Seminar Presentation

Juvenile rheumatoid arthritis

Introduction
• Juvenile rheumatoid arthritis (JRA) is the most common childhood chronic
systemic autoimmune inflammatory disease.

• Chronic inflammation of synovial joints leads to progressive destruction, causing

deformity and eventual failure of joint function.

• The clinical hallmarks of JRA are joint swelling, tenderness and early morning
stiffness associated with a high ESR and C-reactive protein (Chikanza, 2002).
The disease is subdivided into the following subtypes, depending on the mode of
onset and number of joints involved: systemic arthritis, oligoarthritis (less than four
involved joints), polyarthritis (rheumatoid factor–negative) and polyarthritis
(rheumatoid factor–positive).

In this disease, acute joint inflammation is not restrained at its onset, and enters a
chronic phase in which the synovium becomes infiltrated by inflammatory cells,
becomes hyperplastic as a result of stimulation and proliferation of synovial
fibroblasts as well as angiogenesis.

These changes lead to the destruction of articular cartilage and bone.

Epidemiology
The incidence and prevalence are varied among 1.6 to 23 new cases for 100000
children, and 3.8 to 400 cases per 100000 children depending upon study designs,
disease categories, and geographical areas (Cimaz R, 2016).
Lucia Maria Sur, 2021
PRINTO JIA classification criteria (Martini,
2019)
JIA comprises a group of inflammatory disorders that begins before the 18th
birthday and persists for at least 6 weeks; other known conditions are excluded.

Six differen 6 PRINTO JIA categorie has been proposed s:

a) Systemic arthritis: the main modification is that the definition now allows the
inclusion also of patients with fever but without arthritis, as in the adult equivalent,
adult onset Still disease.

b) RF positive arthritis: anti-CCP antibodies have been added to the definition

c) Enthesitis/spondylitis related JIA: definition and nomenclature have been made

more similar to those of the adult counterpart
d)Early onset ANA+: this represents the major novelty. It has been recognized that
this entity, which in the ILAR classification is split into different categories,
represents a homogeneous form of chronic arthritis, which is typical of children.

e)Other JIA: Does not fit the disorders from the above catgories, Arthritis >= 6
weeks.

f)Unclassified JIA: Fits more than 1 disorder from the above catgories, Arthritis >=
6 weeks
Clinical manifestations (Hahn, Y. S, 2010)
Arthritis

An arthritic joint exhibits a number of cardinal signs of inflammation, such as swelling,

erythema, heat, pain, and loss of function.

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. Often, young children do not complain of pain and instead
refuse to use the affected joint entirely.

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.
JRA often affects the cervical spine, and the most common changes in the upper
cervical spine are anterior atlantoaxial subluxation and impaction.

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.
Systemic extra-articular manifestations

Systemic involvement may precede the development of overt arthritis by weeks,

months, or rarely years. It has a characteristic fever and classic rash. The most
prominent feature of systemic involvement is a high spiking fever. Fever may occur
at any time of the day, but characteristically presents in the late afternoon to evening
in conjunction with the rash. Fever associated with systemic onset disease often
responds poorly to the commonly prescribed nonsteroidal anti-inflammatory drugs
(NSAIDs), even at high doses. The classic rash is evanescent (usually coming and
going with the fever spikes).
Another characteristic of systemic onset disease is enlargement of lymph nodes and
spleen.

Uveitis

Chronic, anterior, nongranulomatous uveitis (iridocyclitis) develops in up to 21% of

patients with oligoarticular disease and 10% of patients with polyarticular disease.
The only known independent risk factor for developing uveitis is a positive ANA
test. Symptoms attributable to uveitis (e.g., pain, redness, headache, photophobia,
change in vision) occurs later in the course of their disease.
Assessment (Thatayatikom A, 2022)
• The thorough history taking, including the age of onset, the affected joints, the
duration of arthritis, the associated symptoms or diseases, and physical and MSK
examinations are essential for diagnosis and classification of JIA.

