Psoriasis: Past, Present, and Future

Billi, Allison C.; Guðjónsson, Jóhann E.; Voorhees, John J.

doi:10.1016/j.jid.2019.08.437

Cited by 30 publications

(23 citation statements)

References 131 publications

(132 reference statements)

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“…As is well-evidenced by Davidovici et al the production of pro-inflammatory molecules in psoriasis is not limited to the skin, and therefore psoriasis could be considered as a systemic disease (5,10,33,34). The renowned concept of the "psoriatic march" suggests a growing and worsening systemic chronic inflammatory loop with pleiotropic effects on diverse processes, such as angiogenesis, insulin signaling, adipogenesis, lipid metabolism, and immune cell trafficking (33,35,36).…”

Section: Discussionmentioning

confidence: 99%

Psoriasis and Diabetes, a Dangerous Association: Evaluation of Insulin Resistance, Lipid Abnormalities, and Cardiovascular Risk Biomarkers

et al. 2021

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Aims: Psoriasis is an immune-mediated dermatosis with cardio-metabolic comorbidities. The aim of this study was to assess insulin-resistance, lipid abnormalities, and cardiovascular risk biomarkers in psoriatic patients with or without type 2 diabetes mellitus (T2DM).Methods and materials: We enrolled 425 patients: 86 psoriatics, 69 psoriatics with T2DM, 120 T2DM patients, and 150 healthy subjects. We measured the Psoriasis Area and Severity Index (PASI), body mass index (BMI), insulin-resistance parameters [glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), and with homeostasis model assessment index (HOMA index)], lipidic panel, plasminogen activator inhibitor-1 (PAI-1), homocysteine, soluble adhesion molecules, matrix metalloproteinase, and adipocytokines.Results: FPG, HbA1c, and HOMA-IR were higher in diabetics with psoriasis (p < 0.0001) than in psoriatics. FPI levels were higher in diabetics with psoriasis than in diabetics and psoriatics (p < 0.0001), and higher in psoriatics than controls (p < 0.0001). Psoriatics and diabetics with psoriasis showed higher triglyceride and LDL-C levels (p < 0.0001) than diabetics. Homocysteine was higher in psoriatics and diabetics with psoriasis (p < 0.0001) than in diabetics. PAI-1 was higher in diabetics with psoriasis than diabetics (p < 0.01). sICAM-1 and sVCAM-1 were higher in diabetics with psoriasis than diabetics (p < 0.001 and p < 0.01) and psoriatics (p < 0.001 and p < 0.0001). Visfatin and resistin were lower in psoriatics (p < 0.0001) and in diabetics with psoriasis (p < 0.001 and p < 0.0001, respectively) than diabetics.Conclusions: A limitation of this study is that there is a significant difference in mean age between controls and other study groups: the lack of matching between case and control groups may interfere with the external validity of the study findings. Despite this, the study highlights a pathogenetic link between psoriasis, considered a pre-diabetic condition, and diabetes. Insulin-resistance seems to be the keystone of psoriasis comorbidities. Psoriasis reinforces diabetes, causing a greater cardiometabolic risk.

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Section: Discussionmentioning

confidence: 99%

Psoriasis and Diabetes, a Dangerous Association: Evaluation of Insulin Resistance, Lipid Abnormalities, and Cardiovascular Risk Biomarkers

et al. 2021

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“…Indeed, Voorhes et al suggested in the seventies that an alteration in cAMP levels could be involved in psoriasis [33]. Moreover, a few studies have reported lower levels of cAMP in psoriatic skin, suggesting that low levels of cAMP were linked with enhanced cell proliferation and thus contrasting with finding of Green H [33][34][35][36][37]. The aim of the present study was to therefore compare the use of both cAMP enhancers (CT or ISO) in the reconstruction of psoriatic skin substitutes to establish which one would lead to the better psoriatic phenotype, with traits, such as cell hyperproliferation and disturbed cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

A Tissue-Engineered Human Psoriatic Skin Model to Investigate the Implication of cAMP in Psoriasis: Differential Impacts of Cholera Toxin and Isoproterenol on cAMP Levels of the Epidermis

Simard

Morin

Rioux

et al. 2020

IJMS

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Pathological and healthy skin models were reconstructed using similar culture conditions according to well-known tissue engineering protocols. For both models, cyclic nucleotide enhancers were used as additives to promote keratinocytes’ proliferation. Cholera toxin (CT) and isoproterenol (ISO), a beta-adrenergic agonist, are the most common cAMP stimulators recommended for cell culture. The aim of this study was to evaluate the impact of either CT or ISO on the pathological characteristics of the dermatosis while producing a psoriatic skin model. Healthy and psoriatic skin substitutes were produced according to the self-assembly method of tissue engineering, using culture media supplemented with either CT (10−10 M) or ISO (10−6 M). Psoriatic substitutes produced with CT exhibited a more pronounced psoriatic phenotype than those produced with ISO. Indeed, the psoriatic substitutes produced with CT had the thickest epidermis, as well as contained the most proliferating cells and the most altered expression of involucrin, filaggrin, and keratin 10. Of the four conditions under study, psoriatic substitutes produced with CT had the highest levels of cAMP and enhanced expression of adenylate cyclase 9. Taken together, these results suggest that high levels of cAMP are linked to a stronger psoriatic phenotype.

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“…The “two plaques, one syndrome” hypothesis was proposed since the molecular mechanisms of these two diseases bear a remarkable resemblance to T cell- mediated inflammation [ 10 ]. Although the increased risk of CVDs in psoriasis patients may partly be explained by the hypothesis that chronic skin inflammation and concomitant proinflammatory cytokine activity promote the development of CVDs, the underlying mechanisms remain unclear [ 11 ]. Ixekizumab, a recombinant humanized IgG4-κ monoclonal antibody (mAb) that selectively binds and neutralizes IL-17A, has been employed clinically for psoriasis since 2015 [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients

Cao

Yang

et al. 2021

Lipids Health Dis

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Background Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear. Methods Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases. Results A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P < 0.05). The results for study cohort 2 were largely consistent with the results for study cohort 1. Moreover, the levels of all identified lysophosphatidylcholines were higher in psoriasis patients with coronary heart diseases than in psoriasis without coronary heart disease. Notably, most of these lipidic changes were ameliorated by ixekizumab treatment. Conclusion The results of this non-targeted metabolomic analysis indicate that treatment with IL-17A mAbs can not only ameliorate psoriasis lesions but also restore dysregulated lipid metabolism to normal levels in psoriasis patients. Considering that dysregulated lipid metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipid metabolites in psoriasis patients indicates that IL-17A mAbs might have the potential protective effects against cardiovascular comorbidities.

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Psoriasis: Past, Present, and Future

Cited by 30 publications

References 131 publications

Psoriasis and Diabetes, a Dangerous Association: Evaluation of Insulin Resistance, Lipid Abnormalities, and Cardiovascular Risk Biomarkers

Psoriasis and Diabetes, a Dangerous Association: Evaluation of Insulin Resistance, Lipid Abnormalities, and Cardiovascular Risk Biomarkers

A Tissue-Engineered Human Psoriatic Skin Model to Investigate the Implication of cAMP in Psoriasis: Differential Impacts of Cholera Toxin and Isoproterenol on cAMP Levels of the Epidermis

Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients

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