Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis

AbstractIsolated neuroinflammatory disease has been described in case reports of familial hemophagocytic lymphohistiocytosis (FHL), but the clinical spectrum of disease manifestations, response to therapy and prognosis remain poorly defined. We combined an international survey with a literature search to identify FHL patients with (i) initial presentation with isolated neurological symptoms; (ii) absence of cytopenia and splenomegaly at presentation; and (iii) systemic HLH features no earlier than 3  months after neurological presentation. Thirty-eight (20 unreported) patients were identified with initial diagnoses including acute demyelinating encephalopathy, leukoencephalopathy, CNS vasculitis, multiple sclerosis, and encephalitis. Median age at presentation was 6.5 years, most commonly wit h ataxia/gait disturbance (75%) and seizures (53%). Diffuse multifocal white matter changes (79%) and cerebellar involvement (61%) were common MRI findings. CSF cell count and protein were increased in 22/29 and 15/29 patients, respectively. Fourteen patients progressed to systemic inflammatory dise ase fulfilling HLH-2004 criteria at a mean of 36.9 months after initial neurological presentation. Mutations were detected inPRF1 in 23 patients (61%),RAB27A in 10 (26%),UNC13D in 3 (8%),LYST in 1 (3%), andSTXBP2 in 1 (3%) with a mean interval to diagnosis of 28.3  months. Among 19 patients who underwent HSCT, 11 neurologically improved, 4 were stable, one relapsed, and 3 died. Among 14 n...
Source: Journal of Clinical Immunology - Category: Allergy & Immunology Source Type: research