By Prof Hans Nossent MD, PhD, FRACP   

Juvenile idiopathic arthritis (JIA) is the umbrella term for the various types of chronic arthritis in children. JIA is a complex autoimmune disease where genetic susceptibility and environmental triggers (yet to be identified) lead to an overactive immune response that culminates in chronic joint inflammation, dysfunction, and deformity.

Treatment for JIA often entails the long-term use of various immune-modulating drugs. These drugs can be an incredibly important intervention to help control the disease process. However, they carry risks for significant side effects, including opportunistic infections, stunted growth, reduced fertility, and weight gain.

JIA is a diverse condition that is more frequent in girls than boys and can present in various forms including, but not limited to the following:

• Monoarthritis –affecting a single joint.
• Oligoarticular – the most common type of JIA, affecting a few large joints;
• Polyarthritis –affecting multiple joints – usually five or more.
• Spondylitis –affecting the spine; and
• Systemic JIA or classic Still’s Disease (with high fever, rashes, and arthritis).

In addition, the systemic inflammatory nature of the condition can cause a range of complications outside the joints ranging from chronic anaemia (low level of red blood cells or haemoglobin) to a cytokine storm where signalling proteins called cytokines are produced at an exaggerated rate.

The study of the characteristics of the condition in the JIA population (epidemiological characteristics) varies widely due to differences in genetic background, environmental triggers, and study methodology. High-income countries have reported a JIA prevalence between 16 and 150 per 100,000, but in 1996 a prevalence of 400/100,000 has been reported from Western Australia (WA). This intriguing incongruity remains unresolved as of today.

The outcome in JIA is unpredictable, but more than 50% of patients continue to have lasting symptoms requiring medication. While few Australian data exists, the 2004–05 National Health Survey reported that 22,000 adults ever diagnosed with arthritis in childhood described a persistent disability. This suggests that JIA development in childhood carries long-term physical and socioeconomic consequences and conceivably mental health consequences.

Addressing the late complications of JIA starts by delineating these long-term consequences to find a way forward towards reducing this burden of disease by improving care. Significant changes have taken place in the disease management of JIA with the introduction of effective synthetic disease-modifying drugs in the 1990s and the introduction of biological drugs since 2005.

The Rheumatology team at UWA’s School of Medicine has set out to find answers about the main drivers and consequences of JIA in Western Australia. The research team, which includes Dr Erin Kelty, Prof Charles Inderjeeth, Assoc prof Helen Keen, Prof David Preen, emeritus Prof Prue Manners and Prof Hans Nossent, hope this project will help uncover valuable data about this debilitating childhood disease.

A specific population-level observational cohort study supported by AOWA and Arthritis Australia aims to answer some of the unknowns. The study will follow the disease course in nearly 1,000 persons <17 years of age with a recorded JIA diagnosis in WA Health administrative data over the period 1990-2015. The proposed study is important because it will fill the need for recent and comprehensive Australian data by providing specific epidemiological characteristics of JIA for the first time. Specifically, the data set gathered from the study will allow investigation and identification of potential contributing factors to JIA development, such as (frequent) infections and/or other conditions before the diagnosis of JIA is made.  Furthermore, it will also help to provide accurate estimates for the rate/risk of a range of long-term outcomes such as disease-specific complications, as well as comorbidities (e.g., diabetes, high blood pressure, blood clots, heart disease, severe depression). This will help the development of strategies to prevent the late disease burden of JIA.

Despite lacking detailed medication information, the long observation period covered by the data set will allow us to determine the rate by which comorbidities occur in JIA patients and determine if and what impact changes in disease management have made. The worst possible outcome in JIA is early death, and although unusual in this age group, this study will quantify this risk by comparing age and gender-adjusted mortality rates in JIA with rates in matched controls and the general population and determine. Finally, this study will also examine whether differences in disease frequency and severity exist (in terms of remoteness) to determine if the distance to Perth is a factor in disease outcome.

Expected outcomes of the project that will subsequently be presented here and to local, national and international conferences /scientific journals include:

a) To present current long term Western Australian data of JIA incidence and prevalence based on a large cohort to address the wide variation in reported international data numbers.

b) To describe potential triggering events, e.g. the number and type of severe infections and/or physical trauma in the period before JIA development (“lookback period”).

c) To determine whether a JIA diagnosis increases the likelihood for serious depression requiring admission and/or ED visits for ancillary issues, e.g. accidental or deliberate intoxications.

d) To determine if/how other clinical outcomes have changed over time with newer therapies. This includes the need for joint surgery (synovectomy or replacement), the development of chronic kidney disease, fractures and severe infections.

e) To determine if JIA leads to increased risk for premature death in the longer term and if mortality rates have changed over time.

f) Finally, the data captured by WARDER will allow quantification of direct health care costs associated with JIA in WA.