JuvenileIdiopathicArthritis. Dr Johan Siebert
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1 JuvenileIdiopathicArthritis Dr Johan Siebert 1
2 NORMAL DIARTHRODIAL JOINT Synovial is a thin membrane enclosing the joint space The joint space contains fluid that bathes the joint and reduces friction on motion 2
3 INFLAMED/DAMAGED ARTHRITIC JOINT With inflamation, synovial thickens and secretes more fluid which cause swelling. It also produces warmth/pain. As inflamation progresses, it induces erosion of cartilage, cystic changes and thinning of the bone. 3
4 ARTHRITIS DEFINITION: Arthritis o Arthritis is inflammation of one or more joints o Swelling, warmth, redness, restricted movements and pain o Multiple etiologies: infection, traumatism, autoimmune, aging, rheumatoid, 2 nd to other diseases(lyme, IBD, hepatitis, lupus ) 4
5 JUVENILE IDIOPATHIC ARTHRITIS (JIA) DEFINITION: o It snot a single diseasebut a heterogeneous group of arthritis o definedby the type of clinicalsymptoms duringthe first 6 monthsof illness o Etiologystillpoorlyunderstood. Relatedto: -geneticbackground (HLA associations) -immunologicfactors(tnf α, IL-1, IL-6 ) - environmental factors(infection, trauma ) 5
6 JIA DEFINITION CRITERIA: o Onset< 16 yearsof age o Symptoms must last at least 3 months o Arthritisduration 6 weeks o Arthritisin 1 or more synovial joints o Exclusion of otherdiseases(infections, connective tissue disorders, malignancies ) 6
7 CLASSIFICATION: Juvenile Idiopathic Arthritis(JIA) o Previouslycalledjuvenilechronicarthritisin EU and juvenile rheumatoid arthritis in USA. o Nowreplacedby a new classification by the International Leagueof Associations for Rheumatologyto avoidnomenclature heterogeneity between Europe and USA. o Now called Juvenile Idiopathic Arthritis with 7 disease categories recognized 7
8 CLASSIFICATION: Juvenile Idiopathic Arthritis(JIA) Affected joints 1. Systemic onset (Still) 1 Condition(s) required Daily fever of at least 2 weeks, plus 1 or more of the following: evanescent rash, generalised lymphadenopathy, hepato/splenomegaly, serositis 2. Oligoarthritis < 5 Asymmetric arthritis, spares the hips and sacroiliac joints 3. Polyarthritis (RF+) 5 4. Polyarthritis (RF-) 5 5. Enthesitis-related arthritis 6. Psoriatic arthritis 7. Undifferentiated arthritis Presence of rheumatoid factor (RF+), symmetric polyarthritis of small and large joints Absence of rheumatoid factor (RF-), symmetric polyarthritis of small and large joints Arthritis and/or enthesitis with at least 2 of the following: sacroiliac joint pain; presence of HLA-B27 antigen; acute anterior uveitis; history of ankylosing spondylitis, sacroiliitis with IBD, Reiter's syndrome, or acute anterior uveitis in a 1 st degree relative Arthritis + psoriasis OR arthritis and at least 2 of the following: dactylitis, nail abnormalities (pitting onycholysis), family history of psoriasis (1 st degree relative) Arthritis that does not fit any of the above categories or fits more than one category. 8
9 EPIDEMIOLOGY: Juvenile Idiopathic Arthritis(JIA) o Most commonchronicrheumaticdiseasein children o Prevalence: / (EU, USA) 400/ (Australia) Africa? o an important cause of short- and long-term disability(especially growth retardation) 9
10 FREQUENCY OF RHEUMATOLOGIC DISEASES: Juvenile rheumatoid arthritis 5105 (67%) Systemic Lupus Erythematosus 638 (8%) Henoch-Schonlein purpura 580 (7.7%) Juvenile dermatomyositis 456 (6%) Kawasaki s disease 212 (2.8%) Localized scleroderma 196 (2.6%) Systemic scleroderma 60 (0.8%) Polyarteritis nodosa 35 (0.5%) Other vasculitis 434 (20%) Total: 7578 (20%) Data from patients Adapted from J. Lopez Benitez
