Background and Aims

Background

Familial hemophagocytic lymphohistiocytosis (FHL) is caused by defective cytotoxicity of CD8+ T and NK cells, which leads to uncontrolled activation of T cells and macrophages.

Aims

The description of an uncommon presentation of FHL in a 62 years old woman.

Methods

Patients and Methods

We report the case of a patient referred for evaluation to our clinic by a history of a cerebellar syndrome of subacute onset, with inflammatory lesions of the brain and posterior fossa that improved after corticosteroid treatment. During these episodes, the patient presented as well pancytopenia and hepatosplenomegaly, without signs of hemophagocytosis in bone marrow, not fulfilling other HLH criteria. After evaluation in clinic, we performed an inmunological study, including immunophenotyping, perforin expression and degranulation assessment. Genetic study was performed by Next Gen Sequencing (NGS) with a customised panel of more than 400 genes, including all described immunodeficiencies.

Results

Results

Our patient has no significant elevation of soluble CD25. Presented greatly reduced numbers of NK cells, with normal perforin expression but displayed defective degranulation with impaired NK cells expression of surface CD107a upon K562 cell-mediated stimulation. The genetic study revealed a homozygous mutation in the STXBP2 gene.

Conclusions

Conclusions

FHL is commonly seen in the paediatric age with intense and eventually life-threating instauration of HLH that requires intense immunosupression. Atypical forms with CNS presentation and no systemic expression have been described in literature. Clinical onset in adulthood is clinically challenging and requires for adult specialist, as in this case, a high level of awareness.