of TNF- and IL- 13, and synergizes with these cytokines
to increase IL-6 and IL-8 production36, 37). In addition, IL-17
contributes directly to joint destruction by upregulating matrix
metalloproteinases and stimulating osteoclastogenesis through
receptor activation of nuclear factor-B ligand (RANKL)
induction38-40). IL-17 is increased in JRA patients with active
disease compared with levels in individuals in remission41). Data
from animal models also suggest IL-17 has a role in cartilage
degradation. For instance, IL- 17-deficient mice were demonstrated
to be resistant to induction of collagen-induced arthritis42).
Moreover, joint inflammation and cartilage and bone destruction
were suppressed after administration of anti-IL-17 antibodies in
mice with collagen-induced arthritis1.Anti-inflammatory mediators
in JRA
The two most well-known anti-inflammatory cytokines associated
with JRA are IL-10 and IL-4. IL-10 has been shown to reverse
cartilage degradation mediated by antigen-stimulated mononuclear
cells in adult patients with arthritis. In addition, a single
nucleotide polymorphism connected to lower production of IL-10 is
associated with a more severe type of arthritis. IL-4 inhibits the
activation of Th1 cells, which in turn decreases the production of
TNF- and IL-1 and inhibits cartilage damage1.IL-4 and IL-10
cooperate to inhibit the production of inflammatory cytokines,
including IL-6 and IL-8. Higher levels of IL-4 and IL-10 mRNA
within a joint are allied with a milder oligoarticular course and
non-erosive disease. Foxp3+CD4+CD25+ regulatory T cells (Tregs) are
important for controlling inflammatory processes68). In humans, an
X-linked genetic defect in Foxp3 is the underlying cause of a
condition that presents with multiple autoimmune conditions, which
is named the immuno-dysregulation, polyendocrinopathy, enteropathy
(IPEX) syndrome. Less serious defects in Treg function have also
been put forward as a cause of failed tolerance in several human
autoimmune diseases. However, there is currently no evidence
suggesting defects in Treg function in JRA, although the number of
synovial Tregs is significantly lower in patients with extended
oligoarthritis compared with the number in patients with a milder
course of the disease. Moreover, a higher number of Tregs have been
found within joints of JRA patients compared with the number in
peripheral blood, which indicates an enrichment of Tregs within the
inflamed joints. However, it appears that high numbers of
regulatory cells in the joint fail to moderate the local
inflammatory process. This finding may be related to effector T
cell resistance, suppression at the site of inflammation, or the
attenuation of Treg function by local dendritic cell-derived
cytokines, such as IL-61.
2 . 5. Classification The 3 major subtypes of JRA are based on
the symptoms at disease onset and are designated systemic onset,
pauciarticular onset, and polyarticular onset. Pauciarticular-onset
and polyarticular-onset JRA are further divided into 2 subsets.
Although the major JRA classifications are based on onset type, the
course of the disease is also critical to patient prognosis. For
instance, systemic-onset JRA can eventually become
indistinguishable from polyarticular JRA. Patients with this
pattern of onset and disease course may be particularly difficult
to treat. JRA that begins as pauciarticular-onset disease, with
more extensive joint involvement over time, is frequently referred
to as extended pauciarticular or extended oligoarticular
disease2.Table 1. Key Clinical Characteristics of JRA Onset
Types2
2 . 6. Clinical PresentationArthritis
An arthritic joint exhibits a number of cardinal signs of
inflammation, such as swelling, erythema, heat, pain, and loss of
function. Involved joints are often warm, but are not typically
erythematous. Children with arthritis may not complain of pain
while at rest, but active or passive motion typically elicits
pain.
Joint tenderness is usually maximal at the joint line or just
over the hypertrophied, inflamed synovium. Of note, bone pain or
tenderness is not characteristic of JRA and may instead indicate
the possibility of a malignancy involving bone. Morning stiffness
and gelling following inactivity are common manifestations of joint
inflammation, but young children infrequently describe these
symptoms. Often, young children do not complain of pain and instead
refuse to use the affected joint entirely1, 3.
Figure 2. Swelling and flexion contracture of the right knee of
a representative patient with oligoarticular disease1.