11 EPIDEMIOLOGY: Juvenile Idiopathic Arthritis Frequency Onset age Sex ratio Systemic onset (Still) 4-17% any: 0-16 years F=M Oligoarthritis 27-56% Early childhood; peak at 2-4 years F>>>M Polyarthritis (RF+) 2-7% Late childhood F>>M Polyarthritis (RF-) 11-28% Biphasic distribution; - early peak at 2-4 years - later peak at 6-12 years F>>M Enthesitis-related arthritis 3-11% Late childhood M>>F Psoriatic arthritis 2-11% Biphasic distribution; - early peak at 2-4 years - later peak at 9-11 years Undifferentiated arthritis 11-21%.... F>M 11
12 EPIDEMIOLOGY: Juvenile Idiopathic Arthritis(JIA) o Most commonsubtypein EU isrepresented by oligoarthritis o Most commonsubtypein Africais represented by polyarthritis 12
13 CLINICAL FEATURES: A) Inflammatory symptoms common to all JIA subtypes o Pain on motion o Limitation of joints movements o Morning stiffness o Warmth/swelling at articular level o Redness is unfrequent 13
14 CLINICAL FEATURES: B) Articular manifestations (of 3 of the major subtypes of JIA) Systemic Oligoarticular Polyarticular Affected joints any Large joints, but rarely hips Any, rare to start in hip Destructive arthritis >50% Rare >50% Most frequently affected joints: Hips, cervical spine, wrist, knees, ankles 14
15 CLINICAL FEATURES: C) Extra-articular manifestations Systemic Oligoarticular Polyarticular Fever 100% 0% 30% Rheumatoid rash Rheumatoid nodules Hepatosplenomegaly Lymphadenopathy Uveitis Rare: <1 20 if ANA - 40 if ANA+ 5 if RF - <1 if RF + Pericarditis Pleuritis Abdominal pain
16 CLINICAL FEATURES: 1. Systemic onset(still s disease) Is marked by the severity of the extra-articular manifestations The clinical triad is essential for diagnosis: 1. Quotidianfever up to 39.5 C for 2 consecutive weeks 2. Transient salmon-pink macular rash on trunk and thigh 3. Arthritis affecting both the small and large joints: wrists, knees, ankles, hands and temporomandibular 16
17 CLINICAL FEATURES: 1. Systemic onset(still s disease) Systemic onset is thought to be an autoinflammatory condition unrelated to other forms of childhood arthritis and requiring different therapy (see below) Typically lasts between 2 & 5 yrs before complete resolution 17
18 CLINICAL FEATURES: 1.1 Fever in Still s disease 18
19 CLINICAL FEATURES: 1.2 Rash in Still s disease 19
20 CLINICAL FEATURES: 1.3 Bone abnormalities in Still s disease Growth retardation Micrognathia 20
21 CLINICAL FEATURES: 2. Oligoarticular subtype Large, weight-bearing joints, such as the knees and ankles, are typically affected In cases of asymmetrical arthritis, chronic inflammation may lead to overgrowth of that limb with subsequent leg-length discrepancy Anterior uveitisleads to pain and eye redness, photophobia, diminished visual acuity, synechia, cataract, and even blindness if untreated. 21
22 CLINICAL FEATURES: 2.1 Grothw retardation in oligoarticular subtype Eighteen-month-old girl with arthritis in her right knee. 22
23 CLINICAL FEATURES: 2.2 Uveitis in oligoarticular subtype Synechia Synechia + cataract 23
24 CLINICAL FEATURES: 3. Polyarticular subtype rheumatoid nodules may be seen in patients with RF-positive disease asymmetrical involvement of small joints in the hands is often found Involvement of the cervical spine possible 24
25 CLINICAL FEATURES: 3.1 Nodules and hands involvement in polyarticular subtype 25
26 COMPLEMENTARY EXAMINATIONS: There is no single test to diagnose juvenile arthritis! A) Blood Systemic Oligoarticular Polyarticular Leukocytosis Marked No No Anemia Marked No Mild Elevated ESR Marked Mild Mild ANA (Antinuclear Antibodies) Absent High Low Rheumatoid factor Rare Absent 10-20% in those > 10 years 26
