Category Archives: Psoriasis

Introduction

Psoriasis is a chronic, immune-mediated inflammatory dermatological disease that affects nearly 150 million people worldwide. It is associated with a significant disease burden, a marked negative impact on patients quality of life,1 and places enormous pressure on health systems globally.24 In recent years attention has focused on the inflammatory processes underpinning the pathophysiological changes in psoriasis. In particular, cutaneous inflammation in psoriasis is linked to chronic systemic low-grade inflammation, which is thought to underlie the associations of psoriasis with comorbidities such as psoriatic arthritis, mood disorders including depression, and a range of cardiometabolic disorders that include myocardial infarction, hypertension, obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and hyperuricemia.3,5

One comorbidity of psoriasis that is increasingly recognized as clinically relevant is NAFLD.3,6,7 NAFLD is characterized by excessive hepatic fat storage and is strongly associated with obesity, type 2 diabetes, and metabolic syndrome. Over time, NAFLD can progress to a more severe, inflammatory disease termed non-alcoholic steatohepatitis (NASH) and eventually to the development of cirrhosis.8 NAFLD is the most common liver disease and its prevalence is rising rapidly. US studies have reported a 1035% prevalence in the general population with an average of between 20 and 30%.9 The global prevalence of NAFLD is estimated to be 25%.10,11 The presence of NASH in the general population is difficult to ascertain since it can be confirmed only by liver biopsy. However, rates between 1.5 and 6.5% have been reported.9,10,12 NASH is a potentially progressive disease that can lead to cirrhosis in 1225% of cases within a 10-year period, and it is associated with increased risks for hepatocellular carcinoma and cardiovascular- and liver-related deaths.8,13,14

NAFLD has been shown to occur 1.5 to 3 times more frequently in patients with psoriasis than in the general population.3,11,15 Prevalences of NAFLD ranging up to 65% have been reported in this patient population.16 The increased risk of NAFLD in psoriasis patients is not surprising, as the two diseases share a common link with the metabolic syndrome. However, there may be an association between psoriasis and NAFLD that is independent from the metabolic syndrome, hinging directly on the chronic low-grade systemic inflammatory burden characteristic of these two conditions.5 Importantly, when psoriasis co-occurs with NAFLD the disease severity and morbidity of both conditions may be greater.17

The aim of this review is to evaluate the recent literature on the clinical and pathophysiological associations linking psoriasis with NAFLD, independently of the metabolic syndrome, focusing on the chronic low-grade inflammation underpinning the two disorders. Second, we aimed to assess the potential hepatotoxic and hepatoprotective effects of currently approved systemic psoriasis therapies, in particular dimethyl fumarate (DMF), an oral small molecule with pleiotropic effects that could positively impact NAFLD, focusing on the chronic low-grade inflammation underpinning the two disorders. Second, we aimed to assess the potential hepatotoxic and hepatoprotective effects of currently approved systemic psoriasis therapies, in particular dimethyl fumarate (DMF), an oral small molecule with pleiotropic effects that could positively impact NAFLD.

For this narrative review, a targeted search of PubMed up to 14 July 2021 was conducted using the following search strategies: psoriasis with (a) non-alcoholic fatty liver disease/NAFLD (n = 96), (b) hepatotoxicity 1/1/2010 to 14/7/2021 (n = 72), and (c) hepatoprotection (n = 14); psoriasis treatment with (a) hepatotoxicity 1/1/2010 to 14/7/2021 (n = 68), and (b) hepatoprotection (n = 11). Relevant papers were identified by reviewing abstracts or full papers (if required), and by contributory articles cited in the selected references. The bibliography was augmented by key articles known to the authors and, finally, by individual drug data identified via a search of LiverTox (https://www.ncbi.nlm.nih.gov/books/NBK548744/).

NAFLD is the most common chronic liver disease worldwide and, in the majority of patients, is strongly associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. Individuals with metabolic syndrome have a 4- to 11-fold increased risk of developing NAFLD.18 NAFLD is characterized by fat deposition in the liver, in the absence of viral diseases such as hepatitis B or C, significant alcohol consumption, use of steatosis-stimulating drugs such as methotrexate, steroids, amiodarone and tamoxifen, or certain hereditary conditions including Wilsons disease and cholesteryl ester storage syndrome.19,20

NAFLD includes a wide spectrum of liver conditions with two main histological forms: simple hepatic steatosis (fat deposited, but no damage to liver cells) and NASH, which is characterized by hepatic inflammation that can lead to liver fibrosis. The aberrant pathophysiological processes underlying the progression to NASH are not fully understood, but are thought to include an imbalance of fatty acid metabolism leading to steatosis, and an elevated inflammatory response as a result of oxidative/metabolic stress and dysregulated cytokine production.21 Potential consequences of these processes are the development of lobular hepatitis with perivenular/pericellular (chicken wire) fibrosis, NAFLD-associated cirrhosis and liver failure and, albeit infrequently, hepatocellular carcinoma (Figure 1).5,22

Figure 1 Spectrum of non-alcoholic fatty liver disease (NAFLD). Data from these studies.5,22

In terms of clinical presentation, the majority of NAFLD cases are either asymptomatic or have nonspecific symptoms such as fatigue and abdominal pain, and/or abnormal liver function test results. NAFLD can be diagnosed if > 5% hepatic steatosis is shown by liver ultrasound in the absence of excessive alcohol use.8 The assessment for potential NASH requires additional testing using non-invasive assessment for liver fibrosis such as vibration-controlled transient elastography or magnetic resonance elastography. However, to confirm the diagnosis of NASH, histopathologic assessment of a liver biopsy is required.

