Chisato Tawada ¹, Yoko Ueda ², Yoko Mizutani ¹, Xiaoyu Zang ¹, Kayoko Tanaka ¹, Hiroaki Iwata ¹

Exp Dermatol. 2025 Mar;34(3):e70076. doi: 10.1111/exd.70076.

Reactive oxygen species (ROS) are involved in the pathogenesis of generalised pustular psoriasis (GPP), but this involvement has not been fully elucidated. We performed the diacron-reactive oxygen metabolite (d-ROM) test and the biological antioxidant potential (BAP) test on sera from nine patients with active GPP who were hospitalised and treated at our hospital, (6/9 with GMA) including three patients with pustular psoriasis of pregnancy (PPP). The serum d-ROM and BAP levels were evaluated before treatment and at 1 month of treatment. We also performed immunostaining of 4-hydroxy-2-nonenal (4-HNE) in skin tissues. In the GPP patients, the average d-ROM levels were significantly reduced at 1 month of treatment (reduced to 343.0 ± 82.1 U.Carr from 423.2 ± 95.0 U.Carr, p = 0.005). The Generalised Pustular Psoriasis Area and Severity Index (GPPASI) score correlated with d-ROM levels (r = 0.57, p = 0.10), suggesting that those levels reflect the disease severity. In normal pregnancy, d-ROM values are known to increase from mid-term to late-term. The d-ROM values increased when GPP worsened in the case of PPP. Immunohistochemical staining of 4-HNE was positive for subcorneal pustules, neutrophils, and for the cytoplasm of epidermal keratinocytes, especially in upper epidermal layers. Our findings indicate that 4-HNE may play an important role in GPP and PPP.

Siew Eng Choon ¹, Peter Anthony Foley ^2 3, Pravit Asawanonda ⁴, Hideki Fujita ⁵, Seong-Jin Jo ⁶, Yu-Ling Shi ^7 8, Colin Theng ⁹, Azura Mohd Affandi ¹⁰, Chul Hwan Bang ¹¹, Maria Lorna Frez ¹², Huang Yu Huei ^13 14, Doanh Le Huu ¹⁵, Tae-Gyun Kim ¹⁶, Akimichi Morita ¹⁷, Hazel H Oon ^18 19, Pablo Fernández-Peñas ^20 21, Natta Rajatanavin ²², Suganthy Robinson ¹⁰, Latha Selvarajah ²³, Tsen-Fang Tsai ²⁴

J Dermatol. 2024 Dec;51(12):1579-1595. doi: 10.1111/1346-8138.17471. Epub 2024 Oct 10.

Generalized pustular psoriasis (GPP) is a rare, chronic, heterogeneous, and potentially life-threatening disease characterized by primary, sterile, and macroscopically visible pustules with or without systemic symptoms. There are ethnic differences in the genetic mutations associated with GPP that might affect the clinical manifestations and treatment responses. Currently, there is limited evidence from the patient population in the Asia-Pacific (APAC) region, resulting in a general paucity of information on the effective management of patients with GPP in this region. This modified Delphi panel study aimed to identify current evidence and gain advanced insights to facilitate the development of a regionally tailored APAC consensus on the management of GPP. A systematic literature review (SLR) was conducted to identify published literature and develop consensus statements on (i) definition and clinical course, (ii) diagnosis of GPP, (iii) treatment outcomes, goals, and monitoring measures, and (iv) optimal management strategies and clinical practices. Statements were rated by a panel of dermatologists in two rounds, with the threshold for consensus at ≥80% agreement. Twenty experts from the APAC region reached consensus on 106 statements that were developed based on the SLR and experts’ collective expertise. The experts agreed that GPP is a rare, severe, and potentially life-threatening condition that is distinct from plaque psoriasis. This consensus emphasized the importance of a tailored treatment strategy taking into account the GPP flare severity and each patient’s unique clinical circumstances. The experts reached consensus on the severity classification of GPP flares and recommended first-line and maintenance treatment options for adult GPP, childhood GPP, and GPP in pregnancy. These consensus outcomes have been synthesized into treatment algorithms to guide dermatologists in the APAC region in their clinical decision-making processes.