Any joint can be affected by JRA, but large joint are more
frequently involved than smaller joints. However, small joints of
the hands and feet are also affected, particularly in polyarticular
onset disease. Of note, cricoarytenoid arthritis is unusual but may
be responsible for acute airway obstruction. Inflammation of the
synovial joints in the middle ear has also been detected by
tympanometric studies. The temporomandibular joint and the
cervical, thoracic, and lumbar spine should also be examined in the
case of JRA. JRA often affects the cervical spine, and the most
common changes in the upper cervical spine are anterior
atlantoaxial subluxation and impaction. Subluxation of the
atlantoaxial joints may also occur, rendering the affected child at
risk of injury in an accident or upon attempted intubation prior to
receiving general anesthesia. Scoliosis, which possibly reflects
asymmetric thoracolumbar apophyseal joint inflammation, may also
occur in children with JRA. Small outpouchings of symovium are not
uncommon in individuals with JRA and are particularly evident at
the extensor hood of the proximal interphalangeal joint and around
the wrist or ankle. A synovial cyst in the antecubital area or
anterior to the shoulder may be the initial or sole presentation of
JRA1.Oligoarticular disease develops in at least 50% of children
with JRA during the first 6 months of disease. This subtype is the
only form of JRA without an adult equivalent. Oligoarticular
disease affects up to 4 joints at presentation, with the knee
joints mostly affected, followed by the ankles. In contrast, this
subtype almost never affects the hips, and rarely the smaller
joints of the hands and feet. Oligoarticular disease is
characterized by asymmetric arthritis, early onset (before 6 years
of age), female predilection, high frequency of positive ANAs, and
a high risk of iridocyclitis1.
Polyarticular disease is defined as the presence of arthritis in
5 or more joints during the first 6 months of disease. The
arthritis may be symmetrical and usually involves the large and
small joints of the hands and feet, although the axial skeleton,
including the cervicalspine and the temporomandibular joints, may
also be affected. This subtype includes children with both
RF-negative and RF-positive diseases. Both types affect girls more
frequently than boys. RFnegative patients often develop
polyarthritis in early childhood, whereas RF-positive patients
instead develop arthritis during late childhood and
adolescence1.
Figure 3. Polyarticular disease affects the joints of the wrist
and hand. The proximal and distal interphalangeal joints are
erythematous. There are flexion contractures of the fingers1.
Systemic extra-articular manifestations
Systemic involvement may precede the development of overt
arthritis by weeks, months, or rarely years. In the right clinical
setting, with characteristic fever and classic rash, the diagnosis
of probable systemic onset disease may be made, and confirmation of
the diagnosis can follow when persistent arthritis develops. The
arthritis associated with systemic onset disease is usually
polyarticular affecting both large and small joints. Asymmetric,
oligoarticular arthritis is less common. The systemic pattern is
prominent during the first 4-6 months of disease and rarely occurs
for the first time during the later course of disease1.The most
prominent feature of systemic involvement is a high spiking fever.
Specifically, the temperature of an individual typically rises to
39 or higher on a daily or twice-daily basis, followed by a rapid
return to the baseline temperature or below. Although this
quotidian pattern is highly suggestive of systemic onset disease,
patients may not present this fever pattern. Fever may occur at any
time of the day, but characteristically presents in the late
afternoon to evening in conjunction with the rash. Moreover, the
temperature may be subnormal in the morning. During episodes of
fever, an affected child commonly appears ill when chills are
present, but then appears well when the fever breaks. Fever
associated with systemic onset disease often responds poorlyto the
commonly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs),
even at high doses1.
Figure 4. High intermittent fever in a representative patient
with systemic onset disease1.
In the case of systemic onset disease, intermittent fever is
almost always accompanied by the classic rash. The classic rash is
evanescent (usually coming and going with the fever spikes) and
consists of discrete, circumscribed, salmon-pink macules (2-mm to
10-mm in size) that may be surrounded by a ring of pallor or may
develop central clearing. Lesions are most common on the trunk and
proximal extremities, including the axilla and inguinal areas, but
can also develop on the face, palms, or soles of affected
individuals. The rash tends to be migratory and is strikingly
evanescent: individual lesions last for up to a few hours and leave
no residua. Moreover, the rash may be much more persistent in
children who are systemically very ill, and may reappear with each
systemic exacerbation. Such rash also occurs very rarely in
children with polyarticular onset disease, and likely never occurs
in those with classic oligoarthritis. Individual lesions may be
elicited either by rubbing and/or scratching the skin (the
so-called Koebner response), by a hot bath, or by psychological
stress. The rash is occasionally pruritic but is never
purpuric1.
Figure 5. Typical rash in a patient with systemic onset
disease1.
Pericarditis and pericardial effusions are especially common in
children with systemic onset disease. Pericarditis may precede the
development of arthritis or may occur at any time during the course
of disease, and is usually accompanied by a systemic exacerbation
of disease. Pericarditis tends to occur in older children, but it
is not related to sex, age at onset, or severity of joint disease.