Treatment of NAFLD is limited to optimal management of comorbid conditions such as type 2 diabetes and dyslipidemia, and lifestyle modifications aiming at 710% weight loss through caloric restriction and exercise.8 Weight loss and increased physical activity/exercise can help normalize liver enzyme levels, reduce hepatic inflammation and improve insulin resistance, steatosis and liver histology.23 There are currently no approved pharmacological therapies for NAFLD; oral vitamin E and pioglitazone are options that have shown modest clinical benefits.

The first published evidence in 2001 of a link between psoriasis and NAFLD involved three overweight/obese patients with NASH as confirmed by liver biopsy.24 Since then, various observational and controlled studies have highlighted an increased prevalence of NAFLD in patients with psoriasis.2529 For example, in a large Dutch population-based study (2292 participants aged 55 years) the prevalence of NAFLD was 46% in 118 patients with psoriasis and 33% in individuals without psoriasis.27 Importantly, while elderly study participants with psoriasis were 70% more likely to have NAFLD than those without psoriasis (crude odds ratio [OR] 1.70, 95% confidence interval [CI] 1.172.46), the increased risk was found to be independent of common risk factors such as smoking, alcohol consumption, and the presence of metabolic syndrome and its component disorders. A recent single-center cross-sectional study from Spain reported a 52% prevalence of NAFLD among a cohort of 71 patients with psoriasis.15 Of note, 14% of patients had liver fibrosis as diagnosed with transitional vibration-controlled elastography. A large population-based cohort study, using UK data from 197,130 patients with psoriasis and 1,279,754 matched controls, reported an elevated risk for incident cases of NAFLD among psoriasis patients without systemic therapy (adjusted hazard ratio [HR] 1.18, 95% CI 1.071.30) and an even higher risk for those receiving systemic therapy (adjusted HR 2.23, 95% CI 1.732.87) compared with the control group.30 The risk for incident NAFLD was also increased among patients with psoriatic arthritis, in particular for those receiving systemic therapy (adjusted HR 2.11, 95% CI 1.552.87). In line with these results, a 2015 systematic review and meta-analysis including 7 case-control studies found that patients with psoriasis had a 2-fold increased risk of NAFLD compared with controls (6 studies; n = 267,761; OR 2.15, 95% CI 1.572.94).31 The risk of NAFLD was significantly greater in patients with psoriatic arthritis (3 studies; n = 505 patients; OR 2.25, 95% CI 1.373.71) and in patients with severe psoriasis (2 studies; 51,930 patients, OR 2.07, 95% CI 1.592.71) compared to those with mild psoriasis. Recently, this meta-analysis was updated to include 2 additional studies (for a total of > 3 million patients and nearly 250,000 with NAFLD).32 The analysis was extended to investigate potential risk factors for NAFLD in psoriasis patients which included hypertension, male sex, hyperglycemia and obesity. Reaffirming the findings of the original systematic review, there was a strong association between psoriasis and NAFLD independent of confounders.

In several studies, the presence and severity of psoriasis were associated with a higher prevalence and greater severity of NAFLD, and NAFLD was a strong predictor of higher Psoriasis Area and Severity Index (PASI) scores.25,28,29,31,33 Using Control Attenuation Parameter to assess the degree of fatty liver and body surface area severity of psoriasis, Gandha et al confirmed a positive correlation between the two disorders.34 Furthermore, the progression to more severe forms of liver disease appeared to be higher in patients with psoriasis.35 Roberts et al reported that 48 of 103 (47%) psoriasis patients had NAFLD and 23 of 103 (22%) had biopsy-confirmed NASH, of whom 35% had stage 23 fibrosis.35 The prevalence of NASH was markedly higher than the 12% previously reported in patients with similar demographic characteristics but without psoriasis in the same medical center. Moreover, concomitant NAFLD in patients with psoriasis may confer a higher 10-year cardiovascular risk compared to psoriasis patients without NAFLD.36

In summary, the epidemiologic association between NAFLD and psoriasis is particularly strong given the high prevalence and increased incidence observed among patients with psoriasis. Importantly, this association is more evident in patients with severe psoriasis compared with those with mild psoriasis and is independent of common traditional risk factors such as smoking, alcohol consumption, and the presence of metabolic syndrome and its component disorders.5,31,32

Psoriasis and NAFLD are amongst a number of multifactorial disorders (including cardiovascular diseases and metabolic syndrome) whose pathogenesis is not fully understood, but involves complex interactions between genetic, immunological and environmental factors (Figure 2).5,3742

