Juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a group of paediatric arthritides occurring before the age of 16 that last >6 weeks. It is the most common chronic rheumatic issue in children and is believed to be of an autoimmune aetiology initially.

Pathophysiology

The entire aetiology of JIA remains to be understood. Autoimmunity does seem to play a role in the disease along with environmental and genetic factors too.

Let’s breakdown some of the factors involved in the aetiology and let’s look at the pathophysiology of the disease:

In JIA, chemotactic factors call for the migration of Th1 cells into the synovium. These Th1 cells then initiate an inflammatory cascade leading to the release of pro-inflammatory cytokines such as TNF-α, IL-1 and IL-6. These cytokines promote inflammation of the synovium as well as tissue damage. IL-17 is also implicated and it is known that IL-17 induces RANKL. RANKL activates osteoclast precursors and promotes their differentiation into mature osteoclasts (osteoclastogenesis). These osteoclasts promotes bone resorption, contributing to joint damage and bone erosions seen in JIA.

The persistent inflammation of the synovium results in the release of matrix metalloproteinases (MMPs) which lead to a pannus formation. A pannus is a layer of granulation tissue that forms over the articular cartilage. This pannus invades the articular cartilage and causes its degradation and erosion of the subchondral bone subsequently.

• Genetic factors are seen with variation of HLA such as HLA-A2, HLA-B27, HLA-DRB1.
• Environmental triggers such as infections with Epstein-Barr virus or Parvovirus B19. These may induce molecular mimicry which can trigger an autoimmune response.

⚠️ Risk factors

• Female
• HLA variation
• Family history of autoimmune conditions

🔢 Classification

The International League of Associations for Rheumatology (ILAR) recognises 7 subtypes of JIA:

1. Systemic JIA
2. Olgioarticular/pauciarticular JIA
3. Polyarthritis (RF-negative)
4. Polyarthritis (RF-positive)
5. Psoriatic arthritis
6. Enthesis-related arthritis
7. Undifferentiated arthritis

We will discuss each of these a little further in the presentation section of this document.

😷 Presentation and types

Oligoarticular/pauciarticular JIA

This is the most common subtype of JIA. It is more common in girls.

😷 🔢 Presentation and classification

Based on the number of joints affected we can further classify it in 2 types:

1. Persistent oligoarticular/pauciarticular JIA - always ≤4 joints affected.
2. Extended oligoarticular/pauciarticular JIA - ≤4 joints affected initially (first 6 months) but later on ≥5 joints are involved.

• Anterior uveitis is another feature that is typically associated with the disease.

🔍 Investigations

• ANA - usually positive.
• Rheumatoid factor (RF) - usually negative.

Polyarthritis

This is the second most common form of JIA. It differs from oligoarticular JIA by having ≥5 joints affected at onset.

It too affects girls more commonly.

😷 Presentation

It has a symmetrical distribution of arthritis and affects small joints predominantly (such as hands and feet). It can affect larger joints such as the hips and shoulders too though.

Other features include:

• Mild fever
• Anaemia
• Delayed growth

🔢 Classification

• RF positive polyarthritis - usually occurs in adolescent girls. It is essentially the juvenile form of rheumatoid arthritis.
• RF negative polyarthritis - this is seen in young girls and has a better prognosis.

Systemic JIA (sJIA)

This is also known as Still’s disease. It is a systemic illness with arthritic and inflammatory presentations too and primarily affects young children (both boys and girls). It may also occur in adulthood and is then known as Adult-onset Still’s disease (AOSD).

😷 Presentation

• Salmon pink rash
• High, swinging fever
• Lymphadenopathy
• Weight loss
• Arthralgia

• Myalgia
• Splenomegaly
• Pleuritis
• Pericarditis

A lot of the symptoms overlap with paediatric malignancies and therefore it is important to keep them in the back of the mind.

💡 Key non-infective differentials for fevers lasting >5 days in children are Kawasaki disease, Still’s disease, rheumatic fever and leukaemia.

🔍 Investigations

• ANA and RF - both are usually negative.
• ESR and CRP - raised.
• Thrombocytosis - platelets are an acute phase reactant.
• Ferritin - elevated as ferritin is an acute phase reactant.

🚨 Complications

• Macrophage activation syndrome

Enthesis-related arthritis

An enthesis is an attachment site of a tendon, ligament or fascia into bone. Therefore enthesis-related arthritis is the inflammation at the insertion point on the bone.

It is more common in older boys over 6 years old. The sacoriliac joints are often involved, leading to sacroiliitis. The inflammation may then spread to the lumbar spine, leading to lumbar arthritis.

😷 Presentation

• Arthritis in the lower extremities - usually in the larger joints.
• Asymmetric distribution
• HLA-B27 associated issues - as HLA-B27 presence is implicated in enthesis-related arthritis, we may see associated signs of HLA-B27 such as inflammatory bowel disease and anterior uveitis.

🔍 Investigations

Enthesitis may be elicited by palpating regions such as:

1. Interphalangeal joints in the hand
2. Wrist
3. Greater trochanter
4. ASIS
5. Calcaneus
6. Metatarsal heads on the base of the foot.

Psoriatic arthritis

Psoriatic arthritis is a seronegative inflammatory arthritis that is associated with psoriasis.

😷 Presentations

• Symmetrical polyarthritis affecting small joints - similar to rheumatoid arthritis.
• Asymmetrical arthritis affecting large joints - especially in the lower limb.
• Psoriatic plaques
• Nail pitting
• Onycholysis (separation of the nail from the nail bed)
• Dactylitis
• Enthesitis

Undifferentiated arthritis is when the patient does mot meet the criteria for a single category OR meets the criteria for more than one JIA subtype.

🧰 Management

The primary goals for treatment are:

1. Immediate pain relief
2. Preventing joint damage
3. Maximising function

To ensure this, a paediatric rheumatologist and multi-disciplinary team is required.

💡 It is important to rule out haematological cancers (such as acute lymphoblastic leukaemia) prior to treating JIA seeing as we give steroids for JIA.

🚨 Complications

• Chronic anterior uveitis
• Joint contractures
• Joint erosion
• Faltering growth
• Osteoporosis
• Amyloidosis - it is rare but may occur with Still’s disease. The chronic inflammation of the liver causes it to produce serum amyloid A (SAA) proteins which can be deposited in the kidneys, liver, spleen and GI tract.
• Macrophage activation syndrome - a severe immune response can lead to uncontrolled activation of T-cells and macrophages which leads to a large release of pro-inflammatory cytokines which can lead to DIC, anaemia, thrombocytopenia, coagulopathy. It can be difficult to diagnose due to its overlapping features of other conditions. A low ESR is a key finding which can point to its diagnosis.