Most pericardial effusions are asymptomatic, although some children
have dyspnea or precordial pain that may be transferred to the
back, shoulder, or neck. In many cases, pericardial effusions
develop insidiously, may not be accompanied by obvious cardiomegaly
or electrocardiographic changes, and escape recognition except by
echocardiography. Examination of affected patients may disclose
diminished heart sounds, tachycardia, cardiomegaly, and a
pericardial friction rub, usually at the left lower sternal border.
Pneumonitis or pleural effusions may also occur with carditis, or
may be asymptomatic and detected only as incidental findings on
chest radiographs. Pulmonary rheumatoid nodules that are described
in adult rheumatoid arthritis are rare in childhood1.Another
characteristic of systemic onset disease is enlargement of lymph
nodes and spleen, either alone or in combination. Marked symmetric
lymphadenopathy is particularly common in the anterior cervical,
axillary, and inguinal areas, and may suggest the diagnosis of
lymphoma. Mesenteric lymphadenopathy may cause abdominal pain or
distention and lead to an erroneous diagnosis of an acute surgical
abdomen. Splenomegaly is generally most prominent within the first
years after onset of systemic onset disease. The degree of
splenomegaly may be extreme, but it is uncommonly associated with
Feltys syndrome (splenic neutropenia). Hepatomegaly is less common
than splenomegaly. Furthermore, moderate to severe enlargement of
the liver is often associated with only mild derangement of
function and relatively nonspecific histopathologic changes.
However, massive enlargement of the liver is usually accompanied by
abdominal distention and pain1. Uveitis
Chronic, anterior, nongranulomatous uveitis (iridocyclitis)
develops in up to 21% of patients with oligoarticular disease and
10% of patients with polyarticular disease. However, no patients
with systemic onset disease have been diagnosed as having uveitis
to date. The only known independent risk factor for developing
uveitis is a positive ANA test. The onset of chronic uveitis is
typically insidious and often entirely asymptomatic, although up to
one half of affected children have some symptoms attributable to
uveitis (e.g., pain, redness, headache, photophobia, change in
vision) later in the course of their disease. Uveitis may be
present at the time of diagnosis, may develop during the course of
JRA, or may be an initial manifestation of JRA that is usually
detected in the course of routine ophthalmologic examination. JRA
patients should be screened routinely to prevent delay in diagnosis
of uveitis. The earliest signs of uveitis on slit-lamp examination
are the presence of inflammatory cells and increased protein
concentration in the aqueous humor of the anterior chamber of the
eye. In addition, deposition of inflammatory cells on the inner
surface of the cornea (keratopunctate deposits) may develop later
during the course of disease. Complications of uveitis include
posterior synechiae, cataracts, band keratopathy, glaucoma, and
visual impairment1, 3.2 . 7. DiagnosisHistory
Arthritis must be present for 6 weeks before the diagnosis of
juvenile rheumatoid arthritis (JRA) can be made. Disease onset is
either insidious or abrupt, with morning stiffness or gelling
phenomenon (ie, stiffness after long periods of sitting or
inactivity) being a frequent complaint and arthralgia occurring
during the day. A morning limp that improves with time may be
noted, and a toddler may no longer stand in the crib in the morning
or after naps3,8.
Complaints of joint pain may not be predominant in the patients
history, however; children often stop using joints normally (eg,
develop contractures of joints, decreased wrist range, limp) rather
than complain of pain. Up to a quarter of children with
oligoarticular JRA have no pain3,8.Individuals with JRA may have a
history of school absences, and their ability to participate in
physical education classes reflects the severity of the disease or
acute flares3,8.Systemic-onset JRA is characterized by spiking
fevers, typically occurring once or twice each day, at about the
same time of day, with temperature returning to normal or below
normal. The fever pattern is very useful because infections,
Kawasaki disease, and malignancy usually do not have such a
predictable pattern.
Systemic-onset JRA is usually accompanied by an evanescent rash
(lasting a few hours), which is typically nonpruritic, macular, and
salmon colored on the trunk and extremities. Occasionally, the rash
is extremely pruritic and resistant to antihistamine
treatment3,8.Physical ExaminationJRA is a clinical diagnosis. A
complete physical examination is critical for the diagnosis.
Physical findings are important to provide criteria for diagnosis
and to detect abnormalities suggestive of alternative etiologies.