Figure 2 Common risk factors and associations between psoriasis (PsO) and non-alcoholic fatty liver disease (NAFLD). Reprinted from Prussick RB, Miele L. Non-alcoholic fatty liver disease in patients with psoriasis: a consequence of systemic inflammatory burden? Br J Dermatol. 2018;179(1):1629. 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.5

The pathophysiology of psoriasis is characterized by sustained, self-amplifying inflammatory responses that lead to uncontrolled keratinocyte proliferation and dysfunctional differentiation. Disturbances in both innate and adaptive cutaneous immune responses are responsible for psoriatic inflammation.43 Activation of the innate immune system driven by endogenous signals and cytokines coexists with an auto-inflammatory response in some patients and with T cell-driven auto-immune reactions in others. Thus, psoriasis exhibits traits of an auto-immune disease on an auto-inflammatory background,44,45 with both mechanisms overlapping and possibly potentiating one another. T helper (Th)-1, Th17 and Th22 cells and some of their associated pro-inflammatory cytokines, such as interleukin (IL)-17A and IL-22 and tumor necrosis factor alpha (TNF-) are critically involved in sustaining and maintaining psoriasis.4548 The IL-23/IL-17 immune axis is considered to have a pivotal role in the pathogenesis of psoriasis; in line with this, IL-17- and IL-23-antagonists are highly effective treatments for psoriasis.49,50

The pathogenesis of NAFLD is complex and involves multiple pathways. Important pathophysiological mechanisms include genetic factors, insulin resistance and hyperinsulinemia, oxidative stress and hepatocyte lipotoxicity, hepatic inflammation, fibrosis, and gastrointestinal dysbiosis.21,38,5155 The various factors are encompassed in a multiple hit model for NAFLD development and progression.21,56 In the early stages of NAFLD, insulin resistancepossibly related to an increase in pro-inflammatory cytokinesplays a pivotal role by increasing the release of circulating free fatty acids, followed by abnormal accumulation of triglycerides in liver cells and hepatic steatosis. This may be followed by a phase in which simple steatosis transitions into steatohepatitis as a result of an increased inflammatory response. Additional pathways subsequently involved in NAFLD progression include mitochondrial dysfunction and liver apoptosis, increased oxidative stress, activation of the profibrogenic transforming growth factor- (TGF-) pathway, and hepatic stellate cell activation and injury.5

While the exact underlying mechanisms must still be fully clarified, both psoriasis and NAFLD are strongly associated with low-grade, chronic inflammation, peripheral insulin resistance, and increased levels of oxidative stress.40,57 Elevated insulin resistance and increased release of inflammatory cytokines are also characteristic of the metabolic syndrome and obesity. Adipose tissue produces adipocytokines (or adipokines) such as adiponectin, leptin and resistin, as well as pro-inflammatory cytokines which play important roles in the pathogenesis of both psoriasis and NAFLD.

Besides the important role of adipose tissue in mediating the interplay between skin and liver, (severe) psoriasis may have a direct impact on NAFLD, possibly via mechanisms beyond overweight and obesity. Indeed, NAFLD in the general population can also occur among individuals who are not obese and have a normal body mass index. These individuals are labelled as lean NAFLD.58 Interestingly, compared to healthy subjects, individuals with lean NAFLD have higher mean serum C-reactive protein (CRP) levels, suggesting that systemic inflammation might be one of the pathogenic factors.58

The secretion of pro-inflammatory cytokines from psoriatic tissue into the general circulation may reinforce the prevailing systemic pro-inflammatory milieu associated with NAFLD. IL-6, IL-17, TNF- and CRP produced by the liver (hepatokines) and psoriatic skin have reciprocal direct effects on these organs (Figure 3). The pro-inflammatory effects of adipocytokines and hepatokines are summarized in Table 1. Importantly, there may be a bi-directional relationship between psoriasis and NAFLD through pro-inflammatory pathways, postulated as the hepato-dermal axis.48 Circulating pro-inflammatory cytokines such as TNF- and IL-17 derived from psoriatic skin, upon reaching the liver, could impact liver inflammation and insulin resistance. Conversely, pro-inflammatory mediators stemming from hepatic inflammation could contribute to the onset or exacerbation of cutaneous inflammation in psoriasis. Pro-inflammatory immune modulators released by adipose tissue and the liver are involved in the promotion of hepatic fibrogenesis in NAFLD as well as psoriasis pathogenesis.5,40,48,59 TNF-, for example, is involved in psoriasis inflammation and has been shown to be an independent predictor of hepatic fibrogenesis and disease progression.60 Another relevant cytokine in this context is IL-17, which plays a central role in psoriasis pathogenesis. IL-17 is able to induce hepatic stellate cells activation and subsequent collagen production.50,61 By doing so, IL-17 facilitates the progression from simple liver steatosis to steatohepatitis.50,61,62

Table 1 Cytokine Levels and Effects of Adipocytokines and Hepatokines in Psoriasis and Non-Alcoholic Fatty Liver Disease (NAFLD)

Figure 3 Possible mechanisms linking dysfunctional visceral adipose tissue, psoriatic skin and steatosis.