• There is no specific test for diagnosis and predicting disease activity in JIA.

Laboratory

Initial laboratory tests should include CBC, ESR, CRP, ANA, RF, and HLA-B27
(Thatayatikom, A., 2022).
Imaging

• Radiography remains initial imaging used for symptomatic joints; however, the
radiographic changes are undetectable in an early stage of JIA. The indirect signs of
arthritis in radiography are soft tissue swelling, increased density of soft tissue and joint
space narrowing, bone erosion and deformity, and joint subluxation or ankyloses in th
late stage.

• The US is capable of assessing synovial thickening, joint effusion, tenosynovitis,

enthesitis, and bone erosions. US evaluation of the synovial thickening and the synovitis
is particularly important for the diagnosis (Thatayatikom, A., 2022).

• Magnetic resonance imaging (MRI) is the modality gold standard for the study of JIA. It
is the most sensitive imaging technique detecting synovitis.
• Patient-Reported Outcomes Measurement Information System (PROMIS)
database is used for the multidisplinary assessment of pain in juvenile
idiopathic arthritis.

• A battery of pediatric clinical questionnaires derived from the PROMIS

database was utilized to capture patient reported levels of:

(i) pain intensity (0 to10 numerical rating scale), where 0 is no pain and 10 is the
worst pain imaginable

(ii) pain behavior (external manifestations of pain)

(iii) quality of pain

(iv) anxiety

(v) depressive mood

(vi) psychological stress

(vii) cognitive function

(viii) physical activity

(ix) physical stress

(x) strength impact

Each PROMIS questionnaire assessed pain and other symptoms in the past seven
days.
Physical activity
• Patients with JIA have lower levels of PA, spend less minutes in moderate to vigorous
PA (MVPA) and more time sedentary than healthy controls (Takken. 2008).

• Lower levels of PA were associated with higher disease activity arthritis in weight-
bearing joints, more pain and lower wellbeing (Norgaard M, 2017, Bos GJ, 2016).

• Physical activity needs to be monitored in children with JIA. Objectively measuring

physical activity involves the use of acclerometry. It reflects data in the form of mean
steps per day for the general level of physical activity (Kristine Risum, 2018).
Subjectively measuring physical activity involves interview method using a
guide (Kristine Risum, 2018). Possible questions could be :

1) Do you participate in any organized and/or unorganized physical activity?

If yes, which activity/activities?

2) Do you perceive barriers to being physical active? If yes, how?

3) Do you perceive facilitating factors to being physical active? If yes, which?

4) Do you participate in physical education classes in school? If yes, how

often?
Fatigue and sleep assessment
• It has been reported that fatigue affects 75% of patients with JIA, thus making
fatigue a common problem among this patient population. They also found that
40% of them have poor sleep quality and 69% of the patients slept less than 10 h
(Ela TARAKCI, 2019).

• Fatigue symptoms can be evaluated with Pediatric Quality of Life Inventory-

Multidimensional Fatigue Scale (PedsQL-F). PedsQL-F is a valid and reliable
tool, and it can be used to measure symptom-specific fatigue among patients with
JIA. Fatigue severity can be assessed using a 100-mm VAS.

• Sleep quality can be evaluated with the Pittsburgh Sleep Quality Index (PSQI).
Juvenile Arthritis Disease Activity Score
(JADAS)
The Juvenile Arthritis Disease Activity Score (JADAS) is a measure of absolute
disease activity in JIA and is made up of four components: (1) physician global
assessment of disease activity on a 0–10 visual analog scale (VAS); (2) parent/
patient global assessment of well-being on a 0–10 VAS; (3) count of joints with
active arthritis, evaluated in 71 (JADAS71), 27 (JADAS27), or 10 (JADAS10)
joints; and (4) erythrocyte sedimentation rate (ESR), normalized to a 0–10 scale
(Nordal E, 2012).
Scoring- The JADAS is calculated by making the simple sum of the scores of its
four items, which provides a total score of 0–101, 0–57, and 0–40 for the JADAS71,
JADAS27, and JADAS10, respectively.
s-JADAS (Modified version) (Jessica Tibaldi, 2020)
• The validation analysis of JADAS was conducted only in children with
oligoarthritis and polyarthritis, but not in children with sJIA and active systemic
features. Therefore, a modified version of JADAS was developed to measure the
level of disease activity in sJIA.

