Psoriatic March Research Articles

Psoriasis and Cardiovascular Diseases: An Immune-Mediated Cross Talk?

Psoriasis is a chronic immune-mediated inflammatory skin disease, characterized by well-demarcated scaly, erythematous, infiltrated plaques. The cutaneous-to-systemic expansion of the inflammation in psoriasis leads to the concept of “psoriatic march” or “inflammatory skin march”. Accordingly, psoriasis is thought to be a systemic inflammatory disease associated with numerous comorbidities. Indeed, it’s currently considered an independent risk factor for cardiovascular diseases. Here, we discuss the current knowledge on TNF-α and IL-23/IL-17 mediated pathways linking the psoriatic plaque to the cardiovascular compartment. We further argue the possible involvement of the endothelial compartment in the psoriatic plaque- cardiovascular system crosstalk.

Marcha psoriásica: una mirada desde la fisiopatología hasta el riesgo cardiovascular

Psoriasis is a disease that is not limited to skin involvement, the importance of systemic compromise is recognized more than ever, especially because of the associated comorbidities, which are explained by the marked chronic systemic inflammatory response mediated by pro-inflammatory cytokines (mainly TNF-α, IL23, IL 17), which play an important role in the induction of insulin resistance, endothelial dysfunction, accelerated atherosclerosis and the increased risk of cardio-cerebrovascular events. The relationship with these outcomes has been demonstrated and hence the concept of psoriatic march, a term that is gaining increasing importance aimed at maintaining and reinforcing the approach to a skin disease with systemic compromise, associated morbidity and mortality that can be preventable and manageable. The pathophysiological mechanisms that explain these phenomena are variable, however, new concepts have been identified, which have made it possible to improve the current approach to the disease and thus establish mechanisms to reduce cardiovascular risk in patients with psoriasis.

Psoriasis Comorbidities in Childhood

Psoriasis is multifactorial systemic disease characterized by excessive hyperkeratosis due to impaired keratinocytes proliferation and differentiation. This disease often manifests in childhood and it is usually associated with the development of comorbid conditions some of which are combined by the term «psoriatic march» (obesity, metabolic syndrome, etc.). The course of psoriasis and related comorbidities in children has several specific features that determine topicality of studying all the aspects of clinical diagnosis and prevention in childhood. The article summarizes recent ideas on the prevalence, pathogenesis features and early diagnosis of comorbid diseases in children with psoriasis.

Psoriasis and cardiovascular comorbidity (literature review)

Psoriasis is a chronic immunologically associated inflammatory skin disease associated with systemic concomitant diseases, including arthritis, cardiovascular disease, kidney disease, diabetes mellitus and metabolic syndrome. The evolution of ideas about the essence of this dermatosis has led to the concept of a “psoriatic march”: psoriasis as a chronic inflammatory disease is associated with a systemic pathological process. According to numerous epidemiological studies, up to 5–7 % of the world’s population suffer from psoriasis with a continuing increase in the incidence, including severe and torpid phenotypes that lead to the most able-bodied segments of the population becoming disabled. In recent years, the question arises more often of states comorbid to psoriasis. Dermatosis is often combined with cardiovascular diseases (CVD), mental disorders, immune-mediated diseases such as Crohn’s disease, lupus erythematosus. The main factor contributing to the formation of comorbidity in psoriasis is the commonality of some links in the pathogenesis of dermatosis and the listed diseases.

Psoriatic March

Psoriatic March

Dermal mesenchymal stem cells: a resource of migration-associated function in psoriasis?