Abbreviations: CRP, C-reactive protein; IL-6, interleukin-6; IL-17, interleukin-17; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PAI-1, plasminogen activator inhibitor-1; TGF-, transforming growth factor-beta; TNF-, tumor necrosis factor alpha.

Notes: Reproduced from Mantovani A, Gisondi P, Lonardo A, et al. Relationship between non-alcoholic fatty liver disease and psoriasis: a novel hepato-dermal axis? Int J Mol Sci. 2016;17(2):217.48

High circulating (or hepatic) levels of proprotein convertase subtilisin kexin type-9 (PCSK9) have been shown to play a key role in muscle and liver lipid storage, adipose energy storage and hepatic fatty acids and triglycerides storage and secretion. These effects contribute to involvement of the enzyme in the pathogenesis of both NAFLD63 and psoriasis.64

Other shared pathways between psoriasis and NAFLD include modulation of lipid and glucose metabolism, which both play an important role in the development of metabolic syndrome and keratinocyte proliferation in psoriasis.

In summary, there is significant overlap in the pathophysiological factors underlying psoriasis and NAFLD, mostly relating to pathways involving inflammation, oxidative stress, and glucose and lipid metabolism.

Given the strong pathophysiological links between psoriasis and NAFLD and the high prevalence of NAFLD among psoriasis patients, dermatologists should always screen for possible liver disease in their psoriasis patients. A good understanding of the potential hepatic effects of systemic treatments prescribed for patients with psoriasis would also be clinically important. NAFLD-promoting drugs should be avoided, especially in high-risk patients. On the other hand, systemic therapies that reduce systemic inflammation may have a positive influence and mitigate the risk of developing NAFLD. Below, we summarize hepatotoxic and potential hepatoprotective effects of currently approved systemic psoriasis therapies with a focus on NAFLD.

Hepatotoxic risk is associated with the administration of a number of conventional drugs used in the treatment of psoriasis. Evidence for currently approved systemic psoriasis treatments is presented in Table 2.6587 Patients prescribed these medications should be monitored carefully for hepatotoxicity.

Table 2 Potential Hepatotoxic Effects of Some of the Most Commonly Used Systemic Therapies Used in the Treatment of Moderate to Severe Psoriasis

Perhaps the most substantive evidence, and concern, regarding potential hepatotoxicity relates to methotrexate.6570 Early signs of negative effects of methotrexate on liver function include elevated hepatic transaminase levels, but of even greater concern are methotrexate-induced histological changes including aggravation of underlying fatty liver to NAFLD and steatohepatitis with possible fibrosis and cirrhosis.71,72 These more serious adverse hepatic effects have been reported to occur in about 5% of patients treated with chronic, low-dose methotrexate, although rarely in patients without additional clinical risk factors for hepatotoxicity, such as pre-existing liver disease, excessive alcohol abuse, hepatitis B or C, central obesity and type 2 diabetes.71 Given the hepatotoxic concerns, use of methotrexate is preferably avoided in these high-risk psoriasis patient groups, including those with established NAFLD, and methotrexate is contraindicated if bilirubin values are > 5 mg/dl.73

Cyclosporin may cause dose-dependent, reversible increases in serum bilirubin and liver enzymes, with post-marketing experience reporting hepatotoxicity and liver injury.65,68,74 Cyclosporin can also potentially worsen NAFLD by increasing serum lipid levels.75 Close monitoring of liver function test enzymes and lipid parameters is recommended as abnormal values may necessitate dose reductions.68,74,76 Another frequently occurring adverse event associated with cyclosporin use is hypertension, which would be expected to negatively impact NAFLD.

Cases of liver enzyme increases ( 3 upper limit of normal [ULN]) and elevation of total bilirubin levels ( 2 ULN) have been reported infrequently for dimethyl fumarate (DMF), with resolution after treatment discontinuation. Assessment of serum aminotransferases (eg, alanine aminotransferase [ALT], aspartate aminotransferase [AST]) and total bilirubin levels are recommended prior to treatment initiation and during treatment.68,77 DMF is considered to be a possible rare cause of liver toxicity.78

Acitretin has been associated with transient increases in liver enzymes, but hepatotoxicity has been reported rarely.65 As acitretin frequently causes hyperlipidemia, use is preferably avoided in patients with or at high risk of NAFLD.11,75,79,80

No hepatotoxic effects have been documented for apremilast65 and no routine laboratory monitoring is required. Apremilast is considered to be an unlikely cause of apparent liver injury.78

There is evidence of hepatotoxic risk with TNF- inhibitors such as infliximab, adalimumab, certolizumab and etanercept65,8183 and guidelines advocate monitoring liver enzymes during treatment.65 Furthermore, compared with conventional systemic therapies for psoriasis (methotrexate and cyclosporin), treatment with TNF inhibitors (adalimumab, infliximab and etanercept) was found to be associated with significant increases in bodyweight and body mass index in a network meta-analysis (6 studies and 862 psoriasis patients).84 Increases in body weight might be associated with a reduction in the therapeutic response and/or exacerbations of comorbidities, although this needs to be confirmed in prospective studies. TNF inhibitors should be used cautiously in patients with or at high risk of NAFLD.

