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 a t 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.ResuZts. 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 Renal disease is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) (1-4). The use of immunosuppressive agents has been associated with a better prognosis (5-12). Combined cyclophosphamide (CYC) and glucocorticoid therapy is deemed to yield significant improvement in renal survival (13-15) and positive economic impact, compared with glucocorticoid therapy alone (16). However, several questions regarding the use of CYC in lupus nephritis remain unresolved. The optimum dosage, length of therapy, and method of administration have not been fully established. Toxicity and side effects are major limiting factors.The rate of relapse of nephritis following CYC therapy is largely unknown. This issue is important because recurrent episodes of nephritis may lead to progressive renal failure. In various studies, the rate of relapse of nephritis has ranged between 0 and 50%. However, followup of patients in these studies was short or was not mentioned in the reports (11,13,(17)(18)(19). Boumpas et a1 (20) and found that short courses of intravenous CYC pulses were associated with a higher rate of disease exacerbation than were longer courses. Information regarding the influence of demographic and clinical variables, renal histology, and methods of CYC administration is lack-

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.

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.

Objective. To assess whether an interleukin-1 receptor antagonist gene (IL1RN) polymorphism is associated with disease susceptibility and/or severity in a Spanish population of patients with rheumatoid arthritis (RA).Methods. An 86-bp variable-number tandem repeat polymorphism within IL1RN intron 2 was analyzed by polymerase chain reaction in genomic DNA obtained from 247 unrelated patients with RA (group A) and 287 healthy control subjects. The polymorphism analysis was repeated in a second group of 194 patients with RA (group B). Clinical information from patients in group A was used to compare activity and severity data in patients stratified according to the different alleles or genotypes. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to determine the strength of the association of the different alleles or genotypes with RA activity or severity.Results. In the control group, the allelic frequencies were 76% for IL1RN*1 (4 repeats), 21% for IL1RN*2 (2 repeats), 3% for IL1RN*3 (5 repeats), and 0.3% for IL1RN*4 (3 repeats). In group A patients with RA, both the frequency (OR 1.47, 95% CI 1.1-1.96, P ‫؍‬ 0.007) and carriage rate (OR 1.6, 95% CI 1.1-2.2, P ‫؍‬ 0.01) of allele IL1RN*2 were significantly increased. The increased frequency of IL1RN*2 was confirmed in group B patients with RA (OR 1.44, 95% CI 1.1-1.97, P ‫؍‬ 0.01). In patients with RA, homozygosity for IL1RN*2 was associated with an increased number of affected articular areas during the first year of followup but not with other parameters of disease activity or severity.Conclusion. Our results suggest that IL1RN has a role in determining susceptibility to RA in the Spanish population.