title: Mammalian target of rapamycin (mTOR) inhibitors slow skin carcinogenesis, but impair wound healing.
abstract: BACKGROUND
  Recent studies suggest that patients on mammalian target of rapamycin (mTOR) inhibitors experience a reduction in cutaneous carcinogenesis by an estimated 50% or more compared with calcineurin inhibitors. While randomized trials are running, organ transplant recipients are frequently switched from calcineurin inhibitors to mTOR inhibitors when cutaneous carcinogenesis increases.
  
  
  OBJECTIVE
  To slow carcinogenesis in our patient, a heart transplant recipient with a neuropathic diabetic foot syndrome who had developed cutaneous carcinogenesis at a rate of more than 20 squamous cell carcinomas (SCC) annually.
  
  
  METHODS
  The patient's immunosuppression was switched from the calcineurin inhibitor ciclosporin to the mTOR inhibitor everolimus.
  
  
  RESULTS
  Carcinogenesis slowed to six SCC annually; however, he developed recalcitrant diabetic foot ulcers which were purely neuropathic and nonangiopathic, and a limb-threatening fistulating necrotic erysipelas of the right leg. Both sites responded poorly to antibiotic therapy, offloading and debridement. This skin fistula became chronic and some toes were at risk for minor amputation. In view of the propensity for mTOR inhibitors to impair would healing, immunosuppression was switched back to ciclosporin. All wounds healed rapidly, but skin carcinogenesis rose to former levels.
  
  
  CONCLUSIONS
  This case impressively illustrates the clinical dilemma for mTOR inhibitor use where benefit in carcinogenesis is counterbalanced by impairment in wound healing. Changes in immunosuppressive regimens should thus be made on an individual basis with careful consideration of the relative risks.
authors: Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. laurence.feldmeyer@usz.ch
authors: L
authors: L
authors: Feldmeyer
authors: G F L
authors: GF
authors: Hofbauer
authors: T
authors: T
authors: Böni
authors: L E
authors: LE
authors: French
authors: J
authors: J
authors: Hafner
mesh_terms: D000368:Aged; D065095:Calcineurin Inhibitors; D002311:Cardiomyopathy, Dilated / Q000601:surgery; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D017719:Diabetic Foot / Q000503:physiopathology*; D057915:Drug Substitution; D000068338:Everolimus; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000517:prevention & control*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014034:Toes; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus