Ken Okamura 1, Mariko Nikaido 1, Toru Saito 1, Yosuke Arai 1, Chiharu Yoshioka 1, Makoto Yagi 2, Hitomi Komoriya 3, Nana Takahashi 3, Yutaka Hozumi 1, Tamio Suzuki J Dermatol . 2024 Mar 20. doi: 10.1111/1346-8138.17198.

Payal M Patel 1, Stephanie N Sanchez-Melendez 2 3, Vinod E Nambudiri Exp Dermatol. 2023 Aug;32(8):1227-1234. doi: 10.1111/exd.14787

Generalized pustular psoriasis (GPP) is a clinical entity distinct from psoriasis, associated with a poor clinical prognosis, often resulting in severe systemic complications and mortality. The relapsing nature of the disease with recurrent or intermittent flares imposes a significant burden on patients’ quality of life (QoL). Although inadequately studied, QoL data in GPP patients has been a recent point of investigation. We conducted a literature search on PubMed/MEDLINE using the following search terms: ‘generalized pustular psoriasis’ OR ‘pustular psoriasis’ AND ‘quality of life’. We identified 12 relevant articles that provide insight into the large impact of GPP on the QoL of patients, the burden of the disease and the treatment, and the success of new treatment options in making a clinically important difference to QoL. This review illustrates a need for routine assessment of the QoL in interventional clinical trials for GPP and during physician encounters. This information can help guide clinicians on how to tailor the treatment approach from the patient’s perspective or illustrate whether new therapies offer meaningful benefits to patient care as we enter an era of exciting new treatments for this challenging condition.

Mariko Seishima 1, Hideki Hachiken 1, Takuma Furukawa 1, Junichiro Yamamoto, Ther Apher Dial. 2024 Mar 12. doi: 10.1111/1744-9987.14118

Introduction: Granulocyte and monocyte adsorption apheresis (GMA) is usually performed weekly for refractory skin diseases, such as generalized pustular psoriasis and psoriatic arthritis (PsA).

Methods: Four patients with PsA who were refractory to previous treatments were enrolled. They received five or ten sessions of GMA. We assessed the clinical conditions of each patient and laboratory findings before and after GMA.

Results: GMA was effective in plaque-type skin eruptions in all four patients with PsA. It was also effective in joint symptoms in three patients with PsA with mild symptoms, but was ineffective in one patient with severe joint symptoms.

Conclusion: GMA may be recommended to PsA patients with skin eruptions and mild joint symptoms.

Muhammad Hassan Shakir 1 2, Salman A Basit 1, Syed Muhammad Hussain Zaidi 1, Sarasija Natarajan 1, Omar Z Syed 1, Mohammad Asim Amjad 1, Douglas Klamp, Cureus. 2023 Nov 6;15(11):e48399. doi: 10.7759/cureus.48399. eCollection 2023

Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis. Although perceived to be rare, the disease may well have been underreported due to lack of exposure in low-volume clinical settings and due to the use of rather strict clinical criteria for diagnosis. It presents as cutaneous papules, plaques, or nodules in an asymmetric distribution that follows fever and flu-like symptoms. Data on the disease is ever-expanding. Several associations have been identified, including drugs, infections, malignancies, and autoimmune diseases. Different disease patterns and histological variants have been identified. Pathophysiology is complex and multifactorial but appears to involve mechanisms that negatively influence neutrophil apoptosis and facilitate neutrophil recruitment. The existing diagnostic criteria exclude cases with vasculitis; over time, cases of neutrophilic dermatoses with vasculitis have been reported as SS as long as other criteria were met. Newer diagnostic models have been proposed, some arguing against the exclusion of vasculitis. Steroids continue to be the mainstay of treatment, and steroid responsiveness continues to be a part of the diagnostic criteria, although newer treatment modalities have been used and have shown promise. No established guidelines exist for management. We present a case of Idiopathic SS with vasculitis along with a brief review of the existing literature. We agree to the inclusion of vasculitis as proposed by the newer diagnostic criteria.

Mauro Mastronardi ¹, Elisabetta Cavalcanti ², Nunzia Labarile ¹, Raffaele Armentano ³, Francesco Gabriele ⁴, Margherita Curlo ¹ Ther Adv Chronic Dis. 2023 Nov 3:14:20406223231194190.

