A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis.

OBJECTIVE: To investigate the effectiveness and side effects of oral versus pulse cyclophosphamide (CYC) in combination with corticosteroids (CS) in the treatment of systemic Wegener's granulomatosis (WG). METHODS: Patients with newly diagnosed systemic WG were enrolled in a prospective, randomized trial. At the time of diagnosis, prior to randomization, every patient received a daily injection of methylprednisolone for 3 days, followed by daily oral prednisone (1 mg/kg/day) and a 0.7-gm/m2 pulse of CYC. Patients were then randomly assigned to receive either prednisone plus intravenous pulse CYC (group A) or prednisone plus oral CYC (group B) as first-line treatment. CYC was given for at least 1 year and was then progressively tapered and discontinued. RESULTS: Fifty patients were included in the study: 27 in group A and 23 in group B. At 6 months, 24 group A patients (88.9%) were in remission, versus 18 group B patients (78.3%). At the end of the trial, 18 group A patients (66.7%) and 13 group B patients (56.5%) were in remission. In group A, 66.7% of the patients experienced side effects, versus 69.6% in group B. Infectious side effects were significantly more frequent in group B (69.6%) than in group A (40.7%) (P < 0.05). The incidence of Pneumocystis carinii pneumonia was higher in oral CYC-treated patients (30.4%) than in pulse CYC-treated patients (11.1%). Nine group A patients (33.3%) and 10 group B patients (43.5%) died. Actuarial curves showed that relapses were significantly more frequent in group A (59.2%) than in group B (13%) (P = 0.02). CONCLUSION: Our results indicate that pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality. However, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as oral CYC.

[Pulmonary manifestations of primary Gougerot-Sjögren syndrome. Apropos of 8 cases in a series of 35 patients]. / Manifestations pulmonaires du syndrome de Gougerot-Sjögren primitif. A propos de huit observations dans une série de 35 patients.

Clinical, roentgenologic, functional and broncho-alveolar lavage features of lung involvement in primary Sjögren's syndrome were assessed in a retrospective study of 35 cases. Diffuse interstitial patterns on chest radiography were present in six patients and alveolar patterns were suggestive of lymphoid interstitial pneumonitis or pseudolymphoma in two. Acute and febrile onset mimicked infectious pneumonitis in three patients when dyspnea was the most common clinical feature in others. Patients with primary Sjögren's syndrome and pulmonary disease were older (65 vs 56 years) (P = 0.025), have more frequently extra-glandular manifestations (P = 0.03), keratoconjunctivis sicca (P = 0.018) and biological perturbations (hypergammaglobulinemia (P = 0.03), antinuclear antibodies (P = 0.01) than those without lung involvement. Low diffusion capacity was present in seven patients associated twice to small airways obstruction. Bronchoalveolar lavage revealed in all cases an increased total cells count (mean: 6.96 10(5)/mm3) and a lymphocytic alveolitis (range: 11 to 66%; mean: 38%) associated with an elevated percentage of alveolar neutrophils in four patients. A low CD4/CD8 ratio was related to a pejorative issue. Treatment consisted in corticotherapy combined with oral cyclophosphamide in case of pseudolymphoma.