Hemophagocytic syndrome in a patient with rheumatoid arthritis

Abstract

A 76-year-old man with rheumatoid arthritis, who had been treated with oral prednisolone and methotrexate, presented with high fever and generalized fatigability. Laboratory data demonstrated marked pancytopenia, which we first regarded as a side effect of methotrexate, and leucovorin was administered with granulocyte-colony stimulating factor and transfusions. Because no recovery was recognized, however, bone marrow aspiration was performed, by which hemophagocytic syndrome was diagnosed. After corticosteroid pulse therapy was initiated, the patient’s symptoms were rapidly attenuated and laboratory data rapidly normalized.     

Study protocol of a multicenter registry of patients with rheumatoid arthritis starting biologic therapy in Japan: Tsurumai Biologics Communication Registry (TBCR) Study

Abstract

Biologic agents have proven to be effective against rheumatoid arthritis (RA) in clinical trials and post-marketing surveillance (PMS) studies. However, limited follow-up periods and strict criteria for recruitment might lead to an underestimation of adverse events. To document the long-term course of patients with RA treated with biologics in clinical settings, we established the Tsurumai Biologics Communication Registry (TBCR). First, we retrospectively collected data of patients registered for any biologic PMS study or clinical trial at participating institutes. Thus far, thirteen institutes have joined the registry and 860 patients have been identified. Comparing baseline characteristics by age and initiation year of biologics, young patients had significantly less joint damage and dysfunction and a higher dose of concomitant methotrexate (MTX) compared to older patients. Older age and functional class were significantly related to the incidence of adverse events that resulted in discontinuation of the 1st biologic treatment. The TBCR is in its initial stages, and information on all patients newly starting biologic therapy at participating institutes is being collected prospectively. Differences in baseline characteristics by age and initiation year of biologics need to be carefully evaluated in order to report on drug-related survival and long-term prognosis, using follow-up data in the near future.     

Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review

Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.     

Non-biologic remission maintenance therapy in adult patients with ANCA-associated vasculitis: A systematic review and network meta-analysis

ObjectiveTo determine the comparative efficacy of non-biologic treatments for remission maintenance in ANCA-associated vasculitis.MethodsWe identified all randomized trials comparing leflunomide, azathioprine, methotrexate or mycophenolate mofetil in adult patients with granulomatosis with polyangiitis or microscopic polyangiitis. Relapse-free survival was compared through hazard ratios (HR) using a Bayesian fixed-effects network meta-analysis. Multiple sensitivity analyses were performed to explore biases identified in one trial using original trial data.ResultsThree trials were available (leflunomide-methotrexate, methotrexate- azathioprine, azathioprine-mycophenolate). Mycophenolate was inferior to all treatments, although the 95% credible interval (CrI) of the HR relative to methotrexate crossed 1. Leflunomide was superior to azathioprine (HR 0.43 [95% CrI: 0.14–1.3]) and methotrexate (HR 0.47 [95% CrI: 0.18–1.2]), although the 95% CrI also crossed 1. There was a 90% probability that leflunomide was the best treatment. After down weighting the effect of leflunomide vs. methotrexate for early trial termination and slow MTX dose escalation, there remained a 55% probability leflunomide was best.ConclusionBased on indirect evidence, leflunomide is effective in maintaining remission in granulomatosis with polyangiitis or microscopic polyangiitis relative to other non-biologic treatments. Further randomized trials of leflunomide are needed for confirmation.     

Factors predicting the response to low-dose methotrexate therapy in patients with rheumatoid arthritis: a better response in male patients

Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) throughout the world. In Japan, MTX is recommended by the Japanese Ministry of Health, Labour, and Welfare to be given as the second or third DMARD and at a dosage of no more than 8 mg/week. We analyzed the efficacy of MTX in Japanese patients with RA in order to determine whether it is comparable to that in Western countries, where 15–20 mg/week of MTX is used, as well as to elucidate the factors associated with the favorable response to MTX. Around 8 mg/week of MTX was effective in half of the RA patients in the current study, and male sex was the only factor associated with a good response to MTX from a multivariate regression model analysis. Some of the patients who had a poor response to MTX showed an improvement with the addition of bucillamine or prednisolone. For the remaining patients, an increase in the MTX dosage to more than 8 mg/week or the use of biologics such as the anti-tumor necrosis factor (TNF)-α monoclonal antibody may be required.     

