Juvenile Idiopathic Arthritis (JIA)

Dr Urmila DhakadAssistant professorDept of RheumatologyKGMU, Lucknow23-06-15

Definition - Juvenile Idiopathic Arthritis

• Arthritis of unknown aetiology that begins

before the 16th birthday and persists for at least

6 wks.

• Previously known as juvenile rheumatoid

arthritis (JRA) and juvenile chronic arthritis (JCA).

Criteria for the diagnosis of JIA

All three conditions must be met

Arthritis persisting for longer than 6 weeks

Arthritis beginning before 16 years of age

Exclusion of other conditions associated with

or mimicking arthritis

Classification of JIA

Based on symptoms presented during 1st 6 months of ds - 1. Systemic onset JIA ( 10-15% ) 2. Oligo-articular JIA ( 50 % ) a. Persistent oligo-articular JIA b. Extended oligo-articular JIA 3. Polyarticular JIA (RF negative) ( 15-20% ) 4. Polyarticular JIA (RF positive) ( ≤5% ) 5. Psoriatic arthritis (5-10%) 6. Enthesitis related arthritis ( 5-10% ) 7. Undifferentiated arthritis ( 10-15% )

Systemic onset JIA (SOJIA)

• Quotidian, high spiking fever(> 2 wk) associated

with systemic features

Evanescent, non-fixed, erythematous rash

Hepato-splenomegaly

Serositis

Generalized lymphadenopathy.

Systemic onset JIA (SOJIA)

• Boys > girls.

• Myalgias and abdominal pain during fever

peaks.

• Arthritis - symmetrical and polyarticular; it may

be absent at onset and develop during disease

course.

Erythematous & evanescent rash of SOJIA. Frequently, rash

is obvious only at height of fever and sometimes confined

to axillary region, ant chest wall and inside both thighs.

Systemic onset JIA (SOJIA)

• Lab test - inflammatory response characterized

by leukocytosis, hyperferritinemia, microcytic

anaemia, thrombocytosis, high ESR and CRP .

• Diagnosis of SOJIA can be difficult, especially at

presentation, and D/D includes bacterial or viral

infection, malignancy, and other rheumatic ds.

Oligoarticular JIA

• Oligoarthritis - arthritis that affects 4 or less joints, in

absence of other features ( psoriasis, RF positivity, high

spiking fever). Characterized by –

Female predilection

Early onset asymmetric arthritis (before 6 years of age)

Positive ANA & HLA associations.

High risk for developing chronic iridocyclitis

Categories of Oligoarticular JIA

Persistent oligoarthritis - disease remains

confined to 4 or less joints.

Extended oligoarthritis - arthritis extend to > 4

joints after first six months of ds.

• Involvement of UL joints & high ESR at onset have

been identified as predictors for evolution to

extended type.

Polyarticular JIA (RF negative)

• Arthritis that affects 5 or more joints during first

6 months of disease in absence of RF.

• Two clinical phenotypes can be identified:

(1)Form that is closely similar to adult-onset RF

negative RA. characterized by symmetric synovitis

of large & small joints, high ESR and negative ANA.

Polyarticular JIA (RF negative)

(2) second form that resembles ANA +ve early-

onset oligoarthritis in every aspect other then

number of joint involved during first 6 months of

disease. characterised by early age at onset, +ve

ANA, asymmetric arthritis, female predominance,

high incidence of chronic iridocyclitis.

Polyarticular JIA (RF positive)

• Similar to adult RA. RF is by definition positive.

• Accounts for a small (≤5%) percentage of pts with JIA.

• Primarily affects girls and usually presents in late

childhood or adolescence.

• It can be rapidly progressive and destructive.

• Rheumatoid nodules are common.

• failure to thrive more frequent than in RF –ve type.

• Only JIA category in which Anti CCP are found.

Psoriatic arthritis (PsA)

• Diagnosis of PsA requires simultaneous presence of

arthritis and a typical psoriatic rash

or

• If psoriasis is absent, presence of arthritis plus any 2 of

following:

A) Family history of psoriasis in a first-degree relative;

B) Dactylitis (swelling of one or more digits )

C) Nail pitting.

Enthesitis related arthritis

• An undifferentiated spondyloarthritis.

• Typically begins after age of 6 years, affects boys > girls.

• Characterised initially by LL arthritis & enthesitis

(inflammation at insertion of tendon/ligament/fascia ).

• Most common sites of enthesitis are at insertion of

achilles tendon to calcaneum and insertions of plantar

fascia (calcaneum, base of 5th metatarsal & metatarsal

heads), and around & below patella.

