title: [Oral ulcers in kidney allograft recipients treated with sirolimus].
abstract: BACKGROUND
  Mouth ulcers are a major complication associated with sirolimus and occasionally result in discontinuation of treatment. However, they continue to be poorly understood and the data in the literature is frequently contradictory. The aim of this retrospective study is to help improve knowledge about such ulcers and about associated risk factors.
  
  
  METHODS
  The dossiers of 37 renal transplant patients treated with sirolimus between June 2002 and February 2006 were analysed. The data collected consisted of patient age, gender, reason for transplantation, mean dose of sirolimus given and serum concentrations of the drug, ongoing treatments, presence of viral infection, blood picture and serum concentrations of folate, ferritin, iron and vitamin B12, coexistence of chronic inflammatory intestinal disease and local trauma, and presence or absence of mouth ulcers. Clinical investigation of the ulcers was based on notes and photographs taken during visits for oral mucosal disease. Patients presenting ulcers were treated with clobetasol cream and therapeutic efficacy was assessed in terms of progression of pain and speed of healing.
  
  
  RESULTS
  Mouth ulcers were seen in eight of the 37 patients whose dossiers were examined. The sex ratio (M/F) was 1/1 in patients with ulcers and 3/1 in the 29 other patients. In patients presenting ulceration, the doses of sirolimus administered and serum sirolimus concentrations were respectively 3.2+/-1.05mg and 9.5+/-3.6ng/l versus 3.2+/-1.7mg and 9.8+/-4.1ng/l in patients without ulcers. The diseases responsible for renal failure were comparable in the two groups. 62% of patients with mouth ulcers discontinued sirolimus versus 65% of those without mouth ulcers. Only one patient stopped taking sirolimus partly on account of mouth ulcers. Mycophenolate mofetil was combined with sirolimus in 62.5% of patients with ulceration and in 62% of patients with no ulceration. The forms of ulceration varied, with a fibrinoid base. The edges were not excessively raised and no peripheral erythematous border was observed. Size ranged from 1 to 15mm, with between two and five ulcers being seen. The covering mucosa was involved in all cases, with sparing of the masticatory and specialised mucosa. Histological examination revealed non-specific ulceration associated with a polymorphous inflammatory infiltrate. Treatment with clobetasol reduced pain and shortened healing times between two- and three-fold.
  
  
  CONCLUSIONS
  This study confirmed the incidence of mouth ulcers in renal transplant patients treated with sirolimus. The ulcers did not appear to be attributable to a dose-dependent mechanism, thus corroborating the results reported in the literature. However, a contributory role of transition from tacrolimus to sirolimus in their appearance was not seen in this study. Combination of sirolimus with mycophenolate mofetil appeared to have no bearing on the incidence of mouth ulcers. Clobetasol cream, whether or not given together with an anaesthetic solution, appears to reduce pain and shorten healing times, and could thus avoid discontinuation of treatment on account of mouth ulcers.
authors.affiliation: Pôle d'odontologie et santé buccale, CHU de Bordeaux, hôpital Pellegrin, place Amélie-Raba-Léon, 33000 Bordeaux, France. fricainj@aol.com
authors.forename: J-C
authors.initials: JC
authors.lastname: Fricain
authors.forename: K
authors.initials: K
authors.lastname: Cellerié
authors.forename: V
authors.initials: V
authors.lastname: Sibaud
authors.forename: S
authors.initials: S
authors.lastname: Catros
authors.forename: A
authors.initials: A
authors.lastname: Taïeb
authors.forename: P
authors.initials: P
authors.lastname: Merville
mesh_terms: D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D009061:Mouth Mucosa / Q000473:pathology; D019226:Oral Ulcer / Q000139:chemically induced* / Q000473:pathology; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects* / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus