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Yadav T, Yadav HKS, Raizaday A, Alam MS. The treatment of psoriasis via herbal formulation and nano-polyherbal formulation: A new approach. BIOIMPACTS : BI 2024; 15:30341. [PMID: 40256226 PMCID: PMC12008506 DOI: 10.34172/bi.30341] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 06/27/2024] [Accepted: 07/02/2024] [Indexed: 04/22/2025]
Abstract
Psoriasis is a chronic condition that can strike at any age. This sickness is associated with inflammatory problems that impact all humans in the world. Psoriasis is more common in Scandinavians than in Asian and African populations due to a combination of factors such as age, gender, geographic location, ethnicity, genetic and environmental factors. Immune stimulation, genetic contribution, antimicrobial peptides, and other significant triggers such as medicines, immunizations, infections, trauma, stress, obesity, alcohol intake, smoking, air pollution, sun exposure, and particular disorders cause psoriasis. Numerous clinical research investigations are now underway, and therapeutic alternatives are available. However, these therapies only improve symptoms and do not accomplish a complete cure; they also have dangerous and undesirable side effects. Natural products have gained popularity recently due to their great effectiveness, safety, and low toxicity. Natural formulations of various nanocarriers like liposomes, lipospheres, nanogels, emulgel, nanostructured lipid carriers, nanosponge, nanofibers, niosomes, nanomiemgel, nanoemulsions, nanospheres, cubosomes, microneedles, nanomicelles, ethosomes, nanocrystals, and foams, have significantly contributed and encouraged advancement in psoriasis disease treatment. These phytochemical-loaded new nanoformulations address several issues associated with natural products in conventional dosage forms, such as instability, poor solubility, and limited bioavailability. This article reviews some of the intriguing phytochemicals, as well as their possible molecular target locations and mechanisms of action, which may assist in the development of more specific and selective antipsoriatic medicines. Exploring and understanding phytochemicals' functions will allow for more site-specific psoriasis treatment techniques. This review concluded the psoriasis disease with phytoconstituent loaded herbal or polyherbal nanocarriers and their mechanistic approach.
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Affiliation(s)
- Tejpal Yadav
- Gyan Vihar School of Pharmacy, Suresh Gyan Vihar University, Jaipur, Rajasthan, India
| | | | - Abhay Raizaday
- Department of Pharmaceutics, College of Pharmacy, JSS Academy of Technical Education, Noida, Uttar Pradesh, India
| | - Md Sabir Alam
- SGT College of Pharmacy, SGT University, Gurgaon-Badli Road Chandu, Budhera, Gurugram, Haryana-122505, India
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Lee MY, Han K, Koo HYR, Yu DS, Lee YB. PSORIASIS INCREASES RETINAL VEIN OCCLUSION RISK IN DIABETIC PATIENTS: A Nationwide Population-Based Study. Retina 2024; 44:151-158. [PMID: 37606285 DOI: 10.1097/iae.0000000000003916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/23/2023]
Abstract
PURPOSE The objective of this research was to explore how psoriasis is linked to the occurrence of retinal vein occlusion (RVO) in diabetic population. METHODS This was a retrospective, nationwide, population-based cohort study that examined medical records from January 2009 to December 2012. The study focused on patients ≥20 years of age who had been diagnosed with Type 2 diabetes mellitus (DM). The authors compared the incidence rate of RVO between a group of patients with psoriasis and a group of patients without psoriasis until December 2018 in all subjects. RESULTS Of the 2,745,689 Type 2 DM patients, 23,725 patients were classified in the psoriasis group and the rest of the 2,547,121 individuals in the control group. A total of 497 RVO cases occurred in the psoriasis group (3.14/1,000 person-years) and 42,388 RVO cases in the control group (2.44/1,000 person-years). According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly greater risk of developing RVO compared with control subjects (hazard ratio: 1.216, 95% confidence interval: 1.11-1.33) after adjustments for covariates. CONCLUSION This study demonstrated that psoriasis was an independent risk factor for developing RVO in DM patients. Therefore, physicians need to be vigilant for the occurrence of RVO in DM patients who also have psoriasis.
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Affiliation(s)
- Mee Yon Lee
- Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, College of Natural Sciences, Soongsil University, Republic of Korea; and
| | - Ha Yeh Rin Koo
- Department of Dermatology, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Dong Soo Yu
- Department of Dermatology, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Young Bok Lee
- Department of Dermatology, College of Medicine, The Catholic University of Korea, Republic of Korea
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Tang X. The risk of organ-based comorbidities in psoriasis: a systematic review and meta-analysis. An Bras Dermatol 2022; 97:612-623. [PMID: 35850940 PMCID: PMC9453528 DOI: 10.1016/j.abd.2021.10.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 09/30/2021] [Accepted: 10/04/2021] [Indexed: 02/06/2023] Open
Abstract
Background The close relationship between psoriasis and concomitant diseases is widely accepted. However, a comprehensive analysis of organ-based comorbidities in psoriasis is still lacking. Objective The authors aimed to present the risk of organ-based comorbidities in psoriasis by comparing the general population. Methods The authors retrieved a search of Pubmed, EMBASE, and Cochrane databases for studies reporting organ-based comorbidities in psoriasis versus the general population. Observational studies that met the following criteria were assessed: 1) Psoriasis diagnosis; 2) Cardiovascular or kidney or liver or respiratory or cerebrovascular outcomes; 3) Comparison group of individuals without psoriasis. Pooled Relative Risks (pRRs) and 95% Confidence Intervals (CIs) were calculated by using the random-effect model. Results Fifteen observational studies with 216,348 psoriatic patients and 9,896,962 individuals from the general population were included. Psoriasis showed a greater risk of organ-based comorbidities. Compared to the general population, pRR for all organ-based comorbidities was 1.20 (95% CI 1.11‒1.31) in psoriasis, and pRR was lower in mild 0.61 (95% CI 0.46‒0.81) than in moderate/severe patients. pRR was 1.20 (95% CI 1.11‒1.30) for cardiovascular, 1.56 (95% CI 1.20‒2.04), and 1.75 (95% CI 1.33‒2.29) for cerebrovascular and liver diseases, respectively. pRR for coexisting renal and cardiovascular events was 1.09 (95% CI 1.01‒1.18). pRR for coexisting renal and cerebrovascular events was 1.28 (95% CI 0.99‒1.66). pRR for coexisting renal and liver diseases was 1.46 (95% CI 1.10‒1.94). pRR for coexisting cardiovascular and liver diseases was 1.41 (95% CI 1.11‒1.80). Study limitations There is heterogeneity. Conclusion Psoriasis has a higher risk of single and multiple organ-based comorbidities than the general population. The present study will further improve attention to psoriasis as a systemic inflammatory disease.
