Rational approach to the child with juvenile idiopathic arthritis

Musculoskeletal symptoms are common among children. However, only a minority has arthritis. Incidence of arthritis in United Kingdom is 1 in 10, 000 1 and prevalence 1 in 1000 1 . Arthritis can be defined as inflammation of joints. Inflammation is recognized by its cardinal manifestations viz. pain, redness, warmth, swelling and loss of function. These features are not prominent in some children, particularly those with pauciarticular juvenile idiopathic arthritis (JIA) characterized by low grade inflammation, which could result in delayed diagnosis. Therefore, in children, we use the following criteria to diagnose arthritis 2 :


Introduction
Musculoskeletal symptoms are common among children.However, only a minority has arthritis.Incidence of arthritis in United Kingdom is 1 in 10, 000 1 and prevalence 1 in 1000 1 .Arthritis can be defined as inflammation of joints.Inflammation is recognized by its cardinal manifestations viz.pain, redness, warmth, swelling and loss of function.These features are not prominent in some children, particularly those with pauciarticular juvenile idiopathic arthritis (JIA) characterized by low grade inflammation, which could result in delayed diagnosis.Therefore, in children, we use the following criteria to diagnose arthritis 2 : 1. Swelling or effusion arising from joint even in absence of other features of inflammation.

In absence of swelling -
• Tenderness over a joint / painful movement.
• Limited range of movements.
• Muscle spasm around a joint.
Three of the above 4 criteria should be fulfilled to diagnose arthritis.

Definition of JIA
JIA is defined as a heterogeneous group of diseases characterized by persistent arthritis lasting more than 6 weeks, commencing before 16 years of age, in the absence of a defined diagnosis (e.g.systemic lupus erythematosus).
Diagnosis of JIA could be difficult in some children and delayed in the majority as it takes many days or weeks for characteristic features to appear.Diagnosis is essentially clinical as there are no pathognomonic or diagnostic laboratory tests.Furthermore, some ___________________________________________

Classification
Juvenile arthritis is a heterogeneous group of diseases of unknown aetiology, many of which are clinically and genetically distinct from chronic arthritis in adults.There has been long standing confusion about differences between JCA (Europe) and JRA (North America).JIA is the new term proposed to unify these previous classifications to facilitate research and further knowledge and understanding of biologically significant and clinically homogenous disease entities.The new classification 3,4 given below is predominantly clinical, requires prospective validation and will evolve further with greater understanding of the aetiopathogenesis of these diseases.
(1) Systemic Arthritis with or preceded by fever of at least 2 weeks, documented to be quotidian for at least 3 days, accompanied by one or more of the following:- Arthritis affecting 1-4 joints during first 6 months of disease.Children with a family history of psoriasis or a positive rheumatoid factor are excluded from this group.
• Persistent pauciarticular -Affect up to 4 joints throughout course of disease.
• Extended pauciarticular-Affect up to 4 joints during first 6 months, but progresses to 5 or more joints after 6 months.
(3) Polyarthritis Arthritis affecting 5 or more joints during first 6 months of disease.Children with a family history of psoriasis are excluded.
• Rheumatoid factor negative • Rheumatoid factor positive -associated with positive rheumatoid factor tests on 2 occasions at least 3 months apart.
(4) Enthesitis related arthritis Arthritis and/or enthesitis with at least 2 of the following: • Sacroiliac tenderness / inflammatory spinal pain • HLA B27 • Acute anterior uveitis • Onset in males over eight years • Family history of HLA B27 related medical conditions At present children with antinuclear antibody, rheumatoid factor or inflammatory bowel disease are excluded from this group.
(5) Psoriatic arthritis Arthritis and psoriasis or arthritis with two of the following: • Family history of psoriasis Children with positive rheumatoid factor are excluded from this group.
(6) Other Children with arthritis of unknown cause not fulfilling above categories or who develop more than one category.

Investigations
Laboratory tests help to exclude other diagnoses and to monitor disease activity, detect complications and predict outcome.
• Elevated ESR and C-reactive protein indicate active inflammation.
• Full blood count Characteristic changes are normochromic normocytic anaemia, neutrophil leucocytosis and thrombocytosis, most marked in systemic JIA.
• Synovial fluid analysis is mandatory in assessment of children with a single hot, swollen joint.
• Antinuclear antibodies (ANA) are positive in 50% patients with JIA, but are also found in viral illness, non rheumatic disease and healthy children.They are not diagnostic and must be carefully interpreted in clinical context.However, in presence of JIA.ANA indicate risk of chronic asymptomatic uveitis.
• Rheumatoid factor is a poor diagnostic test but its presence in a child with polyarticular JIA indicates a guarded prognosis.Simple analgesics, such as paracetamol, are extremely useful to minimize pain when used together with regular anti-inflammatory drugs.This can be given early morning, even on an empty stomach, as inflammatory features are most marked on awakening.
Non-steroidal anti-inflammatory drugs (NSAIDs) are indicated in all children with active synovitis These drugs take about 2-4 weeks to act effectively.Therefore changing NSAIDs frequently (unless due to side effects) is not recommended.Combination of NSAIDs should be avoided as it leads to addition of side effects.Children tolerate higher doses of NSAIDs as liver metabolism is efficient.Recommended doses 5 of commonly used NSAIDs are given below.In practice, low dose (<0.5 mg/kg/day) oral prednisolone is used to treat polyarticular JIA who do not respond well to NSAIDs.This is useful as a disease remitting agent while starting methotrexate therapy which can take several months to be effective.When using oral steroids, complications can be minimized by giving them as a single morning dose.Risk of osteopenia associated with long-term steroids can be minimized by giving supplemental calcium and vitamin D therapy.
For children with resistant JIA, various drugs had been used in new combinations and new schedules.For resistant systemic JIA 8 encouraging results had been shown with a combination of pulsed methyl prednisolone (30 mg/kg/day) for 3 days with oral cyclophosphamide 0.4g/m 2 on day 3 together with oral methotrexate 10 mg/m 2 weekly.In this regime these pulses are used every 3 months up to one year.
Intravenous immunoglobulins 8 have been found to be beneficial in polyarticular JIA if given early.It is given at a dose of 1.5-2.0g/kg twice a month for 2 months and then continued monthly for a period of 6 months.
New biological therapies 9 are available for patients not responding to methotrexate 8 .Etanercept and infliximab have been used with dramatic and sustained improvement in this setting.Use of these agents is restricted because of limited availability and high cost.
Use of gene therapy 8 is still at experimental level.Candidate genes encoding for anti-inflammatory.immunosuppressive, chondro-protective and chondroreparative proteins, may be incorporated into synovial lining cells so that their products are secreted directly into joint space.
Slow-release preparations and long acting NSAIDs such as piroxicam are extremely useful to counteract morning stiffness when given in the night.Cox-2 inhibitors are still not licensed for use in children and adolescents.