Ovarian protection with gonadotropin-releasing hormone agonists during cyclophosphamide therapy in systemic lupus erythematosus.

Administration of cyclophosphamide (CYC), an alkylating agent used to treat malignancies and severe rheumatic diseases, creates a risk of ovarian insufficiency that is related to the intensity and duration of therapy and the age of the patient. To preserve reproductive capacity in the appropriate clinical setting, oocyte, embryo, and/or ovarian tissue cryopreservation are recommended. Medical protection with depot gonadotropin-releasing hormone agonists (GNRHa) has emerged as a potential means to preserve both fertility and ovarian function through the suppression of ovarian activity during treatment with alkylators. We review the trials of GNRHa for ovarian protection in both cancer and rheumatic disease patients. Trials in cancer patients receiving CYC alone, or in combination with other gonadotoxic agents that have employed several different GNRHa have yielded mixed results. Trials in lupus patients receiving lower doses of CYC alone utilizing depot leuprolide acetate have tended to show favorable results.

Treatment of primary and secondary immune thrombocytopenia.

PURPOSE OF REVIEW: Medical therapies for the treatment of immune thrombocytopenia (ITP) complicating SLE are increasingly being investigated as alternatives to splenectomy and IVIG. The purpose of this review is to highlight the therapies that are utilized in the treatment of primary ITP and ITP secondary to lupus. RECENT FINDINGS: Corticosteroids are still the standard initial treatment of ITP, with the addition of IVIG when a rapid response is needed. There are few studies dedicated to assessing the efficacy of disease-modifying antirheumatic (DMARD), biologic, and nonimmunosuppressive agents as treatment for lupus thrombocytopenia/lupus ITP. Rituximab and thrombopoeitin mimetics have been the most extensively studied therapies for primary ITP in recent years. Results of trials show adequate initial responses; however, the duration of therapy and sustainability of responses are variable. Splenectomy is less often utilized. SUMMARY: Although corticosteroids, intravenous immunoglobulin and splenectomy have proven to be effective measures to treat immune thrombocytopenia, newer studies have demonstrated positive outcomes of immunosuppressives and thrombopoeitin mimetics. In most cases, the reported duration of therapy was not prolonged. More studies are needed to fully assess the effect of medical therapy in lupus ITP and to determine how long to continue maintenance therapy.

Systemic Lupus Erythematosus for Primary Care.

Systemic lupus erythematosus is a chronic autoimmune condition with variable organ system involvement; manifestations can range from mild to potentially life threatening. Early diagnosis is important, as progression of disease can be halted. Diagnosis is made by review of signs and symptoms, imaging, and serology.

Diagnostic and therapeutic considerations in patients with hypogammaglobulinemia after rituximab therapy.

PURPOSE OF REVIEW: There are no established guidelines for evaluating and treating hypogammaglobulinemia in patients with rheumatic disease who receive B-cell depleting agents. The purpose of this article is to review findings in the work-up and treatment of common variable immunodeficiency (CVID) that can guide our evaluation of patients with autoimmune disease who develop hypogammaglobulinemia after rituximab/B-cell depleting therapy. RECENT FINDINGS: Infection rates are higher in rheumatic disease patients who develop hypogammaglobulinemia than those who do not. However, not all patients who develop hypogammaglobulinemia are at increased risk of developing infection after B-cell depleting therapy. Recent consensus statements have helped refine the diagnosis of impaired immune responses in patients with CVID, and can provide guidance for the diagnostic work-up and therapeutic decision making for patients with secondary drug induced hypogammaglobulinemia. SUMMARY: Based on findings in studies of CVID, assessment of vaccine response in patients with hypogammglogulinemia after rituximab therapy in the setting of recurrent infections can help predict propensity for infection and thus guide decision making with regards to intravenous immunoglobulin supplementation and retreatment with rituximab.

Suppression of normal immune responses after treatment with rituximab.

PURPOSE OF REVIEW: Because rituximab is increasingly used in systemic autoimmune diseases, alone or in combination with other immunosuppressive medication, secondary reduction of normal immune defenses has become a more significant clinical problem. RECENT FINDINGS: The goal of rituximab treatment of immune-mediated conditions is complete depletion of circulating B cells. Studies have suggested that lack of complete B-cell depletion is associated with nonresponse, and B-cell repletion can predict relapse. The resulting prolonged B-cell depletion is associated with risk of adverse effects including hypogammaglobulinemia, increased risk of infection, failure to develop immune responses after vaccination, and neutropenia. Pre-existing hypogammaglobulinemia has been linked to increased risk of reduction of IgG levels and serious infections after rituximab therapy, and concomitant cyclophosphamide therapy has been associated with an increased risk of developing hypogammaglobulinemia. SUMMARY: Although rituximab therapy is effective in the treatment of many systemic autoimmune diseases and has an acceptable safety profile, treating physicians need to keep in mind that pre-existing hypogammaglobulinemia and likely also use of additional immunosuppressive agents can increase the risk of prolonged hypogammaglobulinemia and infection. In keeping with current recommendations for rheumatoid arthritis, we recommend that all patients who undergo rituximab therapy have baseline IgG, IgM, and IgA measurements and also have immunoglobulin levels monitored periodically during treatment.

Utility and Associated Risk of Pulmonary Embolism Computed Tomography Scans in the Michigan Lupus Cohort.

OBJECTIVE: Systemic lupus erythematosus patients are frequently evaluated for chest pain and may have multiple pulmonary embolism (PE) computed tomography (CT) scans. This study was undertaken to determine the incidence of pulmonary embolism in the University of Michigan Lupus Cohort patients who have undergone PE CT scans and to estimate the associated increased risk of breast and lung cancer from radiation exposure. METHODS: We reviewed records of patients in the University of Michigan Lupus Cohort (n = 854) and determined the number and outcome of PE CT scans. Radimetrics software was used to perform individualized calculations of radiation dose to the lung and breast of each patient. We used this dose information, the patient's age at the time of scan, and risks according to the Biological Effects of Ionizing Radiation, report VII, to estimate the increased incidence risks of breast and lung cancer. RESULTS: A total of 182 of 856 patients (21%) underwent 357 PE CT scans. The overall rate of positivity was 7.5%. For patients undergoing their first through third scans, the rate of positivity for PE was 8.8%, whereas patients undergoing their fourth through tenth scans had 1.6% positivity. The highest increase in incidence risk was 0.87% for breast and 0.62% for lung. CONCLUSION: Patients with multiple previous PE CT scans had lower likelihood of a positive result on subsequent scans and higher risks of malignancy. The magnitude of risk should not discourage performance of PE CT when clinically indicated.