title: Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome.
abstract: BACKGROUND
  Tacrolimus is a macrolide immunosuppressant approved in oral and intravenous formulations for primary immunosuppression in liver and kidney transplantation. Topical 0.1% tacrolimus ointment has recently been shown to be effective in atopic dermatitis for children as young as 2 years of age, with minimal systemic absorption. We describe 3 patients treated with topical 0.1% tacrolimus who developed significant systemic absorption.
  
  
  METHODS
  Three patients previously diagnosed as having Netherton syndrome were treated at different centers with 0.1% tacrolimus ointment twice daily. Two patients showed dramatic improvement. All patients were found to have tacrolimus blood levels within or above the established therapeutic trough range for oral tacrolimus in organ transplant recipients. None of these patients developed signs or symptoms of toxic effects of tacrolimus.
  
  
  CONCLUSIONS
  Patients with Netherton syndrome have a skin barrier dysfunction that puts them at risk for increased percutaneous absorption. The Food and Drug Administration recently approved 0.1% tacrolimus ointment for the treatment of atopic dermatitis. Children with Netherton syndrome may be misdiagnosed as having atopic dermatitis. These children are at risk for marked systemic absorption and associated toxic effects. If topical tacrolimus is used in this setting, monitoring of serum tacrolimus levels is essential.
authors.affiliation: Department of Dermatology, Saint Louis University Health Sciences Center, 1755 S Grand, St Louis, MO 63104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Allen
authors.forename: E
authors.initials: E
authors.lastname: Siegfried
authors.forename: R
authors.initials: R
authors.lastname: Silverman
authors.forename: M L
authors.initials: ML
authors.lastname: Williams
authors.forename: P M
authors.initials: PM
authors.lastname: Elias
authors.forename: S K
authors.initials: SK
authors.lastname: Szabo
authors.forename: N J
authors.initials: NJ
authors.lastname: Korman
mesh_terms: D000279:Administration, Cutaneous; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000188:drug therapy* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D012869:Skin Absorption; D013577:Syndrome; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus