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Fujii A, Mizutani Y, Hattori Y, Takahashi T, Ohnishi H, Yoshida S, Seishima M. Sweet's Syndrome Successfully Treated with Granulocyte and Monocyte Adsorption Apheresis. Case Rep Dermatol 2017; 9:13-18. [PMID: 28611630 PMCID: PMC5465522 DOI: 10.1159/000475878] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 04/20/2017] [Indexed: 01/24/2023] Open
Abstract
Sweet's syndrome is a neutrophilic dermatosis characterized by an abrupt onset of painful erythematous lesions showing neutrophilic infiltrates in the dermis. Fever and an elevated neutrophil level are generally observed. Sweet's syndrome may be idiopathic, malignancy-associated, or drug-induced (mainly involving granulocyte colony-stimulating factor (G-CSF) administration). Although systemic corticosteroids are usually effective, the symptoms of Sweet's syndrome recur in some refractory cases. Herein, we report a case of a 55-year-old Japanese woman with recurrent symptoms of fever (>39°C) and painful erythematous lesions on her four extremities, trunk, and neck. Laboratory findings revealed leukocytosis and high levels of C-reactive protein (CRP) and G-CSF. She was diagnosed with a recurrence of Sweet's syndrome, and was exclusively treated with granulocyte and monocyte adsorption apheresis (GMA) therapy once a week for 3 consecutive weeks. After the first session of GMA therapy, all symptoms including the erythematous lesions and fever were completely resolved, and serum G-CSF level was reduced. Leukocyte count, neutrophil count, serum amyloid A protein, and CRP levels were restored within normal ranges by 2 weeks. Thus, GMA therapy can successfully treat a patient with recurrent Sweet's syndrome, potentially related to the restoration of elevated serum G-CSF levels.
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Affiliation(s)
- Asami Fujii
- aDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yoko Mizutani
- aDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yuki Hattori
- aDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Tomoko Takahashi
- aDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hidenori Ohnishi
- bDepartment of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Shozo Yoshida
- cDepartment of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Mariko Seishima
- aDepartment of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan
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Tominaga C, Yamamoto M, Imai Y, Yamanishi K. A Case of Old Age-Onset Generalized Pustular Psoriasis with a Deficiency of IL-36RN (DITRA) Treated by Granulocyte and Monocyte Apheresis. Case Rep Dermatol 2015; 7:29-35. [PMID: 25848350 PMCID: PMC4357681 DOI: 10.1159/000380876] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
A 78-year-old woman who had been suffering from psoriasis vulgaris for 31 years was admitted to hospital because of her erythroderma. A toxic eruption was suspected and she was treated with prednisolone 30 mg daily. However, it was ineffective and, suspecting psoriatic erythroderma, cyclosporine 150 mg daily was administered with tapering of the prednisolone. Two weeks after a dose reduction of cyclosporine to 100 mg/day, erythroderma with widespread generalized pustules and fever developed. Histology of a biopsy revealed inflammatory infiltrates in the skin with a spongiform pustule of Kogoj, which was consistent with generalized pustular psoriasis (GPP). Her pustules improved with additional etretinate 20 mg/day, but the erythroderma persisted and she consulted us. Three sessions of granulocyte and monocyte apheresis once weekly were effective for her condition and decreased her serum levels of IL-6 and IL-8. She had homozygous mutations of c.[28C>T] in IL36RN which cause p.[Arg10Ter]. She is the oldest reported case of GPP with a deficiency of interleukin-36 receptor antagonist (DITRA), although GPP in DITRA has been suggested to usually occur in younger cases with no pre-existing psoriasis vulgaris.
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Affiliation(s)
- Chiharu Tominaga
- Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masaaki Yamamoto
- Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yasutomo Imai
- Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kiyofumi Yamanishi
- Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan
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Mabuchi T, Manabe Y, Yamaoka H, Ota T, Kato M, Ikoma N, Kusakabe Y, Komaba H, Ozawa A. Case of generalized pustular psoriasis with end-stage renal disease successfully treated with granulocyte monocyte apheresis in combination with hemodialysis. J Dermatol 2014; 41:521-4. [DOI: 10.1111/1346-8138.12501] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Accepted: 03/20/2014] [Indexed: 01/31/2023]
Affiliation(s)
- Tomotaka Mabuchi
- Department of Dermatology; Tokai University School of Medicine; Kanagawa Japan
| | - Yasuaki Manabe
- Department of Dermatology; Tokai University School of Medicine; Kanagawa Japan
| | - Hanako Yamaoka
- Department of Dermatology; Tokai University School of Medicine; Kanagawa Japan
| | - Tami Ota
- Department of Dermatology; Tokai University School of Medicine; Kanagawa Japan
| | - Masayuki Kato
- Department of Dermatology; Tokai University School of Medicine; Kanagawa Japan
| | - Norihiro Ikoma
- Department of Dermatology; Tokai University School of Medicine; Kanagawa Japan
| | - Yoshiyuki Kusakabe
- Department of Dermatology; Tokai University School of Medicine; Kanagawa Japan
- Department of Kusakabe Dermatology Clinic; Kanagawa Japan
| | - Hirotaka Komaba
- Department of Nephrology and Metabolism; Tokai University School of Medicine; Kanagawa Japan
| | - Akira Ozawa
- Department of Dermatology; Tokai University School of Medicine; Kanagawa Japan
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Fukunaga K, Matsumoto T. Current status and future perspectives of leukocytapheresis for inflammatory bowel disease. J Gastroenterol Hepatol 2012; 27:997-1003. [PMID: 22414250 DOI: 10.1111/j.1440-1746.2012.07119.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) comprise the idiopathic inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly understood, but an autoimmune disturbance has been suggested to play an important role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an additional adjunct for IBD patients refractory to other conventional therapies, including steroids. The primary aim of CAP should be to suppress such unwanted immunological response by removing circulating inflammatory cells from the blood stream. The first decade has been passed since CAP was approved by Japanese social health insurance policy. It is therefore now an appropriate opportunity to upgrade and summarize our current understandings and/or future perspectives of this unique non-pharmacological and non-surgical strategy for IBD patients. According to several clinical and basic research reports, an early introduction of CAP should produce higher efficacy as compared with CAP applied sometime after a clinical relapse. Likewise, CAP therapy adjusted to patients' body-weight as well as two treatment sessions per week (intensive regimen) should benefit the efficacy rate. The etiology of IBD is not fully elucidated yet. As a result, the major therapeutic strategies in the Western world have been immunosuppressive therapy, including biologics. CAP is an unusual treatment modality for IBD because it seems to have both effectiveness and safety, which should generally be balanced in this type of illness. We now have to develop future strategies with and without combining biologics to improve the quality of life of IBD patients.
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Affiliation(s)
- Ken Fukunaga
- Departments of Lower Gastroenterology and Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
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SHUKUYA R, HASEGAWA T, NIWA Y, OKUMA K, IKEDA S. Granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis. J Dermatol 2011; 38:1130-4. [DOI: 10.1111/j.1346-8138.2011.01279.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Fujisawa T, Murase K, Okumura Y, Kanoh H, Doi T, Yoshida S, Ogura S, Seishima M. Generalized pustular psoriasis successfully treated with granulocyte and monocyte adsorption apheresis. Ther Apher Dial 2011; 15:374-8. [PMID: 21884472 DOI: 10.1111/j.1744-9987.2011.00961.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Generalized pustular psoriasis (GPP) is one of the neutrophilic dermatoses mainly caused by activated neutrophils and monocytes. Granulocyte and monocyte adsorption apheresis (GCAP) is a useful extracorporeal circulation therapy for removal of activated granulocytes and monocytes. In this study, GCAP was used to treat three patients with different types of GPP; the diagnoses indicated patient 1 had GPP, patient 2 had GPP developed from psoriasis vulgaris and patient 3 had GPP based on psoriatic erythroderma. We performed GCAP on each of these patients once a week, for a total of five times. We found that the patients' pustules and edema disappeared and their erythema was reduced by GCAP therapy. Moreover, no adverse effects were observed. Thus, we conclude GCAP could be effective for treating various types of GPP.
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Affiliation(s)
- Tomomi Fujisawa
- Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan
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Adsorptive depletion of alpha4 integrin(hi)- and CX3CR1hi-expressing proinflammatory monocytes in patients with ulcerative colitis. Dig Dis Sci 2010; 55:1886-95. [PMID: 19908144 DOI: 10.1007/s10620-009-0974-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2009] [Accepted: 08/28/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND Two main functionally distinct monocytes phenotypes are known: the CD14(hi)CD16(-) "classical" and the CD14(+)CD16(+) "proinflammatory" phenotypes. The latter phenotype is elevated in patients with ulcerative colitis (UC) and is suspected to have a major role in the immunopathogenesis of UC. AIM To selectively deplete circulating proinflammatory CD14(+)CD16(+) monocyte phenotype. METHODS Seven corticosteroid-naïve patients with UC (clinical activity index = 8.7 +/- 1.3) and seven healthy subjects were included. In patients with UC, granulocyte/monocyte adsorption (GMA) was done with an Adacolumn that selectively adsorbs leucocytes of the myeloid lineage. Blood from all subjects at baseline and from the patients immediately after the first GMA session was processed. Isolated monocytes were subjected to fluorescence-activated cell sorter analyses. RESULTS The seven UC patients achieved remission (CAI <or=4) after 5-10 GMA sessions. GMA induced a strong fall in the ratio (%) of CD14(+)CD16(+) to CD14(hi)CD16(-) monocytes, from 10.0 +/- 1.4 to 3.0 +/- 0.9. Further, expressions of alpha4 integrin (374.8 +/- 26.1 mean fluorescence intensity, MFI) and CX(3)CR1 (49.5 +/- 4.6 MFI) were significantly high on CD14(+)CD16(+)monocytes as compared with on CD14(hi)CD16(-) monocytes (169.2 +/- 17.2 and 33.2 +/- 3.6 MFI, respectively). Additionally, GMA significantly increased the ratio of the CD14(hi)CD16(-)CCR2(low) "immature" monocytes from 3.74 +/- 0.62 to 8.11 +/- 0.56 MFI. CONCLUSIONS We found high expressions of alpha4 integrin and CX(3)CR1 on monocytes in patients with active UC, known to promote the extravasation of CD14(+)CD16(+) monocytes into the mucosa. GMA effectively depletes CD14(+)CD16(+) monocytes and concomitantly increases CD14(hi)CD16(-)CCR2(low) "immature" monocytes; thus GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.
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Novelli G, Rossi M, Ferretti G, Poli L, Pretagostini R, Ruberto F, Morabito V, Cinti P, Nudo F, Mennini G, Berloco PB. Adacolumn treatment in kidney transplant patients with hepatitis C virus. Transplant Proc 2009; 41:1195-200. [PMID: 19460515 DOI: 10.1016/j.transproceed.2009.03.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Patients who have undergone kidney transplantation and suffer from hepatitis C (HCV) cannot be treated with standard therapy (pegylated interferon combined with ribavirin) due to the risk of acute rejection. Furthermore, immunosuppressive therapy facilitates the progression of infection and chronic hepatopathies. Monocytes and macrophages are known to produce extrahepatic breeding sites that spread disease. Our aim was to reduce macrophages, granulocytes, monocytes, proinflammatory cells, and viremia levels using an extracorporeal device: Adacolumn Leukocyte Apheresis (Otzuka Electronics, Japan). METHODS The Adalcolumn filter is filled with 2-mm cellulose acetate beads immersed in sterile saline solution. These carriers absorb granulocytes and monocytes/macrophanges through their FCR receptors. Six patients affected by viral genotype 1b underwent five 1-hour treatments for 5 consecutive days. RESULTS Viremia was reduced in Patients 1, 2, 4, and 6 in association with decreased pro-inflammatory cytokine levels and a normal CD4/CD8 T-cell ratio, after 3 months. Subjects 1 and 3 showed inverted CD4(+)/CD8(+) T-cell ratios, which changed at 4-month follow-up in only patient 1. Subject 5 did not show any changes. CONCLUSIONS The treatment was safe without hemodynamic or infectious complications, suggesting that this method could be used in a greater number of patients to evaluate amelioration of increased viremia.