Other biologicals such as anti-IL17 agents (brodalumab, ixekizumab and secukinumab) and ustekinumab (anti-IL12/23) have been less widely investigated, but have generally exhibited minimal hepatotoxicity (Table 2). A retrospective study of 44 psoriasis patients receiving ustekinumab identified 6 cases (13.6%) of mild elevated transaminases, with no cases of severe hypertransaminasemia.85 Overall, the reported rate of mild-to-moderate serum aminotransferase elevations following ustekinumab therapy was 0.5% to 1.4%. There have been no reports of treatment-related symptomatic acute liver injury or jaundice linked to ustekinumab therapy.78 Interestingly, limited data found no increases in bodyweight in patients treated with ustekinumab.84,88

Analysis of over 3000 patients in clinical trials of the IL-17 antagonist secukinumab in psoriasis showed low rates of serum liver enzyme elevations compared to placebo and no cases of treatment-related liver injury. Post-marketing data have revealed no reports of liver injury due to secukinumab therapy.78 Similarly, clinical trials (> 3000 patients) and post-marketing studies of the anti-IL-17 biologic brodalumab have shown no evidence of liver enzyme elevation nor liver injury attributable to the agent.78 Comparable rates of serum liver enzyme elevations with the IL-17 antagonist ixekizumab and placebo were found in clinical trials, with no treatment-related cases of liver injury. Although post-marketing approval experience with ixekizumab is relatively limited, no cases of treatment-related liver injury have been reported.78 For newer anti-IL-23 biologics recently approved for the treatment of psoriasis (eg, guselkumab, risankizumab, and tildrakizumab), no evidence of acute liver injury or reactivation of hepatitis B or worsening of hepatitis C has been reported to date, but clinical experience with these agents is very limited (Table 2).

Assessment of hepatoprotection can be derived from several different research pathways including in vitro experiments, animal models and monitoring of potential biomarkers (Table 3).89108 Given the common etiology of inflammation between psoriasis and NAFLD, it might be postulated that systemic therapies for psoriasis that attenuate systemic inflammation may also have beneficial effects on NAFLD by targeting pro-inflammatory cytokines.109 However, to date, clinical data are scarce for any direct hepatoprotective effects of systemic psoriasis treatments.

Methotrexate has exhibited beneficial effects on cardiovascular inflammation91,92 as well as decreasing serum levels of PCSK9, which is a likely marker of improved lipid metabolism (Table 3).89 However, a large placebo-controlled RCT failed to show any benefits of methotrexate on the risk of cardiovascular events.110 Furthermore, the potential hepatotoxic risks associated with methotrexate therapy, as discussed earlier, would generally preclude its use in patients with NAFLD.

From the clinical study of Krahel et al,89 acitretin treatment was shown to increase PCSK9 levels, but there was no correlation between these elevated levels and markers of liver function such as transaminases in hepatic steatosis and NASH in high-risk patients (Table 3). Fibroblast growth factors (FGFs) 21 and 23 are markers for cardiometabolic disorders which are common in psoriasis. In one small trial, acitretin was reported to decrease FGF-21 by three-fold which was significantly greater than the reduction observed with methotrexate.90 In an earlier small clinical trial, it was shown that patients with chronic psoriasis treated with acitretin had reduced retinol-binding protein-4 levels and decreased insulin resistance.111 Given the link between psoriasis and increased insulin resistance/diabetes these changes could be clinically meaningful if confirmed in a larger study.111

There is a paucity of data on the potential hepatoprotective effects of cyclosporin. In a small group of patients with moderate to severe psoriasis, comorbidity with diabetes or metabolic syndrome did not affect the efficacy of cyclosporin.93 In another clinical study, cyclosporin significantly improved patients psoriasis symptoms and this was associated with increased transcription activity of TGF1 at the end of treatment in those with or without diabetes, and with or without metabolic syndrome.112 Through inhibition of the enzyme cyclophilin, cyclosporin has shown beneficial effects on liver fibrosis and cirrhosis in some patients. However, calcineurin-related toxicity has limited the possibility of long-term therapy and has required that dosages be kept low.113

Apremilast is a phosphodiesterase 4 inhibitor shown to be clinically effective in patients with psoriasis and/or psoriatic arthritis and also acts as a metabolic modulator. In individual cases, apremilast was shown to improve glucose metabolism114 and lipid profile.115 Similar findings were reported in a 1-year open observational study (Table 3).94