BackgroundPsoriasis is a chronic and systemic, immune-mediated, inflammatory disease. Mesenchymal stem cells have effects on the inflammatory microenvironment, including regulating the proliferation, differentiation, recruitment, and migration of immunocytes.MethodsTo investigate whether dermal mesenchymal stem cells (DMSCs) may act on migration of immunocytes in psoriasis patients, 22 patients with psoriasis and 22 matching healthy controls (age and sex in this study) were recruited. Seven migration-associated genes including chemokine like receptor-1 (CMKLR-1), collagen type VIII alpha1 (COL8A-1), neuropilin and tolloid-like 2 (NETO-2), nik-related kinase (NRK), secreted frizzled-related protein (SFRP), sulfate 6-O-endosulfatase 2 (SULF-2), and synaptotagmin-like protein 2 (SYTL-2) were analyzed by quantitative real-time reverse transcription PCR and western blot. Peripheral blood-derived mononuclear cells (PBMCs) migration to MSCs was measured using a Thanswell chamber system.ResultsWe observed the upregulation of CMKLR-1, COL8A-1, NETO-2, NRK, SYTL-2, and SULF-2 in dermal mesenchymal stem cells derived from patients with psoriasis at both mRNA and protein level, however, a significant downregulation of SFRP-2 between two groups. By contrast, there were no significant between-group differences at the mRNA and protein expression level of NETO-2 and SULF-2. The migration assay showed that in vitro the normal PBMC migration to psoriatic DMSC group was a 6.3 ± 0.7-fold increase compared with the control group.ConclusionsThe results may suggest a potential pathogenetic involvement of DMSCs on migration of monocytes in psoriasis. Immune responses are regulated at the level of DMSCs, which probably represent the cells primarily involved in the “psoriatic march.”

Psoriasis as a risk factor of pulmonary embolism - case report

Introduction. Deep vein thrombosis and pulmonary embolism, known as venous thromboembolism, constitute a major global burden of disease. Both entities share the same risk factors. Psoriasis is a common, chronic skin disease. It also presents multisystemic inflammation, mainly affecting skin and joints, but it is also associated with the significant cardiovascular and metabolic states and comorbidities, on the so-called ?psoriatic march?. Case report. We presented a 78-year-old female patient, with psoriasis associated with pulmonary embolism which is accidentally discovered. We did not find any other predisposing factor of this disease (primary or secondary thrombophilia), except hyperhomocysteinemia. The patient was treated with low molecular weight heparin (enoxaparin), followed by the administration of an oral vitamin K antagonist (warfarin sodium) in the weight adjusted regimens. Additionally, we recommended vitamin B complex, including folate. Supposed link between hyperhomocysteinemia and psoriasis was the decreased serum folate level as the result of increased vitamin utilization in the skin because of increased DNA synthesis. Conclusion. The reported case reflects existing literary knowledge about the increased risk of VTE and arterial thromboembolic events in the psoriatic patients. The highest risk appears in the patients with a severe disease and may be a consequence of systemic inflammation and hyperhomocysteinemia.

Compounds of psoriasis with obesity and overweight.

Many epidemiological studies have confirmed the relationship of obesity and psoriasis, and it is believed that obesity is an independent risk factor for its development and is associated with a worse prognosis. Furthermore, the reduction of body weight, using low-calorie diet combined with exercise, reduces the severity of psoriasis.Visceral adipose tissue is the largest endocrine organ, producing proinflammatory cytokines (TNF-α, IL-6, IL-17) and adipokines (adiponectin, omentin, chemerin). They participate in the development of dyslipidemia, insulin resistance, diabetes, and consequently of the cardiovascular diseases. Macrophages of visceral adipose tissue have a special role and they increase significantly in obesity. They are responsible for the development of inflammation in adipose tissue and produce inflammatory cytokines (TNF alpha, IL-6, Il-8, Il-17, Il-18, MCP-1) and other adipokines: resistin, visfatin, retinol-binding protein 4. This explains the concept of «psoriatic march «and observations of the frequent coexistence of psoriasis with obesity. Inflammation associated with systemic disease, fanned by pro-inflammatory cytokines and adipokines produced by the visceral adipose tissue lead to the development of insulin resistance, endothelial cell damage. Endothelial dysfunction predisposes to the formation of atherosclerotic plaques and faster development of cardiovascular events. Complication of obesity is the development of non-alcoholic fatty liver disease (NAFLD), which states twice as likely in patients with plaque psoriasis and is associated with the severity of the disease. Another consequence is the development of depression. Probably the proinflammatory cytokines can interact with metabolism of neurotransmitters. Obesity also has a significant impact on the treatment of psoriasis, increasing the risk of adverse effects of systemic drugs, reducing the efficacy of biological agents which dose should be adjusted to the weight of the patient. It is a factor responsible for the increased volume of distribution and it causes low titter of drug concentration.