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Affiliation(s)
- G Novelli
- Dipartimento "P. Stefanini" Chirurgia Generale e Trapianti d'Organo, La Sapienza Università di Roma, Rome, Italy.
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Iwakami Y, Sakuraba A, Sato T, Takada Y, Izumiya M, Ichikawa H, Hibi T. Granulocyte and Monocyte Adsorption Apheresis Therapy Modulates Monocyte-Derived Dendritic Cell Function in Patients With Ulcerative Colitis. Ther Apher Dial 2009; 13:138-46. [DOI: 10.1111/j.1744-9987.2009.00668.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Takeda H, Suzuki Y, Takeda Y, Nishise S, Fukui T, Fujishima S, Orii T, Otake S, Sato T, Suzuki K, Nakamuara Y, Kawata S. A multi center study of granulocyte and monocyte adsorption apheresis therapy for ulcerative colitis-clinical efficacy and production of interleukin-1 receptor antagonist. J Clin Apher 2008; 23:105-10. [PMID: 18449931 DOI: 10.1002/jca.20164] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Granulocyte and monocyte adsorption apheresis (GCAP) is a useful strategy for intractable ulcerative colitis, but its mechanisms of therapy is not fully explained. Previously, depleting activated granulocytes and monocytes (GMs) and modifying product of proinflammatory cytokines had been proposed. In addition, activated GMs are releasing anti-inflammatory cytokines, interleukin-1 receptor antagonist (IL-1ra) that may contribute to the clinical efficacy of GCAP therapy. Hence, to investigate contribution of IL-1ra as well as to confirm clinical efficacy of this therapy based on clinical activity index (CAI), we performed a multicenter study. Twenty-five of 38 (65.8%) patients achieved remission state (CAI < or = 4) and two of 38 (5.3%) revealed clinical improvement. Almost effective cases significantly decreased CAI even at 3rd session of GCAP. Plasma level of IL-1ra from outflow of the GCAP column at 30 min was significantly increased rather than inflow. Median exact elevated level of IL-1ra was 221 pg/ml and median of increasing ratio was 1.6 times. Furthermore, the responsive patients, who well released the IL-1ra at outflow more than 100 pg/ml compared with inflow, tended to show clinical effectiveness. While, the increased ratio of IL-1ra in effective cases did not differ from ineffective cases, and there were no significant relationship with improvement of CAI score. These conflict results suggest that the increase of IL-1ra at outflow is not a direct factor to the clinical improvement, but the induction of clinical improvement is accompanied by the release of IL-1ra. The IL-1ra may be involved in the multiple steps for the improvement induced by GCAP.
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Affiliation(s)
- Hiroaki Takeda
- Division of Endoscopy, Yamagata University Hospital, Yamagata, Japan.
