title: Tuberous sclerosis and fulminant lupus in a young woman.
abstract: Tuberous sclerosis is an autosomal dominant disorder characterized by involvement of skin, nervous system, kidneys, and lungs. It results from mutations in 1 of 2 genes: TSC1 (encoding hamartin) or TSC2 (encoding tuberin), leading to dysregulation and activation of the mammalian target of rapamycin (mTOR) pathway. Constitutive activation of mTOR signaling has recently been reported in systemic lupus erythematosus (SLE), and inhibition of this pathway may benefit patients with SLE nephritis. We report a case of a young woman with tuberous sclerosis who developed fulminant SLE, with lower extremity edema, massive proteinuria, and class IV lupus glomerulonephritis. She died despite treatment with high-dose steroids, plasmapheresis, and cyclophosphamide. Although there are no prior reports of coexistence of these 2 rare diseases, this case is of considerable interest because of the possibility that activation of mTOR by the TSC mutations may have led to activation of the immune system and the development of unusually severe SLE.
authors.affiliation: Temple University School of Medicine, Division of Rheumatology, Philadelphia, PA, USA.
authors.forename: Namrata
authors.initials: N
authors.lastname: Singh
authors.forename: Mark
authors.initials: M
authors.lastname: Birkenbach
authors.forename: Tiffany
authors.initials: T
authors.lastname: Caza
authors.forename: Andras
authors.initials: A
authors.lastname: Perl
authors.forename: Philip L
authors.initials: PL
authors.lastname: Cohen
mesh_terms: D000328:Adult; D015897:Comorbidity; D003520:Cyclophosphamide / Q000627:therapeutic use; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy; D010956:Plasmapheresis; D013256:Steroids / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D014402:Tuberous Sclerosis / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy
chemical_list: D013256:Steroids; D003520:Cyclophosphamide; D058570:TOR Serine-Threonine Kinases