What Is Childhood Arthritis?

Introduction

Childhood arthritis also called Juvenile Idiopathic Arthritis (JIA) is an umbrella term describing the different types of arthritis that can be found in children under the age of 16.¹ Most types of JIA  are autoinflammatory and autoimmune disorders. This means that the immune system, whose primary role is to combat external threats such as viruses and bacteria, loses its function and, instead of combating damaged tissue, will release inflammatory substances that attack healthy cells and tissues. This will in turn create symptoms such as joint inflammation, swelling, and discomfort. Some types of JIA, however, have little or no joint-related inflammation and only impact the skin and internal organs.² These symptoms will make it difficult for a child to achieve everyday actions such as walking or dressing.³ 

In this article, we will describe the causes, symptoms, diagnosis, and possible treatments of the different types of JIA.

Symptoms

The symptoms of JIA may vary depending on the type. However, most general symptoms are as follows:

• Joint pain
• Swelling
• Fever
• Tenderness
• Rash
• Exhaustion
• Decreased desire to eat
• Eye inflammation
• Effects on growth and development
• Challenges in everyday tasks like walking, getting dressed and playing.³

Those symptoms might worsen over time, known as flares, or get better which is called remission. For JIA to be considered JIA, the symptoms must last at least 6 weeks, but the length of the disease can last for a few months or years or can continue throughout life.

Types of juvenile arthritis

In Juvenile Idiopathic Arthritis (JIA), the term idiopathic refers to the fact that we do not know what causes the disease. JIA is, therefore, characterised by chronic joint inflammation that lasts for at least six weeks and has no known cause. In 2021, approximately 3 million children suffered from JIA.⁴

Oligoarticular juvenile idiopathic arthritis

The most common type of JIA is Oligoarticular Juvenile idiopathic arthritis, which is characterized for affecting only 4 joints or less and is more likely to affect females under 6 years old. The affected joints are usually medium or large lower-extremity joints (knee and ankle) and are usually asymmetrical.  The disease rarely affects the hips and cannot lead to destructive arthritis. Finally, people affected by oligoarticular JIA are often also affected by uveitis, an eye inflammation that will cause much more of an effect than their arthritis.⁵

Polyarticular juvenile idiopathic arthritis

Polyarticular JIA is the second most frequent type of JIA, and it is defined as arthritis affecting five joints or more in the first 6 months of the disease. It is usually symmetrical, does not affect the hips and can lead to destructive arthritis. Additionally, it leads to anaemia, weight loss, mild fever and can also develop into moderate enlargement of the liver and spleen, as well as mild growth retardation.^5,6

Polyarticular juvenile idiopathic arthritis-rheumatoid factor positivity

Within Polyarticular JIA, there are two subgroups depending on the rheumatoid factor (RF) positivity. The RF is an autoantibody present in the blood of individuals affected by rheumatoid arthritis, the adult form of arthritis. The seronegative polyarticular JIA has milder effects and will usually start either in children between the ages of 2 and 4 years or between 6 and 12 years. The seropositive polyarticular JIA, on the other hand, tends to be more aggressive and will usually start later in childhood or adolescence and essentially appears similarly to adult rheumatoid arthritis.^5,6 

Systemic juvenile idiopathic arthritis

“Systemic” indicates that the illness has the potential to impact the entire body rather than being confined to a particular organ or joint. This disease subtype is characterised by the presence of arthritis and intermittent fever for at least 2 weeks, along with one of the following: a rash, swollen lymph nodes, an enlarged liver or spleen, or inflammation of the body's serous membranes. Symptoms include a fever reaching up to 39.5°C, occurring once or twice daily. This fever often comes with a distinctive salmon pink-coloured rash on the trunk and limbs, which disappears when the fever subsides. Around one-third of patients may experience an enlarged liver and spleen (hepatosplenomegaly) and swollen lymph nodes. Patients may also experience serositis, inflammation of the heart or lung lining, along with chest pain, abdominal pain, and muscle pain.

Diagnosis of systemic juvenile idiopathic arthritis

Blood tests may reveal elevated white blood cell counts, anaemia, and increased high platelet counts. Auto-antibody levels can be elevated in systemic JIA, and the rheumatoid factor (RF) is typically negative.^5,6 

Less common types of JIA

Enthesitis-related arthritis

Enthesitis-related arthritis (ERA) is characterised by the association between arthritis and enthesitis. Enthesitis is inflammation where tendons or ligaments attach to bones. Some children with this condition experience sudden inflammation in the front of the eye, known as uveitis. Unlike most other forms of JIA, enthesitis-related JIA is more frequent in individuals assigned male at birth.⁶ 

Psoriatic juvenile idiopathic arthritis

In this subtype, children exhibit both psoriasis, a skin condition, and joint inflammation.  Additionally, indications of the disease include pitted fingernails and dactylitis, which is swelling in the fingers or toes.⁶ 

Causes and risk factors

The precise origins of JIA  remain uncertain. The most accepted theory suggests that it is influenced by immune responses triggered by a combination of genetic and environmental factors. Among these factors, infections, stress, and trauma are considered the primary contributors.^5,6 

Genetic factors

The elevated occurrence of autoimmune diseases in JIA patients underscores the genetic underpinnings of the condition. Key genetic factors include Human Leukocyte Antigen (HLA) B27 and other HLA tissue types.^5,6

Viruses and bacteria

While genetic factors do not directly cause JIA, they can make the body susceptible to environmental factors such as infection by viruses or bacteria that, in turn, trigger the disorder. Various infections are believed to play a role in JIA, including enteric infections, parvovirus B19, rubella, mumps, hepatitis B, Epstein-Barr virus, mycoplasma, and chlamydia infections.^5,6 

How does joint inflammation arrive?

