Haemophagocytosis and encephalitis in chronic lymphocytic leukaemia

Abstract

A 77-year-old man was hospitalized with progressive confusion and gait disorder of 3 weeks duration. He had been diagnosed with quiescent chronic lymphocytic leukaemia (CLL) 5 years previously without having required treatment. Examination showed fever, confusion, a right hemiparesis and ataxia. A full blood count showed: leucocytes 24·3 × 109/l (neutrophils 1·4 × 109/l, lymphocytes 22·6 × 109/l), haemoglobin concentration 110 g/l and platelet count 57 × 109/l. Serum ferritin was increased to 669 μg/l (normal < 400). Other laboratory tests, including fibrinogen concentration, triglycerides, soluble CD25, lactate dehydrogenase and transaminases levels, were normal. Magnetic resonance imaging (MRI) of the brain showed multiple hyperintensities on fluid-attenuated inversion recovery (FLAIR) sequences spanning the periventricular white matter, corpus callosum, basal ganglia, left internal capsule, midbrain and cerebellum (left). There was a subtle perivascular enhancement on gadolinium. Cerebrospinal fluid (CSF) analysis showed pleocytosis (140 cells/μl) with 85% lymphocytes, a high protein of 0·74 g/l and normal glucose. Despite an extensive workup, no infectious aetiology was identified on CSF testing. Blood cultures were repeatedly negative. Epstein‒Barr virus (EBV) polymerase chain reaction (PCR) on peripheral blood showed 1477 copies/ml and a low-grade EBV reactivation was diagnosed. PCR on the CSF for other herpes virus, flavivirus, enterovirus and EBV was negative. A bone marrow aspirate was hypercellular with a normal number of megakaryocytes and stable CLL. Histiocytes were seen (<0·5% of cells), of which 80% were observed to have engulfed mainly numerous CLL lymphocytes (top right), but also erythroid cells (bottom right). Further diagnostic images are shown in Appendix S1. Whole body positron emission tomography‒computerized tomography (PET-CT) scanning showed no change in the number, size or metabolic activity of lymph nodes or spleen. Vaccination against influenza 1 week before the clinical onset led us to consider a diagnosis of acute disseminated encephalomyelitis (ADEM). The patient was started on intravenous corticosteroids then intravenous immunoglobulin, with progressive clinical, CSF and MRI improvement and normalization of platelet count within 2 weeks. Histiocytes engulfing numerous lymphocytes is an unusual observation. It has rarely been associated with haemophagocytic lymphohistiocytosis (HLH) in CLL. However, the findings of this patient do not meet the diagnostic criteria of HLH. ADEM is a potentially severe inflammatory demyelinating immunomediated cerebral condition triggered by infection or vaccination. ADEM must be differentiated from infectious encephalitis as the treatment is different. CLL is associated with various immunological complications but the coincidence of haemophagocytosis and ADEM is rare. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.