Successful combination therapy of bimekizumab and granulocyte monocyte adsorption apheresis for generalized pustular psoriasis complicated with microscopic polyangiitis
Mild generalised pustular psoriasis patient with a heterozygous hypomorphic MPO variant successfully treated with granulocyte and monocyte adsorption apheresis
Takuya Takeichi 1, Takenori Yoshikawa 1, Muhammad Nasir Iqbal 2, Muhammad Farooq 3, Tomoki Taki 1, Yoshinao Muro 1, Yutaka Shimomura 4, Mariko Seishima 5, Masashi Akiyama 1 Exp Dermatol. 2023 Sep;32(9):1557-1562. doi: 10.1111/exd.14846.
Pathogenic variants in MPO, which encodes the myeloperoxidase, were reported as causative genetic defects in several cases of generalised pustular psoriasis (GPP) in addition to patients with myeloperoxidase deficiency in 2020. However, which clinical subtypes of GPP patients have pathogenic variants in MPO remains largely undetermined, and elucidating this is clinically important. The present report outlines a mild case of GPP with a rare missense heterozygous variant, c.1810C>T p.(Arg604Cys), in MPO. Our structural analysis and functional assays to measure myeloperoxidase activity suggest that the present MPO substitution is a hypomorphic variant in MPO. Thus, the mild phenotype of the present GPP patient might be associated with an incomplete hypomorphic loss-of-function variant in MPO. Additionally, the severe intractable edematous pustules and erythema improved dramatically after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. This is the first report of GMA treatment for GPP associated with a pathogenic variant in MPO, as far as we know. Our findings suggest that GMA might be a useful and powerful tool for controlling GPP in patients with myeloperoxidase deficiency.
A real-world, single-center experience and the immediate impact of granulocyte and monocyte adsorption apheresis on generalized pustular psoriasis
Hideaki Uchida 1, Masahiro Kamata 2, Shota Egawa 1, Mayumi Nagata 1, Saki Fukaya 1, Kotaro Hayashi 1, Atsuko Fukuyasu 1, Takamitsu Tanaka 1, Takeko Ishikawa 1, Takamitsu Ohnishi 1, Kazumitsu Sugiura 3, Yayoi Tada
J Am Acad Dermatol 2022 Nov;87(5):1181-1184. doi: 10.1016/j.jaad.2022.03.001.
Granulocyte and monocyte adsorption apheresis (GMA) is an extracorporeal circulation therapy that removes activated granulocytes and monocytes, which can be easily introduced in clinics and hospitals where hemodialysis is performed. Its safety profile allows for its administration without screening and for its concomitant use with other therapies, indicating that GMA can be a good additional option for GPP treatment. However, the evidence for its efficacy and safety is limited because of the rarity of GPP. Furthermore, its immediate impact on GPP has not been assessed yet. Therefore, we report our real-world experience of 14 patients with GPP treated with GMA after systemic treatment.GMA can be administered with other systemic therapies, including biologics and conventional therapy (objective A). Furthermore, its good safety profile allows GMA administration to a wide range of patients, including elderly patients and those with complications, possible active infection, or malignancy (objectives B and C). Moreover, our study revealed an immediate significant improvement in BT, accompanied by slight decreases in the WBC count and CRP level, indicating that GMA contributes to the rapid suppression of acute inflammation in patients with GPP.
A real-world, single-center experience and the immediate impact of granulocyte and monocyte adsorption apheresis on generalized pustular psoriasis – Journal of the American Academy of Dermatology (jaad.org)
Pustular psoriasis as an autoinflammatory keratinization disease (AiKD): Genetic predisposing factors and promising therapeutic targets
Pustular psoriasis is a chronic inflammatory skin disease characterized by erythematous plaques with sterile pustules. It includes the distinct clinical entities generalized pustular psoriasis (GPP), acrodermatitis continua of Hallopeau (ACH) and palmoplantar pustular psoriasis (PPPP). Recently clarified pathomechanisms of pustular psoriasis indicate that hyperactivation of the skin innate immunity, including of the IL-1/IL-36 axis, plays an important role in the pathogenesis of pustular psoriasis. Autoinflammatory keratinization disease (AiKD) is the umbrella clinical entity for inflammatory keratinization disorders with genetic autoinflammatory pathomechanisms, and pustular psoriasis is a representative AiKD. To date, mutations/variants in five genes-IL36RN, CARD14, AP1S3, MPO and SERPINA3-have been reported to be genetic causative or predisposing factors for pustular psoriasis. The pathogenic mechanisms induced by the mutations/variants in these genes are all closely related to the excessive activation of skin innate immunity and autoinflammation. A number of biologics (e.g., tumor necrosis factor inhibitors, IL-17/IL-17 receptor inhibitors and IL-23 inhibitors) and granulocyte and monocyte adsorption apheresis are used to treat pustular psoriasis. Recently, based on novel information on the pathomechanisms of pustular psoriasis, which are mainly associated with autoinflammation, inhibitors of several pathogenic pathways, including of the IL-1, IL-36, IL-8 and granulocyte colony-stimulating factor signaling pathways, have been studied as emerging treatments.
GS2-03 Japanese apheresis guidelines for the management and treatment of generalized pustular psoriasis, pustulosis palmoplantaris and psoriasis arthropathica
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.
SY5-01 Granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis
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
Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP.
Hideki Fujita 1, Tadashi Terui 1, Koremasa Hayama 1, Masashi Akiyama 2, Shigaku Ikeda 3, Tomotaka Mabuchi 4, Akira Ozawa 4, Takuro Kanekura 5, Michiko Kurosawa 6, Mayumi Komine 7, Kimiko Nakajima 8, Shigetoshi Sano 8, Osamu Nemoto 9, Masahiko Muto 10, Yasutomo Imai 11, Kiyofumi Yamanishi 11, Yumi Aoyama 12, Keiji Iwatsuki 13, J Dermatol . 2018 Nov;45(11):1235-1270.
The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP.
Granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis
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.
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