Juvenile idiopathic arthritis

From Ganfyd

Seven subtypes - strictly speaking you should only diagnose when symptoms present for at least 3 months, but in practice that doesn't mean you delay treatment.

• Oligo (persistent or extended) - Arthritis affecting up to four joints during the first six months of disease. If subsequently more than four joints are affected the term extended oligoarthritis is used, otherwise the term persistent oligoarthritis is used. This is the most common pattern (50% of all JIA) and usually involves large joints of the lower limbs, especially knees. These children have the best prognosis but are at high risk of asymptomatic uveitis (30%, and risk highest in monoarthritis!) and therefore must be screened regularly. In aggressive disease, can develop within 3 months of presentation. Girls mostly ankles, knees or wrists, 50% will be Anti Nuclear Antibody (ANA) positive which is particularly associated with chronic (even subclinical) uveitis. Boys tend to get sacroilitis and be HLA B27 positive, which is associated with acute uveitis...

• Polyarthritis (rheumatoid factor negative) - Arthritis affecting five or more joints during the first six months. Tends not to be hips! If IgM rheumatoid factor is not detected in blood then the child's disease falls in this group, which makes up 17% of all JIA. Severity is very variable.

• Polyarthritis (rheumatoid factor positive) - This subtype accounts for 7% of cases and is characterised by a symmetrical polyarthritis, nodules, and IgM rheumatoid factor being identified at least twice, three months apart. Patients are typically adolescent girls of 10yrs+ and the prognosis is guarded as early joint damage often occurs.

• Systemic onset (SOJIA) accounts for 11% of cases of JIA. It can occur at any age, often in pre-school children although rarely in infancy. Similar incidence rates are seen in males and females.

• Enthesitis related arthritis - This term is used for arthritis and enthesitis (inflammation of tendon insertions eg sternum, around knee (at 2,6 and 10 o'clock positions), tibial tubercle, achilles/plantar, tibialis anterior, flexor digitorum insertion in foot). Often give history of dactylitis. Asymmetric, distal large joints in the lower limbs are commonly affected and there is a high risk of these patients developing ankylosing spondylitis in early adulthood - spine rarely affected early on. BASMI score consists of 5 measurements of spinal mobility. The group also includes arthritis or enthesitis with at least two of:

• • tenderness of the sacroiliac joint and/ or inflammatory spinal pain - HLA B27 positive (10% of normal population) - family history in a first or second degree relative of HLA B27 related disease (ie arthritis, IBD, Reiter's, uveitis)
  • anterior uveitis (usually symptomatic with redness, pain and blurred vision)
  • arthritis after 8 years of age in a boy (esp large lower limb joints)

• Psoriatic arthritis - less obvious places to look for lesions of psoriasis are in umbilicus, behind ear, scalp. But does not need to be present for diagnosis, indeed often isn't, at least initially! The arthritis is usually asymmetrical, mixed large/small joints. Includes children with arthritis and at least two of:
  • dactylitis
  • pitting or onycholysis of nails
  • psoriasis in a first degree relative

• Other arthritis - This group is for children with idiopathic arthritis that does not fit the other groups (or into more than one! eg Crohn's disease & Ulcerative colitis associated arthritis, where features often overlap).

Clinical presentation

Clinically, history of pain, swelling, stiffness. Pain is usually not severe, and often avoided completely by adapting movement; can occur at night, and occurs in the joint line. Degree of pain does NOT predict severity of synovitis. Swelling may be due to effusion or bony overgrowth. Stiffness is usually not so severe as to cause gelling (where sitting still leads to freezing - suggests myasthenia gravis, hypermobility). Bony overgrowth, discrepant leg length (longer with inflammation! Leads to postural scoliosis) and wasting indicate chronicity.

Differential diagnosis

• Benign hypermobility - typically get pain related to exertion, short lasting although may occur at night. Beighton scale used to assess. Can be seen in Marfans and Sticklers (myopia, retinal detachment) syndromes. Transient swelling. Physio doesn't help much! Chronic pain team may need to be involved.

• Reactive arthritis - can last up to 3 months.

• Infective - Rubella, chronic meningococcus

• Henoch Schonlein Purpura before rash develops

• Rheumatic fever

• Behçets - mouth/genital ulcers, uveitis.

• Systemic lupus erythematosus (SLE) - high ESR with normal CRP, low WCC/platelets, typical autoantibodies)
• Dermatomyositis - stiffness, rather than true arthritis. Proximal muscle weakness, high CK

Investigations

• CRP: usually <7 in Mono JIA - else beware infection

• Microscopy of joint fluid: nonspecific

• X Ray: to exclude tumour etc. Lucency in metaphysis may be marrow infiltration in leukaemia, Brodies abscess or Langerhans histiocytosis. Moth eaten appearance and onion skin periosteal reaction suggests tumour or infection.

• Rheumatoid factor very non specific, like other autoantibodies, only significant in discriminating teenage girls with adult type Rheumatoid arthritis.

• US: good but operator dependent.
• MRI probably better - can even predict extension in mono, up to 11 months before clinical signs.

