Novel use of Siltuximab in a patient with VEXAS Syndrome

Abstract

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an increasingly recognized disorder that occurs due to somatic mutations of a ubiquitin-activating enzyme encoded by ubiquitin-like modifier activating enzyme 1 gene, UBA1. Clinical findings associated with VEXAS syndrome include recurrent fevers, polychondritis, periorbital edema, pleural effusions, myocarditis and/or pericarditis, hepatosplenomegaly, myelodysplastic syndrome, cytopenias, inflammatory arthritis, neutrophilic dermatosis, and deep venous thrombosis. Novel renal manifestations like interstitial nephritis are infrequent, and to our knowledge, acute renal failure due to C3 glomerulonephritis (C3GN) has not yet been reported. Overwhelming systemic inflammation can result in morbid end-organ damage and death. While there is no formal guideline or established protocol for its management, treatment of VEXAS syndrome with tocilizumab, an interleukin-6 (IL-6)-directed therapy, has been described in the literature. Here, we report a case of a 71-year-old male patient presenting with C3GN as an initial manifestation of VEXAS syndrome and explore the rationale for our approach to treatment with IL-6 blockade. Our patient was initially treated with two inpatient doses of tocilizumab with successful transition to siltuximab in the outpatient setting. He continues to benefit from ongoing siltuximab treatment for more than one year to date without any safety issues or relapse of VEXAS syndrome.

Keywords: UBA1; C3 glomerulonephritis; Case report; IL-6; Siltuximab; Systemic inflammation; VEXAS.

Fig. 1

Reductions in serum creatinine (top), ESR (middle), and CRP (bottom) were observed following administration of tocilizumab (L) and were sustained on discharge (R) with siltuximab maintenance therapy CRP, C-reactive protein; ESR, erythrocyte sedimentation rate

Fig. 2

Wright Giemsa staining of bone marrow aspirate showing vacuoles in myeloid precursors (panels A and B). Panel B also shows evidence of erythroid dysplasia

Fig. 3

Bilateral lower extremity erythematous skin plaques were observed on Day 1 of readmission

Fig. 4

Comparison of PET scans taken 3 weeks apart on Day 4 (L) and Day 26 (R) of readmission PET, positron emission tomography

Fig. 5

H&E-stained sections of the perinephric infiltrate show fibroadipose tissue with a mixed inflammatory infiltrate comprised of plasma cells, lymphocytes, histiocytes, eosinophils, and neutrophils at 20X magnification (panels A and B) and 10X magnification (panel C) H&E, hematoxylin and eosin