Leukocytapheresis for the treatment of refractory systemic-onset juvenile idiopathic arthritis

Although leukocytapheresis (LCAP) has been reported to be effective for the treatment of various autoimmune disorders, little information has been published yet on the efficacy and safety of LCAP for the treatment of systemic-onset juvenile idiopathic arthritis (SOJIA). A pilot trial of LCAP was therefore conducted on two children with refractory SOJIA using a granulocyte apheresis filter packed with cellulose acetate beads in an attempt to control the disease flares. Following three to eight sessions of LCAP, the joint symptoms gradually resolved without any increase in the dose of corticosteroids. The procedure was associated with a decrease in the serum interleukin-6. No severe adverse effects were observed except for mild nausea. However, efficacy of LCAP sustained in a short time since both patients subsequently developed flares after 3 months of the treatment.     

Leukocytapheresis for the treatment of active pouchitis: a pilot study

BACKGROUND: Pouchitis is a major long-term complication of ileal pouch-anal anastomosis for ulcerative colitis. The aim of this study is to investigate the efficacy of leukocytapheresis for the treatment of active pouchitis. METHODS: Eight patients with active pouchitis received leukocytapheresis weekly for 5 weeks in an open-label treatment protocol together with baseline therapy. RESULTS: Patients showed significant improvement in their pouchitis disease activity index scores, from 9.5 (range, 8-10) to 4.0 (range, 2-8) (P < 0.05). Six (75%) of the 8 treated patients achieved remission. No adverse events were observed. CONCLUSIONS: Leukocytapheresis therapy could be a new therapeutic strategy for patients with pouchitis after ileal pouch-anal anastomosis for ulcerative colitis. These encouraging results lead us to propose a randomized controlled trial.     

Leukocytapheresis for rheumatic disease

Leukocytapheresis (LCAP) is an apheresis technique for depleting pathogenic leukocytes from the circulating blood to improve the condition of the patient. LCAP sensu lato has been applied for the treatment of various rheumatic diseases: other treatments include thoracic duct drainage, photopheresis, centrifugal LCAP, granulocytapheresis (GCAP) and filtration LCAP. Among these modalities, GCAP and filtration LCAP are most commonly used in Japan for two reasons; the equipment and procedure are simple and practical and adverse events are rare and minor. In this article, LCAP, in particular filtration LCAP, for the treatment of rheumatic diseases is reviewed.     

干细胞移植在炎症性肠病治疗中的应用

随着干细胞和炎症性肠病(IBD)研究的深入,干细胞移植在IBD治疗中的应用取得一些进展。此文主要介绍了自体造血干细胞移植,同种异基因造血干细胞移植和间充质干细胞移植在IBD治疗中的应用。     

Drug insight: aminosalicylates for the treatment of IBD

Sulfasalazine and mesalazine (also known as mesalamine; 5-aminosalicylic acid) preparations have for many years been used for the treatment of IBD (i.e. ulcerative colitis and Crohn's disease), for both active disease and the control of remission. It has also been suggested that mesalazine is a chemoprophylactic agent that protects against the development of colorectal cancer. This Review focuses on the latest clinical evidence for the use of these aminosalicylates for the treatment of IBD, and concludes that sulfasalazine and mesalazine are useful for the treatment of both active and quiescent ulcerative colitis, whereas they have no clinical effect on either active or inactive Crohn's disease. Furthermore, evidence is lacking that mesalazine per se is a chemoprophylactic agent.     

Complications of Leukocytapheresis

Abstract: Recently leukocytapheresis (LCAP) has attracted attention as a new therapy for ulcerative colitis. We reviewed the complications associated with LCAP carried out in our department during the period from December 1992 to September 1997. There were side effects during 195 (9.9%) of the 1,978 sessions performed, involving 47 (51.1%) of the 92 patients treated. Moderate reactions, which caused considerable discomfort to the patients and required the transient interruption of the administration or some medical treatment depending on the state, occurred during 31 (1.6%) of all therapy sessions, involving 15 (16%) patients. All patients recovered soon and never fell into a life-threateningly severe state. They also did not have any symptoms afterwards. The common side effects were nausea, vomiting, fever, chills, and nasal obstruction. Reactions such as palpitations, respiratory distress, or chest oppressions were common, especially when heparin sodium (HS) was used as the anticoagulant. The type and frequency of side effects depended somewhat on the length of the therapy series or the duration of one session. Other complications such as clotting in the leukocyte removal filter and/or blood line during administration were encountered frequently. These latter problems occurred during 46% of all sessions, but most of them had little significance. Sessions in which HS was used as the anticoagulant showed more severe clotting than those in which nafamostat mesilate (NM) was used. In our series, we experienced a relatively low rate of serious complications. We require, of course, careful observation during and after each session.     

炎症性肠病的治疗进展

炎症性肠病（inflammatory bowel diseases，IBD）主要包括溃疡性结肠炎（ulcerative colitis，UC）和克罗恩病（crohn’s disease，CD），是一组慢性复发性疾病，病因未明，与肠道免疫机制有关，遗传和环境因素在IBD的发病中起重要作用。随着生活方式的改变，近年来IBD有增多趋势，对IBD发病机制的深入了解，发现分子和细胞介质在肠道免疫炎症过程中起重要作用，出现了环孢菌素、粘膜保护剂、抗肿瘤坏死因子抗体和白细胞去除术等新方法。本文就IBD的治疗进展作一综述。     

Leukocytapheresis Therapy for Severe Ulcerative Colitis

Abstract: Severe attacks of ulcerative colitis are medical emergencies, and surgical treatment is indicated when glucocorticoid therapy is not effective. We have carried out an open clinical study of patients with severe attacks of ulcerative colitis to find out whether leukocytapheresis (LCAP) therapy can improve their outcomes. Nine patients were enrolled in this study. Seven of the nine patients had failed to respond to an intensive intravenous regimen before LCAP. LCAP was performed once a week for 4–5 weeks as intensive therapy using a leukocyte apheresis filter. Six of the 9 patients had an overall improvement after intensive therapy. Three patients reached the remission stage. The percentages of HLA-DR+, HLA-DR+ CD3+, HLA-DR+ CD4+, and HLA-DR+ CD8+ cells in the peripheral blood were higher in the responders than in the nonresponders, but there were no significant differences. In conclusion, LCAP therapy is useful for patients with severe attacks of ulcerative colitis, even those patients who failed to respond to glucocorticoid therapy.     

New pathophysiological insights and modern treatment of IBD

Inflammatory bowel disease (IBD), which comprises two main types, namely, Crohn’s disease and ulcerative colitis, affects approximately 3.6 million people in the USA and Europe, and an alarming rise in low-incidence areas, such as Asia, is currently being observed. In the last decade, spontaneous mutations in a diversity of genes have been identified, and these have helped to elucidate pathways that can lead to IBD. Animal studies have also increased our knowledge of the pathological dialogue between the intestinal microbiota and components of the innate and adaptive immune systems misdirecting the immune system to attack the colon. Present-day medical therapy of IBD consists of salicylates, corticosteroids, immunosuppressants and immunomodulators. However, their use may result in severe side effects and complications, such as an increased rate of malignancies or infectious diseases. In clinical practice, there is still a high frequency of incomplete or absent response to medical therapy, indicating a compelling need for new therapeutic strategies. This review summarizes current epidemiology, pathogenesis and diagnostic strategies in IBD. It also provides insight in today’s differentiated clinical therapy and describes mechanisms of promising future medicinal approaches.     

Predictive Factors of Response to Leukocytapheresis Therapy for Ulcerative Colitis

Abstract. Leukocytapheresis (LCAP) using a leukocyte removal filter was performed for 8 patients with moderate to severe ulcerative colitis (UC). Significant clinical improvement was attained in 5 of 8 patients (62.5%). All of them had been suffering from moderately active colitis and Received corticosteroid therapy. On the other hand, 3 patients with severely active disease and treated with little or no corticosteroid were resistant to LCAP. This result indicates that LCAP is an effective treatment for steroid-resistant cases of UC when combined with steroid therapy. LCAP alone, however, seems to have little efficacy for severely active UC.     

When IBD is not IBD

Entamoeba histolytica colitis can mimic Crohn’s disease. However, a fulminant infection can be life-threatening, especially after exposure to systemic steroids. We present a case of the patient who was initially diagnosed with ileocolonic Crohn’s disease, but developed a hepatic E histolytica abscess while undergoing anti-TNF therapy. After revision of the initial diagnostic biopsies, the diagnosis was questioned and E histolytica was confirmed using PCR and histopathology. As intestinal amoebiasis is the most common form of amoebic infection, care should be taken in case of refractory IBD or at initial diagnosis in patients who travelled to endemic areas. We therefore discuss the epidemiology, clinical features, diagnostic tools and pathophysiology of E Histolytica in order to raise awareness among gastroenterologists treating patients with inflammatory bowel disease.     

Leukocytapheresis Using a Leukocyte Removal Filter

Abstract: Leukocytapheresis (LCAP) long has been investigated with a leukocyte removal filter for the treatment of various kinds of autoimmune related and inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and so on. A lot of patients with such diseases have been reported to respond to LCAP. Asahi Medical Co. has developed the leukocyte removal filter Cellsorba and an extracorporeal treatment unit Plasauto LC so that the LCAP technique can be performed easily with a high performance filter, easy attachment of the blood circuit tubing set, and automatic operation. Cellsorba E has been listed as a medical device reimbursed by Japanese national health insurance to be used in LCAP for active ulcerative colitis since October 2001. Although the effective mechanism of LCAP is still controversial, the removal of activated leukocyte from the peripheral blood and the reaction by blood contacting materials in Cellsorba can be triggers of the immunomodulation for the treatment of immune disorder. This review introduces the development of LCAP technologies and several reports on therapeutic results.