“Inflammatory skin march” in atopic dermatitis and psoriasis

Comorbidities of cardiovascular diseases (CVDs), metabolic syndrome and autoimmune diseases with systemic inflammation are recent topics in medicine. Inflammatory skin diseases such as atopic dermatitis and psoriasis are an active source of diverse proinflammatory cytokines and chemokines, which are readily detectable in the circulation and are likely to be involved in developing comorbidities. Both atopic dermatitis and psoriasis are frequently comorbid with CVD, metabolic syndrome and autoimmune diseases, the consequence of which is called "inflammatory skin march", "psoriatic march" or "march of psoriasis". In this review, we summarize the epidemiological evidence and pathogenetic concepts regarding inflammatory skin march in atopic dermatitis and psoriasis.

The effect of etanercept on vascular endothelial growth factor production by cutaneous mesenchymal stem cells from patients with psoriasis.

ObjectiveTo evaluate prospectively the effect of etanercept (a tumour necrosis factor [TNF]-α inhibitor) on vascular endothelial growth factor (VEGF) production by mesenchymal stem cells (MSC) from patients with psoriasis.MethodsMSCs from lesional and perilesional skin were isolated, cultured and characterized. VEGF production was evaluated at baseline and after 12 weeks’ etanercept treatment.ResultsEtanercept treatment resulted in significant reductions in VEGF production compared with baseline in both lesional MSCs (256.42 ± 3.07 pg/ml per 106 cells at baseline vs 27.66 ± 2.03 pg/ml per 106 cells after treatment) and perilesional MSCs (235.03 ± 2.52 pg/ml per 106 cells vs 41.65 ± 4.72 pg/ml per 106 cells).ConclusionsEtanercept reduces the production of VEGF in MSCs, which may modulate angiogenesis and contributes towards preventing the start of the “psoriatic march”.

Comorbidity in psoriasis

Psoriasis is asystemic chronic inflammatory disease associated with comorbidity. Many epidemiological studies have shown that psoriasis is associated with psoriatic arthritis as well as cardiovascular and metabolic diseases. Furthermore, obesity and psychological diseases such as depression and anxiety disorders are linked with psoriasis and play acentral role in its management. The association of psoriasis and its comorbidity can be partly explained by genetic and pathophysiological mechanisms. Approximately 40psoriasis susceptibility loci have been described with the majority linked to the innate and adaptive immune system. In some associated diseases, such as psoriatic arthritis, an overlap of their genetic susceptibility exists. Pathophysiologically the "psoriatic march" is amodel that describes the development of metabolic and cardiovascular diseases due to the presence of underlying systemic inflammation. Dermatologists are the gatekeepers to treatment for patients with psoriasis. The early detection and the management of comorbidity is part of their responsibility. Concepts for the management of psoriasis and tools to screen for psoriatic comorbidity have been developed in order to support dermatologists in daily practice.

Comprehensive lipid tetrad index, atherogenic index and lipid peroxidation: Surrogate markers for increased cardiovascular risk in psoriasis

Recently, the concept of "psoriatic march" has come to the fore, in which chronic cutaneous inflammation in psoriasis leads to systemic inflammation which, in conjunction with increased oxidative stress, triggers a cascade of events resulting in increased cardiovascular risk in patients with severe psoriasis. We, therefore, decided to study the levels of some biochemical cardiovascular risk markers: lipid peroxidation (malondialdehyde), lipoprotein (a), lipid indices and atherogenic index, in patients with psoriasis and their association with disease severity. Forty five patients with psoriasis and 45 age and gender-matched healthy controls were included in this cross-sectional study. Disease severity was assessed by the Psoriasis Area Severity Index (PASI). Serum malondialdehyde, lipoprotein (a) and fasting lipid profile were estimated in all study subjects. Lipoprotein ratios were computed using standard formulae. Atherogenic index was calculated as ratio of lipoprotein (a)/high-density lipoprotein. In psoriasis, we observed significantly higher levels of malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, lipoprotein (a), lipid ratios, atherogenic index and comprehensive lipid tetrad index, compared to controls. These levels were directly proportional to disease severity. Serum levels of malondialdehyde correlated positively with serum lipoprotein (a), comprehensive lipid tetrad index and atherogenic index. Different morphological types of psoriasis were not included and follow-up post-therapy was not done. A larger sample size would have validated the results further. Our results indicate that psoriasis, especially the severe variants, are associated with increased oxidative stress and dyslipidemia, which correlate positively with atherogenic index and hence, an increased cardiovascular risk.

