13.2a Juvenile idiopathic arthritis: medical aspects

Juvenile idiopathic arthritis (JIA) comprises a group of diseases that are classified according to mode and age of onset. Their aetiopathogenesis is not understood. Initially, the classification criteria suffered because they had been adapted from adult criteria, and subsequently because the criteria developed differently across the continents. The current classification system is a research-based tool devised to ensure homogeneous groups of patients were being studied, both in the United States of America and Europe. It is used clinically but in a less rigorous manner and not all exclusion criteria are adhered to. The treatment principles for all forms of JIA are the same: to control completely the inflammation in the affected joint allowing normal growth, development, and function during childhood.

JIA is found worldwide with an incidence in the United Kingdom of 1:10 000 children. It is defined as an arthritis persisting for at least 6 weeks in a child under the age of 16. The arthritis itself is described as swelling of at least one peripheral joint or at least two of the following signs: limited range of movement; tenderness or pain on movement of a joint; or increased warmth of the skin overlying a joint (Box 13.2a.1). The cause may be a combination of genetic and environmental factors that relate to how the immune system responds to stimuli: the resultant inflammatory response may be limited to the synovium or manifested systemically.

There are a number of important conditions with an associated arthropathy that are not included within this classification system: inflammatory bowel disease, immune deficiencies and reactive arthritis.

Oligo JIA, previously known as pauciarticular JIA, is defined as involvement of up to four joints within the first 6 months of the disease. If more joints are involved after 6 months it becomes extended oligo JIA. Oligo JIA is the largest JIA subgroup accounting for 50% of cases. The disease onset is early (median age 5 years) and there is a female: male ratio of 5:1. The knee is the most commonly affected joint. If the child is anti-nuclear antibody (ANA) positive there is a strong association with uveitis. As the uveitis is asymptomatic, slit-lamp examination every 3 months for the first 2 years of the disease to screen for inflammation and thus prevent blindness is essential. Overall, 60% of cases are in remission by adulthood.

Patients with a family history of psoriasis, who are positive for rheumatoid factor (RF) or HLA-B27 or who have a HLA-B27 associated disease or an inflammatory bowel disease are excluded from a diagnosis of oligo JIA.

Poly JIA patients have more than five joints affected within 6 months of disease onset. It is the second most common subgroup and like oligo JIA, the age of onset is early (median age 6 years) and females are most commonly affected. The arthritis is symmetrical, often involving the wrists, metacarpophalangeal and proximal interphalangeal joint joints, the neck, and the temporomandibular joints (TMJs). If multiple joints are involved in one or more limbs, growth can be delayed.

Similar to oligo JIA, the child may be ANA positive and if so there is a risk of uveitis. Despite treatment, 10–15% of patients with RF-negative poly JIA will have severe functional limitation 10–15 years after disease onset.

RF positive poly patients comprise only 10% of the poly group and only 3% of all JIA cases. There is a marked female preponderance (female: male, 13:1) and the median age of onset is later at 9 years. The arthritis is aggressive, symmetrical, and similar to adult rheumatoid arthritis (Figure 13.2a.1).

The diagnosis of poly JIA (RF positive or negative) is excluded if the child is HLA-B27 positive.

This is the most severe form of the disease. It often presents as a pyrexia of unknown origin. There are three main criteria for diagnosis:

In contrast to the other JIA subgroups the female to male ratio is equal and there is no peak age of onset during the childhood years.

The systemic nature of the disease means that there is a generalized lymphadenopathy with hepatosplenomegaly and possibly a serositis (including pericarditis). Uncontrolled disease leads to osteoporosis and severe growth failure and causes a destructive arthritis in 30–60% of cases.

Patients who are RF or HLA-B27 positive are excluded from this diagnosis.

As the name implies, this subgroup of JIA patients must have an arthritis associated with nail pitting or dactylitis or have a first-degree relative with psoriasis. The condition is commoner in girls and the age of onset is between 7–11 years.

Patients must be RF and HLA B27 negative.

This group of HLA-B27 positive patients used to be labelled as spondyloarthritis but the term is no longer used. It is the only subgroup of JIA that affects males more than females with a later median age of onset at 11 years. (Table 13.2a.1) Asymmetrical large peripheral joint arthritis is associated with enthesitis (inflammation of the muscular or tendinous attachment to bone) and tenosynovitis. Involvement of the axial skeleton is uncommon and usually a late feature.

All patients must be RF negative.

This research group is used to ‘house’ patients who can not be classified into any other category.