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Affiliation(s)
- Xuemei Tang
- Southwest Medical University, Luzhou, Sichuan, China.
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Abstract
The physical examination of the patient with diabetes may have revealed findings that confirm the diagnosis, classify the type of diabetes, and begin to evaluate for the macro- and microvascular complications of diabetes and significant comorbid conditions. While screening for the diagnosis of diabetes occurs with assessment for abnormal blood glucose, given the high rates of morbidity and mortality associated with diabetes, utilization of the physical examination plays a key role in identifying patients at risk for the complications of diabetes. The discussion of elements of the physical examination relevant to the patient with diabetes, both type 1 and type 2, will be discussed in this article.
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Affiliation(s)
- Aamir Malik
- Diabetes and Nutrition, Boston University School of Medicine/Boston Medical Center, Section of Endocrinology, Diabetes and Nutrition, 720 Harrison Avenue, DOB 8th Floor, Boston, MA 02118
| | - Sonia Ananthakrishnan
- Boston University School of Medicine/Boston Medical Center, Section of Endocrinology, Diabetes and Nutrition, 72 East Concord Street, Evans 122, Boston, MA, 02118.
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Mizusawa N, Harada N, Iwata T, Ohigashi I, Itakura M, Yoshimoto K. Identification of protease serine S1 family member 53 as a mitochondrial protein in murine islet beta cells. Islets 2022; 14:1-13. [PMID: 34636707 PMCID: PMC8812782 DOI: 10.1080/19382014.2021.1982325] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The aim of this study was to identify genes that are specifically expressed in pancreatic islet β-cells (hereafter referred to as β-cells). Large-scale complementary DNA-sequencing analysis was performed for 3,429 expressed sequence tags derived from murine MIN6 β-cells, through homology comparisons using the GenBank database. Three individual ESTs were found to code for protease serine S1 family member 53 (Prss53). Prss53 mRNA is processed into both a short and long form, which encode 482 and 552 amino acids, respectively. Transient overexpression of myc-tagged Prss53 in COS-7 cells showed that Prss53 was strongly associated with the luminal surfaces of organellar membranes and that it underwent signal peptide cleavage and N-glycosylation. Immunoelectron microscopy and western blotting revealed that Prss53 localized to mitochondria in MIN6 cells. Short hairpin RNA-mediated Prss53 knockdown resulted in Ppargc1a downregulation and Ucp2 and Glut2 upregulation. JC-1 staining revealed that the mitochondria were depolarized in Prss53-knockdown MIN6 cells; however, no change was observed in glucose-stimulated insulin secretion. Our results suggest that mitochondrial Prss53 expression plays an important role in maintaining the health of β-cells.
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Affiliation(s)
- Noriko Mizusawa
- Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan
- CONTACT Noriko Mizusawa Department of Oral Bioscience, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-Kuramoto-cho, Tokushima City770-8504, Japan
| | - Nagakatsu Harada
- Department of Health and Nutrition, Faculty of Nursing and Nutrition, The University of Shimane, Shimane, Japan
| | - Takeo Iwata
- Department of Functional Morphology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan
| | - Izumi Ohigashi
- Division of Experimental Immunology, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
| | - Mitsuo Itakura
- Division of Genetic Information, Institute for Genome Research, Tokushima University, Tokushima, Japan
| | - Katsuhiko Yoshimoto
- Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan
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Association between baseline insulin resistance and psoriasis incidence: the Women's Health Initiative. Arch Dermatol Res 2021; 314:869-880. [PMID: 34816303 PMCID: PMC9512862 DOI: 10.1007/s00403-021-02298-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 10/26/2021] [Indexed: 11/02/2022]
Abstract
Small-scale studies offer conflicting evidence regarding the relationship/association between psoriasis and insulin resistance by HOMA-IR (homeostasis model assessment of insulin resistance). The purpose of this study was to assess the association between baseline HOMA-IR and psoriasis incidence in a large-scale longitudinal cohort of postmenopausal women. The analysis included 21,789 postmenopausal women from the Women's Health Initiative. Psoriasis diagnosis was defined by fee-for-service Medicare ICD-9-CM codes assigned by dermatologists or rheumatologists, and a 2-year lookback period to exclude prevalent cases. Baseline HOMA-IR was calculated using the updated HOMA2 model. Hazard rates from the Cox regression models were stratified by age (10-year intervals), on WHI component (Clinical Trial or Observational Study), and on randomization status within each of the WHI clinical trials. The complete model also adjusted for ethnicity, waist-hip-ratio, and smoking and alcohol habits. Among participants free of psoriasis at entry, those with high baseline HOMA-IR (≥ 2) compared to low (< 1.4) had significantly higher risk for psoriasis over 21-year cumulative follow-up (HR: 1.39, 95% CI 1.08-1.79, P-trend: 0.011). In postmenopausal women, higher baseline HOMA-IR levels were significantly associated with higher incidence of psoriasis over 21-year cumulative follow-up. Results from this time-to-event analysis indicate that insulin resistance can precede and is associated with an increased risk of psoriasis. Study is limited by Medicare diagnostic code accuracy and cohort age.