Treatment of early rheumatoid arthritis

Recent advances in the understanding of the pathophysiology, aggressive treatment, and early detection of rheumatoid arthritis (RA) have changed the clinical, pathologic, and functional outcomes in patients with RA. Early aggressive treatment of RA has now become the norm in clinical practice rather than the use of the traditional pyramid approach of the last half of the twentieth century. Early treatment with monotherapy of traditional disease-modifying antirheumatic drugs (DMARDs) or biologics, combination traditional DMARD therapy and, especially, combination of biologic therapy and methotrexate, have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. For the individual patient, we still cannot determine which medication or combination of medications will give the most complete response. There have been a number of recent, well-designed clinical trials that have tried to answer this question. Herein we review the evidence-based medicine that addresses these issues.     

Evidence-based use of methotrexate in children with rheumatic diseases: a consensus statement of the Working Groups Pediatric Rheumatology Germany (AGKJR) and Pediatric Rheumatology Austria

Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with non-steroidal anti-inflammatory drugs (NSAID) and physiotherapy. However, in a significant number of cases the disease is resistant to this therapy, and treatment with second line disease-modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as first-choice second-line agent for the treatment of JIA. To increase drug safety, the Working Groups for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words Methotrexate and juvenile arthritis limited to age 0–18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin DRFZ), experience with MTX in adults with rheumatoid arthritis (RA), and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded, and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented.Section Pharmacotherapy of the Working Group Pediatric Rheumatology Germany and Austria: I. Foeldvari; J.P. Haas, A. Haeffner, D. Hobusch,G. Horneff, A. Hospach, R. Keitzer, G. Klaus, M. Metzler, H. Michels, T. Niehues, I. Pilz, M. Sailer Höck, M. Schöntube, L. Schuchmann, K. Schumacher, H.W. Seyberth, E. Siemers, A. Urban, E. Weißbarth-Riedl. Working Group Pediatric Rheumatology North-Rhine-Westfalia: S. Benseler, G. Bürk, S. Fahl, I. Foeldvari, D. Föll, M. Frosch, G. Ganser, S. Kastner, I. Kleine, E. Lainka, K. Mönkemöller, J. Neubert, U. Neudorf, T. Niehues, J. Roth, S. Seeliger, N. Wagner, R. Wieland, H. Winowski.     

甲氨蝶呤联合米非司酮不同方案治疗异位妊娠的疗效探讨

目的：分析甲氨蝶呤联合米非司酮不同方案治疗异位妊娠的临床效果及安全性。方法随机选取该院自2012年12月—2014年12月收治的80例异位妊娠患者作为研究对象,随机将其分为A、B两组,每组40例。 A组患者接受甲氨蝶呤持续肌注联合米非司酮治疗。 B组接受单次肌注甲氨蝶呤联合米非司酮方案治疗,比较两组患者的临床治疗效果及不良反应发生率。结果 A组患者治疗有效率为97.50%,与B组对比差异无统计学意义（P＞0.05）,A组患者治疗时间为（15.86±6.58） d,同样与B组差异无统计学意义（P＞0.05）;两组患者胃肠道反应整体发生率对比差异无统计学意义（P＞0.05）;但A组患者血细胞计数下降20例,占50.00%,明显高于B组,组间对比差异有统计学意义（P＜0.05）。结论在异位妊娠患者的治疗中,采用甲氨蝶呤单次肌注联合米非司酮口服治疗,药物安全性高,疗效确切,患者不良反应发生率相对较低,有较高的临床应用价值,值得推广。