DMF, and its active metabolite monomethylfumarate (MMF), are of particular interest in the context of this review due to their unique multiple mechanisms of action (Figure 4).102,103,105,116,117 These include immunomodulatory and anti-inflammatory mechanisms that are potentially advantageous in psoriatic patients with comorbid NAFLD (Table 3). 116 For example, DMF/MMF regulates cellular responses to oxidative stress by modulating intracellular glutathione levels.102 DMF/MMF also reduces oxidative stress through activation of Nrf2 (nuclear factor erythroid 2related factor 2) which stimulates cytoprotective and anti-inflammatory factors such as HO-1 (heme oxygenase-1);103,106,116 and through inhibiting genes regulated by the transcription factor HIF-1 (hypoxia-inducible factor 1-alpha) and STAT3/STAT1 (signal transducer and activator of transcription) pathways.116 MMF is an agonist for hydroxy-carboxylic acid receptor 2 (HCA2/ GPR109A [G protein-coupled receptor 109A]) which inhibits neutrophil adhesion and recruitment by COX-1 (cyclooxygenase 1) and PGE2 (prostaglandin E2).116 Fumaric acid esters significantly reduced total cholesterol, low-density lipoprotein and apolipoprotein B levels in a prospective trial involving psoriasis patients.96 In animal models, DMF has shown potential to ameliorate acetaminophen-induced hepatic injury in mice,107 as well as liver ischemia/reperfusion injury in rats.104 Improvement of liver function and anti-oxidant status might prove to be a promising treatment approach in patients with psoriasis and comorbid NAFLD.

Figure 4 Proposed mechanisms of action of dimethyl fumarate/monomethyl fumarate (DMF/MMF).

Note: Data from these studies.102,103,105,116,117

Adalimumab was shown to reduce key markers of systemic inflammation including glycoprotein acetylation, CRP, IL-6 and TNF and this was associated with beneficial cardiovascular effects such as improved endothelial dysfunction as measured by flow-mediated dilation.95,96 TNF- inhibitors have been reported to improve insulin resistance in patients with rheumatoid arthritis118,119 and ankylosing spondylitis,118,120 but not in obese patients with either type 2 diabetes121 or metabolic syndrome.122,123 Seitz et al investigated the impact of TNF- inhibitors on the presence of liver fibrosis in patients with psoriatic arthritis and rheumatoid arthritis treated with methotrexate.124 Patients with psoriatic arthritis had a higher incidence of liver steatosis and hyperlipidemia and in this study. TNF- inhibitors exerted a protective effect against the development of liver fibrosis.

Secukinumab has been shown to have neutral effects on fasting plasma glucose, lipid parameters and liver enzymes, while reducing levels of CRP, a marker for systemic inflammation. It was also associated with a reduction in markers of oxidative stress. Secukinumab produced greater improvement in arterial elasticity, coronary artery function and myocardial deformation indices compared with methotrexate and cyclosporin. However, no data are available on the impact of these effects on liver function.97,98

Ustekinumab significantly decreases pro-inflammatory cytokines, such as TNF-, IL-1b, IL-17a and IL-6. VCAM-1 was significantly reduced by ustekinumab at 12 weeks, although this effect was not sustained at 1 year. Overall, ustekinumab transiently reduced aortic vascular inflammation at 12 weeks and, longer term, produced a more durable reduction in inflammatory cytokines associated with cardiovascular disease.101 No published studies have investigated the impact of this effect on liver inflammation and function.

NAFLD is an increasingly prevalent and clinically important comorbidity occurring in up to 65% of patients with psoriasis. The occurrence of NAFLD in psoriasis can have significant morbidity and mortality potential. There are multiple pathophysiological pathways that link psoriasis with NAFLD, in particular systemic inflammation and insulin resistance. Reducing systemic inflammatory burden may provide an opportunity to reduce the progression or even ameliorate NAFLD.

A number of conventional drugs used in the treatment of psoriasis are associated with hepatotoxic risk. Most evidence relates to use of methotrexate which, along with other NAFLD-promoting drugs, is best avoided in psoriasis patients with clinical risk factors for hepatotoxicity or established NAFLD. Despite the expectation that systemic psoriasis treatments might reduce the progression of or even ameliorate NAFLD by targeting pro-inflammatory cytokines, clinical data for direct hepatoprotective effects of these therapies are relatively scarce. Through its pleiotropic mechanisms of action contributing to its anti-inflammatory activity, DMF may have additional hepatoprotective effects of possible advantage in psoriatic patients with NAFLD.

However, real-world data on the effects of DMF in patients with psoriasis and concomitant NAFLD is currently lacking, and further studies with DMF and other systemic psoriasis therapies in routine clinical practice would be needed to inform therapeutic decision-making strategies for psoriasis patients with NAFLD.with DMF and other systemic psoriasis therapies in routine clinical practice would be needed to inform therapeutic decision-making strategies for psoriasis patients with NAFLD.

The authors thank Dr Rob Furlong and Dr Steve Clissold on behalf of Content Ed Net, Spain for editorial support, which was sponsored by Almirall, Barcelona, Spain, and performed in line with Good Publishing Practice (GPP-3) guidelines.

This article was supported by an unrestricted educational grant from Almirall, Barcelona, Spain.

DMWB is a consultant/speaker for AbbVie, Almirall, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Regeneron/Sanofi Genzyme. IK is an employee of Almirall, Barcelona, Spain. SP is a consultant/speaker for AbbVie, Almirall, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, UCB, and Pfizer. The authors report no other conflicts of interest in this work.