27 COMPLEMENTARY EXAMINATIONS: B) Additionnal tests to negatively exclude differential diagnosis o Sickle cell testing o Coagulation panel (prothrombin time) o Anti-streptolysin antibodies to exclude rheumatic fever o Thick smear test o Prepare an extra tube of blood for: - PCR test for viruses, bacteria and parasites, other viral serologies, autoantibodies 27
28 IMAGING SCANS: Juvenile Idiopathic Arthritis(JIA) X-rays, CT-scan, MRI are nonspecific for testing for JIA but they can be taken to exclude other conditions, such as: o Fractures o Tumors o Infection o Congenital defects X-rays may also be used from time to time after the diagnosis to monitor bone development and to detect joint damage. 28
29 DIFFERENTIAL DIAGNOSIS: o All causes of chronicjoint pain trauma, rheumatoid or post-infectious arthritis o Hematological diseases Leukemia, sickle cell disease, hemophilia (bleeding into the joints), malaria, Lyme, o Malignancies Bone tumors, neuroblastoma 29
30 TREATMENTS: Juvenile Idiopathic Arthritis(JIA) o Ultimate goal: o If cure is not achievable: cure control inflammation o If control is not achievable: comfort of the patient o In all circumstances: o Long term: maintain function promote normal growth 30
31 TREATMENTS: Juvenile Idiopathic Arthritis(JIA) Nonsteroidal anti-inflammatory drugs(nsaids) ex: ibuprofen Corticosteroids(intra-articular, oral or IV) Disease-modifying anti-rheumatic drugs(dmards) ex: methotrexate, sulfasalazine, cyclosporine A, Tumor necrosis factor (TNF) blockers ex: etanercept, infliximab, adalimumab Immune suppressants ex: abatacept, rituximab, anakinra, tocilizumab Physical and Occupational Therapy 31
32 TREATMENTS: Juvenile Idiopathic Arthritis(JIA) 32
33 TREATMENT STRATEGIES: Subtype 1st line therapy 2 nd line therapy 3rd line therapy Systemic Active systemic features NSAID IAS Anti-TNFα or Anti-IL1, Anti-IL6R or Cyclosporine or Thalidomide Active arthritis Manage as oligoarticular Anti-IL1 Switch to abatacept or polyarticular,depending or or anti-il1 if treated on nbr of joints involved Anti-TNFα with Anti-TNFα previously Oligoarticular IAS ± NSAID MTX Anti-TNFα Polyarticular MTX ± IAS ± NSAID Anti-TNFα Switch to 2 nd anti-tnfα or Abatacept, Rituximab IAS: intra-articular corticoid injection, MTX: Methotrexate, NSAID: non-steroidal anti-inflammatory drugs 33
34 POOR OUTCOME EARLY PREDICTORS: o Greater severity/extension at onset o Symmetric disease o Precocious hip/wrist involvement o Presence of RF o Prolonged active disease o Early radiographic changes 34
35 LONG TERM OUTCOMES: o Growth retardation (due to corticoids treatments, incomplete suppression of systemic inflammation) o Destruction of joints / osteoporosis o Uneven growth of an arm or leg o Loss of vision or decreased vision from chronic uveitis o Anemia o Swelling around the heart (pericarditis) o Chronic pain, poor school attendance 35
36 SUMMARY: Juvenile Idiopathic Arthritis(JIA) Childhood arthritis (JIA) most often has no relationship to seropositive rheumatoid arthritis ( adults). The diagnosis of JIA can be confirmed if: o The clinical symptoms meet to the definition criteria o The biological panel shows a chronic inflammation o The most frequent differential DX are excluded A confirmation of the DX requires a follow up visit 3 months after the beginning of the illness. 36
37 Juvenile Idiopathic Arthritis SUMMARY JIA Systemic Onset Early onset Oligoarticular Late onset Seronegative Polyarticular Seropositive Oligoarthritis Enthesitisrelated Psoriatic Polyarthritis RF- Polyarthritis RF+ 37
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