• sJADAS was made up of the following five items: (i) physician global assessment
of overall disease activity, measured on a 10-cm visual analogue scale (0-no
activity; 10 - maximum activity); (ii) parent/patient global assessment of well-
being, measured on a 10-cm visual analogue scale (0 -very well; 10 -very poor);
(iii) count of active joints in 10, 27 or 71 joints, depending on the version (i.e.
sJADAS10, sJADAS27 and sJADAS71,
respectively); (iv) ESR or CRP level,
both normalized to a 0–10 scale ; and
(v) the mSMS, composed and scored (0-
10).

The version used in validation analyses

was the sJADAS10 with the total
scoring of 0-50.
 Juvenile Arthritis Multidimensional Assessment Report
(JAMAR) (Bovis. F, 2018)
A multidimensional questionnaire was developed for the assessment of children
with JIA in standard clinical care, which incorporates the traditional PROs
(functional ability, HRQoL, overall well-being, pain) and other PROs such as
morning stiffness, rating of disease course over time, proxy- or self-assessment of
joint involvement, description of side effects of medications, and assessment of
therapeutic compliance and satisfaction with the outcome of the illness. This tool is
named Juvenile Arthritis Multidimensional Assessment Report (JAMAR).
• The JAMAR is available in three versions, one for parent proxy-report (child’s
age 2–18), one for child self-report, with the suggested age range of 7–18 years,
and one for adult patients.

• It includes 15 questions:

 Assessment of physical function (15 items)

Intensity of pain by VAS

Presence of joint pain or swelling

assessment of extra-articular symptoms (fever and rash) (present/absent)

rating of the level of disease activity on a 21-circle VAS

Rating of disease status at the time of the visit (remission, continued activity or
relapse);

Rating of disease course from previous visit (much improved, slightly improved,
stable, slightly worsened or much worsened);

Checklist of the medications the patient is taking (list of choices);

Checklist of side effects of medications;

Report of difficulties with medication administration (list of items);

Report of school/university/work problems caused by the disease (list of items)

Assessment of HRQoL using a ten-item scale through the Physical Health (PhH),
and Psychosocial Health (PsH) subscales (five items each) and a total score.
Assessment of HRQoL using a ten-item scale through the Physical Health
(PhH), and Psychosocial Health (PsH) subscales (five items each) and a total
score. The four-point Likert response, referring to the prior month, is ‘never’
(score = 0), ‘sometimes’ (score = 1), ‘most of the time’ (score = 2) and ‘all the
time’ (score = 3).The total HRQoL score ranges from 0 to 30, with higher
scores indicating worse HRQoL. A separate score for PhH and PsH (range 0–
15) can be calculated.

Rating of the patient’s overall well-being on a 21-numbered circle VAS;

a question about satisfaction with the outcome of the illness (Yes/No)

Juvenile Arthritis Biopsychosocial and Clinical
Questionnaire (JAB-Q) (Unal E, 2018)
• JAB-Q is a valid and reliable multidimensional biopsychosocial outcome tool that can
be used routinely in clinical practice of pediatric rheumatology. The main advantage of
this tool is incorporation of patients' and parents' perspectives separately while
providing a practical and standard setting for the clinician's evaluation.

• The validity of these three scales were determined as moderate. In addition, the test-
retest reliability of the clinician, child and parents' forms were considerably high.

