CASE REPORT

ALLERGY AND IMMUNOLOGY DIVISION

SECONDARY OSTEOPOROSIS IN A CHILD WITH RECURRENT

JUVENILE IDIOPATHIC OLIGOARTHRITIS

Nadya.AR.Bubakar

PEDIATRIC DEPARTMENT - FK-UNHAS/RSUP Dr. WAHIDIN SUDIROHUSODO

INTRODUCTION

Juvenile idiopathic arthritis (JIA) is a group of heterogeneous conditions that includes all
forms of joint inflammation of unknown etiology lasting for at least 6 weeks and with
onset before the age of 16 years. JIA is the most common chronic rheumatic disease in
childhood and is a major cause of short-term and long-term disability. (Giancane G,
2016).

     Epidemiological characteristics of the disease are important to determine the

influence of genetic and environmental factors on the course of the disease. In the
industrial countries, the incidence of JIA is 5–18 and prevalence of JIA is 30–150/100
000 children until 16 years old. In the Czech Republic, the annual incidence of JIA is
13/100 000 and prevalence of JIA is 140/100 000 children until 16 years old
(Brabnikova Maresova, 2011).

Etiology of this disease is still unclear. The most acceptable theory supports the
influence of secondary immunogenic mechanisms due to various genetic and
environmental factors. Infection, along with stress and trauma, are considered the most
responsible etiological factors. Intestinal microbiota appears as a factor that is relevant
to autoimmune diseases, including JIA, according to the latest research. The increasing
frequency of autoimmune diseases among JIA patients shows the genetic basis of the
disease. Human leukocyte antigen (HLA) B27 and other HLA tissue types are the most
commonly mentioned genetic factors (Barut K, 2017).

1
     The goals of therapy must be multidimensional: to control pain, to maintain muscle
movement or strength or function, to induce remission of the disease, to manage
systemic complications and to facilitate normal physical and psychosocial development.
The duration of treatment must be adjusted every 3 months, until the treatment goal is
reached. (Barut K, 2017).

Bone disease in patients with juvenile idiopathic arthritis (JIA) is associatedwith

focal (joint erosion and juxtaarticular osteopenia) and systemic bone loss (generalized
osteopenia or reduction of bone mass density). Pathophysiology of bone loss is
multifactorial and involves particularly proinflammatory cytokines and deleterious effects
of glucocorticoid therapy. Clinical studies in patients with JIA indicate excessive
activation of osteoclastogenesis and reduction of bone formation. Reduction of physical
activity, muscle atrophy caused by high disease activity, and compulsory restriction in
movements are also associated with bone loss. In patients with JIA, the disease can be
complicated by growth cartilage involvement and systemic or local growth retardation. In
the absence of preventive measures, fragility fractures can occur even at an early age .
dini (Brabnikova Maresova, 2011)

Glucocorticoid-induced osteoporosis is the most common form of secondary

osteoporosis. Systemic glucocorticoid therapy is associated with an initial increase in
bone resorption and, more importantly, a decrease in subsequent bone formation, which
leads to microarchitecture damage and an increased risk of fractures. Epidemiological
studies explicitly establish a higher risk of fracture among adults using systemic
glucocorticoid therapy (Hansen KE, 2014).

          This paper reports a case of systemic type of JIA with osteoporosis and nutritional
marasmus in 4 years and 11 months boys.

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Case Report

I. PATIENT IDENTITY
Name : GGK
Medical record : 71-20-84
Date of birth : 28-03-2015
Age : 4 years 11 months
Gender : Male
Weight : 11 kg
Height : 101 cm
ER admission date : 11-03-2020
Address : BTN PURI BAHARI LESTARI BLOK E NO 5 Makassar

PARENT IDENTITY

Dad Mom
Name IS MS
Birth of Date 10/11/1983 1/7/1989
Age 37 years 31 years
Education S2 D4
Profession government Housewife
employess

II. ANAMNESIS
Autoanamnesis.

Chief complaint : Knee pain since 1 week before entering the hospital

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Current medical history

Patients present with complaints of pain in the left knee experienced since 1
week before hospitalization and increase with activity. Complaints accompanied by
swelling that is noticed since 1 month before hospitalization. There is fever, no seizures.
There is no cough and shortness of breath. No vomiting. Children can eat and drink.
Normal yellow bowel movements. Urinate yellow, enough impression.

History of up and down fever from 1 month before entering the hospital. A history
of reddish rashes often appears all over the body from birth. History of joint pain since 3
years ago on the left knee, and right knee . Pain increases if the patient is active. A
history of routine medical treatment at Wahidin Hospital with a diagnosis of JIA since 3
years and getting methyl prednisolone treatment and complaints of reduced pain. There
is no family history of the same disease. History with the same disease was previously
denied.

Personal or social history of the patient

a. Maternal pregnancy history

The patient is the first child. This pregnancy was the desired pregnancy. At the
time of pregnancy the mother was 25 years old. During pregnancy, the mother regularly
checked for pregnancy, taking vitamins and blood boosting tablets. During pregnancy
the mother had never experienced excessive vomiting and had never experienced a
miscarriage before, never consume drugs during pregnancy that was not recommended
by the doctor.

b. Birth history

The patient was born through spontaneous labor in a hospital , born with the help
of a docter. Pregnancy is enough months, crying immediately with unknown APGAR
score and clear amniotic water. The patient was born 9 months old with weight 3100
gram, body length 50 cm.