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Alwehaidah MS, Bakhiet M, AlFadhli S. Mitochondrial Haplogroup Reveals the Genetic Basis of Diabetes Mellitus Type 2 Comorbidity in Psoriasis. Med Princ Pract 2021; 30:62-68. [PMID: 32629455 PMCID: PMC7923845 DOI: 10.1159/000509937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 07/06/2020] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE Published data show a clear link between psoriasis (Ps) and the increasing prevalence of comorbid conditions, such as diabetes mellitus type 2 (DM2). The role of the mitochondrial genomic haplogroup in the potential coexistence of Ps and DM2 comorbidity is the subject of this study. MATERIAL AND METHODS Ninety-eight Kuwaiti individuals were recruited in 4 cohorts (20 healthy controls, 15 with DM2, 34 with Ps, and 29 with Ps and diabetes mellitus). An Ion Torrent S5XL was used to sequence mitochondrial DNA (mtDNA). χ2 test was used to assess differences in the distribution of each haplogroup between cases and controls (p < 0.05). The Bonferroni correction was applied (p < 0.004). The mtDNA haplogroups were analyzed by HaploGrep. RESULTS Haplogroups R0, U, J, T, N, L3, M, H, X, HV, R, and K were detected in the studied population. Haplogroup M had a high risk for Ps (odds ratio (OR) 4.0, p = 0.003). Haplogroup R0 and J had decreased the risk of DM2 (OR 0.28, p = 0.007). CONCLUSION Our results indicated that mtDNA haplogroups have a potential contribution to the pathogenesis of Ps and DM2 comorbidity. We show for the first time that the comorbidity of diabetes in Ps may be related to mitochondrial dysfunction.
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Affiliation(s)
- Materah Salem Alwehaidah
- Department of Medical Laboratory, Faculty of Allied Health, Kuwait University, Sulaibekhat, Kuwait,
| | - Moiz Bakhiet
- Department of Molecular Medicine, College of Medical and Medicine Sciences, Arabian Gulf University, Manama, Bahrain
| | - Suad AlFadhli
- Department of Medical Laboratory, Faculty of Allied Health, Kuwait University, Sulaibekhat, Kuwait
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Risk Factors for the Development of Psoriasis. Int J Mol Sci 2019; 20:ijms20184347. [PMID: 31491865 PMCID: PMC6769762 DOI: 10.3390/ijms20184347] [Citation(s) in RCA: 338] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 08/30/2019] [Accepted: 09/03/2019] [Indexed: 12/12/2022] Open
Abstract
Psoriasis is an immune-mediated genetic skin disease. The underlying pathomechanisms involve complex interaction between the innate and adaptive immune system. T cells interact with dendritic cells, macrophages, and keratinocytes, which can be mediated by their secreted cytokines. In the past decade, biologics targeting tumor necrosis factor-α, interleukin (IL)-23, and IL-17 have been developed and approved for the treatment of psoriasis. These biologics have dramatically changed the treatment and management of psoriasis. In contrast, various triggering factors can elicit the disease in genetically predisposed individuals. Recent studies suggest that the exacerbation of psoriasis can lead to systemic inflammation and cardiovascular comorbidity. In addition, psoriasis may be associated with other auto-inflammatory and auto-immune diseases. In this review, we summarize the risk factors, which can be divided into two groups (namely, extrinsic and intrinsic risk factors), responsible for the onset and exacerbation of psoriasis in order to facilitate its prevention.
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Friis NU, Hoffmann N, Gyldenløve M, Skov L, Vilsbøll T, Knop FK, Storgaard H. Glucose metabolism in patients with psoriasis. Br J Dermatol 2018; 180:264-271. [PMID: 30376181 DOI: 10.1111/bjd.17349] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/23/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Epidemiological studies strongly suggest that psoriasis predisposes to type 2 diabetes. Several theories have been proposed to explain how these disease entities might be pathophysiologically connected. OBJECTIVES Our primary objective was to elucidate whether clinical data support the notion of common pathophysiological denominators in patients with psoriasis and type 2 diabetes, and thus to delineate the association between the two conditions that has arisen on the basis of epidemiological studies. METHODS We reviewed clinical studies investigating parameters of glucose metabolism in patients with psoriasis. The PubMed and Embase databases were searched for studies investigating glucose metabolism in adult patients with psoriasis as a primary or secondary end point. Studies had to include a relevant control group. RESULTS Twenty-six clinical studies reporting on insulin resistance, glucose tolerance or insulin secretion were eligible for review. The results were widely conflicting, with less than half of the studies showing results suggestive of defective glucose metabolism in patients with psoriasis. In general, the studies suffered from a lack of information regarding possible confounders and patient characteristics. Furthermore, the research methods varied, and in all but one study they might not have been appropriate to detect early and subtle defects in glucose metabolism. CONCLUSIONS The available literature does not unequivocally support common pathophysiological denominators in psoriasis and type 2 diabetes. Well-designed clinical studies are needed to expose potential diabetogenic defects in the glucose metabolism in patients with psoriasis.
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Affiliation(s)
- N U Friis
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Kildegårdsvej 28, DK-2900, Hellerup, Denmark
| | - N Hoffmann
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Kildegårdsvej 28, DK-2900, Hellerup, Denmark
| | - M Gyldenløve
- Department of Dermatology and Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - L Skov
- Department of Dermatology and Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - T Vilsbøll
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - F K Knop
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - H Storgaard
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Kildegårdsvej 28, DK-2900, Hellerup, Denmark
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Hongo Y, Ashida K, Ohe K, Enjoji M, Yamaguchi M, Kurata T, Emoto A, Yamanouchi H, Takagi S, Mori H, Kawata N, Hisata Y, Sakanishi Y, Izumi K, Sugioka T, Anzai K. Change of Oral to Topical Corticosteroid Therapy Exacerbated Glucose Tolerance in a Patient with Plaque Psoriasis. Am J Case Rep 2017; 18:1198-1203. [PMID: 29129905 PMCID: PMC5700446 DOI: 10.12659/ajcr.905470] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Psoriasis is known as the most frequent disease treated by long-term topical steroids. It is also known that patients with thick, chronic plaques require the highest potency topical steroids. However, the treatment is limited to up to four weeks due to risk of systemic absorption. CASE REPORT An 80-year-old man was diagnosed with type 2 diabetes 16 years before, and was being administered insulin combined with alpha glucosidase inhibitor. He was diagnosed with plaque psoriasis and his oral steroid treatment was switched to topical steroid treatment due to lack of improvement and poorly controlled blood glucose level. The hypoglycemic events improved after the psoriatic lesions improved. CONCLUSIONS Control of blood glucose level is difficult at the very beginning of topical steroid treatment for psoriasis especially if a patient is receiving insulin treatment. Intense monitoring of blood glucose level during initiation of topical steroid treatment is necessary to prevent unfavorable complications.
