title: Increased incidence of cervical intraepithelial neoplasia in women with systemic lupus erythematosus treated with intravenous cyclophosphamide.
abstract: OBJECTIVE
  To determine if the incidence of cervical intraepithelial neoplasia (CIN) is increased in immunosuppressed women with systemic lupus erythematosus (SLE).
  
  
  METHODS
  Women with SLE were consecutively recruited from University of Michigan outpatient rheumatology clinics. Women with abnormal cervical smears at screening were excluded. Cervical smears were obtained at baseline and at 3 and 7 years. Cervical biopsies confirmed cytologic abnormalities (CIN I-III), and were scored by pathologists in blinded fashion. Data were analyzed according to treatment group: (1) prednisone; (2) azathioprine (AZA); (3) intravenous cyclophosphamide (IVCYC); and (4) IVCYC + AZA + prednisone.
  
  
  RESULTS
  Sixty-one of 89 women screened were eligible for enrollment. The overall 3-year incidence of CIN was 9.8%. Stratified by treatment group, the 3-year incidence of CIN was 0/23 (0%) in prednisone treated patients, 0/4 (0%) in AZA treated patients, 2/8 (25%) in IVCYC treated patients, and 4/26 (15%) in CYC + AZA + prednisone treated patients. A dose relationship was observed between cumulative IVCYC exposure and CIN; each increase of 1 g of IVCYC exposure corresponded to a 13% increased risk of CIN (p = 0.04). At 7 years, 45 patients remained under followup and 6 patients had died of unrelated causes. No cases of CIN were observed at 7 years, although there were 2 cases of atypical squamous cells of unknown significance and one case of condyloma.
  
  
  CONCLUSIONS
  IVCYC + prednisone therapy for SLE is significantly associated with development of CIN.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Ognenovski
authors.forename: Wendy
authors.initials: W
authors.lastname: Marder
authors.forename: Emily C
authors.initials: EC
authors.lastname: Somers
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Johnston
authors.forename: Janice G
authors.initials: JG
authors.lastname: Farrehi
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Selvaggi
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001379:Azathioprine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology; D011241:Prednisone / Q000008:administration & dosage; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D003520:Cyclophosphamide; D001379:Azathioprine; D011241:Prednisone