Miho Hatanaka, Yuko Higashi, Takuro Kanekura

poster at ISFA 2019 pag 104

Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and
systemic flushing accompanied by extensive sterile pustules. Treatments of GPP are usually
topical corticosteroids, activated vitamin D3 ointment, ultraviolet light (UV) therapy, and
oral administration of etretinate, cyclosporine, or methotrexate. Recently, biologics such as
TNF- α; inhibitors, anti-IL-17- and anti-IL-23 antibodies are used. Pustulosis palmoplantaris
(PPP) is a chronic recurrent disorder of the palms and soles characterized by sterile intradermal
pustules. PPP often accompanies joint symptoms. In some instances, PPP is associated with
a focus of infection somewhere in the body; elimination of the infection sometimes improve
symptom. Some treatments of GPP are used for PPP. Psoriatic arthritis (PsA) is a disease
characterized by skin and nail psoriasis together with widespread musculoskeletal inflammation
such as peripheral joint disease, axial joint disease, enthesitis, and dactylitis. Treatment of
PsA is oral administration of NSAID’s, cyclosporine, methotrexate and phosphodiesterase 4
inhibitors for mild to moderate cases. Biologics; TNF- αinhibitors, anti-IL-17- and anti-IL-23
antibodies; have been approved for severe or advanced cases. Granulocyte/monocyte adsorption
apheresis (GMA) is an extracorporeal therapy designed to remove and suppress the functions
of neutrophils, macrophages and monocytes that accumulate in the inflamed tissue and are
involved in the pahogenesis. GMA may be considered as a safe treatment modality with few
side-effects for GPP, PPP and PsA. The effect and safety of GMA have been reported mostly in
case reports. Although the effect and safety of GMA were demonstrated in a multicenter study.
GMA’s utility is expected based on the mechanism of action.

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

Mariko Seishima

poster at ISFA 2019 pag 57

Generalized pustular psoriasis (GPP) is a rare inflammatory skin disorder characterized by a fever, edema, and generalized erythema with neutrophilic pustules. It sometimes occurs in the course of psoriasis vulgaris, or develops suddenly without any history of psoriasis. Mutations of the IL36RN (deficiency of interleukin thirty-six receptor antagonist: DITRA), CARD14 and AP1S3 genes underlie monogenic auto-inflammatory disorders causing GPP. GPP patients are usually treated with oral administration of etretinate, cyclosporine, and metrexate, biologics including TNF α inhibitors, antibodies to IL-17, IL-17 receptor, and IL-23 p19, and granulocyte and monocyte adsorption apheresis (GMA). Cyclosporine, TNF α inhibitors, and GMA are used for GPP in pediatric, pregnant, or lactating patients. GMA is an extracorporeal apheresis that removes activated granulocytes and monocytes using a column packed with cellulose acetate beads. Multicenter study was performed to access efficacy of selectively depleting the myeloid lineage leukocytes in GPP patients. Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Based on the GPP severity scores relative to entry, the overall scores improved, and the area of erythroderma, pustules, and edema decreased. Likewise, Dermatology Life Quality Index (DLQI) improved, reflecting better daily function and quality of life. Twelve out of 14 patients were judged as responders (85.7%), and 10 out of 12 patients maintained the clinical response for10 weeks after the last GMA session without any change in medication. Thus, GMA is estimated to be safe and effective, suggesting a major role of granulocytes/ monocytes in the immunepathogenesis of GPP. Recent study showed that GMA was effective for 100% of DITRA patients and for 64.7% of the patients with IL36RN mutation-negative GPP. Thus, GMA is effective therapy for both DITRA and non-DITRA GPP patients. GMA may be a useful therapy for all GPP patients

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

Hiroshi Kawakami ¹, Yume Nagaoka ², Hirofumi Hirano ¹, Yuka Matsumoto ¹, Namiko Abe ¹, Ryoji Tsuboi ¹, Yoshihiko Kanno ², Yukari 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/

Asami Fujii ¹, Kento Fujii ¹, Mariko Seishima ¹ , Ther Apher Dial. 2019 Jun;23(3):298-299

https://pubmed.ncbi.nlm.nih.gov/31025533/

Hidenori Ohnishi ¹, Tomonori Kadowaki ¹, Yoko Mizutani ², Emi Nishida ³, Rie Tobita ⁴, Namiko Abe ⁴, Yukie Yamaguchi ⁵, Hikaru Eto ⁶, Masaru Honma ⁷, Takuro Kanekura ⁸, Yukari Okubo ⁴, Mariko Seishima ², Toshiyuki Fukao ¹, Shigaku Ikeda ⁹ , Eur J Dermatol. 2018 Feb 1;28(1):108-111.

https://pubmed.ncbi.nlm.nih.gov/29380726/

Asami Fujii ¹, Hidenori Ohnishi ², Mariko Seishima ¹ , Ther Apher Dial. 2018 Feb;22(1):92-93.

https://pubmed.ncbi.nlm.nih.gov/28913961/

Y Koike ¹, M Okubo ¹, T Kiyohara ¹, R Fukuchi ¹, Y Sato ¹, S Kuwatsuka ¹, T Takeichi ², M Akiyama ², K Sugiura ³, A Utani ¹ , Br J Dermatol. 2017 Dec;177(6):1732-1736.

Granulocyte monocyte apheresis, a process associated with few adverse events, promptly controlled the GPP of our paediatric patient, and has potential as a suitable alternative treatment for paediatric patients with DITRA.

https://pubmed.ncbi.nlm.nih.gov/28369922/

Chiharu Tominaga ¹, Masaaki Yamamoto ¹, Yasutomo Imai ¹, Kiyofumi Yamanishi ¹ , Case Rep Dermatol. 2015 Feb 21;7(1):29-35.

 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.

https://pubmed.ncbi.nlm.nih.gov/25848350/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357681/pdf/cde-0007-0029.pdf

Tomotaka Mabuchi ¹, Yasuaki Manabe, Hanako Yamaoka, Tami Ota, Masayuki Kato, Norihiro Ikoma, Yoshiyuki Kusakabe, Hirotaka Komaba, Akira Ozawa, J Dermatol. 2014 Jun;41(6):521-4.

 During maintenance HD twice a week, weekly GMA was started at Tokai University Hospital. The skin symptoms disappeared after five administrations of GMA. We suggest that GMA is an effective therapy for GPP patients with ESRD who are treated with HD.

https://pubmed.ncbi.nlm.nih.gov/24815562/

K Sugiura ¹, K Haruna, Y Suga, M Akiyama, J Eur Acad Dermatol Venereol. 2014 Dec;28(12):1835-6.

https://pubmed.ncbi.nlm.nih.gov/24490830/