A case of VEXAS syndrome associated with EBV-associated hemophagocytic lymphohistiocytosis

• DOI: 10.1016/j.bcmd.2021.102636
• Publication Date: 2021-11-30T19:09:53Z
• Authors: Roy L. Kao; Audrey A. Jacobsen; Charles J. Billin...; Sophia L. Yohe; Amy K. Beckman; Gregory M. Vercel...; David R. Pearson
• Keywords: Male; Epstein-Barr Virus Infections; Herpesvirus 4, Human; 0303 health sciences; 03 medical and health sciences; Myelodysplastic Syndromes; Humans; Middle Aged; Rituximab; Lymphohistiocytosis, Hemophagocytic; 3. Good health

Vacuoles, E1, X-linked, autoimmunity, somatic (VEXAS) syndrome is characterized by a pathogenic mutation in UBA1, which leads to protean complications including autoimmunity and myelodysplasia. A 56-year-old man with steroid-dependent, later steroid-refractory cutaneous polyarteritis nodosa and Sweet syndrome developed recurrent daily fever, macrocytic anemia, thrombocytopenia, acute hypoxic respiratory failure, and anasarca. He was eventually diagnosed with Epstein-Barr virus (EBV) viremia and hemophagocytic lymphohistiocytosis (HLH). He improved clinically with rituximab, ruxolitinib, and increased glucocorticoids before expiring from Pseudomonas sepsis. UBA1 exon 3 mutational analysis in myeloid enriched peripheral blood revealed a c.122T>C (p.Met41Thr) pathogenic variant, consistent with VEXAS syndrome. We describe the first case of EBV-associated HLH in a patient diagnosed with VEXAS syndrome. Early identification of this syndrome will be important in order to offer potential therapies before life-threatening complications arise.