DENVER — Neuropsychiatric lupus is “arguably the least understood manifestation” of systemic lupus erythematosus (SLE) in children, with patients facing substantial barriers and experiencing highly variable clinical practices in the absence of consensus guidelines, according to research presented at CARRA 2025: Childhood Arthritis and Rheumatology Research Alliance Annual Scientific Meeting.
Only 5% of respondents felt completely confident evaluating neuropsychiatric SLE (NPSLE) in the study survey, and the top barriers cited focused on waiting time to access psychology, psychiatry, and neuropsychology, the researchers found. The results reveal a need for consensus guidelines to standardize evaluation and management of NPSLE in youth, the authors concluded.
“There are significant knowledge gaps in NPSLE in children regarding the prevalence, timing of presentation, clinical manifestations, risk factors, diagnosis, management, and outcomes,” lead author Martha Rodriguez, MD, an assistant professor of clinical pediatrics in rheumatology at Indiana University School of Medicine and Riley Children’s Health, both in Indianapolis, told Medscape Medical News. “Most of the current evidence of pediatric NPSLE is mainly extrapolated from adult studies,” and primarily from retrospective, single-center studies with low-quality evidence.
Although the American College of Rheumatology issued guidance in 1999 on NPSLE, these guidelines are not specific to pediatric patients, co-author Ekemini A. Ogbu, MD, MSc, an assistant professor of pediatrics at the University of Cincinnati, director of Neuroinflammatory Disease Services in Rheumatology, and co-director of the Cincinnati Children’s Lupus Center in Cincinnati, told Medscape Medical News. Although a CARRA Mental Health Workgroup recently developed consensus recommendations for mental health screening, diagnosis, and treatment that are relevant to pediatric patients with lupus, a need still exists for “how to address and integrate the multidisciplinary care necessary for these patients,” Ogbu said.
Several other organizations have included mention of neuropsychiatric manifestations of lupus in guideline documents, but no consensus guidelines exist specifically for children, leaving a “critical need for pediatric-specific guidelines and treatment for children with NPSLE,” said senior author Andrea Knight, MD, MSCE, the Canada Research Chair in Mental Health and Chronic Disease of Childhood Clinician Investigator at The Hospital for Sick Children and an associate professor of pediatrics at the University of Toronto, both in Toronto, Ontario, Canada.
“The brain is still developing in childhood and adolescence, and we do not really know what the impact of lupus inflammation and treatment is on the brain during this vulnerable time,” Knight said. She and Ogbu are leading a study of children in the CARRA SLE registry to better understand NPSLE.
Survey Finds Limited Access to Care, Little Time for Assessments
Among 512 eligible respondents, 29% completed the survey designed by the CARRA NPSLE Workgroup and conducted in July to November 2024. Respondents included 149 CARRA member physicians, nurse practitioners, and physician assistants who actively care for children with SLE.
Among the 15 barriers assessed on a Likert scale in the survey, members rated the waiting time to access neuropsychology as the highest barrier, with 45% of members saying it’s “always” a barrier to care, and more than 30% of others saying it “often” is. Waiting time to access psychiatry was cited as “always” a barrier by 35% of respondents, and “often” by about 37%, and waiting time to access psychology had similar responses.
Having limited time during the clinical encounter to assess neurocognitive dysfunction was always a barrier for about 18% of respondents and often a barrier for another 38%. Although more than 40% of respondents said the lack of protocol guidelines was only sometimes a barrier to care, about 13% said it always is and about 37% said it often is.
In terms of initial NPSLE evaluation practices, 90% conducted routine testing for antiphospholipid antibodies, 46% for anti–ribosomal P, 18% for anti-neuronal antibodies, 10% for aquaporin 4 antibodies, and 4% for antiganglioside antibodies. About 1 in 5 (19%) obtained cerebrospinal fluid for analysis in patients with suspected NPSLE, whereas 41% used neuroimaging — primarily brain MRI, magnetic resonance angiography, and magnetic resonance venography with and without contrast (46%), followed by brain MRI with and without contrast (43%) — and 22% used advanced neuroimaging (brain single-photon emission CT, magnetic resonance spectroscopy, PET, or functional MRI). However, 31% lacked access to advanced neuroimaging at their institution, and 52% were unfamiliar with the indications or interpretation of these modalities.
Over half the clinicians (57%) screened for mood disorders in all patients with NPSLE, but only 7% of providers had easy access to neuropsychology and only 10% to psychiatry.
Lack of Access Compounds Complexity of Patients’ Clinical Scenarios
“We clearly have an access problem,” Rebecca E. Sadun, MD, PhD, an associate professor of medicine and pediatrics in rheumatology and immunology at Duke University School of Medicine, Durham, North Carolina, told Medscape Medical News about the findings. The long waiting times for specialists “reflects a known shortage of mental health providers and interferes with the care of lupus patients, including helping to differentiate between cSLE [childhood-onset SLE] patients experiencing cognitive and psychological symptoms due to inflammation in the brain and those experiencing symptoms due to depression and anxiety — all of which stems from the underlying diagnosis and all of which requires timely access to mental health care,” said Sadun, who was not involved in this research.
Sadun found it “staggering” that only 5% of providers felt completely confident in evaluating patients for NPSLE and noted that it’s “likely in part due to the complexity of these clinical scenarios” while also highlighting “the need for additional research and education on NPSLE, so that clinicians can follow more clear guidance on the evaluation and treatment of neuropsychiatric symptoms in patients with lupus.”
The complexity arising from the heterogeneity of neuropsychiatric manifestations in lupus is one reason it’s so poorly understood, Ogbu said, noting that 19 distinct syndromes have been described in NPSLE. “In children, an additional concern is that there are probably other ways that the brain is affected, particularly developmentally, which are not captured within these 19 syndromes,” she said.
Rodriguez further noted that the symptoms can be highly variable, including headaches, mood disorders, cognitive impairment, seizures, psychosis, and even strokes, and it’s difficult to distinguish these as arising from NPSLE vs “primary psychiatric or neurological disorders, medication-related side effects such as steroid-induced psychosis or steroid-induced mood swings, or psychosocial factors related to the burden of having a chronic disease.” With no definitive, objective tests to diagnosis NPSLE, it’s primarily a diagnosis of exclusion with a largely unknown pathogenesis, Rodriguez added.
Although an understanding of the differences in NPSLE between adults and children is still evolving, “the evidence has shown that neuropsychiatric involvement occurs more frequently and aggressively among children and adolescents as compared to patients with adult-onset SLE,” Rodriguez said. That makes multidisciplinary assessment and care even more important since it can affect children’s schooling, educational outcomes, and attainment of financial independence, Ogbu added.
Standardized treatment protocols for NPSLE in children do not exist, and treatments are often the same in children as in adults, but these involve high doses and long courses of steroids, “which can impact children differently in terms of growth and development in addition to the usual adverse effects of steroids,” Knight said. “Also, children with NPSLE tend to be adolescents who are struggling with coping the disease and undesirable steroid effects — weight gain, acne, stretch marks, emotional distress — during a very challenging period of adolescent social development. Developing steroid-sparing treatment strategies for children with NPSLE is really important to improve quality of life and outcomes for these patients.”
The research was supported by CARRA and the Arthritis Foundation. Ogbu is a member of the Pediatric Rheumatology Collaborative Study Group and consulted for Cartesian Therapeutics. No other authors reported disclosures.