Rapidly Progressive Aneurysmal Disease Associated with Epstein Barr Virus-Positive Lymphoproliferative Disease in a CVID patient with NFKB-1 Mutation

Abstract

IntroductionCommon variable immunodeficiency (CVID) is a genetically heterogeneous group characterized by hypogammaglobulinemia and poor immune response to vaccines. CVID patients are at higher risk for autoimmune diseases or malignancy. We demonstrate a rare case of a patient with CVID (NFKB-1 mutation) presenting with features of vasculitis and rapidly progressive aneurysmal disease secondary to an Epstein Barr Virus (EBV)-associated lymphoproliferative disorder. Case descriptionA 36-year-old man with CVID presented with hoarseness and left vocal cord paralysis. Imaging revealed an aortic arch and descending thoracic aorta abnormality concerning for a plaque, vasculitis or focal thrombosed dissection. He later devloped severe back pain and imaging studies demonstrated an abdominal aortic aneurysm, thickening of the common iliac arteries and a focal aneurysm of the right common iliac artery. PET CT scan showed uptake in the upper abdominal aorta extending to the right renal artery and the distal abdominal aorta near the bifurcation extending to the right common iliac artery, concerning for large vessel vasculitis. He was started on high-dose steroids for large vessel vasculitis. One month later, he was hospitalized for disseminated histoplasmosis and disseminated varicella zoster virus (VZV) and started on amphotericin B and acyclovir with steroid taper. Whole exome next-generation sequencing (NGS) revealed NFKB-1 mutation consistent with CVID-12 with autoimmunity. He later developed worsening back pain prompting repeat imaging which showed further progression of his aneurysmal disease. He was also found to have EBV viremia with a titer of 33,700 IU/mL. A left superior gluteal artery biopsy was performed which showed evidence of an EBV+ lymphoproliferative disorder with concern for an EBV-positive fibrin-associated diffuse lymphoproliferative B-cell lymphoma (DLBCL). DiscussionCVID-12 is an autosomal dominant disease resulting from a mutation in NFKB-1. This mutation leads to an impaired immune response associated with recurrent infections and approximately 20% of patients developing lymphomas at some point in their lifetime. However, there are few case reports of CVID associated large vessel aneurysms or vasculitis. Our patient with CVID demonstrated a rare presentation of an EBV-positive lymphoproliferative disorder driving progression of large vessel disease.