Lenalidomide-Induced Large Vessel Vasculitis and Pachymeningitis Complicating Treatment of Follicular Lymphoma: A Case Report

Background Lenalidomide is a cornerstone therapy for hematologic malignancies with direct antineoplastic effects via modification of ubiquitin ligation as well as pleiotropic immunomodulatory effects. Increased T cell and natural killer cell proliferation and Th1 polarization induced by lenalidomide with upregulation of pro-inflammatory cytokines IL-2, IL12 and IFN-y is thought to amplify antitumor immune responses.[1] Although confounded by underlying treatment indication, there are reports of secondary autoimmune diseases evolving during therapy with lenalidomide.[2] To our knowledge, no reports have yet described large vessel vasculitis or meningeal involvement.

Case Report A 66-year-old male was hospitalized with acute fever, headache and back pain 1 month after initiation of rituximab and lenalidomide for relapsed lymphoma. Five years prior after diagnosis of stage IVA follicular lymphoma, he achieved complete radiographic remission with bendamustine and rituximab, and further maintenance was deferred. Six months before his hospitalization, he developed abdominal distension with CT findings of bulky diffuse mesenteric and retroperitoneal lymphadenopathy presumed to reflect lymphoma recurrence. At admission, MRI demonstrated new diffuse pachymeningeal thickening and enhancement with scattered nodularity, and restaging CT noted stable lymphadenopathy but new ill-defined perivascular fat stranding and circumferential wall thickening of the aortic arch and left subclavian artery. At time of lumbar puncture for concern of relapsed lymphoma, he received an empiric single dose of intrathecal methotrexate, cytarabine and hydrocortisone. However, extensive microbiologic and malignancy workup subsequently returned negative including 2 bland CSF samples and an unrevealing retroperitoneal lymph node biopsy. He received no other empiric treatment beyond an initial 3 days of antibiotics. His initial CRP of 255 mg/L steadily decreased and normalized over 2 weeks alongside his symptoms. Repeat imaging at 4 weeks from initial presentation demonstrated a reduction in lymphadenopathy, near resolution of aortitis and no significant dural thickening or enhancement. PET CT body scan subsequently found no abnormal FDG avidity to suggest active large vessel vasculitis, meningitis or malignancy.

Conclusion The temporal relationship with lenalidomide exposure and a complete clinical, biochemical and radiographic resolution without ongoing aggressive systemic therapy suggests his large vessel vasculitis and pachymeningitis were caused by lenalidomide. This case is particularly unique as neither manifestation is yet described in the literature. Considering the more typical association of pachymeningitis with small vessel vasculitis,[3] our case may reflect variable vessel vasculitis induced by lenalidomide.

References [1.] Gribben J. J Clin Oncol 2015;33:2803-11. [2.] Montefusco V. Leuk Lymphoma 2014;55:2032-7. [3.] Mekinian A. Medicine 2018;97:e11413.