title: Effects of oral cyclophosphamide and prednisolone therapy on the endothelial functions and clinical findings in patients with early diffuse systemic sclerosis.
abstract: OBJECTIVE
  The endothelial damage of microvascular structures in systemic sclerosis (SSc; scleroderma) is associated with increased levels of endothelial adhesion molecules and endothelium-associated cytokines, including E-selectin and thrombomodulin. Although there is still no ideal specific pharmacologic therapy for SSc, cyclophosphamide has resulted in clinical improvement in patients with SSc-related active alveolitis. This study was designed to assess the expression of E-selectin and thrombomodulin in patients with early diffuse SSc, and to investigate the effects of oral cyclophosphamide combined with prednisolone therapy on the levels of these endothelium-associated cytokines and on the patients' clinical outcomes.
  
  
  METHODS
  Thirteen patients with early diffuse SSc were treated with oral cyclophosphamide (2-2.5 mg/kg/day) and methylprednisolone (30 mg/every other day) for 1 year. The outcomes were determined as clinical (skin score) and laboratory parameters (including the erythrocyte sedimentation rate, complete blood cell count, levels of C-reactive protein, antinuclear antibody, anti-double-stranded DNA, rate of creatinine clearance, and findings on pulmonary function tests, esophageal manometry, and echocardiography). The concentrations of E-selectin and thrombomodulin were measured in the pretreatment and posttreatment serum samples from the SSc patients and from 12 healthy adults as controls.
  
  
  RESULTS
  In the patients with early diffuse SSc, pretreatment and posttreatment mean levels of E-selectin were 51 ng/ml (range 34.2-135.5) and 33.4 ng/ml (range 23-62.5), respectively (P = 0.01), and those of thrombomodulin were 82 ng/ml (range 35.8-120.5) and 74.6 ng/ml (range 23.3-91.3), respectively (P = 0.016). Clinical and laboratory parameters (the skin score and measures of pulmonary function [forced vital capacity and diffusing capacity for carbon monoxide]) were also improved (P < 0.05 for each) at the end of the followup period.
  
  
  CONCLUSIONS
  Combination therapy with cylophosphamide plus prednisolone is effective in the treatment of early diffuse SSc. Circulating levels of E-selectin and thrombomodulin not only demonstrate the extent of endothelial injury and/or activation, but also could be a useful marker to monitor the disease activity in SSc.
authors.affiliation: Hacettepe University School of Medicine, Sehit Cetin Gorgu Street 17/3, 06570 Maltepe, Ankara, Turkey.
authors.forename: Sule
authors.initials: S
authors.lastname: Apras
authors.forename: Ihsan
authors.initials: I
authors.lastname: Ertenli
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Ozbalkan
authors.forename: Sedat
authors.initials: S
authors.lastname: Kiraz
authors.forename: M Akif
authors.initials: MA
authors.lastname: Ozturk
authors.forename: Ibrahim C
authors.initials: IC
authors.lastname: Haznedaroglu
authors.forename: Veli
authors.initials: V
authors.lastname: Cobankara
authors.forename: Salih
authors.initials: S
authors.lastname: Pay
authors.forename: Meral
authors.initials: M
authors.lastname: Calguneri
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000032:analysis; D004727:Endothelium / Q000737:chemistry / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000276:immunology; D018180:Thrombomodulin / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D015415:Biomarkers; D019040:E-Selectin; D018180:Thrombomodulin; D003520:Cyclophosphamide; D011239:Prednisolone