Tomoyoshi Shibuya,Keiichi Haga,Michio Saeki,Mayuko Haraikawa,Hitoshi Tsuchihashi,Koki Okahara,Osamu Nomura,Hirofumi Fukushima,Takashi Murakami Dai Ishikawa,Shigaku Ikeda,Akihito Nagahara

J Clin Apher.  2020 Sep;35(5):488-492. doi: 10.1002/jca.21821. Epub 2020 Aug 7.

Pyoderma gangrenosum (PG) is an extra-intestinal skin lesion in inflammatory bowel disease (IBD) as is erythema nodosum. Vedolizumab (VED) is a monoclonal antibody that targets α4β7 integrin and has an intestinal selective mechanism. Despite good therapeutic effects on colitis, the effect on extra-intestinal manifestations (EIMs) remains unclear. Here we report a case of ulcerative colitis complicated by PG during treatment with VED, which was successfully treated with prednisolone in combination with adsorptive granulocyte and monocyte apheresis (GMA). The patient was a 50-year-old woman with a past medical history of extensive ulcerative colitis managed by golimumab (GLM). She developed flare symptoms due to loss of response to GLM, and treatment was switched to VED. Her gastrointestinal symptoms were improved with VED treatment with less frequent bowel movements. However, infiltrative erythema with pain appeared on the right lower leg and right knee, and expanded and gradually ulcerated. Her skin lesions were treated with corticosteroid, but showed poor improvement. Therefore, granulocyte and monocyte apheresis (GMA) treatment was administered in combination with prednisolone. After 3 months, the ulcer gradually improved, and at the time of this writing, the eruptions were nearly replaced by epithelial tissue. This case study showed that patients with UC and EIMS may respond well to combination therapy of VED and GMA. GMA has a very favorable safety profile. On the other hand, the causal connection between VED and PG is still unclear. We believe that a combination therapy involving VED and GMA in IBD patients with EIMs warrants consideration.

https://pubmed.ncbi.nlm.nih.gov/32767842/

Takuro Kanekura ¹, Koichi Kawahara ² , Int J Infect Dis 2020 Oct;99:1-2. 

To our knowledge, GMA has a good safety profile; serious adverse effects are rarely reported. Its modes of action together with the findings of this case report support our notion that GMA is a relevant therapeutic option for patients with COVID-19 and warrants an immediate clinical trial to evaluate its full therapeutic efficacy in a large cohort of COVID-19 patients.

https://pubmed.ncbi.nlm.nih.gov/32721534/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834290/pdf/main.pdf

Tetsurou Imai ¹, Hiroshi Yamasaki ^2 3 4, Keiichi Mitsuyama ³, Osamu Yamaga ¹, Gaku Sugihara ¹, Yusuke Kaida ⁵, Ryo Shibata ⁵, Takuma Hazama ⁵, Shinichiro Yoshioka ^2 3, Takuji Torimura ², Kei Fukami ⁵, Norio Yamashita ⁶

Kurume Med J. 2020 Jul 1;66(1):1-7. doi: 10.2739/kurumemedj.MS661002. Epub 2020 Jan 15.

Introduction: Granulocyte and monocyte apheresis (GMA) is an effective treatment strategy for active ulcerative colitis (UC) in Japan. Single needle (SN) apheresis reduces needle puncture pain in patients because it requires only one puncture site. We evaluated whether single-needle apheresis could be a safe and effective means of reducing patient burden. Method: We performed a retrospective study of active UC patients who were treated with either SN apheresis or conventional double-needle (DN) apheresis at the Kurume university hospital from April 2014 to March 2018. All the patients treated with GMA after September 2016 underwent SN apheresis. Thus, the two groups predominantly belonged to different time periods. We assessed the safety of SN apheresis. Result: Six patients underwent SN apheresis, and 6 underwent DN apheresis. The average time to the start of apheresis was significantly reduced from 23.1 minutes in the case of DN apheresis to 12.6 minutes for SN apheresis. In addition, the number of difficult punctures was significantly reduced with SN apheresis. There were no differences in adverse events between SN and DN apheresis. Treatment benefits, remission rate and disease activity were similar between SN and DN apheresis.Conclusion: SN apheresis reduced both the time to treatment initiation and pain during puncture, and there was no difference in the number of blood clotting episodes as compared with DN. Although further comparative studies are needed, SN apheresis may be a safe alternative for patients to reduce the strain of treatment.

https://pubmed.ncbi.nlm.nih.gov/31941846/

https://www.jstage.jst.go.jp/article/kurumemedj/66/1/66_MS661002/_article

Kentaro Tominaga, Kenya Kamimura, Hiroki Sato, Masayoshi Ko, Yuzo Kawata, Takeshi Mizusawa, Junji Yokoyama, and Shuji Terai, World J Clin Cases. 2020 Jun 6; 8(11): 2092–2101.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis clinically characterized by the presence of painful skin ulcerations with erythematous. As it is frequently associated with inflammatory bowel diseases, including ulcerative colitis, gastroenterologists should be familiar with the disease including therapeutic options. Pyoderma gangrenosum is one of the neutrophilic dermatoses often complicated with ulcerative colitis. The corticosteroid and other immune modulator have been used for the treatment, however, as its disease mechanism has not been clarified, there is no additional option for those who showed poor response and refractory to the conventional therapies. Therefore, we have conducted a review focusing on the cytapheresis for PG in cases of inflammatory bowel diseases. A literature search was conducted to extract studies published in the last 20 years, with information on demographics, clinical symptoms, treatment, and the clinical course from a total of 22 cases reported and our recent case. In most patients, cytapheresis was associated with improvement or resolution of PG after failure of conventional therapeutic options such as corticosteroids, antibiotics, immunosuppressive agents and immunoglobulin. Based on the recent reports, we have summarized the clinical course of 23 cases and efficacy of cytapheresis..Cytapheresis is helpful in the majority of patients with PG refractory to medical treatment associated with inflammatory bowel diseases and could be further studied in a multicenter, randomized trial.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281039/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281039/pdf/WJCC-8-2092.pdf

Chie Kurihara, Toshihide Ohmori, Kenichi Inaba, Shunsuke Komoto, Kengo Tomita, Ryota Hokari Gastroenterology 2020 158 (6) Suppl.S-1046

Background: Granulocyte and monocyte adsorptive apheresis (GMA) is non-pharmacological therapy which selective depletion of activated granulocytes and monocytes/macrophages from peripheral blood, and it is used as induction therapy for IBD. However, its therapeutic mechanism has not been well characterized. Recently, it has been reported that Th17 releases chemokines which attract neutrophils, and some neutrophils produce IL17. We investigated that changes in mRNA expression levels of inflammation associated molecules such as cytokines, chemokines in colonic mucosa of ulcerative colitis (UC) patients before and after GMA treatment in order to obtain further understanding of GMA therapeutic mechanisms. Methods: Thirty-two active UC patients (Mayo score ≥ 5 and Mayo endoscopic score ≥ 2) and 10 non-IBD control subjects were enrolled in this study. All UC patients received 10 times of GMA, and colonoscopies were applied before the first GMA and after the last GMA. Control subjects underwent colonoscopies for screening of colon cancer. Assessment of GMA therapeutic efficacy was determined based on Mayo score. Inflammation-related molecules mRNA expressions were determined by quantitative RT-PCR using biopsy specimen of colonic mucosa. Results: GMA treatment efficacy is 11 patients (34.4%) achieved clinical remission, 17 patients (53.1%) were response and 4 patients (12.5%) were non-response. Baseline characteristics such as sex, location of disease, CRP, WBC and Mayo score were not significantly different according to GMA efficacy. In the remission group, mRNA levels in mucosal tissue of IL1β, IL6, IL17, IL23 and GM-CSF which are Th17-asociated cytokines significantly decreased after the last GMA compared to the baseline levels(P<0,05) in contrast, expression of these mRNA tended to increase following GMA treatment in the non-response group. On the other hand, IL12 and IFN- γ which are associated with Th1 did not significantly decrease in the remission group. mRNA levels of leukocyte trafficking associated molecules such as MAdCAM-1, ICAM-1, integrinβ7, IL8 and MIP-1β significantly decreased following GMA treatment in the remission group(P <0.05), whereas only IL8 mRNA expression in the non-response group tended to increase. IL1 β, IL6, GM-CSF which are Th17-asociated cytokines and IL8 mRNA expressions in post-GMA treatment were significantly higher in the non-response group compared to the remission group or control group(P <0.05). Conclusion: In UC patients who achieved clinical remission by GMA, Th17- associated cytokines and leukocyte trafficking associated molecules but not Th1-asociated cytokines decreased significantly. Furthermore, Th17-asociated cytokines increased in the non-responders. These results reaffirm the involvement of neutrophil in the pathophysiology of UC and could be helpful for characterizing of GMA therapeutic mechanism.

https://www.gastrojournal.org/article/S0016-5085(20)33300-X/pdf

Kento Fujii ¹, Tomoko Takahashi ¹, Kanako Matsuyama ¹, Asami Fujii ¹, Yoko Mizutani ¹, Hidenori Ohnishi ², Mariko Seishima ¹ , J Dermatol 2020 Mar;47(3):e84-e85.

https://pubmed.ncbi.nlm.nih.gov/31971270/

Satoshi Tanida ¹, Keiji Ozeki ¹, Tsutomu Mizoshita ¹, Mika Kitagawa ¹, Takanori Ozeki ¹, Mamoru Tanaka ¹, Hirotada Nishie ¹, Takaya Shimura ¹, Eiji Kubota ¹, Hiromi Kataoka ¹ , J Clin Med Res, 2020 Jan;12(1):36-40.

Based on these outcomes, combination therapy with TOF plus intensive GMA was well tolerated and may be useful for induction of clinical remission in patients with refractory UC.

https://pubmed.ncbi.nlm.nih.gov/32010420/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968921/pdf/jocmr-12-036.pdf

Yuki Isami,Yuriko Kawase,Akari Kondo,Wataru Akita,Koji Yasuda,Takeshi Matsutani,Hiroshi Mitsui

J Dermatol. 2020 May;47(5):e213-e215. doi: 10.1111/1346-8138.15303. Epub 2020 Mar 11.

letter.

https://pubmed.ncbi.nlm.nih.gov/32162361/

Tomoyoshi Shibuya ¹, Osamu Nomura ², Kei Nomura ², Koki Okahara ², Keiichi Haga ², Dai Ishikawa ², Naoto Sakamoto ², Tatsuo Ogihara ², Taro Osada ², Akihito Nagahara ² , Digestion, 2020;101(1):46-52. 

Unlike pharmacologicals, the efficacy of Cytapheresis appears to be time dependent. Accordingly, in the elderly, we observed a delayed response, indicating that elderly patients may respond beyond the end of Cytapheresis therapy. Therefore, patients who do not show efficacy at the end of Cytapheresis therapy should be followed up for delayed response. Further, Cytapheresis is favored by patients for its good safety profile.

https://pubmed.ncbi.nlm.nih.gov/31722366/

Anand Padmanabhan ¹, Laura Connelly-Smith ², Nicole Aqui ³, Rasheed A Balogun ⁴, Reinhard Klingel ⁵, Erin Meyer ⁶, Huy P Pham ⁷, Jennifer Schneiderman ⁸, Volker Witt ⁹, Yanyun Wu ¹⁰, Nicole D Zantek ¹¹, Nancy M Dunbar ¹², Guest Editor Joseph Schwartz ¹³ ,J Clin Apher. 2019 Jun;34(3):171-35

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

https://pubmed.ncbi.nlm.nih.gov/31180581/