Non-pharmacological treatments, such as GMA and IVIG, can be considered based on their availability in individual countries

Dimitrii Pogorelov ¹, Anne Tschesche ¹, Galina Balakirski ¹, Silke C Hofmann ¹

Cureus. 2024 May 7;16(5):e59832. doi: 10.7759/cureus.59832. eCollection 2024 May.

Generalized pustular psoriasis of pregnancy (GPPP) is a rare dermatological condition that significantly affects maternal health and pregnancy outcomes. The treatment of this disease might be very challenging, as only a limited number of effective therapeutic options are available. If the use of systemic drugs is considered, they should ideally effectively control the systemic inflammation without harming the fetus. Here, we report the successful treatment of a severe case of GPPP in a 28-year-old woman using the tumor necrosis factor-alpha inhibitor (TNFi) certolizumab pegol. Additionally, we review the existing literature on the use of this class of drugs for treating GPPP. To date, there are only 11 reported cases of this severe skin condition treated with a TNFi. We also discuss the pathogenesis of GPPP and the rationale behind using TNFi for its treatment.

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)

Mariko Seishima ^1 2, Kento Fujii ³, Yoko Mizutani ³ Am J Clin Dermatol 2022 Jun 15. doi: 10.1007/s40257-022-00698-9.

Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disease characterized by sudden widespread eruption of sterile pustules with or without systemic symptoms. GPP may be life threatening in cases with severe complications such as cardiovascular failure, acute respiratory distress syndrome, and serious infections. Impetigo herpetiformis (IH) is a GPP that is induced and exacerbated by pregnancy and occurs most frequently during the last trimester. IH may result in poor or fatal neonatal outcomes, including placental insufficiency, fetal abnormalities, stillbirth, and early neonatal death. Most patients have prompt remission in the postpartum period; however, earlier appearance and more severe symptoms are observed during subsequent pregnancies. Appropriate treatment and close monitoring of the mother and fetus are vital for the management of patients with IH. Particular attention is required for the management of patients with IH to avoid an influence on the fetus. However, data regarding treatments for GPP in pregnant women are sparse. Over the last decade, many patients with IH have been treated with cyclosporine, corticosteroids, tumor necrosis factor-α inhibitors, interleukin (IL)-17 and IL-12/23 inhibitors, and granulocyte and monocyte adsorption apheresis (GMA). GMA may be an important option for patients with IH as it is presently one of the safest available therapeutic options, but there have been no reports to fully confirm its safety in pregnant patients with GPP. Alternatively, based on recent advances in the understanding of the role of the IL-36 axis in the pathogenesis of GPP, biologic agents that target the IL-36 pathway may demonstrate promising efficacy in IH.

Generalized Pustular Psoriasis in Pregnancy: Current and Future Treatments – PubMed (nih.gov)

Asumi Fujii, Yuki Hattori, Miho Kawamura, Yoko Mizutani, En Shu, Mariko Seishima

poster at ISFA 2019 pag 141-142

A 31-year-old woman with the IL36RN gene mutation developed psoriasis at 3 years old. As she had pustular psoriasis at 16 years old, she was treated with cyclosporine (Cys), resulting in remission at 20 years old. Afterwards, she had been maintained by topical treatment for long years.During the first pregnancy at the age of 29, she developed pustular psoriasis at 29 weeks
of gestation. She received one course of granulocyte / monocyte adsorption apheresis (GMA) with Cys and prednisolone (PSL), and gave birth to a girl at 33 weeks of gestation. The baby was a low birth weight child, but is healthy and has no problems in growth and development until now. However, the patient did not sufficiently improve symptoms after delivery. We thus started the treatment with infliximab (IFX) BS at 2 months postpartum. During the second pregnancy at the age of 30, we continued the IFX-BS administration. She had erythema and pustules rapidly enlarged from 23 weeks of pregnancy. Oral administration of PSL and GMA were started. However, we switched the therapy to intensive GMA (twice in a week), because the effect was insufficient. Initially, administration of IFX-BS was scheduled to end at 30 weeks of gestation, but due to unstable symptoms, we considered it was necessary to use another biologics even after 30 weeks of gestation. We switched to non-placental certolizumab pegol (CTZ) from 26 weeks of gestation and continued the administration until delivery, and she gave birth to a girl at 35 weeks of gestation. Although the baby was a low birth weight child, there was no physical abnormality and the baby was discharged after gaining weight. After delivery, administration of CTZ was discontinued and the PSL dose was gradually reduced. However,reintroduction of biologics is under consideration, because erythema and pustules still remain.