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 c. Post Natal History

Shortly after birth, the baby get injection of vitamin K, hepatitis B and Polio
immunization when the patient is discharged from the hospital. Never seizure or blue.

d. Nutritional history

Patients got breast milk for up to 6 six month and then eat 2-3 meals a day with
an adult portion.

e. Immunization history

The patient has received basic immunization according to age.

f. History of children's basic needs

Asuh (physical-biomedical)

Patients get breast milk for 6 month and then the adult food menu.

Asih (psychosocial)

The first child patient, gets enough love from both parents and siblings. The child
is born from the marriage of both parents and is the expected child.

Asah (stimuli)

Parents give full attention to the growth and development of patients.

Family history and socioeconomic background

Father works as an government employess. Mother as housewife. Father income in

one month is around 2-4 million rupiah. Father's last education was strata two and his
mother 4th diploma. During the patient being treated, the patient is always taken care of
by the father and mother. The patient lives with both parents. The closest health facility
is the puskesmas. Patients already have health insurance.

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III. PATIENT INFORMATION
1. Physical examination (objective)
a. Present condition
General condition : Moderate pain

Conciousness : GCS 15 (E4M5V6)

Pulse : 110 x / minute

Respiration Rate : 24 x / minute

Temperature : 38oC

FLACC pain scale : 2 FLACC

b. General State

Organ Description
Skin There is a macular rash all over the body.
Head Normocephal, Mesocephal.
Large fontanell closes.
Hair Straight black
Face Butterfly rash does not appear
Eye No anemic conjunctival and no icteric scleral
Nose Nasal septum in the middle, no rhinorhea.
Ear No otorrhea.
Mouth No cyanotic lips.
Tooth 212/212
212/212
Neck There is no stiff neck
Chest There are xylophone ribs
Lungs There are no subcostal, intercostal and supra sternal
retractions
Sonor percussion, right fremitus equal to left,
bronchovesicular breath sounds in both lung fields, no
additional rales breath sounds, no wheezing.

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 Heart Ictus cordis is not visible. Thrill is not palpable.
Right border is the right parasternal linea.
Left border is the left midclavicularis line.
Pure regular I-II heart sounds.
No heart murmur
Abdomen There is no distension.
Peristaltic impression is normal.
The liver is not palpable.
Spleen is not palpable.
Genitalia There are no abnormalities
Extremities There is swelling in the left knee accompanied by pain
when moved, hard touch, immobile, palpable temperature
and the color same as the surroundings.
Gland There is no enlarged lymph nodes.
Physiological
Normal impression
reflexes
Pathological
No Babinsky Reflex
reflexes

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 Figure 1. Patient's feet and hands
c. Nutritional Status and Anthropometry
Weight (BW) : 11 kg
Height (TB) : 101 cm
Head circumference : 47 cm (Normal 47-53 cm)
Chest circumference : 40 cm
Abdominal circumference : 38 cm
BW / H : under -2SD and -3SD (malnutrition)
BW / U : under -3SD (very low body weight)
H/A : between -2SD and median (normal stature)
Nutritional status : Malnutrition / normal stature

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2. Supporting Investigation
Prodia Lab 17-7-2017 :
Negative result of Ds DNA
Prodia Lab 12-2-2017 :
Negative result of IgE Atopi
Complete Blood Count (10-3-2020):
Hb 10.9 gr / dl, leukocytes 14,700 mm 3, PLT 444,000 mm3, MCV 70 fl, MCH 22 pq, HCT
34%, neutrophils 64.6%, lymphocytes 29.6%, ESR 57 and 85 mm / hour. Ana test was
negative
Urinalysis: light yellow, pH 6.5, SG 1,005, blood, ketones and nitrites are negative

Echocardiography examination results :

Figure 2. Echocardiography of a patient

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Impression : LV and RV functions within normal limits

Genu AP + Lateral D / S X-ray results:

Figure 3. X-ray of D / S Genu

- There is erosion in the epiphyseal regions of os femur sinistra and os patella sinistra
- Decreased bone density
- Looks swelling density on the genu sinistra
Impression according to juvenile rhematoid arthritis.

I. RESUME

A boy aged 4 years 11 months came with complaints of pain in the left knee
experienced since 1 week before entering the hospital and aggravated with activity.
Complaints are accompanied by swelling that is noticed since 1 month before entering
the hospital. There is fever, no seizures. There is no cough and shortness of breath.

10
vomiting. Children can eat and drink. Normal yellow bowel movements. Urinate yellow,
enough impression. History of up and down fever from 1 month before entering the
hospital. A history of reddish rashes often appears all over the body from birth. History
of joint pain since 3 years ago on both of knee the left knee. Pain increases if the patient
is active. A history of routine medical treatment at Wahidin Hospital with a diagnosis of
JIA since 3 years and getting methyl prednisolone treatment. And methyl prednisolon
therapy was continued at the general hospital.no history of same illness.
On physical examination, the general condition was seriously ill, GCS 15,
malnutrition, pulse 110 times / min, RR 24 times / min, temperature 38 oC, pain scale 2
FLACC. In lung bronchovesicular breath sounds, there is no rales in both lung fields and
wheezing is absent. The heart is within normal limits. There is swelling in the left knee
accompanied by pain when moved, palpable temperature and color equal to the
surroundings.
On investigations, from routine blood tests found hypochromic microcytic anemia
and increased ESR. On the X-ray examination of knee, there was a figure of juvenile
rhematoid arthritis.
Patients were treated in the ward and given NSAID, vitamin and malnutrition
management. Parents are given education about the course of the disease,
complications, plans for further diagnosis and further management.