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Affiliation(s)
- Yui Hongo
- Department of Internal Medicine, Saga University Hospital, Saga City, Saga, Japan
| | - Kenji Ashida
- Community Medical Support Institute, Saga University Faculty of Medicine, Saga City, Saga, Japan
| | - Kenji Ohe
- Health Care Center, Fukuoka University, Fukuoka City, Fukuoka, Japan
| | - Munechika Enjoji
- Health Care Center, Fukuoka University, Fukuoka City, Fukuoka, Japan
| | - Miyuki Yamaguchi
- Department of Internal Medicine, Saga University Hospital, Saga City, Saga, Japan
| | - Tsuyoshi Kurata
- Community Medical Support Institute, Saga University Faculty of Medicine, Saga City, Saga, Japan
| | - Akiko Emoto
- Japan Department of Pharmacy, Saga University Hospital Pharmacy, Saga University Hospital, Saga City, Saga, Japan
| | - Hiroko Yamanouchi
- Department of Internal Medicine, Saga University Hospital, Saga City, Saga, Japan
| | - Satoko Takagi
- Department of Internal Medicine, Saga University Hospital, Saga City, Saga, Japan
| | - Hitoe Mori
- Department of Internal Medicine, Saga University Hospital, Saga City, Saga, Japan
| | - Nozomi Kawata
- Department of Internal Medicine, Saga University Hospital, Saga City, Saga, Japan
| | - Yoshio Hisata
- Community Medical Support Institute, Saga University Faculty of Medicine, Saga City, Saga, Japan
| | - Yuta Sakanishi
- Community Medical Support Institute, Saga University Faculty of Medicine, Saga City, Saga, Japan
| | - Kenichi Izumi
- Department of Internal Medicine, Saga University Hospital, Saga City, Saga, Japan
| | - Takashi Sugioka
- Community Medical Support Institute, Saga University Faculty of Medicine, Saga City, Saga, Japan
| | - Keizo Anzai
- Department of Internal Medicine, Saga University Hospital, Saga City, Saga, Japan
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Wu P, Ma G, Zhu X, Gu T, Zhang J, Sun Y, Xu H, Huo R, Wang B, Shen B, Chen X, Li N. Cyr61/CCN1 is involved in the pathogenesis of psoriasis vulgaris via promoting IL-8 production by keratinocytes in a JNK/NF-κB pathway. Clin Immunol 2017; 174:53-62. [DOI: 10.1016/j.clim.2016.11.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Revised: 10/06/2016] [Accepted: 11/11/2016] [Indexed: 12/27/2022]
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Gyldenløve M, Vilsbøll T, Holst J, Zachariae C, Skov L, Knop F. Disturbed postprandial glucose metabolism and gut hormone responses in non-diabetic patients with psoriasis. Br J Dermatol 2016; 175:1085-1088. [DOI: 10.1111/bjd.13789] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- M. Gyldenløve
- Department of Dermato-Allergology; Gentofte Hospital; University of Copenhagen; Hellerup Denmark
| | - T. Vilsbøll
- Center for Diabetes Research; Department of Medicine; Gentofte Hospital; University of Copenhagen; Hellerup Denmark
| | - J.J. Holst
- The NNF Center for Basic Metabolic Research; Department of Biomedical Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
| | - C. Zachariae
- Department of Dermato-Allergology; Gentofte Hospital; University of Copenhagen; Hellerup Denmark
| | - L. Skov
- Department of Dermato-Allergology; Gentofte Hospital; University of Copenhagen; Hellerup Denmark
| | - F.K. Knop
- Center for Diabetes Research; Department of Medicine; Gentofte Hospital; University of Copenhagen; Hellerup Denmark
- The NNF Center for Basic Metabolic Research; Department of Biomedical Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
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Lønnberg AS, Skov L. Co-morbidity in psoriasis: mechanisms and implications for treatment. Expert Rev Clin Immunol 2016; 13:27-34. [DOI: 10.1080/1744666x.2016.1213631] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Ann Sophie Lønnberg
- Department of Dermato-Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Lone Skov
- Department of Dermato-Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
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Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents. BIOMED RESEARCH INTERNATIONAL 2016; 2016:6219730. [PMID: 27525273 PMCID: PMC4971288 DOI: 10.1155/2016/6219730] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Revised: 04/06/2016] [Accepted: 04/19/2016] [Indexed: 02/06/2023]
Abstract
Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases developing in childhood. The incidence of the disease in children increases for unknown reasons at a rate from 3 to 5% every year worldwide. The background of T1DM is associated with the autoimmune process of pancreatic beta cell destruction, which leads to absolute insulin deficiency and organ damage. Complex interactions between environmental and genetic factors contribute to the development of T1DM in genetically predisposed patients. The T1DM-inducing autoimmune process can also affect other organs, resulting in development of additional autoimmune diseases in the patient, thereby impeding diabetes control. The most common T1DM comorbidities include autoimmune thyroid diseases, celiac disease, and autoimmune gastritis; additionally, diabetes can be a component of PAS (Polyglandular Autoimmune Syndrome). The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T1DM. We also present suggestions concerning screening tests.
