Rish K Pai 1, Douglas J Hartman 2, Claudia Ramos Rivers 3, Miguel Regueiro 4, Marc Schwartz 3, David G Binion 3, Reetesh K Pai Clin Gastroenterol Hepatol 2020 Oct;18(11):2510-2517.e5. doi: 10.1016/j.cgh.2019.12.011. Epub 2019 Dec 14.
Complete Resolution of Mucosal Neutrophils Associates With Improved Long-Term Clinical Outcomes of Patients With Ulcerative Colitis
Background & aims: We investigated correlations between histologic features of the colonic mucosa in patients with ulcerative colitis (UC) and clinical outcomes during a 3-year follow-up period. Methods: We obtained baseline biopsies from all colorectal segments (n = 889) from 281 patients with UC enrolled in a prospective study at a single center from 2009 through 2013. Biopsies were assessed in a blinded manner using validated histologic scoring systems (the Geboes score, Nancy histopathologic index, and Robarts histopathologic index). Clinical, endoscopic, and histologic data were collected and tested for correlations with systemic corticosteroid use, hospitalization, and colectomy within 3 years of the index colonoscopy. Results: We found histologic evidence of UC activity (Geboes score ≥ 2B.1) in biopsies from 182 patients (65%) and endoscopic evidence of UC activity in 149 patients (53%) (substantial agreement, κ = 0.60). Histologic features of UC activity were associated with increased rates of systemic corticosteroid use, colectomy, and hospitalization in the entire cohort (P < .05 for all) and associated with increased rates of systemic corticosteroid use in an analysis limited to patients in endoscopic remission (P < .001). In patients in endoscopic remission, only histologic activity was independently associated with use of systemic corticosteroids (multivariate odds ratio, 6.34; 95% CI, 2.20-18.28; P = .001). Similar results were seen when the entire cohort was analyzed. Compared with patients without histologic evidence of UC activity, patients with only a small number of mucosal neutrophils still had higher rates of systemic corticosteroid use (P < .001). Conclusions: Histologic evidence of UC activity, including small numbers of neutrophils in the colonic mucosa, is the only factor independently associated with use of systemic corticosteroids. Complete resolution of neutrophil-associated inflammation should be a target for treatment of UC.
Pyoderma gangrenosum with primary sclerosing cholangitis-associated colitis successfully treated with concomitant granulocyte and monocyte adsorption apheresis with corticosteroids
Clin J Gastroenterol. 2021 Oct;14(5):1561-1566. doi: 10.1007/s12328-021-01460-0. Epub 2021 Jun 8.
An 18-year-old woman was admitted to our hospital with fever, diarrhea and painful skin ulcers in both pretibial areas starting 19 days earlier. The skin lesions appeared deep necrotic ulcers with violaceous undermined borders. She had been diagnosed as ulcerative colitis and primary sclerosing cholangitis (PSC) 6 and 5 years before, respectively, and had stopped having regular check-up and refused medication for years. Her clinical history and skin lesions led us to suspect of pyoderma gangrenosum (PG). The skin biopsy showed aseptic abscess formation with neutrophils infiltration in the dermis without bacteria. Thus, she was diagnosed with PG. 1 mg/kg/day of prednisolone was administered and ten sessions of granulocyte and monocyte adsorption apheresis (GMA) were started. Magnetic resonance cholangiography showed multifocal bile duct strictures due to PSC. Total colonoscopy revealed ulcerative pancolitis with spared normal mucosa in the rectum. After the treatments, her symptoms and the skin lesion improved dramatically. She was discharged on the 45th day with 25 mg/day of prednisolone. In conclusion, this is the first reported case of PG with PSC-associated colitis that showed dramatic response to the concomitant GMA therapy with corticosteroids. Together with previous reports, concomitant GMA therapy with corticosteroids may be an effective treatment for PG.