Effect of biologic therapies targeting tumour necrosis factor-α on cutaneous mesenchymal stem cells in psoriasis

Psoriasis is a Th1 immune-mediated, inflammatory disease, in which skin lesions appear many years before the related metabolic and cardiovascular comorbidities, according to the theory of the 'psoriatic march'. Inducible nitric oxide synthetase (iNOS), tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) are directly implicated in determining both skin lesions and systemic involvement in psoriasis. Reactive oxygen species actively promote the secretion of inflammatory Th1 cytokines directly involved in the pathogenesis of psoriasis. Evaluation of VEGF expression and production, nitric oxide (NO) production, iNOS expression, and the antioxidant response of mesenchymal stem cells (MSCs), both before and after 12 weeks of treatment with the TNF-α inhibitors adalimumab or etanercept. Biochemical, morphological and immunohistochemical analyses were performed in MSCs isolated from nonlesional, perilesional and lesional skin of patients with psoriasis, before and after treatment. The treatments were able to reduce the expression and production of VEGF, the expression of iNOS and the production of NO in MSCs of patients with psoriasis. TNF-α inhibitors also reduced the oxidative damage in MSC membrane and proteins, several antioxidant systems responded to treatments with a general inhibition of activities (glutathione S-transferase and catalase) and these effects were also supported by a general decrease of total oxyradical scavenging capacity towards hydroxyl radicals and peroxynitrite. TNF-α inhibitors are able to change the physiopathological pathway of psoriasis, and our results suggest their therapeutic effects already take place at the level of MSCs, which probably represent the cells primarily involved in the 'psoriatic march'.

The ‘psoriatic march’: a concept of how severe psoriasis may drive cardiovascular comorbidity

There is increasing awareness that psoriasis is more than 'skin deep'. Several recent reviews focussed on biomarkers indicating the systemic dimension of psoriasis and the aspect of comorbidity psoriasis shares with other chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. Of emerging significance is the relationship to cardiovascular disease, as this contributes substantially to the patients' increased mortality. In this viewpoint, we examine currently available evidence favouring the concept of a causal link between psoriasis and cardiovascular disease: systemic inflammation may cause insulin resistance, which in turn triggers endothelial cell dysfunction, leading to atherosclerosis and finally myocardial infarction or stroke. While this 'psoriatic march' is not yet formally proven, it raises clinically and academically relevant questions, and gains support by recent observations of numerous investigators.

Can early treatment with biologicals modify the natural history of comorbidities?

Psoriasis is associated with many burdening comorbidities, which often share similar pathogenic features and follow a progressive pattern. Some of them, such as psoriatic arthritis (PsA) and cardiovascular diseases, are frequently delayed steps of the "psoriatic march," mostly developing after the appereance of cutaneous lesions. Biological agents targeting tumor necrosis factor (TNF) constitute a relatively new and efficient approach to psoriasis. Enticing but somewhat unclear data are available regarding the effects of anti-TNFs on psoriasis comorbidities, ranging from pathomechanisms to clinical outcomes. The ability of anti-TNF drugs to inhibit the structural damage in PsA supports the feasibility of a preventive action on PsA development. In general, effective suppression of inflammation appears to have a key role in preventing some comorbidities. This article briefly reviews the current literature, evaluating possible effects of anti-TNF drugs on the natural history of psoriasis comorbidities. Although further studies are needed, noteworthy considerations can be drawn.