Systemic onset JIA

Features:

• Prolonged pyrexia (see below)
• Intermittent characteristic rash (see below)
• Raised CRP, ESR, ferritin (esp over 1000 - but no specific, also seen in haemophagocytic syndromes, haemochromatosis, liver disorders, malignancy)
• Poor response to IVIG (cf Kawasakis disease)
• Leucocytosis (neutrophilia, can be leukaemoid)
• Thrombocytosis
• Arthritis
• Hepatosplenomegaly
• Generalised lymphadenopathy
• Pericarditis

Can be systemically very unwell and potentially life threatening complications may occur early in the disease course (eg pericarditis, macrophage activation syndrome or haemophagocytic syndrome/lymphohistiocytosis (HLH), sepsis). Start high dose corticosteroids after careful exclusion of other diagnoses, especially infection, Kawasakis disease, and malignancy - difficult when arthritis is absent.

Systemic features may predate the arthritis by several weeks and occasionally longer. Typically involves small joints of the hands and wrists, ankles, hips, knees, and cervical spine - about 30% ultimately develop severe polyarthritis.

There are no pathognomonic tests or agreed diagnostic criteria for SOJIA! Exclude other conditions, look for classic features:

• Quotidian (=daily) evening spiking temperature, that returns to or falls below baseline by the morning.
• Rash is faint, salmon pink maculopapular, most obvious during pyrexia. Usually not on the face so easily missed - typically on the trunk, inner thigh and axillae, especially on areas of trauma or pressure (Koebner phenomenon).

Outcome

JIA is a not a benign disease and outcome is variable. At least a third of patients have ongoing active disease into adulthood and many have sequelae eg:

• joint damage requiring joint replacement
• short stature from chronic disease compounded by steroid toxicity
• localised growth problems (micrognathia or leg length inequality)
• visual loss from uveitis
• osteoporosis: one off DEXA scan not predictive of # (maybe better if serial scans?) so clinical. Minimize steroids; optimize exercise, nutrition, growth/puberty, calc/vitD/bisphosph

Bisphosphonates seem to be effective for increasing bone mass in JIA. Flu-like symptoms with first IV dose can be treated with paracetamol and tend not to recur.

Uveitis

Uveitis occurs in about 10% of patients with non-oligoarthritis, and 30% of ANA positive oligo so pretty common. Almost always asymptomatic, but can lead to blindness due to cataract, glaucoma, synechiae etc. So they all need screening, pref by someone with paediatric experience, and within 6 weeks of diagnosis - most avoidable morbidity due to uveitis developing before or at the time of diagnosis.

• High st optician is not adequate!
• Supposedly no uveitis in SOJIA, or RF+ poly, but refer if diagnosis uncertain or eye symptoms.

2 monthly for 6 months from diagnosis, then 3-4 monthly thereafter.

• Simple rule:
  • everyone until their 11th birthday at least.
  • Poly: don't stop.
  • For those older than 11 at presentation, do for 1 year.
• Complicated rule: length of screening depends on type and age of presentation, refer BSPAR 2006 guideline.

Regular screening only dropped when child able to report subtle changes in vision themselves - but still advised to monitor monocular visual acuity. Or when joint disease has been quiescent for at least 7yrs! Symptoms would be visual loss, photophobia, corneal clouding; possibly manifest as unusual rubbing, blinking, new onset squint.

Treat with topical/systemic steroids, methotrexate, MMF (although not great for joint disease), infliximab (seems better than etanercept).

Multidisciplinary team

Should include nurse specialist, physiotherapist, occupational therapist, paediatric rheumatologist, ophthalmologist, clinical psychologist, social worker, dentist, orthodontist, and orthopaedic surgeon.

Drugs

NSAIDs and intra-articular steroids are used initially. Joint injections are given under general anaesthetic in young children or with Entonox +/or local anaesthesia in older children.

Methotrexate is the disease modifying drug of choice - early use helps to reduce joint damage and minimise the exposure to, and side effects of, corticosteroids. Well tolerated in most children.

Side effects: occasional nausea, mild (reversible) elevations of serum liver enzymes, and mild bone marrow suppression.

Avoid alcohol, as potentiates risk of cirrhosis. Takes 6-8 weeks to become effective so cover interval with intravenous methylprednisolone. The theoretical risk of malignancy and infertility has not so far been borne out in long term outcome studies. Folic acid usually given, improves tolerability (do not exceed 1000 micrograms of folic acid per day, else vitamin B12 deficiency). Methotrexate is given once a week at 10-25mg/m2 - can be oral but subcut route improves bioavailability at doses beyond 10mg/m2. Regular blood tests to monitor inflammatory markers and side effects.

Calcium and vitamin D supplements are often given.

Steroids of very limited benefit in axial disease (may be good for peripheral joints) - TNF blockade (ie etanercept or infliximab) perhaps more effective.

Patients who are refractory to high dose parenteral methotrexate are considered for novel immunosuppressive agents such as Etanercept/infliximab (TNF antibody), autologous stem cell transplantation, or very high dose immunosuppression (eg with IV methylprednisolone, IVIG).

Patients on biologics (incl methotrexate) should avoid live vaccines and beware of contact with chickenpox if non-immune - consider VZIG for prophylaxis, and IV aciclovir for treatment. Not clear when to wean... Many patients do well for a year or so before their condition begins to worsen, swapping to another agent often works, and swapping back is also a useful option.