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Chen HH, Chao YH, Chen DY, Yang DH, Chung TW, Li YR, Lin CC. Oral administration of acarbose ameliorates imiquimod-induced psoriasis-like dermatitis in a mouse model. Int Immunopharmacol 2016; 33:70-82. [DOI: 10.1016/j.intimp.2016.02.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 01/21/2016] [Accepted: 02/01/2016] [Indexed: 01/07/2023]
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Gyldenløve M, Vilsbøll T, Zachariae C, Holst JJ, Knop FK, Skov L. Impaired incretin effect is an early sign of glucose dysmetabolism in nondiabetic patients with psoriasis. J Intern Med 2015; 278:660-70. [PMID: 26174490 DOI: 10.1111/joim.12388] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Patients with psoriasis have an increased risk of type 2 diabetes. The gastrointestinal system plays a major role in normal glucose metabolism, and in healthy individuals, postprandial insulin secretion is largely mediated by the gut incretin hormones. This potentiation is termed the incretin effect and is reduced in type 2 diabetes. The impact of psoriasis on gastrointestinal factors involved in glucose metabolism has not previously been examined. OBJECTIVE To investigate whether the incretin effect, gastrointestinal-mediated glucose disposal (GIGD) and/or secretion of glucagon and gut incretin hormones are impaired in normal glucose-tolerant patients with psoriasis. METHODS Oral glucose tolerance tests and intravenous isoglycaemic glucose infusions were performed in 12 patients with moderate-to-severe psoriasis and 12 healthy matched control subjects. RESULTS In patients with psoriasis, the incretin effect (39% vs. 57%, P = 0.02) and GIGD (53% vs. 61%, P = 0.04) were significantly reduced compared to control subjects. In addition, patients were glucose intolerant and showed exaggerated glucose-dependent insulinotropic polypeptide responses. CONCLUSION These novel findings support the notion that psoriasis is a prediabetic condition and suggest that gastrointestinal-related mechanisms are involved in the increased susceptibility to type 2 diabetes in patients with psoriasis.
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Affiliation(s)
- M Gyldenløve
- Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - T Vilsbøll
- Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - C Zachariae
- Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - J J Holst
- NNF Centre for Basic Metabolic Research, Department of Biomedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - F K Knop
- Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.,NNF Centre for Basic Metabolic Research, Department of Biomedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - L Skov
- Department of Dermato-Allergology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
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Armstrong AW, Guérin A, Sundaram M, Wu EQ, Faust ES, Ionescu-Ittu R, Mulani P. Psoriasis and risk of diabetes-associated microvascular and macrovascular complications. J Am Acad Dermatol 2015; 72:968-77.e2. [DOI: 10.1016/j.jaad.2015.02.1095] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 01/29/2015] [Accepted: 02/04/2015] [Indexed: 10/24/2022]
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18
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Chikin VV, Znamenskaya LF, Mineyeva AA. Pathogenic aspects of treatment of psoriatic patients. VESTNIK DERMATOLOGII I VENEROLOGII 2014. [DOI: 10.25208/0042-4609-2014-90-5-86-90] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
The article describes high incidence and morbidity rate of psoriasis, substantial reduction in the life quality and psychosocial disadaptation of patients, and presents certain particular features of psoriasis pathogenesis taking into consideration the role of immune mechanisms and relation between the disease and other chronic processes in the organism, as a result of which psoriasis is considered to be a multimorbid condition. The multimorbidity of psoriasis is an important factor for selecting a therapy, especially for patients with severe forms of the disease.
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Seufert J, Gallwitz B. The extra-pancreatic effects of GLP-1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems. Diabetes Obes Metab 2014; 16:673-88. [PMID: 24373150 DOI: 10.1111/dom.12251] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Revised: 08/09/2013] [Accepted: 12/13/2013] [Indexed: 01/03/2023]
Abstract
The glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide, liraglutide and lixisenatide have been shown to improve glycaemic control and beta-cell function with a low risk of hypoglycaemia in people with type 2 diabetes. GLP-1 receptors are also expressed in extra-pancreatic tissues and trial data suggest that GLP-1RAs also have effects beyond their glycaemic actions. Preclinical studies using native GLP-1 or GLP-1RAs provide substantial evidence for cardioprotective effects, while clinical trial data have shown beneficial actions on hypertension and dyslipidaemia in people with type 2 diabetes. Significant weight loss has been reported with GLP-1RAs in both people with type 2 diabetes and obese people without diabetes. GLP-1RAs also slow down gastric emptying, but preclinical data suggest that the main mechanism behind GLP-1RA-induced weight loss is more likely to involve their effects on appetite signalling in the brain. GLP-1RAs have also been shown to exert a neuroprotective role in rodent models of stroke, Alzheimer's disease and Parkinson's disease. These extra-pancreatic effects of GLP-1RAs could provide multi-factorial benefits to people with type 2 diabetes. Potential adverse effects of GLP-1RA treatment are usually manageable but may include gastrointestinal effects, increased heart rate and renal injury. While extensive further research is still required, early data suggest that GLP-1RAs may also have the potential to favourably impact cardiovascular disease, obesity or neurological disorders in people without diabetes in the future.
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Affiliation(s)
- J Seufert
- Division of Endocrinology and Diabetology, Department of Medicine II, Albert-Ludwigs University Medical Center, Freiburg, Germany
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20
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Xie S, Chen Z, Wang Q, Song X, Zhang L. Comparisons of gene expression in normal, lesional, and non-lesional psoriatic skin using DNA microarray techniques. Int J Dermatol 2014; 53:1213-20. [PMID: 25041445 DOI: 10.1111/ijd.12476] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES This study was designed to explore the pathogenesis of psoriasis and to identify potential bio-targets. Genome array technology was used to analyze the gene expression profiles of lesional and non-lesional psoriatic skin samples and normal skin samples. METHODS Gene expression profile GSE14905 was downloaded from the Gene Expression Omnibus (GEO) database. This included skin biopsy samples from normal healthy donors (n = 21), lesional skin biopsy samples from psoriasis patients (n = 33), and non-lesional skin biopsy samples from psoriasis patients (n = 28). Differentially expressed genes (DEGs) were identified using the Limma package in R language. Functions of specific DEGs were predicted by Gene Ontology (GO) enrichment analysis. A protein-protein interaction network was constructed to display the interactions among common DEGs. Finally, DAVID and WebGestalt were used to achieve a functional analysis of common DEGs. RESULTS Totals of 1020, 562, and 643 genes, respectively, were identified as being differentially expressed in normal versus lesional, normal versus non-lesional, and lesional versus non-lesional samples. The specific DEGs in the three groups were enriched for several GO terms, including mitotic cell cycle, immune response, and response to organic matter. The 40 common DEGs in the three groups may be involved in the defense response pathway in the development of psoriasis. Furthermore, three genes (RGS1, SOCS3, and NAMPT) may play key roles in distinguishing lesional and non-lesional tissues from normal tissues, and 10 genes (PTRRC, ALDH1A3, SAMSA1, C15orf48, ZC3H12A, SOD2, IL8, LTF, RHCG, and IL7R) may play key roles in distinguishing non-lesional from normal and lesional samples. CONCLUSIONS These genes may be considered as potential diagnostic markers and targets of therapeutics in psoriasis.
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Affiliation(s)
- Shaoqiong Xie
- Traditional Chinese Medicine Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China
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21
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Casagrande SS, Menke A, Cowie CC. No association between psoriasis and diabetes in the U.S. population. Diabetes Res Clin Pract 2014; 104:e58-60. [PMID: 24835483 PMCID: PMC4067950 DOI: 10.1016/j.diabres.2014.04.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2014] [Accepted: 04/17/2014] [Indexed: 11/28/2022]
Abstract
Previous studies have found a positive association between psoriasis and diabetes/diabetes-related complications, but the association has not been studied in a nationally representative U.S. sample. Our analysis of NHANES data indicated that psoriasis was not associated with diabetes but was positively associated with hypertension, overweight/obesity and waist circumference.
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Affiliation(s)
| | - Andy Menke
- Social & Scientific Systems, Inc., Silver Spring, MD, United States
| | - Catherine C Cowie
- Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, United States
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22
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Pietrzak A, Bartosinska J, Blaszczyk R, Chodorowska G, Brzozowski W, Hercogova J, Donica H, Lotti T. Increased serum level of N-terminal Pro-B-type natriuretic peptide as a possible biomarker of cardiovascular risk in psoriatic patients. J Eur Acad Dermatol Venereol 2014; 29:1010-4. [PMID: 24735175 DOI: 10.1111/jdv.12528] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Accepted: 03/17/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Apparently, these days psoriasis is regarded as a systemic disease with frequent cardiovascular comorbidities, such as hypertension, myocardial infarction, valvular defects etc., which may lead to reduced lifespan or even sudden death. Therefore, it is important that biomarkers helpful in early detection or prediction of cardiovascular complications as well as their prevention should be identified. Even though the N-terminal pro B-type natriuretic peptide (NT-proBNP) is a well-known cardiovascular predictor in cardiovascular (CV) patients and in the general population, its usefulness in detection of CV comorbidities in psoriatic patients is still unclear. OBJECTIVE The aim of the study was to determine whether the N-terminal pro B-type natriuretic peptide (NT-proBNP) concentration was increased in psoriatic patients. METHODS The study included 73 psoriatic patients and 45 age-matched healthy individuals. The serum NT pro-BNP concentration as well as lipid profile parameters were assessed in the study and control groups. Correlations between patients' clinical data, their serum NT-proBNP and lipid concentrations were calculated. RESULTS The serum concentration of NT-proBNP was significantly higher in psoriatic patients (109.22 ± 172.59 pg/mL) in comparison with controls (35.82 ± 22.90 pg/mL) (P = 0.000054). In 28 (38.36%) psoriatic patients the lipid profile was within normal limits, whereas in 45 (61.64%) psoriatic patients triglyceride and/or total cholesterol were increased. Moreover, in both psoriatic groups, i.e. normo- and hyperlipidaemic, NT-proBNP concentrations were significantly higher compared to normo- and hyperlipidaemic controls, P = 0.02 and P = 0.001 respectively. A positive correlation was found between the NT-proBNP concentration and duration of psoriasis (P < 0.05). CONCLUSIONS The study findings confirmed higher NT-proBNP concentrations in psoriatic patients, which could be a useful biomarker of CV disease in both normo- and hyperlipidaemic groups.
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Affiliation(s)
- A Pietrzak
- Department of Dermatology, Venereology and Paediatric Dermatology, Medical University, Lublin, Poland
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23
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Murphy-Chutorian B, Han G, Cohen SR. Dermatologic manifestations of diabetes mellitus: a review. Endocrinol Metab Clin North Am 2013; 42:869-98. [PMID: 24286954 DOI: 10.1016/j.ecl.2013.07.004] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Diabetes mellitus affects every organ of the body including the skin. Certain skin manifestations of diabetes are considered cutaneous markers of the disease, whereas others are nonspecific conditions that occur more frequently among individuals with diabetes compared with the general population. Diabetic patients have an increased susceptibility to some bacterial and fungal skin infections, which account, in part, for poor healing. Skin complications of diabetes provide clues to current and past metabolic status. Recognition of cutaneous markers may slow disease progression and ultimately improve the overall prognosis by enabling earlier diagnosis and treatment.
