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Efficacy of cytapheresis for induction therapy and extra-intestinal skin manifestations of ulcerative colitis

Tomoyoshi Shibuya,Osamu Nomura,Kei Nomura,Mayuko Haraikawa,Keiichi Haga,Dai Ishikawa,Taro Osada,Ken Yamaji,Shigaku Ikeda,Akihito Nagahara

Ther Apher Dial 2022 Mar 5. doi: 10.1111/1744-9987.13823. Online ahead of print.

Introduction: In recent years, the prevalence of inflammatory bowel diseases has been increasing in Japan due to the westernization of lifestyles. Many patients have been reported to have extra-intestinal manifestations (EIMs) at least once. Skin lesions occur with a high degree of frequency among EIMs, with erythema nodosum (EN) and pyoderma gangrenosum (PG) the main complications. Cytapheresis is again attracting attention as a treatment with few side effects. Methods: We investigated the therapeutic effect of cytapheresis on ulcerative colitis (UC) and cutaneous EIMs. Between 2008 and 2021, 240 patients with active UC had induction therapy by cytapheresis at our hospital. Results: Remission and response rates were 50.0% and 67.5%, respectively. Apheresis was performed on seven patients with PG and five patients with EN with a good response. Serious adverse events were not observed. Conclusion: This retrospective assessment of efficacy showed that EN and PG responded favorably to cytapheresis.

https://pubmed.ncbi.nlm.nih.gov/35247233/

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Pyoderma gangrenosum with primary sclerosing cholangitis-associated colitis successfully treated with concomitant granulocyte and monocyte adsorption apheresis with corticosteroids

Munenori Kawai 1Chiharu Kawanami 2Akihisa Fukuda 3Hiroshi Seno 3 Clin J Gastroenterol. 2021 Jun 8. doi: 10.1007/s12328-021-01460-0. Online ahead of print

Together with previous reports, concomitant GMA therapy with corticosteroids may be an effective treatment for PG.

https://pubmed.ncbi.nlm.nih.gov/34101129/

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Intensive granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis

Yoko MizutaniKento FujiiMiho KawamuraMadoka InoueYuki H. MizutaniKanako MatsuyamaTomoaki DoiSoichiro NagayaMariko Seishima, https://doi.org/10.1111/1346-8138.15569

Granulocyte and monocyte adsorption apheresis (GMA) is usually performed weekly (consisting of five sessions) for refractory skin diseases, such as generalized pustular psoriasis (GPP). The time to remission of inflammatory bowel diseases has been reported to be significantly shorter in intensive GMA (twice a week) than in regular GMA (once a week).

https://onlinelibrary.wiley.com/doi/abs/10.1111/1346-8138.15569

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Cytapheresis for pyoderma gangrenosum associated with inflammatory bowel disease: A review of current status

Kentaro TominagaKenya KamimuraHiroki SatoMasayoshi KoYuzo KawataTakeshi MizusawaJunji 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

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Impetigo herpetiformis with a CARD14 Thr79Ile variant successfully treated with granulocyte and monocyte adsorption apheresis

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EO5-01 A case of pustular psoriasis deteriorated during the second pregnancy was successfully treated with intensive GMA and certolizumab pegol

Asumi Fujii, Yuki Hattori, Miho Kawamura, Yoko Mizutani, En Shu, Mariko Seishima

poster at ISFA 2019 pag 141-142

A 31-year-old woman with the IL36RN gene mutation developed psoriasis at 3 years old. As she had pustular psoriasis at 16 years old, she was treated with cyclosporine (Cys), resulting in remission at 20 years old. Afterwards, she had been maintained by topical treatment for long years.During the first pregnancy at the age of 29, she developed pustular psoriasis at 29 weeks
of gestation. She received one course of granulocyte / monocyte adsorption apheresis (GMA) with Cys and prednisolone (PSL), and gave birth to a girl at 33 weeks of gestation. The baby was a low birth weight child, but is healthy and has no problems in growth and development until now. However, the patient did not sufficiently improve symptoms after delivery. We thus started the treatment with infliximab (IFX) BS at 2 months postpartum. During the second pregnancy at the age of 30, we continued the IFX-BS administration. She had erythema and pustules rapidly enlarged from 23 weeks of pregnancy. Oral administration of PSL and GMA were started. However, we switched the therapy to intensive GMA (twice in a week), because the effect was insufficient. Initially, administration of IFX-BS was scheduled to end at 30 weeks of gestation, but due to unstable symptoms, we considered it was necessary to use another biologics even after 30 weeks of gestation. We switched to non-placental certolizumab pegol (CTZ) from 26 weeks of gestation and continued the administration until delivery, and she gave birth to a girl at 35 weeks of gestation. Although the baby was a low birth weight child, there was no physical abnormality and the baby was discharged after gaining weight. After delivery, administration of CTZ was discontinued and the PSL dose was gradually reduced. However,reintroduction of biologics is under consideration, because erythema and pustules still remain.

http://www.atalacia.com/isfa/data/abstract.pdf

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SA6-03 MicroRNA and granulocyte and monocyte adsorption apheresis on neutrophilic skin diseases

Yuko Higashi, Munekazu Yamakuchi, Takuro Kanekura

poster at ISFA 2019 pag 126

Neutrophilic skin diseases are a group of disorders characterized by intense dermal infiltration of neutrophils without infection. They include a variety of diseases, such as pyoderma gangrenosum, pustular psoriasis, and palmoplantar pustulosis. We demonstrated that granulocyte and monocyte adsorption apheresis (GMA) is a useful treatment modality for such refractory skin diseases. Microarray analysis of microRNAs (miRNAs) was performed using sera of patients with neutrophilic skin diseases before and after GMA. Several miRNAs significantly increased in patients compared to control subjects. The expression of three
miRNAs decreased after apheresis, suggesting that these miRNAs might be involved in the pathogenesis of neutrophilic skin decreases. To prove the function of these miRNAs, HL-60, a human acute promyelocytic leukemia cell line, was differentiated by the treatment of alltrans retinoic acid (ATRA). When HL-60 was differentiated to neutrophilic cells, the HEstaining shows an increased cytoplasm to nucleus ratio, condensated chromatin, and nuclear segmentation. The expression of three miRNAs increased during the neutrophilic differentiation. Stimulation of ATRA-treated HL-60 by some cytokines altered miRNA expressions. Moreover, manipulation of these miRNAs changed proliferation of cultured keratinocytes. These data
suggest that miRNAs play an important role in regulating neutrophilic differentiation and proliferation of keratinocytes in case of neutrophilic disorders such as psoriasis. These miRNAs could be markers of disease severity and response of GMA.

http://www.atalacia.com/isfa/data/abstract.pdf

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Evaluation of the efficacy of granulocyte and monocyte adsorption apheresis on skin manifestation and joint symptoms of patients with pustulotic arthro-osteitis

Hiroshi Kawakami 1Yume Nagaoka 2Hirofumi Hirano 1Yuka Matsumoto 1Namiko Abe 1Ryoji Tsuboi 1Yoshihiko Kanno 2Yukari Okubo 1 J Dermatol 2019 Feb;46(2):144-148.

We concluded that granulocyte and monocyte adsorption apheresis is a therapeutic option to consider when pustulotic arthro-osteitis is recalcitrant to conventional therapy.

https://pubmed.ncbi.nlm.nih.gov/30549087/

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Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP.

Hideki Fujita 1Tadashi Terui 1Koremasa Hayama 1Masashi Akiyama 2Shigaku Ikeda 3Tomotaka Mabuchi 4Akira Ozawa 4Takuro Kanekura 5Michiko Kurosawa 6Mayumi Komine 7Kimiko Nakajima 8Shigetoshi Sano 8Osamu Nemoto 9Masahiko Muto 10Yasutomo Imai 11Kiyofumi Yamanishi 11Yumi Aoyama 12Keiji Iwatsuki 13, J Dermatol . 2018 Nov;45(11):1235-1270. 

 The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP.

https://pubmed.ncbi.nlm.nih.gov/30230572/

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Clinical and immunological effects of adsorptive myeloid lineage leukocyte apheresis in patients with immune disorders.

Takuro Kanekura 1, J Dermatol 2018 Aug;45(8):943-950

These actions render GMA a unique non-pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations.

https://pubmed.ncbi.nlm.nih.gov/29782055/

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