• The clinician’s form in JAB-Q comprised assessment of child’s overall status, walking,
posture, and joints. Validity of this form compared to JADAS, was moderate. JADAS is
a tool evaluating the disease activity only.
• Patient form (child form) consists of questions related to the child’s functionality,
psychosocial status, school performance, and fatigue from his/her own
perspective. Moderate validity levels were obtained when CHAQ scale was
accepted as the gold standard.

• In the parent form of JAB-Q, the main complaints and school performance of the
child are questioned from the perspective of his/her parents. Furthermore, there
are items to evaluate the psychosocial status of the parents which is very
important in JIA since it has been known that pain behaviors of children are
affected by the parents’ attitude.
MANAGEMENT
• Physical activity (PA) and exercise are important components of a healthy
lifestyle for all children including children with JIA (Long AR, 2010).

• Current PA recommendations for children include participation in 60 minutes of

moderate to vigorous activity per day, with vigorous activity completed on at least
3 days per week (NHS guidelines).
Physical Activity Intervention Durations, Frequencies, Intensities,
Modes, and Levels of Supervision Among the Exercise Arms (n = 23)
Included in the 13 Studies
Maura D
Iversen, 2022
Results
• Within the 13 RCTs of PA interventions, eleven studies (84.6%) included a measure of pain,
seven studies(53.8%) incorporated measures of aerobic capacity, fitness or functional
performance, 8 studies (61.5%) measured ROM and 7 studies (53.8%) assessed quality of life.

• Fifty-two percent of intervention arms incorporated strengthening exercise alone or combined

with other exercise, with 61.9% performed 3x/week. About 43.5% of sessions lasted >45 to
≤60 minutes and 65.2% of programs were ≥12 to <28 weeks.

• In all studies, health outcomes improved across a variety of domains.

• The interventions in this study were generally of a low to moderate intensity and children
were more adherent to low intensity exercise program.
Radha Bhende,
2022
Clinical Pilates Exercises
• Clinical pilates exercises has been proven to effective in improving functional
status, general health perception and pain in children with juvenile idiopathic
arthritis (JIA) (Mendonca TM, 2013).

• Protocol: To be performed for 3 times a week for 6 weeks by a physiotherapist

trained in clinical mat pilates and experienced in the field. Each session contains
10 min of warm-up phase, 40 min of Clinical Pilates exercises and 10 min of
cool down phase (Bilge Basakci Calik, 2021).
• Clinical Pilates exercises in individuals with
JIA reduced disease activity and also
increased dexterity, upper limb coordination,
general motor skills and daily activity.

• Significant improvements in manual

dexterity, upper limb coordination and
general motor skills are seen as the result of
increased proximal muscle strength and
stabilization by exercise and this increase is
reflected positively to the distal joints of the
extremities.
Watsu therapy
• Watsu (Water-Shiatsu), is a therapy at consists of passive movement sequences,
muscle stretching and massages during assisted immersion in warm water.

• Exercises include slow offering, accordion, water breath dance, free spine, one leg
offering, two leg offering, etc.

• It has been proved to improve acute and chronic pain, physical function in chronic
conditions and improves sleep.

• Watsu therapy improves HRQoL in the short term related to physical functioning,
sensation of pain, disability index, and functional health status compared to
conventional hydrotherapy in patients with acute or subacute JIA (Ramírez, 2019)
Hydrokinesiotherapy
Patients with juvenile idiopathic arthritis report muscle weakness along with muscle
atrophy due to lack of use of the affected joint cause of pain and swelling.
Hydrokinesiotherapy is a method that has been proved to be effective in easing pain
and improving muscle strength and girth by performing strengthening exercises in
the water.

Protocol: 10 individual sessions of hydrokinesiotherapy of approximately one hour

(10 weeks). The intervention took place in a therapeutic pool, heated to a
temperature of 36°C (Jorge, 2019).
Schedule for Hydrokinesiotherapy
in order to improve pain and
muscle strength.
• There was a reduction of the score and the intensity of the pain, after the
intervention. It also showed an increase of 1cm in all measurements of muscle
trophism of the arms, and 15cm above the anatomical reference point of the right
thigh, after the hydrokinesiotherapy.
Patient education (Amir Mendelson, 2017)
• Patient education is very important to increase the knowledge regarding the
condition and to improve the adherence. And it is a challenging task to educate the
young children.