II. WORKING DIAGNOSIS:

1. Systemic type of Juvenile idiopathic arthritis
2. Nutritional marasmus
3. Iron deficiency anemia DD / anemia of chronic disease

III. PLANNING
a. Plans for diagnostic support
- Juvenile idiopathic arthritis tracking: Complete blood count, CRP.
- Tracking the causes of anemia: check peripheral blood smears,
reticulocytes and ferritin.
b. Medical treatment plan

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 - IVFD Kaen 3B 16 drops / minute
- Ibuprofen 100 mg / 8 hours / oral
- Ampicillin 250 mg / 6 hours / intravenously
- Gentamycin 25 mg / 12 hours / intravenously
- Elkanes syr 1 x 5 ml / oral
- Kalnic syr 1 x 5ml / oral
- Folic acid 1 mg / 24 hours / oral
- Vitamin A 200,000 iu / oral
- Vitamin B kompleks 1 tab/24 hours /oral
- Vitamin C 50 mg/12 hours /oral

c. Nutritional therapy
Management of malnutrition
Day 1 stabilization phase
Energy 80 x 11 kg = 880 kcal
11 gr protein
Milk f75 = 145 ml / 3 hours / oral

d. Monitoring plan
- Monitoring the patient's general condition includes subjective complaints
and vital signs.
- Monitoring disease progression, and complications and response to
treatment.

e. Providing information and education communication

- Provide an explanation to parents about the condition suffered by patients
including causes, course of illness, complications, prognosis and plans for
further action.
- Explain the importance of cooperation and support from the family so that
the treatment process can run smoothly.

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IV. FOLLOW UP
Day-2 Care 12/3/2020
Complaints: there is reduced joint pain, there is a rash on the whole body. No
fever, no seizures. No coughing and shortneess of breath, no vomiting. Children eat and
drink. Defecate yellow soft. Urination: yellow, sufficient impression. General condition of
severe pain, GCS awareness 15, malnutrition, pulse 96 times / minute, breathing 24
times / minute, temperature 37.1 oC, pain scale 1 FLACC. There are xylophone ribs. In
lung bronchovesicular breath sounds, there is no rales in both lung fields and wheezing
is absent. The heart is within normal limits. There is swelling in the left knee
accompanied by pain when moved, palpable temperature and color equal to the
surrounding, there is wasting

Wahidin Hospital's abdominal ultrasound (12-3-2020):

Figure 4. Abdominal ultrasound

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There is no apparent abnormality on this abdominal ultrasound.

Elbow X-ray AP/Lateral - Wahdin Hospital (12-3-2020)

Figure 5. Elbow X-ray

Impression: Osteoporosis

Assesment :
1. Systemic type of Juvenile idiopathic arthritis
2. Nutritional marasmus
3. Osteoporosis
4. Iron deficiency anemia DD / anemia of chronic disease

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Therapy: IVFD kaen 3B 16 drops/minute, Ibuprofen 100 mg/8 hours/oral, 2/ Ampicillin
250 mg/6 hours/intravenously, 2/ Gentamicin 25 mg/12 hours/intravenously, Elkane syr
1 x 5 ml/oral, Kalnic syr 1 x 5ml/oral, Folic Acid 1mg/24 hours/oral, management of
malnutrition stabilization phase – Day 2 - calorie 990 kcal, milk f75 8 x 165 ml

Day-4 Care 14/3/2020

Complaints: There is reduced joint pain, there is a rash on the whole body. No
fever, no seizures. No coughing and shortneess of breath, no vomiting. Children eat and
drink. Defecate yellow soft. Urination: yellow, sufficient impression. General condition of
severe illness, GCS 15, malnutrition, pulse 120 times / min, breathing 28 times / min,
temperature 36.1oC, pain scale 1 FLACC. There are xylophone ribs. In lung
bronchovesicular breath sounds, there is no rales in both lung fields and wheezing is
absent. The heart is within normal limits. There is swelling in the left knee accompanied
by pain when moved, palpable temperature and color equal to the surrounding, there is
wasting

Complete Blood Count (13-3-2020):

Hb 11 gr/dl, leukocytes 18.600 mm 3, PLT 401.000 mm3, MCV 69 fl, MCH 22 pq,
HCT 34%, ureum 17mg/dl, creatinine 0,39 mg/dl, sgot 29 U/l sgpt 12 U/l, Albumin 3,1
gr/dl, cholestrol 100 mg/dl, ferritine 97 ng/dl, malaria (DDR) negative.
Prodia Lab : Hs CRP 121,6 mg/l ( N 0,6-7,9)
Blood smears suggest leukocytosis as a sign of infection
Thorax X-ray

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 Figure 6. Thorax X-ray
Impression : Bilateral Bronchopnemonia

Assesment :
1. Systemic type of Juvenile idiopathic arthritis
2. Nutritional marasmus
3. Osteoporosis
4. Mix Iron deficiency anemia andanemia of chronic disease

Therapy: IVFD kaen 3B 16 drops/minute, Ibuprofen 100 mg/8 hours/oral, 3/

Ampicillin 250 mg/6 hours/intravenously, 3/ Gentamicin 25 mg/12 hours/intravenously,
Elkane syr 1 x 5 ml/oral, Kalnic syr 1 x 5ml/oral, Folic Acid 1mg/24 hours/oral,
management of malnutrition transition phase – Day 2 – 1100 ccal - milk f100 8 x 140 ml

Day-6 Care 16/3/2020

Complaints: There is reduced joint pain, there is a reduced rash on the whole
body. No fever, no seizures. No coughing and shortneess of breath, no vomiting.
Children eat and drink. Defecate yellow soft. Urination: yellow, sufficient impression.
General condition of severe pain, GCS awareness 15, malnutrition, pulse 100 beats /
minute, breath 22 beats / minute, temperature 36,7 oC, pain scale 1 FLACC. There are
xylophone ribs. In lung bronchovesicular breath sounds, there is no rales in both lung
fields and wheezing is absent. The heart is within normal limits. There is swelling in the