Environmental and genetic factors, along with viruses, bacteria, or autoimmune responses, will first activate T-lymphocytes (white blood cells) and cause them to release signalling molecules called cytokines. These activated T-lymphocytes and cytokines will then play a role in damaging the joints. Macrophages (immune cells), in response to the release of cytokines, will produce pro-inflammatory cytokines such as interleukin (IL) 1 and 6, and tumor necrosis factor (TNF)-α. These will then also contribute to inflammation and tissue damage in the joints.^5,6 

Chemical markers of Inflammation

Acute markers are blood tests used to assess the level of inflammation in the body. When the body releases pro-inflammatory cytokines, it will increase acute phase markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The rising levels of inflammation will cause an increase in the synovial fluid within the affected joints. Synovial fluid is a lubricating fluid found in joints, and an increase in its volume can be a sign of inflammation within the joint. Synovitis is an inflammation of the synovial membrane lining the joint, and it is characterised by enlargement of the villi within the synovium (villous hypertrophy) and increased blood flow (hyperaemia) in the tissue beneath the synovium. The proportion of T-lymphocytes in synovial fluids can vary among different JIA subtypes, which may contribute to differences in treatment responses among these subgroups

Risk factors for developing the condition may include a family history of arthritis or an autoimmune disorder.⁵ 

Diagnosis

If patients come with symptoms such as joint inflammation, fever, stiffness, or rashes, then they should be brought in to get X-rays and lab tests to be officially diagnosed. Diagnosing JIA relies on clinical criteria, and the process can be delayed due to the disease's gradual progression and the lack of specific lab tests. Various measures, such as visual scales, joint assessment, and specialized scores, are used to gauge disease activity in JIA patients. It is important to note that in 25% of JIA cases, the patient does not report pain, but swelling is simply observed.⁵

Treatment

The most effective strategy for handling a child diagnosed with JIA involves a diverse team of experts, including a paediatric rheumatologist, ophthalmologist, orthopaedic surgeon, specialized nurse, physical therapist, occupational therapist, and psychologist.

Effective treatment for Juvenile Idiopathic Arthritis (JIA) is crucial, focusing on pain control, preserving joint function, achieving disease remission, managing systemic complications, and supporting normal development. Regular assessment of disease activity and patient compliance is essential for optimising treatment goals. Various medications are safe and effective in paediatric rheumatology. There are Biologic DMARDs (Disease-Modifying Antirheumatic Drugs) such as Anakinra that will, for example, specifically target and block the action of interleukin-1 (IL-1) responsible for causing joint inflammation and pain. Non-biologic DMARDs such as Sulphasalazine and Leflunomide also inhibit enzymes, which will prevent certain immune responses.⁵ 

Ongoing research and advancements

Finally, the introduction of innovative biological treatments, early and aggressive intervention strategies, and precise steroid injections directly into affected joints have significantly enhanced the outlook for JIA. However, despite these advancements, some patients still experience active and progressing disease. Various JIA subtypes have different prognoses, requiring tailored monitoring and intervention, particularly for those at higher risk. While biological therapies are generally effective and safe, there's an increased risk of infections. The connection between TNF blockers and childhood malignancy is not firmly established, and psychosocial support can enhance treatment outcomes. Furthermore, JIA patients are more susceptible to cardiovascular issues, emphasizing the importance of routine heart screening.⁵ 

Conclusion

To conclude, we have seen that Juvenile Idiopathic Arthritis (JIA) encompasses various forms of childhood arthritis, most of which involve autoimmune and autoinflammatory responses. JIA can manifest symptoms like joint pain, swelling, fever, and fatigue, making daily activities challenging. The disease's types, including Oligoarticular, Polyarticular, Systemic, and Enthesitis-related arthritis, present different clinical profiles. The causes of JIA are multifactorial, involving genetic factors and environmental triggers like infections. Inflammation in the joints is driven by T-lymphocytes and cytokines, leading to elevated markers of acute inflammation and synovial changes. Risk factors include a family history of arthritis or autoimmune disorders.

Diagnosis relies on clinical criteria and may involve X-rays and lab tests. Treatment is multidimensional, aiming to control pain, preserve joint function, achieve remission, manage complications, and support normal development. Medications like Biologic and Non-biologic DMARDs play a vital role in symptom management. Advancements in JIA treatment, including biological therapies, early interventions, and targeted steroid injections, have improved outcomes. Tailored monitoring and psychosocial support can enhance treatment success, while routine heart screening is essential due to increased cardiovascular risk among JIA patients. Continued research and innovation offer hope for further progress in managing this complex condition.⁵

This table here summarises the different features of JIA: