Leukocyte Apheresis in the Management of Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disease that affects the colon and rectum. Its pathogenesis is probably multifactorial including the influx of certain cytokines into the colonic mucosa, causing disease activity and relapse. The hypothesis of removing such cytokines from the circulation by leukocytapheresis was implemented to reduce disease activity, maintain remission, and prevent relapse. Many recent reports not only in Japan, but also in the West, have highlighted its beneficial effects in both adult and pediatric patients. Large placebo-controlled studies are needed to confirm the available data in this regard. In this article, we shed some light on the use of leukocyte apheresis in the management of autoimmune diseases, especially ulcerative colitis.     

Adsorptive Monocyte-granulocytapheresis (M-GCAP) for refractory Crohn's disease

Six patients with active Crohn's disease (CD) unresponsive to conventional medications (CM) were treated with Monocyte-granulocytapheresis (M-GCAP). CD patients who scored 200-400 points in Crohn's disease activity index (CDAI) in spite of receiving CM, including enteral nutrition, for at least 2 weeks were enrolled in our double series trial. Each series had 5 weekly M-GCAP and 2 follow-up weeks, and each M-GCAP treated 1,800 ml of patient's peripheral blood. After the 1st series, patients who decreased more than 50 points on the CDAI were deemed responders and enrolled in the second series. Patients with a CDAI score less than 150 points were considered in remission. The patients' quality of life was evaluated using an index (IBDQ) before and after the 1st series. The CDAI was significantly decreased comparing before and after the 1st series (258.2 +/- 36.2 vs. 166.5 +/- 16.6; P < 0.02). 50% of patients (3/6) responded to the therapy, and one case (16.7%) could be induced to remission. Significant removal was revealed only for white blood cells (25.6 +/- 16.9%; P < 0.05), especially granulocytes (29.5 +/- 22.5%; P < 0.05). A statistically significant improvement of IBDQ was revealed in the responders' group (162.3 +/- 17.2 vs. 189.3 +/- 11.5; P < 0.03). M-GCAP could be an effective adjunctive therapy for active CD patients unresponsive to CM allowing them to maintain a high QOL. However, it might be difficult to improve patients who could not be induced to remission after the 1st series by applying another series.     

Granulocytapheresis versus methylprednisolone in patients with acute ulcerative colitis: 12-month follow up

Aim: To evaluate granulocytapheresis (GCAP) in active ulcerative colitis (UC), with particular attention to the long‐term effects of such treatment. Methods: We included 80 patients with UC. Activity of the disease was evaluated by clinical activity index and endoscopic index. Patients were randomly divided in two groups: Group A received a five‐session (1 session/week) treatment with GCAP, Group B were treated with i.v. or i.m. methylprednisolone (MP). Concomitant therapy with oral 5‐aminosalicylic acid (5‐ASA) 2.4 g/day was maintained in both groups. Subjects who achieved a remission were clinically and endoscopically followed for 12 months after the end of GCAP or MP. Results: Remission was observed in 72.5% of those treated with GCAP versus 50% of those treated with MP. After a 12‐month follow up, a sustained remission was recorded in 40% of those treated with GCAP and in 25% of those treated with MP. During the GCAP only a transient mild headache was recorded in 10% of patients, whereas side‐effects were observed in 50% of those treated with MP (P < 0.05). Conclusion: GCAP results were superior to MP for the treatment of UC, even though no statistically significant difference was observed. Side‐effects in the GCAP group were significantly lower than in the MP group. This new therapeutic approach seems able to maintain the condition of remission for a longer time after a flare. In fact, the patients who had obtained a remission after a course of CGAP showed fewer relapses during the follow up compared to the patients treated with MP.     

Case of generalized pustular psoriasis with end‐stage renal disease successfully treated with granulocyte monocyte apheresis in combination with hemodialysis

Granulocyte monocyte apheresis (GMA) is an extracorporeal apheresis instrument that removes activated neutrophils and monocytes. Generalized pustular psoriasis (GPP) is characterized by neutrophil infiltration into the epidermis that causes Kogoj's spongiotic pustule. Thus, GMA is one of the useful therapies for GPP, and it was approved for the treatment in 2012 in Japan. Herein, we report a case of GPP with end‐stage renal disease (ESRD) successfully treated with GMA in combination with hemodialysis (HD). A 54‐year‐old Japanese female visited our outpatient clinic because of erythema with pustules on her trunk and extremities over the past 4 months. Histopathological examination showed an intraepidermal pustule filled with numerous neutrophils and spongiosis. These findings led to the diagnosis of GPP. She had ESRD and had been treated with HD twice a week for approximately 4 years. During maintenance HD twice a week, weekly GMA was started at Tokai University Hospital. The skin symptoms disappeared after five administrations of GMA. We suggest that GMA is an effective therapy for GPP patients with ESRD who are treated with HD.     

Extracorporeal leukocyte removal therapy for patients with ulcerative colitis

Background: The purpose of the present paper was to investigate efficacy of leukocytapheresis (LCAP) or granulocytapheresis (GCAP) in pediatric patients with ulcerative colitis (UC), including reduction of the total dose and side‐effects of corticosteroids. Methods: Courses of five Japanese adolescents with UC were analyzed. Four patients had recurrent UC with repeated remissions and exacerbations despite therapy including 5‐aminosalicylic acid in combination with a corticosteroid. The other patient had a first attack. Effectiveness of adding LCAP or GCAP was assessed with regard to short‐term changes in clinical activity, complications, and longer‐term outcome. Results: Clinical improvement was attained in three patients, while the other two did not improve and underwent colectomy. One of the two patients had moderately severe complications from LCAP and showed increased clinical activity during LCAP. The other, who began therapy with LCAP alone, had moderate improvement only after addition of a corticosteroid. Conclusion: Additional studies are needed to determine optimum timing of LCAP or GCAP and initiation of remission‐maintenance therapy.     

Granulocytapheresis in patients with refractory ocular Behcet's disease

Intraocular inflammation (uveoretinitis) is one major complication of Behcet's disease (BD) and responds poorly to drug therapy. This open prospective study was to assess the efficacy of selective granulocytapheresis in patients with refractory uveoretinitis of BD. Fourteen patients aged 20-56 years were treated. Granulocytapheresis was done with an Adacolumn filled with cellulose acetate leucocyte carries or beads that adsorb granulocytes and monocytes from the blood in the column. Each patient received 5 Adacolumn sessions at one session/week over 5 consecutive weeks. The study was designed to allow each patient to serve as his or her own control. The total numbers of ocular attacks (OA) were monitored for 6 months before and after 5 Adacolumn sessions. The number of OA (mean +/- SD) per patient for the 6 months before Adacolumn was 4.21 +/- 1.6 and for the 6 months post Adacolumn was 2.93 +/- 1.39 ( P = 0.0275). Nine patients (64%) improved and 5 did not change or worsened. Further, for a sub-group (n = 7) with duration of BD > or =5 years, the number of OA were 4.71 +/- 1.89 for the first 6 months and 2.29 +/- 1.38 for the second 6 months ( P = 0.0054). The corresponding values for a sub-group (n = 7) with duration of BD<5 years were 3.71 +/- 1.25 and 3.57 +/- 1.13, indicating that patients with long duration of BD are better responders. We conclude that granulocytapheresis might be effective and safe for patients with refractory ocular BD. Further studies are necessary to fully evaluate the clinical efficacy of granulocytapheresis for BD.     

Granulocytapheresis in the treatment of patients with active ulcerative colitis

In recent years, considering the role of inflammatory processes and the involvement of the immune system in ulcerative colitis, granulocytapheresis, a technique for removing circulating leukocytes and preventing their migration into the intestinal mucosa, has been proposed for the treatment of acute ulcerative colitis. Initially introduced for the treatment of patients who did not respond to conventional therapy only, this new therapy may become a useful and safe method to induce clinical remission in patients with acute disease. This article will review the clinical applications and issues concerning the use of granulocytapheresis in ulcerative colitis.     

Rapidly Progressing Aseptic Abscesses in a Patient with Ulcerative Colitis

Aseptic abscesses (AAs) are extraintestinal manifestations of inflammatory bowel disease (IBD). IBD-associated AAs are rare in Japan. We treated a 45-year-old man with ulcerative colitis (UC)-associated AAs. During remission, multiple progressive abscesses were detected in the spleen; he underwent splenectomy because an infectious disease was suspected. Although his condition improved temporarily after splenectomy, a large liver abscess was noted, and a diagnosis of UC-associated AAs was made. Granulocytapheresis (GCAP) and infliximab (IFX) administration resolved the abscess. This is the first reported case of UC-associated AAs in a Japanese patient treated by splenectomy, GCAP, and IFX.