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Cuadrado E. Granulocyte/monocyte apheresis as immunotherapic tool: cellular adsorption and immune modulation. Autoimmun Rev 2008; 8:292-6. [PMID: 18804557 DOI: 10.1016/j.autrev.2008.09.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2008] [Accepted: 09/02/2008] [Indexed: 12/15/2022]
Abstract
Cellular apheresis is now established as a rational therapeutic procedure in certain inflammatory and autoimmune diseases, particularly in inflammatory bowel diseases, but the efficacy of this procedure can not be fully explained solely on the basis of removal of granulocytes and monocytes. It is suggested that a selective modulator increase of regulatory T cells contributes to beneficial effect of adsorptive leukocytapheresis in patients with these pathologies. Though currently applied as second-line medication, it could be considered in the future as an effective alternative to the use of immune suppressive regimens or biological agents and taken into account to establish a tailor's patient therapy in inflammatory and autoimmune conditions.
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Affiliation(s)
- Emilio Cuadrado
- Hospital Donostia, Sección de Inmunología, Paseo doctor Begiristain s/n, San Sebastián 20014, País Vasco, Spain.
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Seishima M, Mizutani Y, Shibuya Y, Nagasawa C, Aoki T. Efficacy of granulocyte and monocyte adsorption apheresis for pustular psoriasis. Ther Apher Dial 2008; 12:13-8. [PMID: 18257807 DOI: 10.1111/j.1744-9987.2007.00536.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Granulocyte and monocyte adsorption apheresis (GCAP) has recently shown remarkable effects on ulcerative colitis, which is characterized by inflammation and neutrophil infiltration. Pustular psoriasis often shows histological findings of neutrophilic pustules in the epidermis, and in Japan is usually treated with etretinate or immunosuppressive agents. However, there are some resistant cases to these therapies. We performed GCAP on one patient with generalized pustular psoriasis (patient 1) and on one patient with acrodermatitis continua, a subtype of pustular psoriasis limited to acral lesions (patient 2). Patient 1, a 44-year-old woman suffering from alcoholic liver cirrhosis and osteoporosis as a result of the liver cirrhosis, received two GCAP sessions because cyclosporine was ineffective. Patient 2, a 66-year-old man with hypertension who had suffered from a brain infarction 4 years before, had five GCAP sessions because etretinate was ineffective. GCAP remarkably improved the skin lesions in both patients. No adverse effects were observed either during or after treatment. From these findings, GCAP could be an effective therapy for refractory cases of pustular psoriasis.
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Affiliation(s)
- Mariko Seishima
- Department of Dermatology, Ogaki Municipal Hospital, Ogaki City, Japan.
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Okuma K, Mitsuishi K, Hasegawa T, Tsuchihashi H, Ogawa H, Ikeda S. A case report of steroid and immunosuppressant-resistant pyoderma gangrenosum successfully treated by granulocytapheresis. Ther Apher Dial 2008; 11:387-90. [PMID: 17845399 DOI: 10.1111/j.1744-9987.2007.00498.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Granulocytapheresis (GCAP) therapy is a newly developed therapeutic modality for inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Pyoderma gangrenosum (PG) is a chronic inflammatory skin disease characterized by the appearance of erythematous macules and plaques with pustules or nodules that rapidly progress to ragged, undermined multiple ulcers. We attempted GCAP therapy in a patient with PG resistant to prednisolone and various other immunosuppressants. GCAP therapy was initiated at three- to four-day intervals and a good response from all skin lesions, with eventual total epithelialization, was observed after 10 sessions of this therapy. Furthermore, circulating levels of inflammatory cytokines such as interleukin-8 (IL-8) and granulocyte colony stimulating factor (G-CSF) also decreased after the GCAP therapy. Our results suggest that GCAP is a safe and useful tool for the treatment of intractable PG, and that IL-8 and G-CSF are likely to be involved in the pathogenesis of PG.
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Affiliation(s)
- Keiko Okuma
- Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan.