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24
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Dalamaga M, Papadavid E. Metabolic co-morbidities and psoriasis: The chicken or the egg? World J Dermatol 2013; 2:32-35. [DOI: 10.5314/wjd.v2.i4.32] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2013] [Revised: 09/25/2013] [Accepted: 10/18/2013] [Indexed: 02/06/2023] Open
Abstract
Accumulating evidence supports that psoriasis may be a potential multisystem inflammatory disease associated with a range of co-morbidities showing an overlapping pathology and an important health impact such as metabolic diseases. Psoriasis is associated with an increased risk of obesity, metabolic syndrome (Mets) and diabetes mellitus type 2, following a “dose-response” relationship from mild to severe psoriasis. Conversely, recent evidence from large prospective studies suggests that obesity constitutes a risk factor for psoriasis and psoriatic arthritis. Also, a dyslipidemic profile may precede psoriasis onset. Both obesity, Mets and psoriasis, characterized as chronic inflammatory states, stem from a shared underlying pathophysiology exhibiting common genetic predisposition and risk factors such as high caloric intake, physical inactivity and psychological stress. Excess weight may potentiate the inflammation of psoriasis through the deregulation of adipocytokines while, at the same time, it may help the development of Mets. Interestingly, recent translational data has shown that psoriasis, through increased T-helper inflammatory cytokines in skin and sera, may exert a plethora of effects on insulin regulation and lipid metabolism. Larger population-based prospective cohort and longitudinal studies are needed to unravel the association between psoriasis and metabolic co-morbidities. The recognition of the intricate complex interplay between psoriasis and metabolic co-morbidities may help dermatologists to be aware of associated metabolic co-morbidities in order to screen for metabolic diseases and manage holistically and effectively the psoriatic patient.
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25
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Soboleva AG, Bruskin SA, Nikolaev AA, Sobolev VV, Mezentsev AV. Role of receptor for advanced glycation end-products in pathogenesis of psoriasis. Mol Biol 2013. [DOI: 10.1134/s0026893313050191] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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26
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Coto-Segura P, Eiris-Salvado N, González-Lara L, Queiro-Silva R, Martinez-Camblor P, Maldonado-Seral C, García-García B, Palacios-García L, Gomez-Bernal S, Santos-Juanes J, Coto E. Psoriasis, psoriatic arthritis and type 2 diabetes mellitus: a systematic review and meta-analysis. Br J Dermatol 2013; 169:783-93. [DOI: 10.1111/bjd.12473] [Citation(s) in RCA: 101] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/10/2013] [Indexed: 12/14/2022]
Affiliation(s)
- P. Coto-Segura
- Dermatology Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
- Unit of Psoriasis; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - N. Eiris-Salvado
- Dermatology Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
- Unit of Psoriasis; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - L. González-Lara
- Dermatology Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - R. Queiro-Silva
- Unit of Psoriasis; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
- Rheumatology Department ; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - P. Martinez-Camblor
- Oficina de Investigación Biosanitaria de Asturias and Statistical Department; Oviedo University; 33006 Oviedo Asturias Spain
| | - C. Maldonado-Seral
- Dermatology Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - B. García-García
- Dermatology Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - L. Palacios-García
- Dermatology Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - S. Gomez-Bernal
- Dermatology Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - J. Santos-Juanes
- Dermatology Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
| | - E. Coto
- Unit of Psoriasis; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
- Molecular Genetics Department; Hospital Universitario Central de Asturias; 33006 Oviedo Asturias Spain
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Montaudié H, Albert-Sabonnadière C, Acquacalda E, Fontas E, Danré A, Roux C, Ortonne JP, Lacour JP, Euller-Ziegler L, Passeron T. Impact of systemic treatment of psoriasis on inflammatory parameters and markers of comorbidities and cardiovascular risk: results of a prospective longitudinal observational study. J Eur Acad Dermatol Venereol 2013; 28:1186-91. [PMID: 23981008 DOI: 10.1111/jdv.12255] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Accepted: 07/25/2013] [Indexed: 12/16/2022]
Abstract
BACKGROUND Several markers of comorbidities and cardiovascular (CV) risk are disturbed in moderate to severe psoriasis (PsO). The effect of systemic treatments of psoriasis on these markers remains poorly understood. OBJECTIVES To study the frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk associated with moderate to severe PsO and psoriatic arthritis (PsA), and to assess their evolution under systemic treatments. METHODS Monocentric prospective study on patients with PsO and PsA starting a systemic treatment for their psoriasis. The following markers were evaluated at baseline (M0), 3 months (M3) and 6 months (M6); weight, fasting blood glucose, blood pressure, uric acid, hepatic steatosis, smoking, lipid, metabolic and inflammatory parameters. RESULTS Forty-three patients, 31 PsO and 12 PsA, were included. Forty completed the study. Response to treatment was good, with 71% of the population obtaining a Psoriasis Area and Severity Index (PASI) of 75. All patients had at least one comorbidity, and 45% had two or more. A statistically significant decrease was observed only for inflammatory parameters (C-reactive protein [CRP], P = 0.004) and erythrocyte sedimentation rate (ESR, P = 0.002). We did not observe any correlation between the PASI and CRP (correlation coefficient 0.128, P = 0.438) or ESR (correlation coefficient 0.294, P = 0.069) for responding patients. CONCLUSIONS We observed a high frequency of disturbance of inflammatory parameters and markers of comorbidities and CV risk in a population with moderate to severe PsO and PsA, most of which were not detected before. A significant decrease in inflammatory parameters was noted after the introduction of systemic therapy, while other parameters remained unaffected by the treatment, except the weight that increased under biologics therapies.
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Affiliation(s)
- H Montaudié
- Department of Dermatology, University Hospital of Nice, Nice, France
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28
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Khalid U, Hansen PR, Gislason GH, Lindhardsen J, Kristensen SL, Winther SA, Skov L, Torp-Pedersen C, Ahlehoff O. Psoriasis and new-onset diabetes: a Danish nationwide cohort study. Diabetes Care 2013; 36:2402-7. [PMID: 23491525 PMCID: PMC3714512 DOI: 10.2337/dc12-2330] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Psoriasis is associated with increased risk of cardiovascular events and increased prevalence of cardiovascular risk factors. Diabetes mellitus (DM) is a major contributor to cardiovascular morbidity and mortality that may be associated with psoriasis, but conflicting results have been presented and nationwide data on the risk of new-onset DM in patients with psoriasis have not been reported. RESEARCH DESIGN AND METHODS The study comprised a Danish population ≥ 10 years of age on 1 January 1997 who were followed until new-onset DM, death, or 31 December 2009. Information on comorbidity, concomitant medication, and socioeconomic status was linked on an individual level. The primary study end point was DM requiring pharmacotherapy. Incidence rates for the development of DM events per 1,000 observational years were calculated and adjusted. Incidence rate ratios (IRRs) were estimated by Poisson regression. RESULTS A total of 4,614,807 subjects were eligible for analysis, with a maximum follow-up of 13 years. In the study period, 52,613 patients with psoriasis, including 6,784 patients with severe psoriasis, were identified. The overall incidence rates for new-onset DM were 3.67 (CI 3.65-3.69), 6.93 (6.63-7.25), and 9.65 (8.68-10.73) for the reference population, mild psoriasis, and severe psoriasis, respectively. Compared with the reference population, the IRR of new-onset DM was increased in all patients with psoriasis, i.e., IRR 1.49 (CI 1.43-1.56) and 2.13 (1.91-2.37) for those with mild and severe psoriasis. CONCLUSIONS In this nationwide cohort, psoriasis was associated with increased incidence rates of new-onset DM. The association remained statistically significant after adjustment for confounding factors.