16
left knee accompanied by pain when moved, palpable temperature and color equal to
the surrounding, there is wasting
Assesment :
1. Systemic type of Juvenile idiopathic arthritis
2. Nutritional marasmus
3. Osteoporosis
4. Mix Iron deficiency anemia andanemia of chronic disease

Therapy: Ibuprofen 100 mg/ 8 hours/ oral, 1/ cefixime 2 x 5 ml/oral, Elkane syr 1 x 5
ml/oral, Kalnic syr 1 x 5ml/oral, Folic Acid 1mg/24 hours/oral, management of
malnutrition transition phase – Day 4 – calories 1320 kcal, 8 x 165 ml f100 milk,
outpatients

Definitive diagnosis:
1. Systemic type of Juvenile idiopathic arthritis
2. Nutritional marasmus
3. Short stature
4. Anemia of chronic disease

Prognosis
Qua ad vitam : bonam
Qua ad functionam : dubia
Qua ad sanationem : dubia

Discussion
Juvenile rheumatoid arthritis is a group of heterogeneous conditions that includes
all forms of arthritis of unknown etiology and lasts for at least 6 weeks and with a
beginning before the age of 16 years. The JIA classification of ILAR facilitates the
approach of diagnosis, prognosis, and management of pediatric arthritis (Giancane G,
2016).

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 JIA is the most common rheumatological condition in childhood and consists of
subtypes including oligoarticular, polyarticular, and systemic onset. Polyarticular JIA
includes a mixture of patients with a broad spectrum of etiological risk factors, unique
disease course, and therapeutic challenges. Children with polyarticular JIA tend to have
more refractory journeys compared to those who have less affected joints. Because of
the prolonged course of active disease, they are at higher risk for joint damage,
resulting in worse functional outcomes and decreased quality of life (Oberle EJ, 2014).
According to the International League of Associations for Rheumatology criteria
(ILAR), JIA is defined as chronic arthritis (‡6 weeks duration) with no known cause
occurring in children before the 16th birthday. The 6-week minimum duration to define
chronicity and onset before the 16th birthday to define “juvenile” are based on expert
opinion rather than derived from data. The ILAR classification categorizes JIA into 7
mutually exclusive categories based on the number of joints involved, extra-articular
features, and serology identified in the first 6 months of disease presentation (Table 1).
This categorization attempts to cluster similar JIA presentations into distinct categories
to improve research into etiology, disease course, longterm outcomes, response to
treatment, and development of future therapies. This classification system will likely
evolve and be refined over the next few decades as knowledge of this disease
increasesi.(Shanoi, 2017)

Epidemiology
JIA is the most common chronic rheumatic disease in children and the main
cause of short-term and long-term disability. Reported incidents and prevalence in
Europe and North American Populations range from 2 to 20 and from 16 to 150 per
100,000. However, extraordinary disparities in the frequency of JIA subtypes have been
noted in various geographical regions or ethnic groups. In western countries,
oligoarthritis is the most common subtype, while polyarthritis predominates in Costa
Rica, India, New Zealand, and South Africa. In Asia, systemic arthritis accounts for a
greater proportion of children's arthritis (Giancane G, 2016).
In a study in Bandung, 28 children were diagnosed with JIA. Patients' age varies
from 2 to 14 years with an average age when first diagnosed 8.25 ± 3.62 years. More

18
women than men with a ratio of 1.8: 1. JIA Incidence in Dr. Hospital Hasan Sadikin in
2011 amounted to 1.3 / 100,000 (Ghrahani R, 2012).
This patient is a boy aged 4 years 11 months.

Etiopathogenogenesis
Etiopathogenogenesis of this disease is still unclear. The most acceptable theory
supports the influence of secondary immunogenic mechanisms due to various genetic
and environmental factors. Infection, along with stress and trauma, are considered the
most responsible etiological factors. Intestinal microbiota appears as a factor that is
relevant to autoimmune diseases, including JIA, according to the latest research. The
increasing frequency of autoimmune diseases among JIA patients shows the genetic
basis of the disease. Human leukocyte antigen (HLA) B27 and other HLA tissue types
are the most commonly mentioned genetic factors. Various infections are considered
responsible for the pathogenesis of JIA: enteric infections, parvovirus B19, rubella,
mumps, hepatitis B, Epstein-Barr virus, mycoplasma and chlamydia infections. T
lymphocytes that are triggered by potential and secreted cytokines cause joint damage.
Macrophages, which are induced by released mediators, produce proinflammatory
cytokines (interleukin (IL) 1, IL-6, tumor necrosis factor (TNF) -α). Thus, acute phase
markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] are increased
and acute joint inflammation occurs with an increase in synovial fluid. Synovial
inflammation (synovitis) is characterized by villous hypertrophy and hyperemia of
subsinovial tissue. Synovial hypertrophy and synovitis secondary to chronic
inflammation are known as "pannus". The percentage of T lymphocytes in synovial fluid
varies between different JIA subtypes, perhaps explaining the difference in treatment
response between JIA subgroups (Bar K, 2017).