The diagnosis of JRA is based on the physical finding of arthritis
in at least 1 joint that has persisted for at least 6 weeks, with
other causes excluded, in an individual younger than 16
years3,8.Arthritis is defined as either intra-articular swelling on
examination or as limitation of joint motion in association with
pain, warmth, or erythema of the joint. The hips, temporomandibular
joint, and small joints in the spine do not demonstrate swelling
when affected by synovitis but demonstrate the combination of loss
of motion and pain. The physical findings in JRA are a reflection
of the extent of joint involvement3,8.In synovitis, in which there
is synovial proliferation and an increase in joint volume, the
joint is held in a position of maximum comfort. Limbs with
synovitis are generally held in flexion. Range of motion often is
limited only at the extremes. In synovitis, the fingers may appear
swollen, and the range of motion becomes painful. The wrist goes
into flexion. In the knee, the parapatellar fossae often are
obliterated, and a doughy synovium may be palpable. A soft, boggy
swelling is appreciated in the popliteal fossa3,8.The hip is held
in an attitude of flexion, abduction, and external rotation.
Attempted range of motion will be painful to a varying degree.
Guarding is an early sign of synovitis8.2 . 8. Laboratory TestThe
diagnosis of juvenile rheumatoid arthritis (JRA) is based on the
history and physical examination findings. No laboratory studies
are diagnostic for JRA, and indeed, all laboratory study findings
may be normal in children with this disorder. However, laboratory
studies help to exclude other underlying disorders, classify the
type of arthritis, and evaluate for extra-articular manifestations
of JRA. Imaging of affected joints is usually indicated8.
Inflammatory Markers
The erythrocyte sedimentation rate (ESR) or C-reactive protein
(CRP) level is usually elevated in children with systemic-onset JRA
(with a disproportionate increase in the CRP) and may be elevated
in those with polyarticular disease; however, it is often within
the reference range in those with oligoarticular disease. When
elevated, inflammatory markers can be used to monitor disease
activity8.Complete Blood Count and Metabolic PanelLymphopenia is
not uncommon because of emigration of activated lymphocytes out of
the circulation into synovium. However, neutropenia is uncommon
and, particularly with lymphocytosis or thrombocytopenia, raises
the possibility of acute lymphocytic leukemia8.A complete blood
count, liver function tests (to exclude the possibility of viral or
autoimmune hepatitis), and assessment of renal function with serum
creatinine levels should be done before starting treatment with
nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate (MTX),
or tumor necrosis factoralpha inhibitors8.
Antinuclear Antibody Testing
As many as 70% of children with oligoarticular JRA have positive
ANA assays. However, a positive ANA should also raise suspicion
ofsystemic lupus erythematosus(SLE). Overlap between the
manifestations of the two disorders may lead to initial
misdiagnosis of SLE as JRA8.A positive ANA is a marker for
increased risk of anterior uveitis. Children younger than 6 years
at arthritis onset with a positive ANA finding are in the highest
risk category for development of uveitis and need slit lamp
screening every 3-4 months. Titers do not correlate with disease
activity8.Additional Laboratory Tests
In systemic-onset JRA, total protein and albumin levels are
often decreased during active disease, and fibrinogen, ferritin and
D-dimer levels are often elevated. Laboratory results that can help
to rule out JRA include angiotensin-converting enzyme (ACE)
elevation, which may be indicative of sarcoidosis, and
antistreptolysin 0 (AS0) and anti-DNAse B elevations, which may
indicate acute rheumatic fever or poststreptococcal
arthritis8.Perform a urinalysis to exclude the possibility of
infection (as a trigger for JRA or transient postinfectious
arthritis). Proteinuria (>0.5 g/d or 3+ positive on dipstick
testing) or cellular casts is consistent with renal involvement in
SLE. In patients with systemic-onset JRA, the following test
results are indicative of the development of macrophage-activating
syndrome (MAS)8:
Falling ESR
Normalization or decrease in white blood cell (WBC) count
Low platelets
Elevated liver enzymes
Increased ferritin
Increased triglycerides
Low fibrinogen
Erratic fevers
Hemorrhages (disseminated intravascular coagulationlike
pattern)
Radiography
When only a single joint is affected, radiography is important
to exclude other diseases, such as osteomyelitis. Basic
radiographic changes in JRA (see the images below) include the
following8, 9:
Soft tissue swelling
Osteopenia and/or osteoporosis
Joint-space narrowing
Bony erosions
Intra-articular bony ankylosis
Periosteitis
Growth disturbances
Epiphyseal compression fracture
Joint subluxation
Synovial cysts
Figure 6. Ankylosis in the cervical spine at several levels due
to long-standing juvenile rheumatoid arthritis (also known as
juvenile idiopathic arthritis)8.
