title: Cyclosporine-induced pain syndrome in a child undergoing hematopoietic stem cell transplant.
abstract: OBJECTIVE
  To report a case of calcineurin-induced pain syndrome (CIPS) in a child undergoing his second hematopoietic stem cell transplant (HSCT).
  
  
  METHODS
  A 6.1-year-old child received cyclosporine and methotrexate for acute graft-versus-host disease (aGVHD) prophylaxis after his first HSCT for acute myeloblastic leukemia. Amlodipine was given for the treatment of hypertension. Symptoms of CIPS were not observed. After the second HSCT at the age of 6.7 years, the child received cyclosporine (target trough whole blood cyclosporine concentration range 150-200 microg/L), starting on day -3, and mycophenolate mofetil for aGVHD prophylaxis. With the first cyclosporine dose, the patient complained of leg pain that was most severe during the cyclosporine infusion. Analgesic agents and a change from intravenous to oral administration of cyclosporine were ineffective in controlling the pain. Magnetic resonance imaging findings on day 10 showed periosteal soft tissue changes and mild bone marrow edema of the femora and tibiae. Tacrolimus was substituted for cyclosporine on day 20; on day 21 amlodipine was initiated to manage hypertension. Trough whole blood tacrolimus concentrations ranged from 1.7 to 6.2 microg/L. Pain was reduced in severity by day 29 and completely resolved once tacrolimus was discontinued on day 42. In this case, CIPS was considered to be probably associated with cyclosporine according to the Naranjo probability scale.
  
  
  CONCLUSIONS
  CIPS is hypothesized to result from calcineurin-induced vascular changes that disturb bone perfusion and permeability, leading to intraosseous vasoconstriction and bone marrow edema. In our patient, symptoms were most acute during the infusion, when whole blood cyclosporine concentrations were likely to be the highest. Our patient's symptoms were resolved when tacrolimus was substituted for cyclosporine and amlodipine was initiated.
  
  
  CONCLUSIONS
  Interventions aimed at reducing pain associated with CIPS may include the initiation of calcium-channel blocker therapy and conversion to an alternative calcineurin inhibitor.
authors.affiliation: University of Toronto, Ontario, Canada.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Lavoratore
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Navarro
authors.forename: Eyal
authors.initials: E
authors.lastname: Grunebaum
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.forename: Alicia
authors.initials: A
authors.lastname: Koo
authors.forename: Tal
authors.initials: T
authors.lastname: Schechter
authors.forename: Adam
authors.initials: A
authors.lastname: Gassas
authors.forename: John J
authors.initials: JJ
authors.lastname: Doyle
authors.forename: L
authors.initials: L
authors.lastname: Lee Dupuis