Enthesitis related arthritis

• Hip involvement is frequent at presentation.

• Symptoms of sacroilitis and spinal arthritis are

uncommon at presentation.

• Uveitis - red eyes, photophobia and pain.

• Family history of similar disease is often +ve.

• HLA-B27 found in 50% of pts, while ANA is -ve.

Undifferentiated arthritis

• A category that includes patients who do not

fulfill inclusion criteria for any category, or

fulfill the criteria for more than one category.

• About 10-15% of all JIA cases are included in

this category.

Clinical features of JIA

• Pain

• joint swelling

• limping

• Early morning stiffness

Investigations in children with arthritis

• No diagnostic tests exist. It is a clinical diagnosis.

• Investigations have important role in excluding a

wide range of differential diagnoses.

• RF & ANA - are of no use for diagnosis. should

only be used after diagnosis has been made.

RF - help sub-classify children with polyarthritis

ANA - determining risk of chronic ant uveitis.

• Full blood count

• Acute phase response (CRP and ESR)

• ASO titers and other serology for infection.

• Coagulation studies (haemophilia)

• Autoantibodies (CTDs are suspected)

• Biochemistry -for muscle enzymes, endocrinopathies.

• Urine analysis and uinary catecholamines: to exclude

renal involvement or neuroblastoma

• Imaging -including plain x-rays of affected jts

may be useful to exclude fracture, AVN,

osteomyelitis, neoplasm and bone dysplasia.

• USG of jts is useful to confirm effusion and USG

of abdomen may help to exclude neuroblastoma.

• Aspiration of jt for synovial fluid microscopy and

culture is must in suspected septic arthritis.

Differential diagnosis of JIA

Child presenting with a single inflammed joint -

Septic arthritis : Staph aureus, H influenzae (non-

immunised), M tuberculosis, Salmonella (sickle

cell ds), Pseudomonas (puncture wounds).

Reactive arthritis: secondary to extra-articular

bacterial / viral infections e.g. strep, enteric

bacteria, hepatitis B, parvovirus, EBV, varicella.

Haemarthrosis: trauma or bleeding diathesis

Malignancy: leukaemia or lymphoma should

always be considered. Most common is ALL.

Solid tumour

A child presenting with > 1 inflamed joint

Connective ts diseases: SLE, Dermatomyositis,

Sarcoidosis, MCTD, HSP.

Reactive arthritis

Malignancy

Immunodeficiency associated arthritis

IBD associated arthritis

Other: chronic recurrent multifocal osteomyelitis,

cryopyrin-associated periodic syndromes.

Child presenting with prominent systemic features

Connective tissue diseases, Neoplasia

Infection, Inflammatory bowel disease

Auto-inflammatory disorders:

o characterised by recurrent fever and arthritis

often accompanied by abdominal pain & rash.

o Results of gene mutations and so present from

birth or at a very early age.

o Familial Mediterranean fever, hyper-IgD

syndrome, cryopyrin associated periodic fever

syndromes, TNF receptor associated syndromes.

Treatment of JIA

Goals of Treatment of JIA

• Suppression of inflammation

• Pain management

• Preservation of muscle strength

• Prevention of jt destruction, muscle atrophy,

asymmetric growth and other long-term

sequelae.

Treatment of JIA

Non-steroidal anti-inflammatory drugs (NSAIDs)

Used in higher doses relative to body weight,

than in adults because children have increased

rates of metabolism and renal excretion.

Majority of early JIA patients respond partialy to

NSAIDs and need more aggressive treatment.

• Glucocorticoids

Intra-articular steroids - Single injection resolves

signs of inflammation for several months

Pulses of IV methylprednisolone - For control of

severe systemic arthritis. lifesaving in case of

pericarditis with tamponade or MAS.

Oral steroids - Chronic use can lead to adverse

effects: growth and immune suppression, cataract,

DM, AVN, vertebral collapse and Cushing syndrome.

Disease modifying anti-rheumatic drugs (DMARDs)

Methotrexate - effective in approximately 70% of

children with polyarthritis but much less so in

systemic arthritis

Sulfasalazine - particularly effective in ERA. Also

efficacious in oligoarthritis and polyarthritis.

Leflunomide

Biologicals –

• Whose ds is not controlled with NSAIDs, steroids

and DMARDs or who are intolerant of it.

• Significantly alter natural history and stopped

progression of ds in a substantial portion of pts.