Figure 7. Widespread osteopenia, carpal crowding (due to
cartilage loss), and several erosions affecting the carpal bones
and metacarpal heads in particular in a child with advanced
juvenile rheumatoid arthritis (also known as juvenile idiopathic
arthritis)8.Ultrasonography
On ultrasonograms, inflamed synovium can appear as an area of
mixed echogenicity lining the articular cartilage; the vascularity
of the synovium can be assessed with Doppler flow studies. Serial
measurements of synovial thickness and effusion volumes have been
used to monitor disease progression.It can be helpful to evaluate
joints that are difficult to palpate, such as the hip and shoulder.
Some researchers claim that ultrasonography is more sensitive than
plain radiography in the detection of cartilage erosions and
effusions. Ultrasound has the advantages of no exposure to ionizing
radiation; it can be done in the clinic is an awake, moving child;
and it can help guide injections8, 9.
Computed Tomography and Magnetic Resonance Imaging
CT scanning is the best method for analyzing bony abnormalities,
but it has been largely superseded by MRI in the overall assessment
of JRA. The major disadvantage of CT scanning is that it involves a
substantial radiation dose. Perform CT scanning of the long bones
when considering osteoid osteoma is suspected8, 9.MRI is helpful
when considering trauma in the differential diagnosis. In addition,
imaging of the TMJ, sacroiliac joint, cervical spine, midfoot, hip,
or shoulder is useful in diagnosing inflammatory arthritis8, 9.MRI
provides the most sensitive radiologic indicator of disease
activity. The modality can depict synovial hypertrophy, define soft
tissue swelling, and demonstrate excellent detail of the status of
articular cartilage and overall joint integrity8, 9. To improve
visualization of synovial hypertrophy and improve detection of
cartilaginous erosions when an inflammatory arthritis is suspected,
contrast-enhanced sequences should be performed8, 9.Synovitis and a
joint effusion may have similar hyperintensity on T2-weighted (T2W)
and short-tau inversion recovery (STIR) images. Therefore,
gadolinium-enhanced T1-weighted (T1W) MRIs are necessary to
accurately define active synovitis8, 9.
Figure 8. (A) T2-weighted MRI shows high signal in both hips,
which may be due to hip effusions or synovitis. High signal
intensity in the left femoral head indicates avascular necrosis.
(B) Coronal fat-saturated gadolinium-enhanced T1-weighted MRI shows
bilateral enhancement in the hips. This indicated bilateral active
synovitis, which is most pronounced on the right. Because the image
was obtained with fat saturation, the hyperintensity in both hips
is pathologic, reflecting an inflamed pannus8.2 . 9. TreatmentsFor
all patients, the goals of therapy are to decrease chronic joint
pain and suppress the inflammatory process. Accomplishing these
goals will lead not only to improved short-term and long-term
function but also to normal growth and development2.First-line
therapy includes nonsteroidal anti-inflammatory drugs (NSAIDs). In
addition, intra-articular corticosteroid injections have been shown
to be safe and effective, may have beneficial effects on growth
parameters, and can be administered with little psychologic trauma,
even in young patients. Cognitive-behavioral pain management
techniques have also been successful in reducing pain intensity in
pediatric patients. Physical therapy is important not only for
reducing pain but also for maintaining joint and muscle
function2.
Preventing eye damage is another important goal of JRA therapy.
Because of the risk of chronic uveitis in patients with JRA,
careful ophthalmologic surveillance is essential. Pharmacotherapy
of uveitis with methotrexate and cyclosporin A may be beneficial in
decreasing the severity of this condition2. The toxicities
associated with therapeutic agents pose a significant problem in
effective treatment. For instance, agents that work by general
immunosuppression may be associated with increased susceptibility
to infection, complication of vaccine administration, or increased
oncogenic risk. The distinction between symptom control and
prevention of erosive disease must also be recognized. Many of the
agents that are most effective at pain and symptom control,
including corticosteroids and NSAIDs, have no effect on erosive
disease. Even methotrexate, which is known to have
disease-modifying activity, may relieve symptoms and signs without
halting disease progression in some patients2.
Disease-Modifying Antirheumatic Drugs
The term disease-modifying antirheumatic drugs (DMARD) is
limited to agents that retard radiologic progression of disease.
