Objective. Cyclophosphamide (CYC) therapy for systemic lupus erythematosus (SLE), a disease predominantly affecting women of childbearing age, causes an unacceptably high incidence of irreversible premature ovarian failure (POF). This study was performed to evaluate the effectiveness of depot leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a), for protection against POF during CYC therapy.Methods. Young women with severe SLE treated in a standardized protocol of monthly intravenous bolus CYC were offered treatment with GnRH-a (depot leuprolide acetate; a 3.75-mg monthly injection during the standard CYC regimen). Patients treated with GnRH-a were compared with controls individually matched by age (؎5 years) and by cumulative CYC dose (؎5 gm). Reproductive status was determined after a minimum followup of 3 years after CYC therapy. The primary outcome was time to POF. Paired summary statistical analyses, Kaplan-Meier survival estimates, and Cox regression analyses were performed to assess differences in outcome between groups.Results. POF developed in 1 of 20 women treated with GnRH-a (5%) compared with 6 of 20 controls (30%) matched by age and cumulative CYC dose (matched odds ratio 0.09, P < 0.05). Kaplan-Meier estimates demonstrated improved cumulative ovarian protection over time in the GnRH-a-treated group (P ؍ 0.04).Conclusion. Treatment with GnRH-a during CYC therapy was associated with a significant reduction of POF in young women with severe SLE.Cyclophosphamide (CYC) administration prolongs survival and reduces end-organ damage in patients with severe rheumatic diseases such as systemic lupus erythematosus (SLE), Wegener's granulomatosis, and polyarteritis nodosa. However, treatment with CYC and other alkylating agents such as chlorambucil is associated with an unacceptably high incidence of significant toxicities, including premature ovarian failure (POF; hypergonadotropic hypogonadism), with consequent irreversible amenorrhea and infertility (1-3). This has particular significance in the SLE population, since lupus disproportionately affects women of reproductive age. In experimental animals, CYC exposure results in DNA crosslinking in granulosa cells, reduced numbers of granulosa cells, decreased circulating levels of progesterone and estrogen, and ovarian fibrosis (4,5). In humans, CYC-induced damage to the ovary is generally regarded as cumulative and irreversible, due in part to progressive reduction of a limited number of cells (2).The incidence of POF in both the rheumatic disease and cancer populations treated with CYC ranges from 12% to 83% depending on variables such as patient characteristics and mode of administration. Both age at initiation of therapy and the cumulative CYC dose are strong predictors of POF (1-3,6-9). A study of breast cancer patients showed that the cumulative CYC doses associated with a 50% incidence of ovarian failure were 20.4 gm, 9.3 gm, and 5.2 gm among women in their 20s, 30s, and 40s, respectively (10).
We describe the first documented case of Mycoplasma felis infection in a woman who had common variable immunodeficiency and who presented with septic arthritis of the left hip and right knee. M. felis was isolated from both joints. She had been exposed to cats before the diagnosis of M. felis septic arthritis was made. Both of the patient's joints were surgically debrided, and she was treated with doxycycline for several months. In spite of initial improvement, destruction of her hip was noted. Subsequently, she underwent hip arthroplasty; histopathological examination of the bone at the time of surgery showed chronic osteomyelitis, and doxycycline therapy was continued.
We were most interested to read Prof. Pritzker's assessment of the state of research into the crystal induced arthropathies 1 . We wish to assure Prof. Pritzker and the wider rheumatology community that, rather than being a "dwindling endangered species whose interests are seen to be peripheral to those of most rheumatologists," those researchers involved in studying the crystal induced arthropathies are enthusiastic, energetic, and productive.In recent years, work in this field has led to critical advances in our understanding of the basic science and epidemiology of crystal induced arthropathies 2-6 . Further, the prospect of new agents to treat these diseases is cause for great enthusiasm. For management of acute crystal induced arthropathies, components of the inflammasome, and particularly interleukin 1, provide new therapeutic targets. The development of novel uratelowering therapies, such as febuxostat and PEG-uricase for treatment of chronic gout, should also have a major impact on longterm management of this prevalent disease, in preventing acute gout attacks and the consequences of chronic gout such as disfiguring tophi, joint damage, and disability 7,8 .As a reflection of the interest in gout within the rheumatology community, gout sessions have been included in the scientific programs of the 2 last EULAR annual meetings, the 2 last ACR annual meetings, and as Special Interest Groups (SIG) or Workshops in the last 3 OMERACT meetings. EULAR has recently supported a Task Force on Gout, resulting in the publication of Evidence Based Recommendations for Diagnosis and Management 9,10 , and the ACR and EULAR have funded an international project for validation of acute gout flares. The number of presentations at ACR and EULAR meetings is 10 times that of a decade ago, and the number of original papers on gout in high impact international journals now exceeds that of reviews, a situation inverse to that observed a decade ago. In addition, as the reader may observe, the group of investigators devoted to gout does not have the appearance of an endangered species (Figure 1).It is for these reasons that we do not share Prof. Pritzker's pessimistic view regarding the state of research into the crystal induced arthropathies. The number of investigators may be small, but recent progress has been significant and is likely to translate into important new treatments for patients with these diseases.
Rationale and Objectives The study aimed to determine if intrathoracic fat volumes are associated with the presence and severity of systemic sclerosis (SSc), defined by the presence of pulmonary arterial hypertension (PAH). Materials and Methods A total of 265 patients were included in the study, 202 of whom had SSc (134 had SSc with no PAH and 68 had SSc-associated PAH) and who underwent high-resolution computed tomography, and 63 controls who underwent coronary computed tomography angiography with calcium scoring. Intrathoracic and epicardial (EFV) fat volumes were quantified by manual tracing of the mediastinum and the pericardium, the difference of which represents the extrapericardial fat volume. Associations between these three fat volumes and the presence and severity of SSc, adjusted for cardiovascular risk factors and interstitial lung disease, were evaluated by logistic regression analysis. Results Of the 202 patients with SSc, the mean age was 54 years (ranged from 20 to 86), and 79% (192 of 202) were women. Adjusted EFV (odds ratio [OR]: 1.065; 95% confidence interval [CI]: 1.046–1.084, P = < 0.0001), ≤extrapericardial fat volume (OR: 1.028, 95% CI: 1.017–1.038, P = < 0.0001), and intrathoracic fat volume (OR: 1.033, 95% CI: 1.023–1.043, P = 0.001) were associated with the presence of SSc. Only EFV was associated with SSc severity (adjusted OR: 1.010, 95% CI: 1.003–1.018, P = 0.007). Conclusion Increased epicardial fat volume is associated with the presence and severity of SSc, independent of cardiovascular risk factors and interstitial lung disease.
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