Pediatric CNS-isolated hemophagocytic lymphohistiocytosis

Abstract

ObjectiveTo highlight a novel, treatable syndrome, we report 4 patients with CNS-isolated inflammation associated with familial hemophagocytic lymphohistiocytosis (FHL) gene mutations (CNS-FHL).MethodsRetrospective chart review.ResultsPatients with CNS-FHL are characterized by chronic inflammation restricted to the CNS that is not attributable to any previously described neuroinflammatory etiology and have germline mutations in known FHL-associated genes with no signs of systemic inflammation. Hematopoietic stem cell transplantation (HCT) can be well tolerated and effective in achieving or maintaining disease remission in patients with CNS-FHL.ConclusionsEarly and accurate diagnosis followed by treatment with HCT can reduce morbidity and mortality in CNS-FHL, a novel, treatable syndrome.Classification of evidenceThis study provides Class IV evidence that HCT is well tolerated and effective in treating CNS-FHL.

A Rare Neurological Presentation of Familial Hemophagocytic Lymphohistiocytosis

“…It may be a presentation of many underlying immune-mediated diseases such as autoimmune gliopathies, small vessel primary angitis of CNS (PACNS), CNS lymphoma, and CNS HLH. Our patient even fulfilled the CLIPPERS criteria proposed by Tobin et al 17 Similar to our case, two pediatric patients who were initially diagnosed as CLIPPERS but later on confirmed as FHLH have been described in the literature by Benson et al 18 However, there were no systemic manifestations of HLH in these patients. Out of the four patients reported by Benson et al of isolated CNS HLH with a primary HLH genetic mutation, one had biallelic PRF1 mutations.…”

“…She met no systemic HLH criteria except decreased NK cell activity. 18 Despite inadequate immunosuppressive therapy for HLH, our patient initially did show partial response and thereafter had prolonged periods of remission in between episodes. In adult cases of PACNS, primary CNS lymphoma and CNS lymphomatoid granulomatosis initially presenting with CLIPPERS features, including histological characteristics, have been reported.…”

Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO)

“…However, patients may also rarely present with isolated CNS inflammation, without complete or even any systemic signs of HLH. Though rare, this isolated disease is an important forme fruste of HLH, which often presents insidiously with patients experiencing substantial delays in diagnosis . Cerebrospinal fluid analysis shows pleocytosis and hyperproteinemia, and brain biopsy reveals T‐cell and histiocytic infiltrates.…”

Haematopoietic Stem Cell Transplantation for Primary Haemophagocytic Lymphohistiocytosis

“…Early intervention with CNS directed therapy appears key. HSCT is curative in these cases, but cannot revert manifest CNS damage (47).…”