Only 3 DMARDs have been proved to be effective in controlling
disease activity in double-blind, placebo-controlled studies of
children with JRA: methotrexate, sulfasalazine, and, more recently,
etanercept2.
Diet and Activity
No specific diet helps in the treatment of JIA. However, because
active JIA has been associated with decreased osteoblastic activity
and a risk of osteopenia, encourage the inclusion of at least 3
servings of calcium-rich foods each day. Consider supplementation
when poor calcium intake persists. Rarely, overall caloric intake
is poor and supplementation is required. TMJ disease may also
compromise the childs diet8.Encourage patients to be as active as
possible. Bed rest is not a part of the treatment. In fact, the
more active the patient, the better the long-term prognosis.
Children may experience increased pain during routine physical
activities. As a result, these children must be allowed to
self-limit their activities, particularly during physical education
classes. A consistent physical therapy program, with attention to
stretching exercises, pain modalities, joint protection, and home
exercises, can help ensure that patients are as active as
possible8.
RehabilitationObjectives of physical therapy and rehabilitation
in JRA include the following15: (a) controlling pain, (b)
preventing limitation and restoring ROM in affected joints, (c)
maintaining and improving muscle strength, (d) increasing and
maintaining endurance for activities of daily living, (e)
minimizing the effects of inflammation, and (f) ensuring normal
growth and development10.To achieve these objectives, raising
awareness about the disease in patients and families is one of the
most essential components of treatment. A study by Andr et al16
documented that through education, physical exercises, coping
strategies, and problem-solving skills, families became more
involved in the treatment, better understood their childrens
condition, and were able to find more efficient solutions, with a
subsequent improvement in the quality of life of their
children10.In JRA, home-based programs are important to support the
treatment. There are three basic rules for home programs: first,
the most appropriate treatment is the simplest, least painful, and
least expensive; second, stretching and strengthening exercises
should be customized according to the daily activities that the
patient is unable to perform; and third, all treatments must be
followed closely by a health care professional10.
2 . 10. Prognosis
The course of the disease is highly variable. Only approximately
one quarter of patients with polyarticular onset are in remission
at 5 years after disease onset, and more than two thirds develop
erosions within the first 5 years of the disease. The extended
oligoarthritis phenotype has a similar prognosis2.As might be
expected from the high frequency of erosions in patients with
polyarticular disease, polyarticular onset and polyarticular
disease course both have been identified as significant risk
factors for disability. Other factors that determine disability
include female gender and the presence of rheumatoid factor. Lower
remission rates have been observed in patients with polyarticular
onset, rheumatoid factor, persistent morning stiffness,
tenosynovitis, subcutaneous nodules, or antinuclear antibody. Poor
outcomes are also associated with early involvement of the small
joints of the hands and feet and rapid appearance of erosions2.The
most challenging patients to treat are those with poor prognostic
indicators. These patients are likely to require more aggressive
therapy, as well as early initiation of treatment. A recent study
of predictive factors that influence the outcome of patients with
JRA or juvenile spondyloarthropathy found that patients who
developed erosions and disability tended to have received treatment
later thanthose who did not2.Table 2. Poor Prognostic Indicators
for Patients With JRA2
CHAPTER III
MEDICAL REPORT3. 1. Case
DP, a 15 years and 10 months old boy, with a body weight of 25
kg, was admitted to the non-infection ward of H Adam Malik General
Hospitals Pediatric Division on 4 May 2012 at 09.30 AM with a chief
complaint of swelling on the joints.PERSONAL ANAMNESIS
Name
: DPAge
: 15 years and 10 months
Sex
: MaleInitial Body Weight : 25 kilogram
Body Height
: cm
Religion
: ChristianiRace
: Batak
Address
: Lingkungan IX Sikkam Kel. SibaAdmission Date: 04 May 2012
Medical Record: 51.37.45ANAMNESIS OF DISEASE:
Chief complaint: swelling of the jointsResume:
Swelling was felt by the patient since 4 month ago. Sweeling
felt on the knee joints. The knee joint could not be moved by the
patient. Pain and burning sensation was felt and become worsen in 4
months. The patient could not walk since 4 months ago. The knee
could not be straightened. History of recurrent fever since 9
months ago, but now the patients did not have a fever. Defecation
and urination was normal. Nausea and vomiting were not found.