Su1934-Safety of granulocyte and monocyte adsorptive apheresis in patients with inflammatory bowel disease undergoing concomitant treatment with immunosuppressant medications: a multicenter cohort study
Maki Miyakawa, Hiroki Tanaka, Tomoyoshi Shibuya,Taro Osada, Eiji Hosoi Gastroenterol. 2019 156 (6) Suppl.S-666–S-667
Background: Few studies have assessed the safety of granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) undergoing concomitant treatment with multiple immunosuppressant medications. To address this research gap, we investigated adverse effects associated with GMA in patients with IBD treated with multiple immunosuppressants who participated in the “Post-marketing surveillance study on the safety and response of GMA treatment in patients with Crohn’s disease or ulcerative colitis with at least one special situation who received Adacolumn® (PARTICULAR).” Methods: The PARTICULAR study was a retrospective, multicenter cohort study of patients with ulcerative colitis (UC) or Crohn’s disease (CD) who received GMA between November 2013 and March 2017. Patients meeting at least one of the following special situation were enrolled: elderly (<=65 years) or pediatric/adolescent (>=18 years) patients, patients with anemia, or patients undergoing concomitant treatment with multiple immunosuppressants. GMA was performed using Adacolumn® (JIMRO, Takasaki, Japan). Each patient received up to 11 GMA sessions, and all adverse events (AEs) during the study period were recorded. The incidence of AEs was investigated relative to the number and type of immunosuppressants using univariate and multivariate logistic regression analyses. Results: A total of 437 patients (368 UC, 69 CD) from 93 institutions were included. Of these, 140, 169, 101, and 27 patients received none, 1, 2, and >=3 immunosuppressants, respectively. In total, 125 patients received multiple immunosuppressants. Concomitant prednisolone, immunomodulators, anti-tumor necrosis factor agents, and calcineurin inhibitors were administered in 189, 151, 89, and 24 patients, respectively. The incidence of AEs was 11% in all 437 patients and 8%, 12%, 12%, and 26% in patients receiving none, 1, 2, and >=3 immunosuppressants, respectively. In multivariate logistic regression analysis, anemia and concomitant immunosuppressants were independently associated with the incidence of AEs. Particularly, a higher number of concomitant immunosuppressants showed an increasing trend with odds ratios related to AEs. In contrast, concomitant corticosteroids were associated with a reduced risk of AEs. Nausea/vomiting and headache were the most common AEs in patients on multiple immunosuppressant medications (5.6% and 3.2%, respectively). Conclusions: Concomitant treatment with immunosuppressants was independently associated with the incidence of AEs such as nausea/vomiting and headache in patients with IBD receiving GMA. As the number of concomitant immunosuppressants increased, the incidence of AEs also increased. However, our data also suggest that GMA is safe in patients with IBD receiving prednisolone.
Pyoderma Gangrenosum with Ulcerative Colitis Successfully Treated by the Combination of Granulocyte and Monocyte Adsorption Apheresis and Corticosteroids
Intern Med. 2016;55(1):25-30. doi: 10.2169/internalmedicine.55.5422. Epub 2016 Jan 1.
A 36-year-old woman was admitted to our hospital due to swelling and redness of the left lateral malleolus and dorsum of the left foot with severe pain, with a flare-up of ulcerative colitis (UC). A pathologic examination by skin biopsy led to a diagnosis of pyoderma gangrenosum (PG). She was treated with the intravenous administration of prednisolone (60 mg/day), and granulocyte and monocyte adsorption apheresis (GMA) was performed twice-a-week for 5 weeks. This treatment dramatically improved both the skin and colonic mucosal lesions. These results suggest that a combination of GMA and corticosteroids might be recommendable to induce the remission of serious PG complicated with UC.
Efficacy, safety and cost analyses in ulcerative colitis patients undergoing granulocyte and monocyte adsorption or receiving prednisolone
Background: Patients with ulcerative colitis (UC) are treated with prednisolone (PSL), which causes adverse side effects. Extracorporeal granulocyte/monocyte adsorption (GMA) with an Adacolumn depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested to evaluate the efficacy, safety and the treatment cost for PSL and GMA. Methods: Forty-one patients with active UC had achieved remission with GMA, at 1 or 2 sessions/week, up to 10 sessions (n=24) or with orally administered PSL (1mg/kg bodyweight, n=17). Clinical activity index (CAI) ≤4 was considered clinical remission. Following remission, patients received 5-aminosalicylic acid (2250-3000mg/day) or sulphasalazine (4000-6000mg/day) as maintenance therapy and were followed for 600 days. The total treatment cost was assessed based on 1€=150JPY. Results: PSL was tapered after two weeks, and discontinued when a patient achieved remission. The average time to the disappearance of at least one major UC symptom (haematochezia, diarrhoea, or abdominal discomfort) was 15.3 days in the GMA group and 12.7 days in the PSL group, while time to remission was 27.9 days in the GMA group and 27.6 days in the PSL group, CAI 0.8 and 2.0, respectively. The Kaplan-Meier plots showed similar remission maintenance rates over the 600 days follow-up period. The average medical cost was 12739.4€/patient in the GMA group and 8751.3€ in the PSL group (P<0.05). In the GMA group, 5 transient adverse events were observed vs 10 steroid related adverse events in the PSL group (P<0.001). Conclusions: In appropriately selected patients, GMA has significant efficacy with no safety concern. The higher cost of GMA vs PSL should be compromised by good safety profile of this non-pharmacological treatment intervention.
Leukocytapheresis in a girl with severe ulcerative colitis refractory to corticosteroids, infliximab, and cyclosporine A
Although medical therapy remains the first-line treatment for UC, colectomy may be required for patients with severe medically refractory disease. Leukocytapheresis (LCAP) has been reported as a new line of therapy in
patients with UC. Only 2 pediatric case series, not including patients on immunosuppressive therapy or biologicals, treated with granulocytapheresis have been reported. The patient reported by us is the youngest to the best of our knowledge in which this LCAP technique was used . She had severe colitis refractory to corticosteroids, infliximab and yclosporine A. We were able to avoid colectomy and the procedure was well tolerated.
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