Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide.

OBJECTIVE: To determine the cumulative rate of relapse of lupus nephritis that has been treated successfully with cyclophosphamide (CYC), and to estimate the association between time to relapse and demographic, clinical, laboratory, and treatment variables. METHODS: This was an observational study of 48 systemic lupus erythematosus (SLE) patients who were treated successfully with CYC between 1979 and 1993 and followed up thereafter at 3 university hospitals. Demographic and clinical variables, laboratory data during the first month of nephritis, and therapy-related variables were recorded from charts. Renal biopsy specimens were retrieved and analyzed by a pathologist. Relapse of nephritis was the outcome of interest. Descriptive analysis of patients who did and those who did not have a relapse was performed by chi-square test, Fisher's exact test, and Wilcoxon 2-sample test. The cumulative rate of relapse was computed using the actuarial method. Univariate comparisons of time to relapse were computed by log-rank test. Proportional hazards modeling was used to assess the combined effect of patient characteristics that have been hypothesized to be prognostic factors. RESULTS: Nephritis relapsed in 11 patients. Previous hematologic disorder, arthritis or arthralgia, and the use of CYC in oral form were more frequent in patients who had a relapse. The cumulative rate of relapse was 25% and 46% at 5 years and 10 years, respectively. A significant univariate difference in time to relapse was found when patients were stratified by time from diagnosis to initiation of CYC treatment (< or = 5 months versus > 5 months; P = 0.02). By multivariate analysis, age < 29 years at nephritis onset (relative risk [RR] 6.29, 95% confidence interval [95% CI] 1.13-34.94, P = 0.03) and delay of > 5 months from onset of nephritis to initiation of CYC therapy (RR 3.66, 95% CI 1.06-12.63, P = 0.04) were independently associated with time to relapse. CONCLUSION: A selected population of SLE patients may have long-term remission of renal disease following successful CYC therapy. Patients in whom CYC treatment is delayed or who are young at the time of nephritis onset are at increased risk of relapse.

Magnetic resonance imaging of the brain in systemic lupus erythematosus.

Magnetic resonance imaging (MRI) of the brain is a sensitive method to detect parenchymal tissue lesions. Its value in the diagnosis of central nervous system (CNS) lupus is disputed. To address this question, we have conducted an open and prospective study in a population of 44 SLE patients. We investigated 24 patients (mean age 33 +/- 13 yr) with past or active CNS lupus (group A) that included organic brain syndrome (12), migraine (8), focal neurological signs (7), seizures (2), myelopathy (1) and narcolepsy-cataplexy (1), and 20 patients (mean age 32 +/- 12 yr) without CNS lupus (group B). Health controls comprising nine females and one male aged 31 +/- 9 yr were also studied for comparison (group C). MRI was performed using sagittal T1-weighted images, axial and coronal spin density, and T2-weighted images. All scans were read blindly. Thirteen patients in group A and 10 in group B had well-identified lesions on sequences with long repetition time. Lesions were mostly multiple, small, punctate areas of increased signal at periventricular or subcortical white matter of both cerebral hemispheres. The number and location of lesions were not significantly different in both groups. None of the group C patients had MRI lesions. The presence of lesions was significantly associated with age at study and disease duration, but not with the presence of CNS lupus. In summary, MRI abnormalities are detected in neurologically asymptomatic SLE patients. Whether this represents subclinical brain involvement remains unknown.

Menstrual disorders in girls with systemic lupus erythematosus treated with cyclophosphamide.

To study the ovarian toxicity associated with cyclophosphamide in girls with systemic lupus erythematosus (SLE), we retrospectively reviewed the charts of 30 SLE girls aged 16 yr or younger at diagnosis, followed at three university hospitals. Gynaecological history was extracted from the charts or obtained prospectively. Ten had not received cyclophosphamide therapy, six were treated with daily oral cyclophosphamide, 10 with intravenous pulses and four with daily oral and intravenous pulses. Median oral cyclophosphamide dose was 38 g (inter-quartile range 75) and median intravenous dose 12.95 g (inter-quartile range 6.2). Six girls had oligomenorrhoea (20%) and one amenorrhoea (3%). Two treated with oral cyclophosphamide had oligomenorrhoea (33%) and one amenorrhoea (17%), two treated with both oral and intravenous pulses had oligomenorrhoea (50%), and none of those treated with intravenous pulses alone had menstrual disturbances (50% oral vs 0% intravenous pulses; P = 0.016). Girls who had menstrual disturbances had received higher doses of cyclophosphamide than those who did not (medians: 63 vs 15 g; P < 0.05). In summary, menstrual disturbances in SLE girls treated with cyclophosphamide are related to the total dose and perhaps to the administration method.

Cutaneous infection with rapidly growing mycobacteria in patients with systemic rheumatic disease.

We report two patients with systemic rheumatic disease being treated with steroids whose cases were complicated by subcutaneous nodules. In both, clinical and histological features suggested cutaneous infection and M. chelonae was isolated from skin specimens. Antibiotic therapy in both and surgery in one led to healing after a prolonged course. A review of the literature and our experience with these two patients suggest that rheumatic patients on steroid therapy are at risk of infection with these unusual pathogens. Knowledge of the risk factors and the distinctive picture of cutaneous mycobacteriosis should improve its diagnosis and therapy.