Biju Vasudevan ¹, Pankaj Das ¹, Siddharth Bhatt ¹ Indian J Dermatol Venereol Leprol. 2023 May 28:1-11.

Pustular psoriasis is a distinct subset of psoriasis that presents with involvement of the skin in the form of sterile pustules along with systemic manifestations. Though it has been conventionally grouped under the umbrella of psoriasis, recent research has shed light on its pathogenetic mechanisms associated with the IL-36 pathway, which is distinct from conventional psoriasis. Pustular psoriasis in itself is a heterogeneous entity consisting of various subtypes, including generalized, localized, acute, and chronic forms. There is confusion regarding its current classification as entities like deficiency of IL-36 antagonist (DITRA) which are closely related to pustular psoriasis both in their pathogenetic mechanism and its clinical manifestations, are not included under pustular psoriasis. Entities like palmoplantar pustulosis, which presents with similar clinical features but is pathogenetically distinct from other forms of pustular psoriasis, are included under this condition. Management of pustular psoriasis depends upon its severity; while some of the localized variants can be managed with topical therapy alone, the generalized variants like Von Zumbusch disease and impetigo herpetiformis may need intensive care unit admission and tailor-made treatment protocols. The advent of newer biologics and better insight into the pathogenesis of pustular psoriasis has opened the way for newer therapies, including tumor necrosis factor-alpha inhibitors, interleukin-1 inhibitors, interleukin-17 inhibitors, and granulocyte monocyte apheresis. It continues to be an enigma whether pustular psoriasis is actually a variant of psoriasis or an entirely different disease entity, though we feel that it is an entirely different disease process.

Pustular psoriasis: A distinct aetiopathogenic and clinical entity – PubMed (nih.gov)

Pustular psoriasis: A distinct aetiopathogenic and clinical entity – Indian Journal of Dermatology, Venereology and Leprology (ijdvl.com)

Laura Gnesotto ¹, Guido Mioso ¹, Mauro Alaibac ¹

Exp Ther Med 2022 Jun 24;24(2):536. doi: 10.3892/etm.2022.11463. eCollection 2022 Aug. DOI: 10.3892/etm.2022.11463

Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal treatment that selectively removes activated myeloid lineage leukocytes from peripheral blood. This technique consists of a column with cellulose acetate beads as absorptive leukocytapheresis carriers, and was initially used to treat ulcerative colitis. A literature search was conducted to extract recently published studies about the clinical efficacy of GMA in patients with different skin disorders, reporting information on demographics, clinical symptoms, treatment and clinical course. Dermatological diseases, in which GMA has been performed, include generalized pustular psoriasis, pyoderma gangrenosum, palmoplantar pustular psoriasis, Behcet’s disease, Sweet’s syndrome, adult-onset Still’s disease, impetigo herpetiformis, reactive arthritis, acne and hidradenitis suppurativa syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus. In most patients, GMA was started after the failure of conventional therapeutic options and it was helpful in the majority of cases. Based on the information summarized, GMA could be considered a valid non-pharmacological treatment option for patients with several dermatological conditions, which are difficult to treat with other pharmacological preparations.

 PASH syndrome; cutaneous allergic vasculitis; granulocyte and monocyte apheresis; neutrophilic dermatoses; reactive arthritis; systemic lupus erythematosus.

https://pubmed.ncbi.nlm.nih.gov/35837066/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257973/

Masashi Akiyama 

J Dermatol Sci 2022 Jan;105(1):11-17. doi: 10.1016/j.jdermsci.2021.11.009. 

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.

Pustular psoriasis as an autoinflammatory keratinization disease (AiKD): Genetic predisposing factors and promising therapeutic targets – PubMed (nih.gov)

Pustular psoriasis as an autoinflammatory keratinization disease (AiKD): Genetic predisposing factors and promising therapeutic targets – Journal of Dermatological Science (jdsjournal.com)

Yuko Higashi, Munekazu Yamakuchi, Takuro Kanekura

poster at ISFA 2019 pag 126

Neutrophilic skin diseases are a group of disorders characterized by intense dermal infiltration of neutrophils without infection. They include a variety of diseases, such as pyoderma gangrenosum, pustular psoriasis, and palmoplantar pustulosis. We demonstrated that granulocyte and monocyte adsorption apheresis (GMA) is a useful treatment modality for such refractory skin diseases. Microarray analysis of microRNAs (miRNAs) was performed using sera of patients with neutrophilic skin diseases before and after GMA. Several miRNAs significantly increased in patients compared to control subjects. The expression of three
miRNAs decreased after apheresis, suggesting that these miRNAs might be involved in the pathogenesis of neutrophilic skin decreases. To prove the function of these miRNAs, HL-60, a human acute promyelocytic leukemia cell line, was differentiated by the treatment of alltrans retinoic acid (ATRA). When HL-60 was differentiated to neutrophilic cells, the HEstaining shows an increased cytoplasm to nucleus ratio, condensated chromatin, and nuclear segmentation. The expression of three miRNAs increased during the neutrophilic differentiation. Stimulation of ATRA-treated HL-60 by some cytokines altered miRNA expressions. Moreover, manipulation of these miRNAs changed proliferation of cultured keratinocytes. These data
suggest that miRNAs play an important role in regulating neutrophilic differentiation and proliferation of keratinocytes in case of neutrophilic disorders such as psoriasis. These miRNAs could be markers of disease severity and response of GMA.

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

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

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/

Tomomi Fujisawa ¹, Chisato Tawada, Yoko Mizutani, Tomoaki Doi, Shozo Yoshida, Shinji Ogura, Mariko Seishima, Ther Apher Dial. 2014 Jun;18(3):238-43.

Palmoplantar pustulosis (PPP) is characterized by neutrophilic pustules with erythema, which are limited to the hands and feet. Although granulocyte and monocyte adsorption apheresis (GMA) has shown remarkable effects on generalized pustular psoriasis, there are few reports of PPP treated with GMA. We treated three refractory PPP patients using GMA weekly for 5 weeks. The skin eruptions were assessed by a 5-grade score for scales, pustules, and erythema. GMA decreased the total grade from 9 to 2 in patients 1 and 2, and from 7 to 3 in patient 3. The GMA effects were estimated to be excellent in all three patients. Pustule formation and pain disappeared in all cases. The treatment effect lasted for at least 5 months after GMA. GMA was also effective for relieving the arthralgia in one patient, but it recurred at 6 weeks. Based on these findings, GMA could be an effective therapy for refractory PPP.

https://pubmed.ncbi.nlm.nih.gov/24965289/