Investigations should be used to help make a correct diagnosis and to exclude other similar conditions.

Changes consistent with an inflammatory response such as anaemia, a raised platelet and white cell count, and a high erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Patients with oligo JIA may have no such changes.

Patients with systemic JIA may show a transaminitis.

A positive ANA or RF test clarifies diagnosis and influences prognosis. If the RF level is very high, a diagnosis of systemic lupus erythematosus (SLE) must be considered. HLA-B27 should be performed if the differential diagnosis includes psoriatic arthritis or ERA.

The presence of a fever may necessitate a septic screen, virological investigations, and a test to exclude Borrelia. If TB is suspected a Mantoux test (and a chest radiograph) should be performed.

Plain radiographs may show surprisingly little abnormality but in the more established case there may be periarticular osteoporosis, marginal erosions, and, at the wrist, carpal crowding. MRI will demonstrate synovial hypertrophy with contrast highlighting areas of active synovitis.

Synovial biopsy is not required routinely but may be useful in excluding tuberculosis (TB) or sarcoidosis. Similarly, bone marrow aspirate (BMA) and measurement of urinary vanillyl mandelic acid (VMA) in patients with systemic disease excludes leukaemia and neuroblastomas (Box 13.2a.3).

The list of differential diagnoses varies a little from subgroup to subgroup of JIA. A careful history and complete examination are essential prerequisites for a correct diagnosis and may influence the line of further investigation. Sepsis should always be considered when only one or two joints are affected (some cases of oligo JIA) but it is less likely in systemic JIA where the involvement (unlike with sepsis) is symmetrical. (Table 13.2a.2).

Patient and parent education is very important, as the diagnosis of ‘arthritis’ is often associated with incorrect preconceptions.

In some cases, all that is required for management is analgesic medication and relative rest. Non-steroidal anti-inflammatory drugs (NSAIDs) help pain, stiffness, and fever whilst physiotherapy maintains range of movement and muscle strength or helps rebuild muscle that may have wasted secondary to lack of activity and the release of inflammatory cytokines.

Other cases require a more structured medical management plan.

If only a few joints are involved, intra-articular steroids may be used under general anaesthetic for children under 8 years and nitrous oxide for older patients. The steroid of choice is triamcinolone hexacetonide at a dose of 1mg/kg for each large joint.

Oral or intravenous steroids are used if systemic features are present or if there is multiple joint involvement.

Occupational therapy has an important role particularly in patients with systemic disease or multiple joint involvement. Hand therapy is important but overall, joint splintage is not used frequently; the emphasis is on maintaining the activities of daily living with joint movement and normal weight-bearing activity when possible (physiotherapy).

A generalized growth failure may occur due to disease activity, more commonly in patients with systemic JIA than with poly JIA. However, a localized failure of growth may occur at any affected joint and premature fusion of a growth plate may lead to a clinically apparent limb length difference. Some patients demonstrate an overgrowth phenomenon secondary to the inflammatory response and the associated increase in blood flow. This too may lead to limb length inequality or an alteration in limb alignment: commonly increased knee valgus.

Pubertal delay is uncommon and seen only in severe disease.

Amyloidosis is only seen in some systemic JIA patients after years of uncontrolled inflammation documented by persistently elevated ESR/CRP levels. With improvements in medical therapy, the incidence of amyloidosis has fallen.

This can occur secondary to any systemic inflammatory disease. Macrophage activation within the bone marrow causes macrophages to ingest red blood cells, platelets and fibrinogen. The patient becomes unwell acutely with a marked fall in platelets, fibrinogen, and ESR. The condition can be fatal.

Both complications can occur in patients with uncontrolled inflammation particularly in multiple joints and are thus more common in systemic JIA (and some poly JIA cases).

Restriction of joint movement secondary to pain and soft tissue contracture is common and all efforts must be taken to minimize this. Loss of cartilage leads to a reduction in joint space, problems with malalignment, and abnormal joint loading often requiring orthopaedic management (see Chapter 13.2b).

TMJ involvement in childhood may lead to micrognathia with dental and cosmetic consequences (Figure 13.2a.2). If associated with inflammation or fusion (Figure 13.2a.3) of the cervical spine there may be significant restriction of neck extension. Both problems may cause anaesthetic difficulties.

Atlantoaxial dislocation is rare but has been noted in patients with poly JIA and ligamentous laxity.

Avascular necrosis of the hips is not uncommon and may be related at least in part to treatment with steroids, or persistent active disease (Figure 13.2a.4).