• Adverse events: infections, neutropenia, and

increased aminotransferase levels

TNF alpha blockers – Etanercept, Infliximab.

polyarthritis/extended oligoarthritis. less

effective in patients with systemic JIA.

Anti IL-1 drugs – Anakinra, Canakinumab.

effective in pts with SOJIA

Anti IL-6 drugs – Tocilizumab. efficacious in

severe, persistent SOJIA

Other drugs

• Hydroxychloroquine - RF positive polyarthritis.

• Cyclosporine A - efficacious in treating MAS

associated with SOJIA.

• Cyclophosphamide – severe recalcitrant SOJIA for

whom even biological therapies are not working.

• Autologous stem cell transplantation - recalcitrant

SOJIA unresponsive to all other therapies.

Complications of JIA

(1) Macrophage activation syndrome (MAS):

• Occur in aprox. 7% of pts with systemic JIA.

• Secondary haemophagocytic histiocytosis

occurring in active ds.

• Associated with high morbidity and mortality.

Characterised by –

Diffuse intravascular coagulation.

Hepatosplenomegaly

Pancytopenia

Abrupt decrease in ESR

High serum levels of ferritin, liver enzymes and

triglycerides.

Bone marrow examination shows active

Phagocytosis by macrophages and histiocytes.

Treatment - MP pulse therapy and cyclosporine.

(2) Chronic anterior uveitis:

Most important complication of oligoarthritis.

Often clinically silent and insidiously progressive.

It is especially associated with +ve ANA. Every 3 monthly

eye check up is suggested.

(3) Growth disturbance, atrophy, contrature, and mis-

alignment

are major concerns in chronic arthritis.

Successful control of ds and decreased use of steroids

have reduced this complication

(4) Cardiac disease:

Pericardial involvement occurs almost exclusively

with systemic-onset disease.

Myocarditis and endocarditis are much rarer

(5) Osteoporosis –

JAO and growth arrest lines are common.

Generalised OP may be observed, especially in

patients with a polyarticular course.

Other complicationsof JIA

(6) Intercurrent infections

(7) Anaemia

(7) Secondary amyloidosis

Summary

• Diagnosis - typical clinical features, persistent

swelling of 1 or more jts, before 16th b’day,

without any clear cause.

• Mimickers of JIA-septic arthritis, osteomyelitis,

neoplasia ( ALL), neuroblastoma and lymphoma.

• Subtypes -oligoarthritis, extended oligoarthritis,

ERA, PsA, RF -ve & RF +ve polyarthritis and SOJIA.

• No pathognomonic investigations for diagnosis.

Laboratory investigations may be helpful-

To exclude differential diagnoses (mimickers)

To sub-classify JIA

To monitor disease

• Multidisciplinary treatment is required including

nursing staff, physiotherapists, occupational

therapists and psychologists.

• Treatment for JIA - usually proceeds in a step-

wise escalating approach, beginning with

NSAIDs and I/A steroids, early use of DMARDs

for higher risk JIA groups.

• Biologicals - Anti TNF, IL-1 and IL-6, for SOJIA

which cannot be treated effectively with

methotrexate.

• Complications of JIA - chronic ant. uveitis,

dental decay, anaemia, osteoporosis and

growth disturbance.

• Life threatening complications & adverse

effects of Tx include sepsis, MAS, Reye

syndrome and amyloidosis.

Multiple choice questions (MCQs)

MCQ - 1

Following is true about systemic onset JIA-

A. It usually occurs in children under 5 yrs of age

B. Fever lasts for more then two weeks

C. Only cervical lymphadenopthy is seen

D. ANA is always present

E. DIC is a recognized complication

MCQ - 2

Following are true about oligo-articular JIA

except–

A. More common in females

B. It is usually seen after the age of 8 years

C. High risk for developing chronic iridocyclitis

D. Associated with ANA positivity

MCQ-3

All are true for Enthesitis related arthritis except -

A. Typically begins after age of 6 years

B. It affects boys more than girls.

C. Characterised initially by upper limb arthritis

D. HLA-B27 found in 50% of patients

E. ANA is negative.

MCQ-4

All are complications of JIA except -

A. Intercurrent infections

B. Pulmonary embolism

C. Anaemia

D. Osteoporosis

E. Chronic anterior uveitis

MCQ - 5

All are feutures of Macrophase activating syndrome

except -

A. Hepatosplenomegaly

B. Pancytopenia

C. Abrupt decrease in ESR

D. Low serum level of ferritinE. Elevated levels of liver enzymes and triglycerides.