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19. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142(7):15921609. doi:10.1053/j.gastro.2012.04.001

20. Golabi P, Otgonsuren M, de Avila L, et al. Components of metabolic syndrome increase the risk of mortality in nonalcoholic fatty liver disease (NAFLD). Medicine (Baltimore). 2018;97(13):e0214. doi:10.1097/MD.0000000000010214

21. Takaki A, Kawai D, Yamamoto K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int J Mol Sci. 2013;14(10):2070420728. doi:10.3390/ijms141020704

22. Gisondi P, Galvan A, Idolazzi L, et al. Management of moderate to severe psoriasis in patients with metabolic comorbidities. Front Med (Lausanne). 2015;2:1. doi:10.3389/fmed.2015.00001

23. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367378. doi:10.1053/j.gastro.2015.04.005

24. Lonardo A, Loria P, Carulli N. Concurrent non-alcoholic steatohepatitis and psoriasis. Report of three cases from the POLI.ST.E.N.A. study. Dig Liver Dis. 2001;33(1):8687. doi:10.1016/S1590-8658(01)80144-4

25. Gisondi P, Targher G, Zoppini G, et al. Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009;51(4):758764. doi:10.1016/j.jhep.2009.04.020

26. Gisondi P, Barba E, Girolomoni G. Non-alcoholic fatty liver disease fibrosis score in patients with psoriasis. J Eur Acad Dermatol Venereol. 2016;30(2):282287. doi:10.1111/jdv.13456

27. van der Voort EA, Koehler EM, Dowlatshahi EA, et al. Psoriasis is independently associated with nonalcoholic fatty liver disease in patients 55 years old or older: results from a population-based study. J Am Acad Dermatol. 2014;70(3):517524. doi:10.1016/j.jaad.2013.10.044

28. Madanagobalane S, Anandan S. The increased prevalence of non-alcoholic fatty liver disease in psoriatic patients: a study from South India. Australas J Dermatol. 2012;53(3):190197. doi:10.1111/j.1440-0960.2012.00905.x

29. Abedini R, Salehi M, Lajevardi V, et al. Patients with psoriasis are at a higher risk of developing nonalcoholic fatty liver disease. Clin Exp Dermatol. 2015;40(7):722727. doi:10.1111/ced.12672

30. Ogdie A, Grewal SK, Noe MH, et al. Risk of incident liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis: a population-based study. J Invest Dermatol. 2018;138(4):760767. doi:10.1016/j.jid.2017.10.024

31. Candia R, Ruiz A, Torres-Robles R, et al. Risk of non-alcoholic fatty liver disease in patients with psoriasis: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2015;29(4):656662. doi:10.1111/jdv.12847

32. Phan K, Onggo J, Charlton O, et al. Relationship between psoriasis and non-alcoholic fatty liver disease - Updated systematic review and adjusted meta-analysis. Australas J Dermatol. 2019;60(4):e352e355. doi:10.1111/ajd.13015

33. Yang YW, Keller JJ, Lin HC. Medical comorbidity associated with psoriasis in adults: a population-based study. Br J Dermatol. 2011;165(5):10371043. doi:10.1111/j.1365-2133.2011.10494.x

34. Gandha N, Wibawa LP, Jacoeb TNA, et al. Correlation between psoriasis severity and nonalcoholic fatty liver disease degree measured using controlled attenuation parameter. Psoriasis (Auckl). 2020;10:3944. doi:10.2147/PTT.S272286

35. Roberts KK, Cochet AE, Lamb PB, et al. The prevalence of NAFLD and NASH among patients with psoriasis in a tertiary care dermatology and rheumatology clinic. Aliment Pharmacol Ther. 2015;41(3):293300. doi:10.1111/apt.13042

36. Romero-Prez D, Belinchn-Romero I, Bellot P, et al. Nonalcoholic fatty liver disease puts patients with psoriasis at greater cardiovascular risk. Australas J Dermatol. 2019;60:e304e310. doi:10.1111/ajd.13098

37. National Guideline Centre (UK). Non-alcoholic fatty liver disease: assessment and management. London: National Institute for Health and Care Excellence (UK); 2016. (NICE Guideline, No. 49.) 5, Risk factors for NAFLD. Available from: https://www.ncbi.nlm.nih.gov/books/NBK384735. Accessed November 10, 2021.

38. Friedman SL, Neuschwander-Tetri BA, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24(7):908922. doi:10.1038/s41591-018-0104-9

39. Kamiya K, Kishimoto M, Sugai J, et al. Risk factors for the development of psoriasis. Int J Mol Sci. 2019;20:4347. doi:10.3390/ijms20184347

40. Ganzetti G, Campanati A, Molinelli E, et al. Psoriasis, non-alcoholic fatty liver disease, and cardiovascular disease: three different diseases on a unique background. World J Cardiol. 2016;8(2):120131. doi:10.4330/wjc.v8.i2.120

41. Grelj J, Mlinari-Raan I, Marko PB, et al. Polymorphisms in GNMT and DNMT3b are associated with methotrexate treatment outcome in plaque psoriasis. Biomed Pharmacother. 2021;138:111456. doi:10.1016/j.biopha.2021.111456

42. Heitmann J, Frings VG, Geier A, et al. Non-alcoholic fatty liver disease and psoriasis - is there a shared proinflammatory network? J Dtsch Dermatol Ges. 2021;19(4):517528.