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Matsumoto T, Fukunaga K, Kamikozuru K, Tozawa K, Yokoyama Y, Kusaka T, Onishi K, Miwa H, Nakamura S. Cytapheresis as a Non-Pharmacological Therapy for Inflammatory Bowel Disease. Transfus Med Hemother 2007; 35:18-23. [PMID: 21547106 DOI: 10.1159/000111763] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2007] [Accepted: 10/09/2007] [Indexed: 01/01/2023] Open
Abstract
SUMMARY: Although inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic recurrent disease with unknown etiology. Recent immunological studies suggest close relation to autoimmune status featured by antibodies against colonic epithelial cells. For patients with IBD, 5-aminosalycilates are often used in case of mild disease, and corticosteroids are standard therapy for moderate-to-severe disease. However, we often encounter patients who are resistant to or dependent of conventional therapy, which are likely to lead to future problems in quality of life due to adverse effects of drugs used, especially corticosteroids. Extracorporeal leukocyte removal therapy (cytapheresis) is one of the adjunctive therapies for IBD patients refractory to steroids. By removing circulating activated leukocytes, especially granulocytes and lymphocytes, impaired immune response is suppressed. In the present article recently published studies are reviewed in order to reflect the current state of the art in the use of cytapheresis for treating IBD, especially UC and CD. Although there are only few randomized controlled trials, clinical experience so far suggests that cytapheresis has superior efficiency than conventional therapies in steroid-resistant moderate-to-severe UC. Moreover, cytapheresis features its safety characteristic compared with other conventional medications for severe UC, cytapheresis is regarded as safe treatment regimen.
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Affiliation(s)
- Takayuki Matsumoto
- Division of Lower Gl Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
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Seishima M, Mizutani Y, Shibuya Y, Nagasawa C, Aoki T. Efficacy of granulocyte and monocyte adsorption apheresis for three cases of refractory pyoderma gangrenosum. Ther Apher Dial 2007; 11:177-82. [PMID: 17497998 DOI: 10.1111/j.1744-9987.2007.00424.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Pyoderma gangrenosum presents with chronic skin ulcers and is histologically characterized by neutrophil infiltration throughout the dermis. It is also occasionally associated with ulcerative colitis, a type of inflammatory bowel disease, against which granulocyte and monocyte adsorption apheresis (GCAP) has recently shown remarkable efficacy. We performed GCAP on three refractory cases of pyoderma gangrenosum with painful bilateral leg ulcers and hereby report the results obtained. Patient 1 was a 43-year-old woman with a four-year history of recurrent painful skin ulcers treated with prednisolone and cyclosporine. Patient 2 was a 29-year-old woman who had been suffering from pyoderma gangrenosum with severe pain for two weeks, associated with an 11-year history of ulcerative colitis treated with prednisolone and salazosulfapyridine. Patient 3 was a 63-year-old man with a three-year history of recurrent ulcers with pain, suffering from rheumatoid arthritis treated with prednisolone and cyclophosphamide. The sizes of the lesions were reduced in all three patients following a weekly GCAP treatment for 10 or 11 consecutive weeks, and the re-epithelialization of ulcers were additionally observed in two patients. The pain disappeared dramatically in all three patients following two sessions of GCAP therapy. No adverse effects were observed for up to at least eight months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, with regards to refractory cases of pyoderma gangrenosum.
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Affiliation(s)
- Mariko Seishima
- Department of Dermatology, Ogaki Municipal Hospital, Ogaki, Japan.
