Shigaku Ikeda ¹, Hidetoshi Takahashi ², Yasushi Suga ³, Hikaru Eto ⁴, Takafumi Etoh ⁵, Keiko Okuma ⁶, Kazuo Takahashi ⁷, Takeshi Kanbara ⁸, Mariko Seishima ⁹, Akimichi Morita ¹⁰, Yasutomo Imai ¹¹, Takuro Kanekura ¹²

J Am Acad Dermatol 2013 Apr;68(4):609-617. doi: 10.1016/j.jaad.2012.09.037. Epub 2013 Jan 17.

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.

https://pubmed.ncbi.nlm.nih.gov/23332516/

Kyoko Furusawa, Toshio Hasegawa, Shigaku Ikeda, Ther Apher Dial. 2012 Aug;16(4):379-80.

https://pubmed.ncbi.nlm.nih.gov/22817129/

Akiko Suzuki ¹, Kunitaka Haruna, Yuki Mizuno, Yoshiyuki Kuwae, Yuka Ono, Kazuko Okumura, Osamu Negi, Yasuko Kon, Kaori Takeuchi, Kenji Takamori, Shigaku Ikeda, Yasushi Suga,Ther Apher Dial. 2012 Oct;16(5):445-8.

Generalized pustular psoriasis (GPP) is a rare form of psoriasis characterized by the presence of variable numbers of sterile pustules appearing in erythematous and scaly lesions, which are associated with moderate to severe constitutional symptoms. It can be life-threatening especially in the elderly; therefore, medical care must be performed in rapid succession of treatment especially in refractory cases. We have performed granulocyte and monocyte adsorption apheresis (GCAP) on three GPP cases associated with several systemic and laboratory findings. As a result, the edema, erythema and numbers of sterile pustules on the skin lesions were reduced dramatically in all three patients after the first sessions of GCAP therapy. The sizes of the psoriatic lesions were reduced in all three patients following a weekly GCAP treatment for 5 consecutive weeks. Psoriasis area and severity index on discharge had improved in all three patients. No serious adverse effects were observed for up to at least 8 months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, especially for recalcitrant cases of GPP.

https://pubmed.ncbi.nlm.nih.gov/23046369/

Tomomi Fujisawa ¹, Kana Murase, Hiroyuki Kanoh, Masao Takemura, Hidenori Ohnishi, Mariko Seishima, Ther Apher Dial. 2012 Oct;16(5):436-44.

Generalized pustular psoriasis (GPP) is a subtype of psoriasis with strong association with activated neutrophils. Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal intervention for selective depletion of activated granulocytes and monocytes. However, the immunological mechanism(s) for the effect of GMA on patients is not fully defined yet. We investigated the effects of GMA on the ratio of CD14(+) CD16(+) proinflammatory monocytes/CD14(+) monocytes and cytokine/chemokine production by these leukocytes including CXCL8, CCL2, CCL3, CCL4, CCL5 and tumor necrosis factor (TNF)-α in five patients with active GPP. CD14(+) CD16(+) monocytes were significantly elevated in patients with active GPP, and GMA markedly reduced the CD14(+) CD16(+) /CD14(+) ratio together with improvement of patients’ clinical symptoms. The serum levels of CXCL8, CCL3 and CCL4 were increased in active GPP patients. Likewise, CCL2 production from monocytes was increased in active GPP patients. Further, CCL3 and CCL4 production from monocytes in active GPP patients were reduced after a course of GMA. Serum CCL5 level and the release of CCL5 from monocytes in active GPP were significantly reduced, but TNF-α level in active GPP was similar to controls. Based on these results, we believe that in addition to neutrophils, elevated CD14(+) CD16(+) proinflammatory monocytes are part of the immune pathology in GPP. Accordingly, selective depletion of CD14(+) CD16(+) monocytes by GMA should be therapeutic in this condition.

https://pubmed.ncbi.nlm.nih.gov/23046368/

Tomomi Fujisawa ¹, Kana Murase, Yoko Okumura, Hiroyuki Kanoh, Tomoaki Doi, Shouzo Yoshida, Shinji Ogura, Mariko Seishima

Ther Apher Dial 2011 Aug;15(4):374-8. doi: 10.1111/j.1744-9987.2011.00961.x. Epub 2011 Jun 7.

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.

https://pubmed.ncbi.nlm.nih.gov/21884472/

Tomomi Fujisawa ¹, Kana Murase, Yoko Okumura, Hiroyuki Kanoh, Tomoaki Doi, Shouzo Yoshida, Shinji Ogura, Mariko Seishima,Ther Apher Dial. 2011 Aug;15(4):374-8.

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.

https://pubmed.ncbi.nlm.nih.gov/21884472/

Ryoko Shukuya ¹, Toshio Hasegawa, Yusuke Niwa, Keiko Okuma, Shigaku Ikeda , J Dermatol. 2011 Dec;38(12):1130-4.

Granulocyte and monocyte adsorption apheresis (GCAP) is an extracorporeal circulation therapy that removes activated granulocytes and monocytes. GCAP was initially approved for the treatment of ulcerative colitis, which is attributed to activated granulocytes and macrophages that infiltrate the target tissues. Generalized pustular psoriasis (GPP) is also supposed to be caused by activated neutrophils. In this study, we treated two patients with refractory GPP by using GCAP. Patient 1, a 68-year-old woman who had liver cirrhosis, underwent seven GCAP sessions. Patient 2, a 26-year-old woman who had systemic lupus erythematosus and had been treated with systemic corticosteroids, underwent eight GCAP sessions. In both patients, GCAP resulted in an immediate improvement in skin lesions and fever reduction, without any adverse effects. We suggest that GCAP is an effective therapy for refractory GPP.

https://pubmed.ncbi.nlm.nih.gov/22007872/

Mariko Seishima ¹, Yoko Mizutani, Yoshinao Shibuya, Chikako Nagasawa, Takahiko Aoki

Ther Apher Dial 2008 Feb;12(1):13-8. doi: 10.1111/j.1744-9987.2007.00536.x.

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.

https://pubmed.ncbi.nlm.nih.gov/18257807/