Walter Jauregui ¹, Yozahandy A Abarca ², Yasmin Ahmadi ³, Vaishnavi B Menon ⁴, Daniela A Zumárraga ⁵, Maria Camila Rojas Gomez ⁶, Aleeza Basri ⁷, Rohitha S Madala ⁸, Peter Girgis ⁹, Zahra Nazir ¹⁰

Cureus. 2024 Sep 3;16(9):e68569. doi: 10.7759/cureus.68569. eCollection 2024 Sep.

Psoriasis (PS) and inflammatory bowel disease (IBD) are immune-mediated chronic conditions that share pathophysiological processes, including immune system dysfunction, microbiome dysbiosis, and inflammatory pathways. These pathways result in increased turnover of epithelial cells and compromised barrier function. The assessment of the literature suggests that immunopathogenic mechanisms, such as tumor necrosis factor (TNF)-α signaling and IL-23/IL-17 axis dysregulation, are shared by PS and IBD. Clinical characteristics and diagnostic approaches overlap significantly, and advances in biomarker identification benefit both conditions. Current treatments, namely biologics that target TNF-α, IL-17, and IL-23, show promising results in decreasing inflammation and controlling symptoms. Precision medicine approaches are prioritized in prospective therapeutic procedures to tailor pharmaceuticals based on specific biomarkers, perhaps improving outcomes and minimizing side effects. This study thoroughly examines and evaluates the body of research on PS and IBD. Several papers were examined to compile data on clinical features, diagnosis, therapies, pathophysiology, epidemiology, and potential future therapeutic developments. The selection of articles was based on three methodological qualities: relevance and addition to the knowledge of IBD and PS. The retrieved data were combined to provide a coherent summary of the state of the knowledge and to spot new trends. The overview of the latest studies demonstrates that both PS and IBD share pathophysiological foundations and therapeutic approaches. With a spotlight on particular biomarkers, advances in precision medicine provide a promising path toward enhancing therapeutic effectiveness and minimizing side effects.

in CD Moderate to severe Oral corticosteroids. Consider enteral nutritional therapy. TNF inhibitors are recommended to be considered for steroid-dependent or refractory patients. If pharmacotherapy or nutrition therapy is ineffective or unable to adapt, the combination with granulocyte monocyte apheresis (GMA) can be considered.

Chiamaka L Okorie ¹, Krithika Nayudu ², Vinod E Nambudiri ^3 4

Exp Dermatol. 2024 Jan;33(1):e14934. doi: 10.1111/exd.14934. Epub 2023 Sep 19.

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.

5.3 Granulocyte and monocyte apheresis (GMA) The use of GMA warrants further exploration.

James Krueger ¹, Lluís Puig ², Diamant Thaçi ³

Am J Clin Dermatol. 2022 Jan;23(Suppl 1):51-64. doi: 10.1007/s40257-021-00658-9. Epub 2022 Jan 21.

Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disorder characterized by sudden widespread eruption of superficial sterile pustules with or without systemic inflammation. GPP flares can be life-threatening if untreated due to potential severe complications such as cardiovascular failure and serious infections. Currently, there are no GPP-specific therapies approved in the USA or Europe. Retinoids, cyclosporine, and methotrexate are the most commonly used non-biologic therapies for GPP. The evidence that supports the currently available treatment options is mainly based on case reports and small, open-label, single-arm studies. However, recent advances in our understanding of the pathogenic mechanisms of GPP and the identification of gene mutations linked to the disease have paved the way for the development of specific targeted therapies that selectively suppress the autoinflammatory and autoimmune mechanisms induced during GPP flares. Several biologic agents that target key cytokines involved in the activation of inflammatory pathways, such as tumor necrosis factor-α blockers and interleukin (IL)-17, IL-23, and IL-12 inhibitors, have emerged as potential treatments for GPP, with several being approved in Japan. The evidence supporting the efficacy of these agents is mainly derived from small, uncontrolled trials. A notable recent advance is the discovery of IL36RN mutations and the central role of IL-36 receptor ligands in the pathogenesis of GPP, which has defined key therapeutic targets for the disease. Biologic agents that target the IL-36 pathway have demonstrated promising efficacy in patients with GPP, marking the beginning of a new era of targeted therapy for GPP.