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Yokoyama Y, Fukunaga K, Fukuda Y, Tozawa K, Kamikozuru K, Ohnishi K, Kusaka T, Kosaka T, Hida N, Ohda Y, Miwa H, Matsumoto T. Demonstration of low-regulatory CD25High+CD4+ and high-pro-inflammatory CD28-CD4+ T-Cell subsets in patients with ulcerative colitis: modified by selective granulocyte and monocyte adsorption apheresis. Dig Dis Sci 2007; 52:2725-31. [PMID: 17404876 DOI: 10.1007/s10620-006-9560-z] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2006] [Accepted: 08/03/2006] [Indexed: 12/12/2022]
Abstract
Low-CD25(High+)CD4(+), a subset of regulatory CD25(+)CD4(+) T cells and high-inflammatory CD28(-)CD4(+) T cells can exacerbate ulcerative colitis (UC). This study sought to investigate the frequency of CD25(High+)CD4(+) and CD28(-)CD4(+) T cells in patients with UC and the changes in these cells during Adacolumn granulocyte and monocyte adsorption apheresis (GMA). Subjects were 12 patients with active UC, 11 with quiescent UC, and 14 healthy volunteers (HVs). The mean clinical activity index was 15.7 +/- 2.2 in active UC and 4.5 +/- 1.1 in quiescent UC. Peripheral blood samples were stained with CD4, CD25, and CD28 antibodies for flow cytometry. Patients with active UC received GMA and blood samples were examined before and after the first GMA session. Patients with active UC (P < 0.04) or quiescent UC (P < 0.02) had a higher percentage of CD28(-)D4(+)T cells compared with HVs, while the percentage of CD28(+)CD4(+) T cells was lower in both UC groups compared with HVs (P = 0.03 and P < 0.02). Patients with active UC had a lower percentage of CD25(High+)CD4(+)T cells compared with quiescent UC patients (P < 0.001). A significant increase in CD25(High+)CD4(+) T cells was associated with GMA (P < 0.03). Low CD25(High+)CD4(+) and high CD28(-)CD4(+) are prominent features in UC. The increase in CD25(High+)CD4(+) T cells induced by GMA should contribute to improved immune function. Additional studies are warranted, since a low frequency of CD25(High+)CD4(+) (-) and a high frequency of CD28(-)CD4(+) (-) expressing T cells might be a predictor of clinical response to GMA.
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Affiliation(s)
- Yoko Yokoyama
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
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Takemoto K, Kato J, Kuriyama M, Nawa T, Kurome M, Okada H, Sakaguchi K, Shiratori Y. Predictive factors of efficacy of leukocytapheresis for steroid-resistant ulcerative colitis patients. Dig Liver Dis 2007; 39:422-9. [PMID: 17379587 DOI: 10.1016/j.dld.2007.01.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2006] [Revised: 11/02/2006] [Accepted: 01/11/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND The effectiveness of leukocytapheresis against ulcerative colitis has been reported. However, the efficacy of this therapy for steroid-resistant ulcerative colitis patients has hardly been examined. AIMS The aims of this study are to evaluate the efficacy of leukocytapheresis for steroid-resistant ulcerative colitis patients and to identify clinical factors that predict the efficacy of this therapy for these patients. METHODS Clinical factors of 71 steroid-resistant ulcerative colitis patients who underwent leukocytapheresis analysed. RESULTS Of those analysed, 53 (75%) patients showed an initial response to leukocytapheresis. Among cases with initial response, however, only 19 (27%) patients maintained remission for more than 6 months. Steroid-dependent course (Odds ratio =5.53, 95% confidence interval; 1.24-24.73) and a high C-reactive protein degree (Odds ratio=1.6, confidence interval; 1.09-2.35) were predictors of initial response to leukocytapheresis. Rapid response, which means remission induction within three leukocytapheresis sessions, was the only predictor of maintenance of remission for more than 6 months after successful leukocytapheresis therapy (odds ratio=8.01, confidence interval; 1.08-59.37). CONCLUSIONS Leukocytapheresis was effective for steroid-resistant ulcerative colitis patients. However, relapse was frequently observed within short periods after the initial response to this therapy. Patients without a rapid response should be treated with alternative or additional therapies.
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Affiliation(s)
- K Takemoto
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
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Yamamoto T, Umegae S, Matsumoto K. Safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis. World J Gastroenterol 2006; 12:520-5. [PMID: 16489663 PMCID: PMC4066082 DOI: 10.3748/wjg.v12.i4.520] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double-blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs ¥145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.
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