title: Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: a case series.
abstract: BACKGROUND
  Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced Fanconi syndrome.
  
  
  METHODS
  Descriptive case series with two cases of Fanconi syndrome associated with FAE treatment diagnosed at two Dutch university nephrology departments, three cases reported at the Dutch and German national pharmacovigilance databases and six previously reported cases.
  
  
  RESULTS
  All 11 cases involved female patients with psoriasis. The median age at the time of onset was 38 years [interquartile range (IQR) 37-46]. Patients received long-term FAEs treatment with a median treatment duration of 60 months (IQR 28-111). Laboratory tests were typically significant for low serum levels of phosphate and uric acid, while urinalysis showed glycosuria and proteinuria. Eight (73%) patients had developed a hypophosphataemic osteomalacia and three (27%) had pathological bone fractures. All patients discontinued FAEs, while four (36%) patients were treated with supplementation of phosphate and/or vitamin D. Five (45%) patients had persisting symptoms despite FAEs discontinuation.
  
  
  CONCLUSIONS
  FAEs treatment can cause drug-induced Fanconi syndrome, but the association has been reported infrequently. Female patients with psoriasis treated long term with FAEs seem to be particularly at risk. Physicians treating patients with FAEs should be vigilant and monitor for the potential occurrence of Fanconi syndrome. Measurement of the urinary albumin:total protein ratio is a suggested screening tool for tubular proteinuria in Fanconi syndrome.
authors.affiliation: Department of Dermatology , Erasmus Medical Center , Rotterdam , The Netherlands.
authors.forename: Deepak M W
authors.initials: DM
authors.lastname: Balak
authors.affiliation: Department of Dermatology , Leiden University Medical Center , Leiden , The Netherlands.
authors.forename: Jan Nico
authors.initials: JN
authors.lastname: Bouwes Bavinck
authors.affiliation: Division of Nephrology, Department of Medicine , Leiden University Medical Center , Leiden , The Netherlands.
authors.forename: Aiko P J
authors.initials: AP
authors.lastname: de Vries
authors.affiliation: Netherlands Pharmacovigilance Centre Lareb , 's-Hertogenbosch , The Netherlands.
authors.forename: Jenny
authors.initials: J
authors.lastname: Hartman
authors.affiliation: Department of Dermatology , Erasmus Medical Center , Rotterdam , The Netherlands.
authors.forename: Hendrik A Martino
authors.initials: HA
authors.lastname: Neumann
authors.affiliation: Division of Nephrology and Transplantation, Department of Internal Medicine , Erasmus Medical Center , Rotterdam , The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.affiliation: Department of Dermatology , Erasmus Medical Center , Rotterdam , The Netherlands.
authors.forename: Hok Bing
authors.initials: HB
authors.lastname: Thio
keywords: fumarates; hypophosphataemia; osteomalacia; proteinuria; proximal tubular dysfunction