19
Figure 7. Development of JIA. (Smolen JS, 2018)

Figure 8. Pathology of JIA. (Smolen JS, 2018)

20
Classification and clinical manifestations

Over the past few decades, several classification systems for chronic joint stretching
have been proposed. The current scheme, based on criteria established by the
Pediatric Task Force of the International League of Associations for Rheumatology
(ILAR), introduces the term unifying JIA and describes seven disease categories, on the
basis of clinical and laboratory features that have taken place within the first 6 months of
illness ( Giancane G, 2016).

Some classifications according to the American College of Rheumatology (ACR), ILAR

and european league against rheumatism (EULAR):

Table 1. Classification of JIA. (Oberle EJ, 2014)

Criteria for diagnosis of JIA according to ILAR

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 Juvenile idiopathic arthritis (JIA) a diagnosis of exclusion which, when suspected,
requires a complete clinical evaluation, including for family history and recent
pathological events, and special attention to morning pain and stiffness. Detailed
physical examination should always be done by examining all joints of the body at both
the first evaluation and follow-up visit (Giancane G, 2016).

Systemic arthritis

This subtype of the disease, characterized mainly by systemic symptoms, affects

women and men with the same frequency and can occur at any time during childhood.
The presence of arthritis and intermittent fever for at least 2 weeks plus one of the
following defines the disease: typical rash, general lymphadenopathy,
hepatosplenomegaly or serositis (Barut K, 2017).

The temperature rises to 39.5°C once or twice a day. Intermittent fever is

generally accompanied by a typical salmon pink rash, which usually occurs in the body
and proximal limbs and disappears with a decrease in fever. Occasionally, polyarticular
arthritis, including large and small joints, can appear during the course of the disease. In
general, symptoms of systemic fever and rash recover after the appearance of
polyarthritis, which makes distinguishing it from ordinary polyarticular JIA difficult. Fever
and other systemic symptoms can last for months but rarely more than 6 months (Barut
K, 2017).

Hepatosplenomegaly and lymphadenopathy are seen in about one third of

patients. Serositis, including pericarditis and pleurisy, can be seen, appearing with
marked chest pain. Abdominal pain and myalgia can occur during peak fever.
Leukocytosis, hypochromic microcytic anemia, thrombocytosis, increased acute phase
reactants and increased levels of transaminases may be noted. Increasing ferritin levels
is a relevant problem for SJIA. Auto antibodies, ANA, and negative rheumatoid factors.
Possible complications of sJIA include osteopenia, osteoporosis, growth retardation,
erosive arthritis, and amyloidosis. Macrophage Activation Syndrome (MAS), a severe
and life-threatening complication of sJIA, is seen in 5-8% of cases. This is associated
with serious morbidity and mortality. Disseminated / severe intravascular coagulation

22
features (thrombocytopenia, increased fibrin degradation products, increased D-dimer
levels, increased prolonged prothrombin time and partial thromboplastin time) can
occur. ESR drops sharply associated with hypofibrinogenaemia. Typically, liver
enzymes, lactate dehydrogenase (LDH), triglycerides and ferritin levels increase,
sometimes with extreme hyperferritinaemia, hypoalbuminemia and hyponatremia (Barut
K, 2017).

Exclusion factors for the classification of systemic arthritis are not included, but if
no classic signs of systemic disease are found, the similarities with infectious diseases
or malignancies must be removed by appropriate laboratory examinations (Barut K,
2017).

Oligoarthritis

Oligoarticular JIA is the most common JIA subtype in developed countries, and is
generally seen among female patients younger than six. It is further divided into two
subgroups: persistent (no more than four joints affected during the course of the
disease) and extended (after an initial 6 month period, the total number of affected joints
exceeds four). Oligoarticular JIA mainly involves the lower extremity joints, such as the
knee and ankle joints. The hip joint is rarely affected (Barut K, 2017).

Exclusion criteria namely:

1. Family history of psoriasis, at least at level 1 or 2 pedigree, with confirmation by

dermatologist

2. Family history of illness that is medically proven to be associated with HLA-B27 at

least at level 1 or 2 of the pedigree

3. RF is positive

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4. An HLA-B27 positive boy with onset arthritis after 8 years of age

5. Systemic arthritis.

JIA Polyarthritis

Polyarticular JIA is defined as arthritis of five or more joints during the first 6 months of
the disease. The disease is divided into two subgroups, according to positive RF. The
frequency of disease varies in different geographical regions with the estimated
frequency of RF-negative JIA polyarticular 11-30% and RF-positive 2-10% (Barut K,
2017).

RF polyarthritis is negative

Negative RF polyarthritis is arthritis of 5 or more joints during the first 6 months of pain,
a negative RF test with positive RF exclusion factors and systemic arthritis.

Positive RF polyarthritis

Positive RF polyarthritis is arthritis of 5 or more joints during the first 6 months of pain,
with a positive RF test at two examinations with a distance of at least 3 months with the
exclusion factor ie.

1. The RF test was negative at 2 checks with a distance of at least 3 months

2. Systemic arthritis.

 Psoriatic arthritis

According to ILAR criteria, the disease is defined by arthritis along with a psoriasis rash
or two of the following: dactylitis; nail pitting or onycholysis; as in psoriasis. Articular
involvement varies from symmetric small joint arthritis to asymmetric lower extremity
joint arthritis and can eventually develop into polyarthritis which mimics seropositive
rheumatoid arthritis. Involvement of the distal interphalangeal joint usually shows
psoriatic arthritis (Barut K, 2017).

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The definition of psoriatic arthritis, namely:

1. Arthritis and psoriasis, or

2. Arthritis and at least 2 of the signs:

a. dactylitis

b. nail disorders (pitting or onycholysis)

c. family history of psoriasis, at least at level 1 or 2 in the pedigree, with dermatological

confirmation.

Exclusion.