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

Kazuki Yanagisawa ¹, Minoru Murakami ², Yuya Kondo ¹, Shun Oguma ¹, Shun Kobayashi ¹, Hiroshi Miyasaka ¹, Tomoaki Shinohara ³, Akihisa Tomori ³, Yui Nakano ², Shunichi Furuhata ², Masaya Ikezoe ² , Ther Apher Dial 2019 Jun;23(3):217-223.

In patients with active ulcerative colitis (UC), adsorptive granulocyte/monocyte apheresis (GMA) is expected to promote remission. We conducted a retrospective cohort study to evaluate the efficacy and safety of GMA in patients with active UC. Twenty‐one UC patients including five pregnant or lactating mothers and four elderly patients (aged >60 years) received up to 10 GMA sessions. UC severity was evaluated at baseline and after GMA therapy according to Lichtiger’s Clinical Activity Index (CAI). We defined clinical remission as CAI ≤4. Overall, the median CAI score after GMA therapy had decreased from 9 to 4 (P < 0.001). The clinical remission rate was 62%, but in the elderly and pregnant or lactating mothers, the remission rates were 100% and 60%, respectively. No severe adverse effects were seen in this study. Our results may support GMA as an effective and safe treatment for active UC patients, including elderly patients and pregnant cases.

https://pubmed.ncbi.nlm.nih.gov/31025815/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852531/pdf/TAP-23-217.pdf

Tomoyoshi Shibuya ¹, Keiichi Haga ¹, Masato Kamei ¹, Koki Okahara ¹, Shoko Ito ¹, Masahito Takahashi ¹, Osamu Nomura ¹, Takashi Murakami ¹, Masae Makino ¹, Tomohiro Kodani ¹, Dai Ishikawa ¹, Naoto Sakamoto ¹, Taro Osada ¹, Tatsuo Ogihara ¹, Sumio Watanabe ¹, Akihito Nagahara ¹ , Intest Res. 2018 Jul;16(3):484-488.

Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings.

https://pubmed.ncbi.nlm.nih.gov/30090048/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077305/pdf/ir-16-484.pdf

Shingo Kato, Akira Ishibashi, Kaori Sugiura, Kazuhito Kani, Tomonari Ogawa, Hajime Hasegawa, Koji Yakabi, Contrib Nephrol 2018;196:200-208.

GMA decreases inflammatory cytokines and upregulates regulatory T cells. Intensive GMA is significantly more effective than weekly GMA in patients with IBD. The frequency of GMA sessions per week positively correlates with treatment effects. GMA can be safely used in pregnant women and children because of its low adverse event rates. Maintenance therapy and rescue therapy for loss of response of anti-tumor necrosis factor (TNF)-α antibodies are effective. Optimal patients who responded to combination therapy with infliximab and GMA showed aggravation characteristics against infliximab treatment at week 4. Key Message: Prospective randomized blinded studies using a sham column should be performed for the loss of response against anti-TNF-α antibodies.

https://pubmed.ncbi.nlm.nih.gov/30041228/

Giuseppina Perrone ¹, Roberto Brunelli ¹, Eleonora Marcoccia ¹, Ilaria Zannini ¹, Miriam Candelieri ¹, Maria Gozzer ², Claudia Stefanutti ³

When approaching TA in pregnancy, clinicians have to consider the severity of disease, the strength of the indications, and the gestational age. Each case must be evaluated individually on the basis of existing evidence since, despite the increasing use, specific guidelines for apheresis in pregnancy are still lacking.

https://pubmed.ncbi.nlm.nih.gov/27412826/