Background: Chronic lymphocytic infiltration with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a neuro-inflammatory syndrome first described in 2010. It has a relationship with lymphoproliferative disorders that has not been fully elucidated. This case represents an unusual progression of CLIPPERS to Epstein-Barr Virus (EBV)-related lymphomatoid granulomatosis (LYG). The exact connection between CLIPPERS and LYG remains poorly understood.
Case presentation: We present a case of a 75-year-old man who was diagnosed with CLIPPERS with initial response to immunosuppression but later progressed to EBV-related LYG. EBV polymerase chain reaction (PCR) was detected in his cerebrospinal fluid (CSF), and repeat imaging revealed findings that were uncharacteristic for CLIPPERS; thereby prompting a brain biopsy which led to a diagnosis of EBV-related LYG. This case highlights the following learning points: 1) CLIPPERS cases are often part of a spectrum of lymphomatous disease, 2) CLIPPERS can be associated with EBV-related lymphoproliferative disorders such as LYG, and 3) EBV detection in CSF should prompt earlier consideration for brain biopsy in patients.
Conclusions: Our case highlights the difficulty in distinguishing CLIPPERS from other steroid-responsive conditions such as neoplastic and granulomatous diseases. Given the association of CLIPPERS with EBV-related LYG as demonstrated in this case, we recommend testing for EBV in CSF for all patients with suspected CLIPPERS. An early referral for brain biopsy and treatment with rituximab should be considered for patients with suspected CLIPPERS who test positive for EBV in their CSF.
Keywords: CLIPPERS; Chronic lymphocytic infiltration with pontine perivascular enhancement responsive to steroids; EBV; Epstein-Barr Virus; LYG; Lymphoma; Lymphomatoid granulomatosis.