1. RF is positive

2. Systemic arthritis.

 Arthritis associated with enthesitis (ERA)

These patients exhibit characteristics of JIA and juvenile spondyloarthropathies. Over

the years, different names have been used for the same clinical entity, including type 2
oligoarticular JIA, seronegative enthesopathy and arthropathy, arthropathy associated
with HLA B27 or adolescent spondyloarthropathy with early onset. The term ERA is
defined by the Durban classification. This disease is usually seen among men, after the
age of six years. The main characteristics of patients include RF and ANA negative with
the findings of enthesopathy and asymmetric arthritis in the lower extremities. HLA B27
positivity is reported in 65-80% of patients. Enthesopathy is inflammation at the site of
tendon attachment to bone. Weiss et al. reported enthesopathy at one location in 47%
and at three different locations in 18% of patients during the same clinical examination.
The Achilles tendon is the site most commonly affected. Insertion of the quadriceps
patellar tendon, and calcaneal and metatarsal insertions of the plantar fascia can also
be affected. Affected sites are characterized by pain and sensitivity (Barut K, 2017).

25
The definition of ERA namely

1. Arthritis and enthesitis, or

2. Arthritis or enthesitis with at least 2 of the signs:

a. sacroiliac joint pain and / or inflammatory back pain

b. the existence of HLA-B27

c. a family history of illness that is medically proven to be HLA-B27-related at

least at level 1 or 2 pedigree

d. anterior uveitis which is usually associated with eye pain, redness, or

photophobia

e. onset of arthritis in boys after the age of 8 years.

Exclusion Factor.

1. Psoriasis, at least at level 1 or 2 pedigree, with dermatological confirmation

2. Systemic arthritis.

 Other arthritis

Definition. Arthritis in children with unknown causes that persists for at least 6
weeks, but:

1. Does not meet the criteria of one of the categories, or

2. Meet the criteria of more than one category.

Exclusion. Patients who meet the criteria of one of the categories.

26
 In these patients diagnosed with systemic type JIA due to a fever that often goes
away arising since the disease progresses.

Patients in this case were also diagnosed with malnutrition based on WHO or
CDC anthropometry curves and clinical manifestations. Nutritional therapy given to
these patients is in accordance with WHO recommendations. The patient underwent 3
stages of the stabilization, transition and rehabilitation phase. On the first day, patients
received f75 formula milk with 80kcal / kgbb calorie requirements, 200,000 vitamin A
international units of folic acid 5 mg, vitamin C 100 mg and vitamin b complex and
administration of antibiotics ceftazidim and gentamicin. This is according to the WHO
protocol for malnourished patients who provide minimum micronutrient intake for 2
weeks and food intake in the stabilization phase with foods low in osmolarity and low in
lactose with protein requirements of 1-1.5 grams / kg / day and infection prophylactic
therapy. In the next phase, this phase is called the rehabilitation or growth phase where
the patient needs a patient's calorie intake of 10ml / day to 150-220kcal / kgbb / day and
replaces f75 with f100 and increases protein requirements to 4-6 grams / kgbb / day.
(Ministry of Health, 2012) These patients are malnourished patients and are managed
according to the malnutrition protocol.

Supporting investigation

As mentioned briefly above, the diagnosis of JIA is basically clinical. There are
no laboratory tests or study combinations that can confirm the diagnosis of JIA.
However, laboratory studies can be used to provide evidence of inflation, support
clinical diagnosis of JIA, monitor therapeutic toxicity, and better understand disease
pathogenesis.

Haematological disorders generally reflect the degree of inflammatory disease.

Useful laboratory investigations include blood cell count (CBC) and inflammatory
markers such as ESR and C-reactive protein (CRP) erythrocytes. However, the level of
ESR and CRP in active JIA varies. In general, ESR is a useful measure for active
disease at onset and during follow-up visits with children with JIA, especially in
polyarticular or systemic onset. In addition, ESR sometimes helps in monitoring the

27
efficacy of therapy. CBC can show anemia of chronic disease if there has been a long-
standing inflammation. Anemia associated with JIA is caused by chronic disease (low
serum iron, low total iron binding capacity, adequate storage of hemosiderin), although
iron deficiency also plays an important role. It has been established that plasma iron
transport and the amount of iron available for erythropoiesis is reduced in individuals
with systemic disease. Leukocytosis often occurs in children with active disease, and
the platelet count can increase dramatically in cases with severe systemic or
polyarticular involvement). Serum immunoglobulin concentrations, IgG, IgA, and IgM,
previously determined in 200 juvenile rheumatoid arthritis patients, which indicate
abnormalities in the distribution of these immunoglobulins in JIA). Serum
immunoglobulin levels are reported to correlate with disease activity and acute phase
response) (Kim KH, 2010).

In a study of the diagnostic utility of rheumatoid factor (RF) serology in children,

the RF test proved positive in children with JIA and diseases other than JIA). As such,
RF evaluation is not useful as a diagnostic tool for JIA. However, children with high RF
titers may represent a different subgroup than the number of children with greater
seronegative disease. RF testing should be done in patients with polyarthritis, because
its presence has prognostic significance). The presence of anti-nuclear antibodies
(ANA) considers the risk for the development of asymptomatic uveitis, especially in
individuals with oligoarticular onset disease, although ANA assessment must be
performed in all JIA patients. Citrullinated peptide (anti-CCP) anti-cyclic antibodies are
not routinely tested in JIA patients, but can indicate severe disease. Human leukocytic
antigen (HLA) B27 should be examined in children who have arthritis-related symptoms
of enthesitis and can demonstrate susceptibility to the development of axial arthritis.
Furthermore, if there is a concern that arthritis is part of an underlying connective tissue
disease or vacuulitis, then it might be useful to test dsDNA, extractable nuclear antigens
(ENA), C3, C4, and immunoglobulin levels. Finally, because most rheumatological tests
lack the desired specificity, the results must always be interpreted in the context of the
patient given (Kim KH, 2010).