The patient was referred from regional hospital with the
diagnosis of Rheumatoid Arthritis. The patient was transfused with
1 bag blood in that hospital. PHYSICAL DIAGNOSTIC:
Status Presence:
General Condition
Sensorium: Alert, Temperature: 37( C
Disease Condition
Anemic (+), icteric (-), edema (-), dyspnea (-), cyanosis (-),
edema (+)
Nutrition Status
Age
: 15 years and 10 months
Body Weight: 25 kilogram
Body Length: 104 cm
Health status/Disease status/Nutritional status: Moderate /
Moderate / PoorLocalised status:Head:
Eyes: Light Reflex +/+, isocoric pupil, pale conj.palp.inf
+/+,
Ears: within normal range, Nose: within normal range, Mouth:
within normal rangeNeck:
Lymph node enlargement (-)
Thorax:Fusiform symmetrical, retraction (-)
HR = 120 x/i, regular, murmur (-)
RR = 24 x/I, regular, ronchi (-/-)Abdomen: Soft, peristaltic (+)
normal
Liver: not palpableSpleen: not palpableExtremities: Pulse: 120
x/i, regular, pressure/volume adequate, warm acral, CRT< 3,
edema pretibial: (+/+), edema on the poplitea: (+/+), blood
pressure: 100/70 mmHg
Differential Diagnosis: Juvenile Rhematoid Arthritis Acute
Lymphocytic Leukemia Acute Rheumatic FeverDiagnosis: Juvenile
Rhematoid ArthritisTherapy:
IVFD D5 NaCl 0,45% 10 gtt/i mikro
Ibuprofen 3x400 mgTreatment/Diagnosis Plan: Complete Blood
Count, RFT, LFT, Electrolyte
Allergy Immunology referral Eye Departmen referral3. 2.
DiscussionDP, a 15 years and 10 months old boy, with a body weight
of 25 kg, was admitted to to the non-infection ward of H Adam Malik
General Hospitals Pediatric Division on 4 May 2012 at 09.30 AM with
a chief complaint of swelling on the joints Swelling was felt by
the patient since 4 month ago. Sweeling felt on the knee joints.
The knee joint could not be moved by the patient. Pain and burning
sensation was felt and become worsen in 4 months. The patient could
not walk since 4 months ago. The knee could not be straightened.
History of recurrent fever since 9 months ago, but now the patients
did not have a fever. Defecation and urination was normal. Nausea
and vomiting were not found.
On further questioning, The patient was referred from regional
hospital with the diagnosis of Rheumatoid Arthritis. The patient
was transfused with 1 bag blood in that hospital.
Juvenile Rheumatoid Arthritis, persistent arthritis in 1 or more
joints for at least 6 weeks if certain exclusionary conditions have
been eliminated 2. JRA is the most common chronic rheumatic
illness1. Patients with JRA often have symptoms including
arthritis, fever, rash, arthritis, enlargement of lymph nodes and
spleen, and uveitis 1. In this patient, DP, experienced swelling,
pain, and burning sensation of the joints which realized 4 month
ago. He also has history of fever since 9 months ago. The diagnosis
of juvenile rheumatoid arthritis (JRA) is based on the history and
physical examination findings. No laboratory studies are diagnostic
for JRA, and indeed, all laboratory study findings may be normal in
children with this disorder8. From anamnesis, DP experienced
symptoms of arthritis and had history of fever since 9 months ago.
From physical examination, there was a swelling of the joints (knee
joint). When the joint was moved, the patient complained of pain
and burning sensation. From the laboratory results, the hemoglobin
was 9,1 g%, LED 27 mm/h, qualitative CRP was positive, rheumatoid
factor was negative, ANA was 8, and Anti ds-DNA was 15,3. For all
patients, the goals of therapy are to decrease chronic joint pain
and suppress the inflammatory process. Accomplishing these goals
will lead not only to improved short-term and long-term function
but also to normal growth and development2. First-line therapy
includes nonsteroidal anti-inflammatory drugs (NSAIDs). The patient
was given ibuprofen as a first line therapy. Ibuprofen inhibits
inflammatory reactions and pain by decreasing prostaglandin
synthesis. The pediatric dosage is 30-50 mg/kg/d PO divided qid,
not to exceed 2.4 g/d.3. 3. Summary
A case report of Juvenile Rheumatoid Arthritis in a 15 year and
10 month old boy who was admitted to the non-infection ward of H
Adam Malik General Hospitals Pediatric Division on 4th May 2012 was
made. The diagnosis was established from history taking, physical
examination, and laboratory examination. The goals of therapy are
to decrease chronic joint pain and suppress the inflammatory
process. The patient still being treated in the non-infection ward
of H Adam Malik General Hospitals Pediatric Division.REFERENCES
1. Hahn YS, Kim JG. 2010. Pathogenesis and Clinical
Manifestations of Juvenile Rheumatoid Arthritis. Korean J Pediatr
2010;53(11):921-9302. Ilowite NT. 2002. Current Treatment of
Juvenile Rheumatoid Artrhitis. Pediatrics 2002;109;1093. Abraham,
Rudolph. 2006. Buku Ajar Ilmu Pediatri Rudolph.Jakarta: EGC
4. Olson JC. 2003. Juvenile Idiopathic Arthritis: An Update.
Winconsin Medical Journal. Vol. 102(7): 45-505. Rudis J. 2012.
