Review an interesting case of a rare disease, its associated complications, and the relevant literature.

Dipeptidyl-peptidase-like protein-6 (DPPX) antibody-associated encephalitis is a rare disease that presents with a triad of central nervous system hyperexcitability, weight loss and diarrhoea. The clinical course is protracted. Rarely there is an association with B-cell neoplasms. Immunotherapy is recommended to manage anti-DPPX encephalitis, though treatment duration and long-term outcomes are less certain, and relapses are common.

Review of case notes and literature.

A 54-year-old man presented with three months of abdominal pain, diarrhoea and 38 kg of weight loss. He was recently diagnosed with chronic lymphocytic leukaemia (CLL), managed conservatively due to minimal disease activity. While admitted in hospital for gastrointestinal investigations, over three days he became encephalopathic with hallucinations, tonic-clonic seizures, and then status epilepticus. He was admitted to the intensive care unit and received anti-seizure medication. Magnetic resonance imaging showed mild diffuse cortical hyperintensities, consistent with encephalitis. Cerebrospinal fluid revealed a lymphocytic pleocytosis (53 white cells, predominantly lymphocytes) and DPPX antibodies were positive. He was treated with high-dose intravenous methylprednisolone and intravenous immunoglobulin. His hallucinations and gastrointestinal symptoms resolved. His cognitive deficits persisted, scoring 60/100 on the Addenbrooke’s cognitive examination (ACE-III) after two weeks of treatment. He received weekly rituximab for four weeks. Two months later his ACE-III improved to 72/100. He commenced ibrutinib, but 18 months later he re-presented with an anti-DPPX encephalitis relapse. This was treated with high-dose intravenous methylprednisolone and plasmapheresis, with modest improvement in symptoms. Though his CLL remains indolent, there is a plan to re-start rituximab with venetoclax, in an attempt to prevent further encephalitis relapses.

This case highlights the classic presentation of anti-DPPX encephalitis, its association with B-cell neoplasms, and propensity for recurrence. There are acute and long-term management issues to consider when treating rare autoimmune conditions.