Shigaku Ikeda1, Hidetoshi Takahashi2, Yasushi Suga3, Hikaru Eto4, Takafumi Etoh5, Keiko Okuma6, Kazuo Takahashi7, Takeshi Kanbara8, Mariko Seishima9, Akimichi Morita10, Yasutomo Imai11, Takuro Kanekura12. 1. Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: ikeda@juntendo.ac.jp. 2. Department of Dermatology, Asahikawa Medical University, Asahikawa, Japan. 3. Department of Dermatology, Juntendo University Urayasu Hospital, Chiba, Japan. 4. Department of Dermatology, St Luke's International Hospital, Tokyo, Japan. 5. Department of Dermatology, Tokyo Teishin Hospital, Tokyo, Japan. 6. Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan. 7. Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 8. Department of Dermatology, Yokohama City University Medical Center, Yokohama, Japan. 9. Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan. 10. Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 11. Department of Dermatology, Hyogo College of Medicine, Hyogo, Japan. 12. Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Abstract
BACKGROUND: Generalized pustular psoriasis (GPP) is a chronic autoimmune disease characterized by fever, erythema, and neutrophilic pustules over large areas of the skin. GPP does not respond well to pharmacologic intervention. OBJECTIVE: We sought to assess efficacy of selectively depleting the myeloid lineage leukocytes in patients with GPP. METHODS: Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Eligible patients had more than 10% of their skin area covered by pustules. Treatment with oral etretinate, cyclosporine, methotrexate, prednisolone, and topical prednisolone/vitamin D3 was continued if had been initiated well in advance of study entry. Five sessions of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn (JIMRO Co Ltd, Takasaki, Japan) were administered (1 session/wk over 5 weeks) to selectively deplete Fcγ receptor and complement receptor bearing leukocytes. Efficacy was assessed by measuring the skin areas covered by pustules at baseline and 2 weeks after the last GMA session. RESULTS: One patient did not complete the first GMA session. Based on the GPP severity scores relative to entry, the overall scores improved (n = 14, P = .0027), and the area of erythroderma (P = .0042), pustules (P = .0031), and edema (P = .0014) decreased. Likewise, Dermatology Life Quality Index improved (P = .0016), reflecting better daily function and quality of life. Twelve patients were judged as responders (85.7%), and 10 patients maintained the clinical response for 10 weeks after the last GMA session without any change in medication. LIMITATIONS: This study was unblinded and without a placebo arm. CONCLUSION: GMA in this clinical setting was safe and effective, suggested a major role for granulocytes/monocytes in the immunopathogenesis of GPP.
BACKGROUND: Generalized pustular psoriasis (GPP) is a chronic autoimmune disease characterized by fever, erythema, and neutrophilic pustules over large areas of the skin. GPP does not respond well to pharmacologic intervention. OBJECTIVE: We sought to assess efficacy of selectively depleting the myeloid lineage leukocytes in patients with GPP. METHODS: Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Eligible patients had more than 10% of their skin area covered by pustules. Treatment with oral etretinate, cyclosporine, methotrexate, prednisolone, and topical prednisolone/vitamin D3 was continued if had been initiated well in advance of study entry. Five sessions of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn (JIMRO Co Ltd, Takasaki, Japan) were administered (1 session/wk over 5 weeks) to selectively deplete Fcγ receptor and complement receptor bearing leukocytes. Efficacy was assessed by measuring the skin areas covered by pustules at baseline and 2 weeks after the last GMA session. RESULTS: One patient did not complete the first GMA session. Based on the GPP severity scores relative to entry, the overall scores improved (n = 14, P = .0027), and the area of erythroderma (P = .0042), pustules (P = .0031), and edema (P = .0014) decreased. Likewise, Dermatology Life Quality Index improved (P = .0016), reflecting better daily function and quality of life. Twelve patients were judged as responders (85.7%), and 10 patients maintained the clinical response for 10 weeks after the last GMA session without any change in medication. LIMITATIONS: This study was unblinded and without a placebo arm. CONCLUSION: GMA in this clinical setting was safe and effective, suggested a major role for granulocytes/monocytes in the immunopathogenesis of GPP.
Authors: Ia Khmaladze; Tiina Kelkka; Simon Guerard; Kajsa Wing; Angela Pizzolla; Amit Saxena; Katarina Lundqvist; Meirav Holmdahl; Kutty Selva Nandakumar; Rikard Holmdahl Journal: Proc Natl Acad Sci U S A Date: 2014-08-18 Impact factor: 11.205
Authors: Alexander V Alekseyenko; Guillermo I Perez-Perez; Aieska De Souza; Bruce Strober; Zhan Gao; Monika Bihan; Kelvin Li; Barbara A Methé; Martin J Blaser Journal: Microbiome Date: 2013-12-23 Impact factor: 14.650