By Priya van Oosterhout

Graphic design by Lauren Jones

Affecting approximately 1 in 1 000 Canadians,¹ systemic lupus erythematosus (herein referred to as lupus) is a complex, multisystem autoimmune disease. In lupus, the immune system attacks various tissues in the body, resulting in a wide array of symptoms, such as extreme fatigue, seizures, joint pain, and rash.² It is estimated that 20% of lupus cases worldwide are diagnosed in childhood,³ often translating to a lifetime of ongoing treatment. Furthermore, people with childhood-onset lupus tend to have more brain involvement (referred to as neuropsychiatric lupus) compared to those with adult-onset lupus, with higher rates of depression, anxiety, cognitive difficulties, and even psychosis.⁴ All of this begs the question: how does childhood-onset lupus affect brain functioning and development?

This is a question being addressed by Dr. Andrea Knight, a paediatric rheumatologist at the Hospital for Sick Children, and a Canada Research Chair in Mental Health and Chronic Disease of Childhood. Dr. Knight completed her medical education at the Columbia College of Physicians and Surgeons, then went on to pursue her paediatric residency and paediatric rheumatology fellowship at the Children’s Hospital of Philadelphia. While becoming a clinician-scientist was not initially on her radar, she began to notice during her fellowship that many of her rheumatology patients were struggling with mental health. Dr. Knight explains, “We were getting better and better over time at treating the inflammation with new exciting drugs coming out, but there was still a lot of psychological burden for the kids and their families.” Dr. Knight asks: is it because of the stress of having a serious chronic illness like lupus? Or is it that children’s brains are more vulnerable to inflammation? Or could it be both? And how do we improve our treatment for these children?

It remains unclear why patients with childhood-onset lupus have more brain involvement with the disease, and research and treatment hasn’t advanced significantly in this field in the past decades. We know that these symptoms can persist even with aggressive immunotherapy, but until we understand the relationship between lupus and the young brain, the development of specialized therapeutics is not possible.

Now back at the University of Toronto with her own research lab, Dr. Knight is in pursuit of understanding the cognitive deficits associated with childhood-onset lupus. Her team has created a multidisciplinary longitudinal study to paint a comprehensive picture of the adolescent brain with lupus. Employing psychological, pain-related, and cognitive measures, alongside neuroimaging and blood sample analysis, she emphasizes that this study “may end up being one of the largest cohorts in the world with this amount of data for paediatric lupus.” While the work is still ongoing, her lab’s preliminary findings demonstrate an impact of lupus on the brain both structurally and functionally, even in patients without a clinical diagnosis of neuropsychiatric lupus. With a plan to follow her participants for three years, Dr. Knight and her team are hoping to be able to map trajectories for brain function and development in childhood-onset lupus as her participants reach adulthood.

Beyond characterizing how lupus impacts brain functioning and mental health, Dr. Knight has also begun developing and testing interventions to help her patients with these challenges. The first of these interventions was a remotely-delivered cognitive behavioural therapy program called Treatment and Education Approach for CHildhood-onset lupus (TEACH), developed by psychologist Dr. Cunningham based at Michigan State University. Currently being tested internationally at multiple sites, including the Hospital for Sick Children in Toronto, TEACH aims to help people with childhood-onset lupus manage their struggles with depression, fatigue, and pain. Additionally, Dr. Knight and her team are also working on a Canadian-based mindfulness intervention for young patients with juvenile arthritis and their caregivers, which has already been met with a lot of enthusiasm by participants. Though not directly related to lupus, programs like this can be applied across rheumatologic diseases, creating new strategies for mental wellbeing. She adds that it is, “really exciting to be able to take what we initially characterized and then move towards intervention.” While medication is an important aspect of treating mental health, strategies like therapy and mindfulness—which help individuals learn how to manage their own wellbeing—are also essential.          

Dr. Knight is not only conducting her own research here in Toronto: she is also shaping how mental health in paediatric rheumatology is being investigated internationally. She is a member of the Childhood Arthritis and Rheumatology Research Alliance (CARRA), a primarily North American network of clinical providers and researchers. Soon after finishing her fellowship, Dr. Knight established CARRA’s Mental Health Working Group, which in many ways, was the first of its kind. Firstly, she conducted a needs-based assessment across CARRA rheumatologists, surveying her colleagues around the globe about the mental health needs and practices in their clinics. She explains how it was, “very eye-opening to see that most of our rheumatology colleagues thought this was important, but admitted that as a whole, they weren’t really doing a great job of integrating this into care.” From these results and a subsequent systematic review of the literature, Dr. Knight and her team were able to create a prioritized research agenda, ranking mental health research topics in terms of importance, feasibility, and actionability in clinical practice. Some of these prioritized topics include mental health screening, support for patients and families, and identifying the relationship between mental health and chronic inflammatory disease. Creating this prioritized agenda helps ensure that the resources going towards addressing mental health for youth with rheumatologic disease are focused on answering the most critical questions in the field.

                  When asked about the future of research in the field of childhood-onset lupus, Dr. Knight hopes for a better understanding of the interface between paediatric rheumatologic disease and the impact it has on the brain and mental health. She emphasizes the importance of a multidisciplinary approach, stating that, “different expertise and specialists have brought my research to another level in terms of really transcending the existing paradigms to move it forward.” Dr. Knight envisions a future with more targeted tools and interventions, so that rheumatologists around the world can treat their patients in all domains of the disease.

References

1. Ardoin SP, Daly RP, Merzoug L, et al. Research priorities in childhood-onset lupus: results of a multidisciplinary prioritization exercise. Pediatr Rheumatol Online J. 2019;17(1):32. doi: 10.1186/s12969-019-0327-4
2. Lupus Canada. What Is Lupus? [Internet]. Newmarket: Lupus Canada; [cited 2025 Feb 15]. Available from: https://www.lupuscanada.org/what-is-lupus/
3. Lupus Canada. Lupus FAQs: We Asked the Experts [Internet].  Newmarket: Lupus Canada; [cited 2025 Feb 24].  Available from: https://www.lupuscanada.org/lupus-faq/
4. Levy DM, Peschken CA, Tucker LB, et al. The 1000 Canadian faces of lupus: influence of ethnicity on disease in the pediatric cohort. Arthritis Care Res. 2013;65(1):152-160. doi: 10.1002/acr.21779