• Medikidz, a medical education organization for children, has developed comic

books to support children’s education with regards to their health and well-
being.The comic book Neta and the Medikidz explain JIA has been published
internationally in several languages.
• According to , it was found that comic book Neta and the Medikidz is effective in
enhancing knowledge in children regarding JIA. As it is a tool that combines
illustrations and text, it taught them about their disease in a way that regular visits
with the doctor did not.

• Hence such educational medium can be used in order to enhance the knowledge
about a certain disease and in order to improve the adherence in young children.
References
• Iversen, M. D., Andre, M., & von Heideken, J. (2022). Physical Activity Interventions in
Children with Juvenile Idiopathic Arthritis: A Systematic Review of Randomized
Controlled Trials. Pediatric Health, Medicine and Therapeutics, 13, 115.
• Karastamati, C., Chandolias, K., Grammatikou, G., & Hristara-Papadopoulou, A.
(2021). The Effectiveness of Hydrotherapy-Halliwick Concept in Children With Juvenile
Idiopathic Arthritis: Assessment and Treatment. The Journal of Aquatic Physical
Therapy, 29(2), 35-39
• Paulo LT, Len CA, Hilario MOE, Pedroso SA, Vitalle MS, erreri MT. Fatigue in children
with juvenile idiopathic arthritis: reliability of the “Pediatric Quality of Life
InventoryMultidimensional Fatigue Scale”. Rheumatol Int 2015; 35: 133-139.
• Pollard LC, Choy EH, Gonzalez J, Khoshaba B, Scott DL. Fatigue in rheumatoid
arthritis reflects pain, not disease activity. Rheumatology (Oxford) 2006; 45: 885-889.
• Hahn, Y. S., & Kim, J. G. (2010). Pathogenesis and clinical manifestations of juvenile
rheumatoid arthritis. Korean journal of pediatrics, 53(11), 921.
• Cimaz R. Systemic-onset juvenile idiopathic arthritis. Autoimmun Rev. 2016
• Ramírez, N. P., Cares, P. N., & Peñailillo, P. S. M. (2019). Effectiveness of Watsu therapy in
patients with juvenile idiopathic arthritis. A parallel, randomized, controlled and single-blind
clinical trial [Efectividad de la terapia Watsu en pacientes con artritis idiopática juvenil. Un
ensayo clínico controlado paralelo, aleatorio y simple ciego]. Rev Chil Pediatr, 90(3), 283-92.
• Tarakci, E., ARMAN, S. N., Barut, K., Şahin, S., Adrovic, A., & Kasapçopur, Ö. (2019).
Fatigue and sleep in children and adolescents with juvenile idiopathic arthritis: a cross-
sectional study. Turkish Journal of Medical Sciences, 49(1), 58-65.
• Thatayatikom, A., Modica, R., & De Leucio, A. (2022). Juvenile Idiopathic Arthritis. In
StatPearls [Internet]. StatPearls Publishing.
• Bhende, R., Shinde, S. B., & Shinde, R. V. (2022). Physiotherapy for juvenile rheumatoid
arthritis: A systematic review. DPU’s Journal of Ayurved, Homeopathy and Allied Health
Sciences, 1(1), 1.
• Jorge, M. S. G., Vogelmann, S. C., & Wibelinger, L. M. (2019). Effects of
hydrokinesiotherapy in pain, trophism and muscle strength in a child with juvenile idiopathic
arthritis. Case report. BrJP, 2, 88-92.
• Long AR, Rouster-Stevens KA. The role of exercise therapy in the management of
juvenile idiopathic arthritis. Curr Opin Rheumatol. 2010;22(2):213–217.
• National Health Service (NHS). Physical activity guidelines for children and young
