Encephalitis and encephalopathy in children represent a diagnostic challenge. We describe a patient with relapsing encephalitis in whom the differential diagnosis included acute disseminated encephalomyelitis, human herpesvirus 6 encephalitis, and hemophagocytic lymphohistiocytosis (HLH). Because of its rarity, HLH is often overlooked as a differential diagnosis in encephalitis, especially in the isolated CNS forms. As this case illustrates, inborn errors of immunity can underlie isolated encephalitis and should be included in the differential diagnosis of these presentations. Background Pediatric neuroinflammatory diseases represent a heterogeneous group of immune-mediated conditions affecting the CNS, including demyelinating diseases, autoimmune encephalopa-thies, autoinflammatory conditions, and neurodegenerative diseases. Among these falls acute disseminated encephalomyelitis (ADEM), an inflammatory, demyelinating condition usually affecting children and young adults days to weeks after an acute infection or vaccination. It is characterized by multifocal or diffuse gray and white matter damage and increased intensity lesions on T2/fluid-attenuated inversion recovery (FLAIR) MRI sequences. The hypothesized pathogenesis is immune-mediated white matter damage triggered by an acute infection, followed by a secondary autoimmune response, with lymphocyte and macrophage infiltration of perivascular regions. Viral encephalitis is one differential diagnosis in children presenting with symptoms compatible with ADEM. Human herpesvirus 6 (HHV-6) is a common cause of febrile seizures in children and can cause infectious encephalitis, more often in immunocom-promised patients. 3CNS manifestation of HHV-6 may or may not present with abnormal findings on MRI, and the imaging pattern is related to the immune status of the patient. Typical findings in the immunocompromised patient include hyperintense signal on the T2- and FLAIR-weighted sequences in the mesiotemporal regions, with or without diffusion restriction, and usually without enhancement. Nonimmunocompromised patients may present with a pattern of widespread T2 hyperintensities and areas of subcortical diffusion restriction. Of interest, HHV-6 infection has been described in association with ADEM and other forms of autoimmune encephalitis. CNS inflammation is also a common feature of hemophagocytic lymphohistiocytosis (HLH), a life-threatening systemic inflammatory disease due to a genetic (primary HLH) or acquired cause (secondary HLH), characterized by lymphocyte and macrophage activation and multiorgan infiltration. We here describe the diagnostic process and clinical course of a child with HLH presenting with 2 episodes of encephalitis and HHV-6 infection to highlight the importance of searching for underlying inborn errors of immunity (IEIs) in children presenting with various forms of encephalitis.
NSTL
Lippincott Williams & Wilkins
