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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.

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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.

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Efficacy of cytapheresis for remission induction and dermatological manifestations of ulcerative colitis.

Osamu Nomura 1Taro Osada 1Tomoyoshi Shibuya 1Dai Ishikawa 1Keiichi Haga 1Tomohiro Kodani 1Naoto Sakamoto 1Tatsuo Ogihara 1Ken Yamaji 2Sumio Watanabe 1 , J Clin Apher 2018 Feb;33(1):21-28.

In this retrospective efficacy evaluation, cytapheresis was effective as remission induction therapy with steroid sparing effect and desirable safety profile. Further, patients with EN or PG responded favorably to cytapheresis.

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Treatment of a Case of Ulcerative Colitis with Sacroiliitis Using Granulocyte and Monocyte Adsorption Apheresis

Hitoshi Ichikawa 1Jin ImaiHajime MizukamiTakayuki ShiraiNorihito Watanabe, Tokai J Exp Clin Med. 2017 Jul 20;42(2):64-66.

Unlike conventional medication, GMA apheresis has no serious adverse effects. We present the first report of a UC patient with sacroiliitis, who responded well to GMA therapy. GMA apheresis may be considered a new treatment option for UC-associated spondyloarthropathy that is refractory or tolerant to conventional treatment.

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Granulocyte and monocyte adsorption apheresis for paradoxical reaction to infliximab.

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Successful treatment of neutrophilic dermatosis in patient with Crohn’s disease with granulocyte and monocyte adsorption apheresis.

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Granulocyte and Monocyte Adsorption Apheresis for Refractory Skin Diseases due to Activated Neutrophils, Psoriasis, and Associated Arthropathy.

Masanao Sakanoue 1Koichiro TakedaKazuhiro KawaiTakuro Kanekura, Ther Apher Dial. 2013 Oct;17(5):477-83.

Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is designed to remove activated granulocytes and monocytes. We previously demonstrated that GMA was useful for treating neutrophilic dermatoses and associated arthropathy as it adsorbs Mac-1 (CD11b/CD18)-expressing neutrophils to the CA beads by the binding of complement component (iC3b) and CD11b expressed on activated neutrophils. The objective of this study is to further assess the clinical effectiveness of GMA in the treatment of neutrophilic dermatoses and associated arthropathy. The effect of GMA for skin lesions and joint lesions was assessed in 44 and 23 patients, respectively. Mac-1 expression on peripheral neutrophils was measured by flow cytometry. Skin lesions and arthropathy improved in 39 of 44 patients (88.6%) and 22 of 23 (95.6%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, 27.1 ± 6.66 MFI (mean fluorescence intensity) before treatment, was reduced to 17.9 ± 3.02 MFI by GMA (P < 0.05). Clinical effectiveness of GMA for the treatment of intractable neutrophilic dermatoses and associated arthropathy was further confirmed.

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The efficacy of intensive granulocyte and monocyte adsorption apheresis in a patient with Crohn’s disease complicated by extensive subcutaneous aseptic neutrophilic abscesses.

Shingo Kato 1Eriko HosomiFumi AmanoTaisuke KobayashiKazuhito KaniRyuichi YamamotoTomonari OgawaAkihiko MatsudaYoshiki SatoSeiichi IzakiTetsuya MitaraiKoji Yakabi, J Crohns Colitis. 2012 Aug;6(7):787-91.

Background and aims: Subcutaneous aseptic abscess is one phenotype of neutrophilic dermatitis. We were interested to see if a case of steroid refractory Crohn’s disease (CD) complicated by subcutaneous aseptic neutrophilic abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA). Methods: The patient was a 21-year-old male with worsening severe CD while on oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and multiple painful subcutaneous nodules throughout his body. Skin biopsy showed chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma. Because biologics were feared to increase the risk of bacteraemia as the result of germ culture on his pus was not known at the time, we decided to treat this case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days (daily GMA) were initiated. Results: On admission, his CD activity index (CDAI) was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at 2 sessions/week (total 10 sessions). The patient’s CDAI fell to <150, and the skin lesions re-epithelialized. Conclusions: In this CD case complicated by subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our impression is that when biopsy reveals neutrophil infiltrate is a major feature of the lesions, GMA should be considered. As GMA appears to have no safety concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week should be preferred over the routine weekly GMA.

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Adalimumab therapy following granulocyte and monocyte adsorptive apheresis in a patient with Crohn’s disease accompanied by chronic myeloid leukemia

Tsutomu Mizoshita 1Satoshi Tanida 2Shigeru Kusumoto 3Keiji Ozeki 2Hironobu Tsukamoto 2Masahide Ebi 2Yoshinori Mori 2Hiromi Kataoka 2Takeshi Kamiya 2Takashi Joh 2,Clin J Gastroenterol. 2012 Aug;5(4):302-6.

A 52-year-old woman was diagnosed with Crohn’s disease (CD) of the large intestine in May 2001. Her disease was accompanied by the development of chronic myelogenous leukemia (CML) in December 2003. Remission of her CML has been maintained up to the present with tyrosine kinase inhibitors. Clinical and endoscopic remission of the patient’s CD was maintained with salazosulfapyridine (3000 mg/day) and occasional prednisolone (≤20 mg/day) from 2001 to 2010. However, in December 2010 the patient complained of abdominal pain and diarrhea more than 10 times a day. Endoscopy showed serpiginous (snake-like) ulcers in the transverse colon and aphthous ulcers in the sigmoid colon. Intensive granulocyte and monocyte adsorptive apheresis (GMA) (two sessions per week, total of ten sessions) was performed, and the CD activity index (CDAI) decreased from 259 to 175. Six adalimumab injections were administered to improve the remaining inflammatory mucosa. Two months after induction therapy with adalimumab, the CDAI decreased from 175 to 107 without side effects. Endoscopy revealed mucosal healing of the colonic inflammatory lesions. We experienced a case of a patient with CD accompanied by CML. We successfully treated the patient by a combination of intensive GMA and adalimumab

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Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic autoantibody-asociated vasculitis:A pilot study of 21 patients

Midori Hasegawa 1Atsushi OhashiNao KabutanSaori HiramatsuMasao KatoKazutaka MurakamiMakoto TomitaKunihiro NabeshimaYoshiyuki HikiSatoshi Sugiyama, Ther Apher Dial. 2006 Oct;10(5):412-8.

 From these results, cytapheresis can be considered a safe and effective treatment for MPO-ANCA-associated vasculitis. As for the mechanism of its action, soluble tumor necrosis factor receptor 1 (sTNFR), sTNFR2 and interleukin 1 receptor antagonist were elevated soon after cytapheresis and those levels 2 h after the cytapheresis procedure were higher than before the procedure in some cases. These elevations might be related to the efficacy of cytapheresis.

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