people.
• Mendonca TM, Terreri MT, Silva CH, Neto MB, Pinto RM, Natour J, et al. Effects of
Pilates exercises on health-related quality of life in individuals with juvenile idiopathic
arthritis. Arch Phys Med Rehabil. 2013;94:2093-102
• Calık, B. B., Kabul, E. G., Korkmaz, C., Tekin, Z. E., Yener, G. O., & Yuksel, S. (2020).
The efficacy of clinical Pilates exercises in children and adolescents with juvenile
idiopathic arthritis: A pilot study. Revista Colombiana de Reumatología (English Edition),
27(4), 269-277.
• Martini, A., Ravelli, A., Avcin, T., Beresford, M. W., Burgos-Vargas, R., Cuttica, R., ... &
Pediatric Rheumatology International Trials Organization (PRINTO. (2019). Toward new
classification criteria for juvenile idiopathic arthritis: first steps, pediatric rheumatology
international trials organization international consensus. The Journal of rheumatology,
46(2), 190-197.
• Chikanza, I.C. Juvenile Rheumatoid Arthritis. Pediatr-Drugs 4, 335–348 (2002).
• Takken T, Van Brussel M, Engelbert RH, Van Der Net J, Kuis W, Helders PJ.
Exercise therapy in juvenile idiopathic arthritis: a Cochrane Review. Eur J Phys
Rehabil Med. 2008;44:287–97.
• Norgaard M, Lomholt JJ, Thastum M, Herlin M, Twilt M, Herlin T. Accelerometer-
assessed daily physical activity in relation to pain cognition in juvenile idiopathic
arthritis. Scand J Rheumatol. 2017;46:22–6
• Bos GJ, Lelieveld OT, Armbrust W, Sauer PJ, Geertzen JH, Dijkstra PU. Physical
activity in children with juvenile idiopathic arthritis compared to controls. Pediatr
Rheumatol Online J. 2016;14:42.
• Risum, K., Hansen, B. H., Selvaag, A. M., Molberg, Ø., Dagfinrud, H., & Sanner, H.
(2018). Physical activity in patients with oligo-and polyarticular juvenile idiopathic
arthritis diagnosed in the era of biologics: a controlled cross-sectional study.
Pediatric Rheumatology, 16(1), 1-10.
• Bovis, F., Consolaro, A., Pistorio, A., Garrone, M., Scala, S., Patrone, E., ... & Ruperto,
N. (2018). Cross-cultural adaptation and psychometric evaluation of the Juvenile Arthritis
Multidimensional Assessment Report (JAMAR) in 54 languages across 52 countries:
review of the general methodology. Rheumatology International, 38(1), 5-17.
• Unal, E., Batu, E. D., Sonmez, H. E., Arici, Z. S., Arin, G., Karaca, N. B., ... & Ozen, S.
(2018). A new biopsychosocial and clinical questionnaire to assess juvenile idiopathic
arthritis: JAB-Q. Rheumatology international, 38(8), 1557-1564.
• Tibaldi, J., Pistorio, A., Aldera, E., Puzone, L., El Miedany, Y., Pal, P., ... & Ravelli, A.
(2020). Development and initial validation of a composite disease activity score for
systemic juvenile idiopathic arthritis. Rheumatology, 59(11), 3505-3514.
• Nordal, E., Zak, M., Berntson, L., Aalto, K., Peltonieli, S., Nielsen, S., ... & Rygg, M.
(2012). Juvenile arthritis disease activity score (JADAS) based on C-reactive protein
predicts DMARD treatment in juvenile idiopathic arthritis in a Nordic multicenter cohort.
Pediatric Rheumatology, 10(1), 1-2.
• Mendelson A, Rabinowicz N, Reis Y, Amarilyo G, Harel L, Hashkes PJ, Uziel Y. Comics
as an educational tool for children with juvenile idiopathic arthritis. Pediatr Rheumatol
Online J. 2017 Sep 02;15(1):69.
THANK YOU