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

Pyoderma gangrenosum in ulcerative colitis patient treated with vedolizumab: adsorptive granulocyte/monocyte apheresis as a new therapeutic option refractory cases – a case report and literature review – PubMed (nih.gov)

Pyoderma gangrenosum in ulcerative colitis patient treated with vedolizumab: adsorptive granulocyte/monocyte apheresis as a new therapeutic option refractory cases – a case report and literature review – PMC (nih.gov)

Grisell Starita-Fajardo 1, David Lucena-López 1, María Asunción Ballester-Martínez 2, Montserrat Fernández-Guarino 2, Andrés González-García Int J Mol Sci. 2023 Oct 26;24(21):15622. doi: 10.3390/ijms242115622

Neutrophilic dermatoses (NDs) are a group of noninfectious disorders characterized by the presence of a sterile neutrophilic infiltrate without vasculitis histopathology. Their physiopathology is not fully understood. The association between neutrophilic dermatoses and autoinflammatory diseases has led some authors to propose that both are part of the same spectrum of diseases. The classification of NDs depends on clinical and histopathological features. This review focuses on the recent developments of treatments in these pathologies.

AM Varghese1, PK Uppala2, RK Keelu1, SV Sai Krishna3, NV Kandra1, U Uttaravalli4, VS Somarouthu5 and M K Balijepalli
SA Pharmaceutical Journal 90, 51, 2023

Sweet syndrome (SS) is an uncommon auto-inflammatory disorder presenting with acute pyrexia, leucocytosis and erythematous skin lesions with dense neutrophilic dermal infiltration. SS is seen as adverse reaction to some drugs, microbes and is associated with certain myeloproliferative or haematological neoplasms and is also seen with autoimmune diseases like inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, etc. A female aged 43 years, came to the hospital with high fever and erythematous, pus-filled plaques and nodules on her face, neck, shoulders and extremities, after taking cotrimoxazole (antibacterial agent) in tablet form 480 mg twice daily for five days for urinary tract infection. The diagnosis of SS was arrived upon from the biopsy reports showing predominant neutrophilic infiltrate, and relevant laboratory tests. Treatment included oral prednisone (corticosteroid) and the symptoms resolved in two months.

Matteo Megna 1, Elisa Camela 2, Angelo Ruggiero 1, Teresa Battista 1, Fabrizio Martora 1, Sara Cacciapuoti 1, Luca Potestio. Clin Cosmet Investig Dermatol. 2023 Jun 28:16:1677-1690. doi=10.2147/CCID.S407812

Generalized pustular psoriasis (GPP) is a severe and rare form of psoriasis, being a potentially life-threatening condition, characterized by recurring episodes or flares of widespread cutaneous erythema with macroscopic sterile pustules. An irregular innate immune response is linked to GPP, which is considered an auto-inflammatory disorder, while innate and adaptive immunopathogenic responses are involved in psoriasis pathogenesis. In consequence, different cytokine cascades have been suggested to be mainly involved in the pathogenesis of each different psoriasis form, with the interleukin (IL)23/IL17 axis implied in plaque psoriasis, and the IL36 pathway in the GPP. As regards GPP treatment, conventional systemic drugs available for plaque psoriasis are usually used as the first-line treatment option. However, contraindications and adverse events often limit the use of these therapies. In this scenario, biologic drugs may represent a promising treatment option. To date, even if 12 different biologics have been approved for plaque psoriasis, none of these is approved for GPP where they are employed off-label. Recently, spesolimab, an anti-IL36 receptor monoclonal antibody, has been recently approved for GPP. The purpose of this article is to assess the current literature about the use of biological therapies for the treatment of GPP to establish the basis for a shared GPP management algorithm.

Toshiyuki Yamamoto, Kenshi Yamasaki, Keiichi Yamanaka, Mayumi Komine, Tamihiro Kawakami, Osamu Yamamoto, Takuro Kanekura, Tetsuya Higuchi, Toshiya Takahashi, Yoshiaki Matsushima, Nobuyuki Kikuchi, Japanese Dermatological Association Pyoderma Gangrenosum Treatment Guidelines Drafting Committee Journal of Dermatology 50 (9) 2023, e253-e275 doi.org=10.1111/1346-8138.16845

Pyoderma gangrenosum (PG) is a rare, neutrophilic skin disease. For the purpose of accurate diagnosis and proper treatment of PG, the Japanese clinical practice guidance for PG developed by the Japanese Dermatological Association was published in 2022. In this guidance, clinical aspects, pathogenesis, current therapies, and clinical questions on PG are described from the viewpoints of current knowledge and evidence-based medicine. Here, the English version of the Japanese clinical practice guidelines for PG is presented and is intended to be widely referred to in the clinical examination and treatment of PG.

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.

Mild generalised pustular psoriasis patient with a heterozygous hypomorphic MPO variant successfully treated with granulocyte and monocyte adsorption apheresis – PubMed (nih.gov)

Mild generalised pustular psoriasis patient with a heterozygous hypomorphic MPO variant successfully treated with granulocyte and monocyte adsorption apheresis – Takeichi – 2023 – Experimental Dermatology – Wiley Online Library