Pearls & Oy-sters: Homozygous Complement Factor I Deficiency Presenting as Fulminant Relapsing Complement-Mediated CNS Vasculitis.

Abstract

A 36-year-old man presented multiple times with fever, headache, alteration of mental status, and focal neurologic deficits. MRI revealed extensive white matter lesions that were partially reversed between episodes. Workup revealed persistently low complement factor C3, low factor B, and absent alternative complement pathway activity. Biopsy revealed neutrophilic vasculitis. Genetic testing revealed a homozygous variant in complement factor I (CFI), which was thought to be pathogenic. CFI regulates complement-mediated inflammation, and deficiency in this factor leads to unchecked alternative pathway activity and decrease in C3 and factor B through consumption. The patient has remained stable since starting IL-1β inhibition. Complement factor I is a rare disorder that should be considered in patients with atypical relapsing neurologic disease associated with neutrophilic pleocytosis.