Adult-onset CLIPPERS with systemic Hemophagocytic Lymphohistiocytosis related to PRFN1 mutation: A case report.
Bruno Lemarchant1, Genevieve de Saint Basile2, Helene Zephir1, Julie Boucher1, Guillaume Taieb3
1CHU Lille, 2Hôpital Necker, APHP, 3CHU Montpellier
Background:
Recently, in a cohort of patients presenting with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), one third exhibited familial hemophagocytic lymphohistiocytosis (HLH) gene mutations. As none of them displayed systemic signs of HLH, implication of these mutations in the pathophysiology of CLIPPERS remains to be established.
Design/Methods:
In a patient with CLIPPERS features, genetic analysis of genes implicated in familial HLH was performed, and systemic HLH criteria were searched.
Results:
A 43-year-old man, with a medical history of macrophagic activation syndrome of unknown origin, presented with clinical and radiological features of CLIPPERS. Genetic analysis revealed a PRFN1 mutation, and ancillary tests showed multiple mediastino-hilar lymph nodes on PET scan. Nodal biopsy showed a lymphohistiocytic infiltrate together with aggregates of histiocytes resembling loose granulomas. Evolution was favorable under steroid sparring therapy with Infliximab and Methotrexate.
Conclusions:
We describe the first case of adult-onset CLIPPERS accompanied by systemic HLH in the setting of PRFN1 mutation. Interestingly, histological findings in lymph nodes match with those described in brain biopsy of CLIPPERS patients. Thus, we speculate that CLIPPERS features in mutated patients might be a central nervous system (CNS) expression of HLH. The CNS-restricted manifestations in some mutated patients could be due to other genetic and/or environmental factors. The genetic diagnosis of these patients is needed to better describe their phenotype and propose the appropriate treatment.