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 Conventional radiography is the most easily available, fast, and inexpensive
method for evaluating connections. Ultrasonography is often the best way to identify
intra-articular fluid, especially in joints such as the hips and shoulders, where the fluid
may be difficult to demonstrate clinically. Increased use of standard magnetic
resonance imaging (MR) and advancements in more functional MR techniques over the
past decade have improved assessment of joint disease in JIA. Compared to
ultrasonography or plain radiography, MR imaging is very powerful in detecting
inflammatory changes in joints and cartilage damage. MR imaging can also accurately
evaluate the more recent manifestations of JIA, including erosion, loss of joint space,
cartilage damage, and ligament involvement. In addition, bone scanning using
technetium-99m is also useful for detecting the initial stages of arthritis. Unfortunately,
there is no single modality that meets every current imaging requirement, but methods
for detecting JIA are dramatically increasing (Kim KH, 2010).
In this patient the results of laboratory tests found an increase in ESR, chronic
disease anemia, and an increase in CRP with genu results in accordance with JIA.

Governance
The management of pediatric rheumatic diseases aims to achieve normal
physical and psychological development and status in order to lead an optimal life.
Optimal treatment efforts if possible carried out by pediatricians, rheumatologists,
nurses, physiotherapists, occupational therapists, and social workers. In addition,
collaboration and consultation with experts in the fields of ophthalmology, dental-mouth,
orthopedics, cardiology, psychiatry, nephrology, dermatology, and other fields are often
requested for cooperation. Assistance for patients and families needs to be done by
psychologists, psychiatrists, and other sources in the community.
For AIJ, there is a tendency for dictamentous therapy to develop different
treatment protocols for the oligoarthritis, polyarthritis, and systemic groups. Anti-
inflammatory drugs that have been approved to be given to young children are
ibuprofen and diclofenac in large children (Sherry DD, 1996; Cassidy JT, 1990).

29
 Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the traditional initial
approach. Ibuprofen, indomethacin, tolmetin and naproxen are the most commonly
used agents. This group of drugs is used primarily in children under 12 years. In
patients with oligoarticular JIA, remission of the disease can be induced by NSAIDs.
The main characteristics of this drug are its analgesic effect in lower doses and anti-
inflammatory effects when used in higher doses. Treatment response is seen in the first
1-3 days with pain relief. This type of drug is considered tolerable in pediatric patients,
despite stomachaches and headaches which can sometimes be seen as side effects
(Barut K, 2017).
The steroid drug group is characterized by the most potent anti-inflammatory
activity. However, their use is limited due to many side effects and low efficacy in
preventing joint damage. Intraarticular administration (methylprednisolone acetate,
triamcinolone hexacetonide) has been shown to be effective in inducing remission in
oligoarticular JIA patients, even with a single injection. Oral or parenteral steroids have
the ability to relieve systemic symptoms in patients with forms of systemic disease.
Symptoms such as joint pain, swelling, sensitivity or carditis associated with disease,
hepatitis, lung disease and fever show a significant response to steroid treatment.
However, because of the many side effects, use in low doses or on alternative days is
recommended for patients who are able to control the disease. The most commonly
used steroid dose is up to 1 mg / kg / day (Barut K, 2017).

Table 2. Drugs used in the treatment of JIA

30
Figure 9. Definition and achievement of targets in JIA management (Hinze C, 2015).

31
Figure 10. Simplified approach to the treatment of patients with JIA. DMARDs, disease
modifying antirheumatic drugs; IAS, intra-articular steroids; IL, interleukin; NSAIDs, non-
steroidal anti-inflammatory drugs; TNF, tumour necrosis factor. (Prince F, 2011)
These patients have been given NSAIDs namely ibuprofen with steroid
management and the patient's condition has improved and the patient has osteoporosis
complications due to long-standing steroids.
Osteoporosis in JIA
Osteoporosis is a disorder characterized by bone mass reduction and alterations
in the micro-architecture of the bone tissue resulting in bone fragility and, consequently,
an elevated risk of fractures. (Galindo-Zavala R, 2020)
During childhood and adolescence in patients with JIA, when the peak of bone
mass is attained in the healthy people, the accrual of bone mass is suppressed through
direct and indirectmechanisms, namely by the inflammatory disease, by drug therapy
and immobilization . In JIA, both synovial-derived and soluble cytokines are involved.
Osteopenia or osteoporosis occurs in all of the JIA forms, most typically in systemic and
polyarticular forms of disease. The low bone mass is associated with the high activity of
The disease and with the number of involved joints in JIA patients, also with the
reduction of bone formation. Reduced bone mineral density is observed at all sites of

32
the skeleton in the children and adolescents with JIA and also in adults with JIA. In the
cross-sectional study, the low BMD in lumber spine and hip was found in 40–52% adult
patients with JIA. However, even the full remission of the disease in young adults is not
able to completely normalize BMD at all skeletal sites. In 229 young adults with a past
history of JIA, persistently low BMD was observed at the femoral neck and on total
body. In another study, 41% of adults with a history of JIA had osteopenia. (Brabnikova
Maresova, 2011).

