CNS Involvement in HLH (CNS-HLH)

CNS disease is considered to be a result of the pathologic immune response in HLH. CNS involvement is frequently found at diagnosis or can occur anytime in the further course of systemic HLH but has also been reported as primary or only manifestation. Diagnosis is based on the presence of neurological symptoms and abnormalities on neuroradiological imaging and a pathological cerebrospinal fluid analysis. Due to the unspecific clinical picture and the wide spectrum of neuroradiological findings, a variety of other inflammatory conditions and vascular diseases of the CNS have to be considered in the differential diagnosis, especially in cases in which no systemic HLH features are present. The devastating effect of ongoing inflammation in the CNS can lead to increased mortality and major long-term consequences. Therefore, rapid diagnosis and treatment are mandatory. Patients with CNS-HLH should be given systemic HLH treatment without delay. Although not evaluated systematically, it is also accepted that these patients benefit from intrathecal administration of MTX and steroids. Early stem cell transplant in genetic disease has also been shown to halt CNS disease and prevent further sequelae.