Adult-onset CLIPPERS with systemic Hemophagocytic Lymphohistiocytosis related to PRFN1 mutation: A case report. (P4-5.032)

Abstract

<h3>Objective:</h3> NA <h3>Background:</h3> 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. <h3>Design/Methods:</h3> In a patient with CLIPPERS features, genetic analysis of genes implicated in familial HLH was performed, and systemic HLH criteria were searched. <h3>Results:</h3> 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 <i>PRFN1</i> 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. <h3>Conclusions:</h3> We describe the first case of adult-onset CLIPPERS accompanied by systemic HLH in the setting of <i>PRFN1</i> 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. <b>Disclosure:</b> Dr. Lemarchant has nothing to disclose. The institution of Dr. De Saint Basile-Chazelas has received research support from LHF espoir: patient association. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for BIogen Idec. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for novartis. Helene Zephir has received personal compensation in the range of $0-$499 for serving as a Consultant for BMS. Helene Zephir has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Julie Boucher has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Julie Boucher has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Julie Boucher has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Julie Boucher has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Julie Boucher has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis . Julie Boucher has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Guillaume Taieb has nothing to disclose.