Proinflammatory cytokines, such as tumor necrosis factor α (TNFα), interleukin

1 (IL-1), interleukin 6 (IL-6) a interleukin 17 (IL-17), present in arthritic joint can cause an
excessive osteoclastogenesis. TNFα significantly elevates bone resorption [and
attenuates osteoblastogenesis and bone formation. IL-1 also accelerates osteoclast
maturation. In patients with rheumatoid arthritis, treatment with TNFα antibodies
demonstrably reduces joint erosions. IL-17, which is produced by T-lymfocytes induces
osteoclast differentiation by increasing expression of RANKL and RANK. On the
contrary, IL-17 suppresses expression of osteoprotegerin in osteoblasts resulting in
prevalence of bone resorption over bone formation and bone loss.

Matrix metalloproteinases (MMPs) are responsible for cartilage destruction and

periarticular bone erosions in juvenile idiopathic arthritis. MMP1/tissue inhibitor of
metalloproteinases 1 (TIMP1) and MMP3/ TIMP1 ratios are significantly higher in all the
forms of JIA in comparison to healthy controls. These ratios significantly correlate with
disease activity and could be efficacious biomarkers for monitoring of disease
development. (Brabnikova Maresova, 2011).
Glucocorticoid-induced osteoporosis is the most common form of secondary
osteoporosis. Systemic glucocorticoid therapy is associated with an initial increase in
bone resorption and more importantly, subsequent reduced bone formation, leading to
microarchitectural deterioration and increased fracture risk. Epidemiologic studies have
unequivocally established a higher risk of fracture among adults taking systemic
glucocorticoid therapy. The absence of a synthesized evidence base regarding
glucocorticoid use in children is a barrier to guidelines to monitor bone health in this

33
patient population. Glucocorticoid use in growing children might decrease peak bone
mass and increase life-long risk of fracture. However, in the disease for which
glucocorticoid therapy is given might also adversely affect skeletal health, glucocorticoid
therapy might improve appetite, increase physical activity, control the underlying
disease, and/or reduce inflammatory cytokines, thereby improving skeletal health.
(Hansen KE, 2014).

Figure 11 Pathophysiology of glucocorticoid-induced. (Briot K, 2014)

Patients treated with systemic GCs lose bone mass more markedly during the
first 3–6 months of treatment, mainly trabecular bone. This loss depends on the dose
and treatment duration. Although lower doses are less harmful than higher doses, there
appears to be no unequivocally safe dose since fracture risk have been reported to
persist with prednisone (or equivalent) doses of 2. 5 a 7. 5 mg/ day. Calcium and
vitamin D supplementation have not shown any clinically significant effect on BMD in
studies performed in healthy children In contrast, some studies have reported a
favorable effect in patients with chronic diseases that favor osteoporosis such as
cerebral palsy. On the other hand, no side effects have been reported . Thus, although

34
there are no studies that assess the effect of supplementation on the incidence of
fractures, calcium supplementation is considered advisable in children and adolescents
with low BMD or osteoporosis, especially those patients with a low dietary intake the
nutritional factors also affect bone health and therefore, healthy diet habits with optimal
intake of foods rich in calcium and vitamin D should be recommended to patients
accompanied by calcium supplements (500-1000 mg / day) and vitamin D supplements
(400 IU / day ) to prevent glucocorticoid induced osteoporosis when glucocorticoids are
used for ≥ 3 months. (Galindo-Zavala R, 2020).

Prognosis
The prognosis of JIA depends on the level of joint damage in the patient,
complications such as chronic iridocyclitis and amyloidosis caused by the disease, and
complications caused by the disease and therapeutic agent, such as osteoporosis,
growth failure, and psychological problems.
Prognostic factors in JIA are related to many variables that must be evaluated
according to different subtypes. ILAR recently proposed six different categories called
the Durban criteria, based on the eponym juvenile idiopathic arthritis (JIA). The purpose
of this classification is to determine homogeneous groups according to their clinical and
biological features. Prognostic factors are classified into various JIA categories. Poor
systemic outcomes correlate with markers of disease activity, such as fever and
polyarticular involvement, in the first 6 months. The joint risk of damage to oligoarthritis
correlates with the severity of arthritis in the first 2 years. Polyarthritis with positive
rheumatoid factor is associated with signs of disability in adulthood. In a group of
psoriasis patients, patients at risk of developing sacroiliitis are higher in men and HLA-
B27-positive patients. Patients associated with inflammation of the intestine, arthritis
with involvement of the lower limbs, knees, and tarsals are also at greater risk of
developing sacroiliitis. Chronic uveitis is a complication of JIA that is observed mainly in
patients with oligoarthritis associated with positive antinuclear antibodies in serum.
Secondary amyloidosis was observed mainly in children with systemic JIA (Anne-Marie
P, 2001).

35
 The prognosis in this patient is dubia due to the therapeutic response and
complications in the joints and bone osteporosis.

.
SUMMARY

One case was reported of a boy, 4 years and 11 months old, with oligoarticular
juvenile idiopathic arthritis, with secondary osteporosis and nutritional marasmus. The
diagnosis is made based on clinical symptoms, physical examination and supporting
examination. The terapy of this patient is symptomatic and supportive. Prognosis Quo
ad vitam dubia; Qua ad sanationem et functionam dubia.

36
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90–101. doi: 10.4274/balkanmedj.2017.0111.
Buku bagan tatalaksana anak gizi buruk, 2012. Kementrian kesehatan RI.

Ghrahani, R. et al. (2012) ‘Distribusi Subtipe Juvenile Idiopathic Arthritis di Bandung

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Giancane, G. et al. (2016) Juvenile idiopathic arthritis: Diagnosis and treatment’,
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