Juvenile Rheumatoid Arthritis. Available from:
http://pediatrics.med.nyu.edu/conditions-we-treat/conditions/juvenile-rheumatoid-arthritis6.
Subramaniam S. 2009. Ethiopathogenesis of Rheumatoid Arthritis May
be Misunderstood of Non-Infectious-A Review on Infectious Etiology
of RA. Asian Journal of Medical Sciences 1(2): 1-97. Samee ERAE,
Chennawy FE, Shambaky AYA. 2011. Clinical and Genetic Study of
Juvenile Rheumatoid Arthritis. New York Science Journal,
2011;4(4)8. Sherry DD. 2011. Juvenile Idiopathic Arthritis.
Available from:
http://emedicine.medscape.com/article/1007276-overview9. Hekmatnia
A. 2011. Imaging in Juvenile Rheumatoid Arthritis. Available from:
http://emedicine.medscape.com/article/409980-overview#a2310. Cakmak
A, Bolukbas N. 2005. Juvenile Rheumatoid Arthritis: Physical
Therapy and Rehabilitation. Southern Medical Journal. Vol. 98(2):
212-216EKG
ECHO
Follow Up (05/5/2012) on 06.00 pm
S: pain and swelling of the joints
O: General Status: Sensorium: Alert, Temp: 37 C, BB: 25 kg, PB:
104 cm, Anemic (+), Dyspnea (-), Cyanosis (-), Edema(+), Icteric
(-)
Localized Status :
Head
: Eye: light reflex: +/+ , isochoric pupil,
Pale Inferior conjunctiva palpebra : +/+
Ear/Nose/Mouth : in normal range
Neck: Lymph nodes enlargement (-),
Thorax: Simetris Fusiformis, Retraction (-)HR =116x/i, regular,
murmur (-)
RR = 24x/i, regular, wheezing (-/-), ronchi (-/-)Abdomen : Soft,
peristaltic (+) N
Liver: not palpable
Spleen: not palpable
Extremities: Pulse: 116 x/i regular, pressure/volume: adequate,
warm acral, Capillary refill time < 3, blood pressure: 100/70
mmHg, edema pretibial (+/+), edema on the poplitea (+/+)
Anogenital : male, within normal range.
A : Juvenile Rheumatoid Arthritis
P : IVFD D5 NaCl 0,45% 10 gtt/s micro
Diet MB 1600 kkal + 50 gr protein
Ibuprofen 3x400 mg
Recommendation : Complete Blood Count, RFT, LFT, Electrolyte
ASTO, RF
ANA, anti ds-DNA
CRP
Allergy Immunology referral Eye Departmen referral
Lab Results:
Hematology
Complete Blood Count:
Hemoglobin: 9,1 g% Neutrofil: 57,8%
Erithrocyte: 4,27x106/mm3 Lymphocyte: 24 %
Leucocyte: 10,6x103/mm3 Monocyte: 7,9 %
Hematocrit: 29,9 % Eosinofil: 9,9 %
Trombosit: 488x103/mm3 Basofil: 0,4%
MCV: 70 fL
MCH 21,3 pg
MCHC: 30,4 g%
LED: 27 mm/jam
LE cell : negative
Clinical Chemistry:
Liver
Total Bilirubin: 0,19 mg/dl
Direct Blirubin: 0,1 mg/dl
Alkali Phosphatase: 92 U/L
AST/SGOT : 15 U/L
ALT/SGPT : 16 U/L
Carbohydrate Metabolism
Random Blood Glucose: 84,9 mg/dl
Kidney
Ureum : 13,7 mg/dl
Creatinin : 0,26 mg/dl
Uric Acid : 3,1 mg/dl
Electrolyte
Calcium (Ca) : 8,3 mg/dl
Sodium (Na) : 136 mEq/L
Potassium (K) : 4,3 mEq/L
Chloride (Cl) : 102 mEq/L
Immunoserology
ASTO: