P137 Growing up on biologics: a case report of development of NMDAr encephalitis in a young person with JIA on abatacept
Authors: Close Rosie , Bale Peter , Gallagher Kathy , Ambegaonkar Gautam , Rossor Thomas , Abbassi Natalie , Armon Kate 
Published: April 2020

Background

A 12-year-old female with JIA on biologic medication (IV abatacept every three weeks) presented with a first generalised tonic-clonic seizure on background of preceding headache and fatigue. The seizure self-terminated but disorientation and encephalopathy ensued. MRI brain demonstrated lesions with high signal intensity in the left periventricular and right occipital regions. The clinical picture and radiological imaging suggested a broad differential diagnosis including CNS infection, JC virus associated progressive multifocal leucoencephalomalacia (PML), acute disseminated encephalomyelitis (ADEM) and Anti-N-methyl-d-aspartate receptor (NMDAr) encephalitis. She was commenced on IV ceftriaxone, acyclovir and clarithromycin. All bloods including inflammatory markers and infection serology were unremarkable. CSF was acellular and JC virus PCR negative. NMDAr encephalitis was initially considered unlikely (pre-existing immunosuppression, abnormal MRI brain and no evidence of ovarian teratoma on abdominal MRI pelvis). However more classical clinical features developed including further seizures, significant movement disorder, cognitive dysfunction, sleep and speech dysfunction. Anti-NMDAr antibodies in both serum and CSF were positive. She made a good recovery following IV steroids, plasmapheresis and rituximab and was discharged home after a 10-week admission. NMDAr encephalitis developed three years after commencing abatacept treatment. Previous immune modulating treatment included methotrexate (since age 2 years), Etanercept (age 5-8 years) and Tocilizumab (aged 8-10 years). Flares of disease following a period of control necessitated the changes in therapy.

Methods

A literature review was conducted to explore the relationship between NMDAr encephalitis and biologic medication. A yellow card report and information request to abatacept manufacturer were also submitted.

Results

No previous cases of NMDAr encephalitis in patients on abatacept or paediatric cases related to biologic therapy are described. There are reports of adults developing NMDAr encephalitis on Adalumimab for Crohn’s disease and etanercept for rheumatoid arthritis. NMDAr encephalitis has also been described in patients on immune checkpoint inhibitors for malignant melanoma (nivolumab and ipilimumab). Known triggers of production of anti-NMDA receptor antibodies include tumours (ovarian teratoma; rarely associated in patients under 12 years) and viral infections. Developing autoimmune disorders on biologic medication is well reported, most notably psoriasis and inflammatory bowel disease. In relation to abatacept specifically, the development of anti-nuclear antibodies (ANA) and psoriasis have been described. However, patients with autoimmune disorders are known to be of increased risk for additional immune disease. A new cohort of patients are emerging who have received multiple biologic medications and the development of autoimmune conditions despite immunosuppression needs to be considered.

Conclusion

We describe the first case of NMDAr encephalitis occurring in a child on abatacept therapy, and the first case in JIA. We are unable to determine what contribution a history of autoimmune disease or immunomodulating therapy has made on its development in this case.

Disclosures

R. Close: None. P. Bale: None. K. Gallagher: None. G. Ambegaonkar: None. T. Rossor: None. N. Abbassi: None. K. Armon: None.