Due to its rarity and lack of well-designed clinical studies, EP treatment guidelines have not been updated in recent years (2)
Due to its rarity and lack of well-designed clinical studies, EP treatment guidelines have not been updated in recent years (2). currently based on small case series and reports. Few studies have compared available treatment options for EP, and further clinical studies are necessary to provide clinical data and optimal treatment guidelines for EP patients. Here, we provide a comprehensive review of the background of EP, assess the available clinical data on the efficacy of targeted therapies, and aim to provide a foundation for clinical decision making for this rare form of psoriasis. 1.?Introduction Erythrodermic psoriasis (EP) is a rare and severe subset of psoriasis characterized by prominent erythema affecting at least 80C90% of the body surface Methazolastone (1) (Figure 1), and is classically accompanied by fever, chills, headache, and general discomfort (2). Due to severe and extensive skin barrier defect, EP patients can present with systemic symptoms such as dehydration, fatigue, staphylococcal infection, insomnia, weight changes, cachexia, and electrolyte abnormalities (3). The onset can be explosive, or can be more gradual, triggered by various factors, including emotional stress, sunburns, infections, or drugs (4C6). A frequent cause of EP is the sudden withdrawal of plaque psoriasis treatment, including steroids, cyclosporin, and methotrexate (7). It has also recently been described after discontinuation of anti-IL-17A treatments (8). It has been shown that serum interferon- (IFN-) level correlates positively with disease severity (as measured by psoriasis area and severity index (PASI)), and that this level is higher in the EP patients (9). In addition, vascular changes and expression of intercellular adhesion molecules are much higher in EP skin lesions than those in plaque psoriasis (10). However, the use of these observations as a clinical biomarker for EP has not been attempted, and to date, there are no specific biomarkers to predict or monitor the development of EP. Open in a separate window Figure 1. The clinical features of erythrodermic psoriasis (EP).Erythrodermic psoriasis involves over 80C90% of the total body surface area. EP differs clinically in several ways from chronic plaque with the lesions lacking the sharp demarcation from uninvolved skin. The lesions frequently lack the thickness seen in chronic plaque psoriasis and the scale is different, being finer and powdery.. Although EP is considered to be a subtype of psoriasis, the pathogenic mechanisms involved are not identical to plaque psoriasis (summarized in Table 1). In 2005, it was demonstrated that serum immunoglobulin E level was significantly higher in EP patients compared to patients with plaque psoriasis, a finding typically associated with Th2 immune responses (11). Similarly, and consistent with increased Th2 responses playing a role in EP, several studies showed that the serum level of interleukin (IL)-13 and IL-4 were significantly higher in EP Methazolastone patients compared to patients with plaque psoriasis (12, 13). While the association with IL-13 is highly intriguing as mentioned above, one case report of a patient with history of AD treated with the anti-IL-4R antagonist dupilumab, which targets both IL-4 and IL-13, led to development of erythrodermic psoriasis (14), suggesting more of a regulatory role for IL-13 in the pathogenesis of erythrodermic psoriasis. Moreover, microarray analysis of biopsies of chronic plaque Methazolastone psoriasis and EP demonstrated that IL-17A was the major shared pathway for plaque psoriasis and EP (15), and consistent with this, Moy observed via immunohistochemical staining that Th17 cell was Methazolastone the most predominant T cell subset in EP lesions (16). Consistently, published case series indicated that most EP patients achieved complete clearance with anti-IL-17A treatment (15), suggesting that IL-17A may be the dominant cytokine in EP development. Recent publications have reported the association of mutations of the gene in a family with prominent presentation of EP (17), but this signaling pathway has been implicated in pustular forms of psoriasis (18), where IL-36 activation is prominent (19). Further in-depth mechanistic and functional studies are thus needed to better characterize the immunological network and crosstalk in the pathogenesis of EP. Table 1. Summary of the possible pathogenesis of erythrodermic psoriasis (EP) gene in a family with prominent presentation of EP was detected (17).EP may have genetic background similar to pustular psoriasis.Other factorsIn erythroderma, circulating ICAM-1, VCAM-1, and E-selectin levels were significantly elevated (109).Cell adhesion mechanisms NKSF2 may be part of EP pathogenesis. Methazolastone Open in a separate window Abbreviations: EP:.