title: Tocilizumab reverses cerebral vasculopathy in a patient with homozygous SAMHD1 mutation.
abstract: An auto-inflammatory syndrome consequent to SAMHD1 mutations involves cerebral vasculopathy characterized by multifocal stenosis and aneurysms within large arteries, moyamoya, chronic ischemia, and early-onset strokes (SAMS). While this condition involves the innate immune system, additional clinical features mimic systemic lupus erythematosus. Mutations in this gene can also cause a subset of the rare genetic condition Aicardi-Goutières syndrome. To date, no established therapy successfully prevents disease progression. We report a corticosteroid-dependent SAMS patient, a 19-year-old male of Old Order Amish ancestry, with diffuse cerebral arteriopathy identified through contrast brain magnetic resonance arteriography (MRA) and MRI. He received subcutaneous adalimumab every 2 weeks for 9 months with minimal response. Then, he started intravenous tocilizumab (6 mg/kg/dose) every 4 weeks. He sustained steadily normalizing cerebral vasculopathy and lab abnormalities resolved, allowing prednisone reduction. We conclude that the cerebral vasculopathy of the homozygous SAMHD1 mutation-mediated auto-inflammatory disease SAMS responded favorably to tocilizumab infusion therapy.
authors.affiliation: Division of Rheumatology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229-3029, USA. michael.henrickson@cchmc.org.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0002-3038-3482
authors.initials: M
authors.lastname: Henrickson
authors.affiliation: DDC Clinic for Special Needs Children, Middlefield, OH, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D000076106:SAM Domain and HD Domain-Containing Protein 1 / Q000235:genetics*; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; C502936:tocilizumab
keywords: Aicardi-Goutières syndrome; Cerebral vasculopathy; Moyomoya; SAMHD1 mutation; Tocilizumab