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Affiliation(s)
- Usman Khalid
- Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
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29
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Wagener FADTG, Carels CE, Lundvig DMS. Targeting the redox balance in inflammatory skin conditions. Int J Mol Sci 2013; 14:9126-67. [PMID: 23624605 PMCID: PMC3676777 DOI: 10.3390/ijms14059126] [Citation(s) in RCA: 144] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2013] [Revised: 04/10/2013] [Accepted: 04/16/2013] [Indexed: 12/17/2022] Open
Abstract
Reactive oxygen species (ROS) can be both beneficial and deleterious. Under normal physiological conditions, ROS production is tightly regulated, and ROS participate in both pathogen defense and cellular signaling. However, insufficient ROS detoxification or ROS overproduction generates oxidative stress, resulting in cellular damage. Oxidative stress has been linked to various inflammatory diseases. Inflammation is an essential response in the protection against injurious insults and thus important at the onset of wound healing. However, hampered resolution of inflammation can result in a chronic, exaggerated response with additional tissue damage. In the pathogenesis of several inflammatory skin conditions, e.g., sunburn and psoriasis, inflammatory-mediated tissue damage is central. The prolonged release of excess ROS in the skin can aggravate inflammatory injury and promote chronic inflammation. The cellular redox balance is therefore tightly regulated by several (enzymatic) antioxidants and pro-oxidants; however, in case of chronic inflammation, the antioxidant system may be depleted, and prolonged oxidative stress occurs. Due to the central role of ROS in inflammatory pathologies, restoring the redox balance forms an innovative therapeutic target in the development of new strategies for treating inflammatory skin conditions. Nevertheless, the clinical use of antioxidant-related therapies is still in its infancy.
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Affiliation(s)
- Frank A. D. T. G. Wagener
- Authors to whom correspondence should be addressed; E-Mails: (F.A.D.T.G.W.); (D.M.S.L.); Tel.: +31-24-3614082 (F.A.D.T.G.W.); Fax: +31-24-3540631 (F.A.D.T.G.W. & D.M.S.L.)
| | | | - Ditte M. S. Lundvig
- Authors to whom correspondence should be addressed; E-Mails: (F.A.D.T.G.W.); (D.M.S.L.); Tel.: +31-24-3614082 (F.A.D.T.G.W.); Fax: +31-24-3540631 (F.A.D.T.G.W. & D.M.S.L.)
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Johnson-Huang LM, Lowes MA, Krueger JG. Putting together the psoriasis puzzle: an update on developing targeted therapies. Dis Model Mech 2013; 5:423-33. [PMID: 22730473 PMCID: PMC3380706 DOI: 10.1242/dmm.009092] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Psoriasis vulgaris is a chronic, debilitating skin disease that affects millions of people worldwide. There is no mouse model that accurately reproduces all facets of the disease, but the accessibility of skin tissue from patients has facilitated the elucidation of many pathways involved in the pathogenesis of psoriasis and highlighted the importance of the immune system in the disease. The pathophysiological relevance of these findings has been supported by genetic studies that identified polymorphisms in genes associated with NFκB activation, IL-23 signaling and T helper 17 (Th17)-cell adaptive immune responses, and in genes associated with the epidermal barrier. Recently developed biologic agents that selectively target specific components of the immune system are highly effective for treating psoriasis. In particular, emerging therapeutics are focused on targeting the IL-23–Th17-cell axis, and several agents that block IL-17 signaling have shown promising results in early-phase clinical trials. This review discusses lessons learned about the pathogenesis of psoriasis from mouse-and patient-based studies, emphasizing how the outcomes of clinical trials with T-cell-targeted and cytokine-blocking therapies have clarified our understanding of the disease.
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Affiliation(s)
- Leanne M Johnson-Huang
- The Rockefeller University, Laboratory for Investigative Dermatology, New York, NY 10065, USA
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31
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Lowes MA, Russell CB, Martin DA, Towne JE, Krueger JG. The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol 2013; 34:174-81. [PMID: 23291100 DOI: 10.1016/j.it.2012.11.005] [Citation(s) in RCA: 372] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Revised: 11/20/2012] [Accepted: 11/28/2012] [Indexed: 12/22/2022]
Abstract
Psoriasis is a complex inflammatory process resulting from activation of the well-defined interleukin (IL)-23/T17 cytokine axis. We review the role of key cytokines IL-17 and IL-23 in psoriasis, as well as tumor necrosis factor (TNF)α, focusing on therapeutic cytokine interventions and what they reveal about psoriatic inflammation. The potential role of recently described epidermal IL-36RN and CARD14 genetic mutations in psoriasis pathogenesis is also explored, because they augment keratinocyte responses to proinflammatory cytokines. The discovery of these genetic mutations in familial and pustular psoriasis suggests new links between cytokine-induced gene products and IL-1 family members from keratinocytes, which may regulate features of the disease, including epidermal hyperplasia and neutrophil infiltrating responses.
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Affiliation(s)
- Michelle A Lowes
- Laboratory for Investigative Dermatology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
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