43. Harden JL, Krueger JG, Bowcock AM. The immunogenetics of psoriasis: a comprehensive review. J Autoimmun. 2015;64:6673. doi:10.1016/j.jaut.2015.07.008

44. Liang Y, Sarkar MK, Tsoi LC, et al. Psoriasis: a mixed autoimmune and autoinflammatory disease. Curr Opin Immunol. 2017;49:18. doi:10.1016/j.coi.2017.07.007

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Non-alcoholic fatty liver disease in patients with psoriasis | PTT - Dove Medical Press

The announcement of the 2021 Outstanding Volunteer Leader of the Year Award came at the end of the National Psoriasis Foundations virtual October Community Conference. I felt honored to be one of the nine finalists and thought that any of the other nominees would be deserving of this honor.

To my great surprise,I heard my name announced as the winner and saw my picture flash on the screen. My wife, Lori, gave me a hug, while those at the conference messaged me their congratulations.

Volunteering is a big part of who I am. Over the years, Ive given my time and energy to local food banks, churches, schools, and youth sports teams, and as a church minister I recruited and supported volunteers. Ive volunteered with the National Psoriasis Foundation (NPF) for years, hoping to improve the lives of those impacted by psoriatic disease.

A fellow NPF volunteer at the conference rightly noted that we dont do what we do for the recognition; we do it to help others. Still, Ive personally experienced many benefits from volunteering that I hope encourage you to volunteer as well.

Here are five ways volunteering has made my life better plus one pitfall to watch out for.

One great benefit of volunteering is meeting people who care about the same causes you do, with similar values. My first advocacy event with the NPF introduced me to a community of people from diverse backgrounds, all united by a desire to help the psoriatic disease community.

One experience that stands out was in April 2015, when I drove 30 minutes to the California State Capitol in Sacramento to join fellow NPF volunteers for the first annual California Lobby Day. Our mission was to talk to state legislators about bills related to access to medical care. The connections and friendships I made at the Lobby Day are ones I still greatly appreciate today.

I become particularly self-focused when my psoriasis is not doing well. Self-care is important during those times, but I also find myself losing perspective and imagining worst-case scenarios.

For me, volunteering can help remedy this by redirecting my focus outward. For instance, organizing the first Sacramento Team NPF Walk came at a tough time for me. I felt challenged by my work on many fronts and my psoriasis was flaring, which was causing me to stress about potentially changing biologics.

Putting my attention on the event led me to see my difficulties in a new light. I found joy in planning the Walk path, talking to dermatology offices, and inviting participants to join the fundraiser. All this gave me more energy to address my own personal concerns.

RELATED: How to Beat the Psoriasis-Stress Cycle

Finding ways to make a difference through volunteering can give your life meaning and purpose.

Im motivated by making a difference in the lives of others. Whether its serving a Thanksgiving meal to those who experience food insecurity or teaching a youth baseball player how to field a grounder, I want to uplift others. In the process, I find my own life is enriched.

Ive dedicated my NPF volunteer work to areas where I feel I can have the greatest impact, such as using education to reduce the stigma that often accompanies psoriasis. Through fundraising events, I also hope to assist in bringing about better treatments and a cure, and I strive to support fellow patients in advocating for themselves and others.

Volunteering can provide opportunities to develop or utilize your skill set. Ive grown my teaching skills as a youth coach, and my social media engagement has increased as an NPF Social Ambassador. Ive taught and trained volunteers on how to lead a meeting and mentor college students at church.

Im a reserved and introverted person, but volunteering has also taught me a lot about boldness and assertiveness. At work Ive cultivated skills in public speaking and leading teams, but asking legislators to support a bill that would help those in the chronic illness community felt different and even scary.

In some of those legislative meetings, I was the one who needed to give the ask. Over time it became more natural for me to assert myself in those situations and, consequently, in other areas of my life.

Its easy for me to get overwhelmed by the size and needs of the psoriasis community. When I think about the more than 8 million people in the United States and 125 million worldwide living with psoriatic disease, I feel small. Instead of doing something proactive, I sometimes find myself complaining.

Volunteering provides a positive direction to channel that unproductive energy. Instead of bemoaning the problem, I can be part of the solution. Joining a patient advocacy organization like the NPF brings me together with others who are rowing in the same direction. Together, we can bring about a cure for psoriasis and improve lives.

RELATED: You Yes, You! Can Become a Psoriasis Patient Advocate

While I love to volunteer, I do find myself overcommitted from time to time. I want to do it all, but when my health warrants more attention or work is especially busy, Ive learned when to pull back or say no.

Still, there are so many ways to contribute to the betterment of others through volunteering, and what compels me may be different than what excites you. If you have time and energy to offer, consider how you can get involved and experience the joy of giving to others.

Learn more about volunteering with the National Psoriasis Foundation.

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Psoriasis Volunteering: Benefits and Pitfalls - Everyday Health

This article was originally published here

PLoS One. 2021 Dec 9;16(12):e0259852. doi: 10.1371/journal.pone.0259852. eCollection 2021.

ABSTRACT

This study aimed to investigate the perceived threat, mental health outcomes, behavior changes, and associated predictors among psoriasis patients during the COVID-19 pandemic. The COVID-19 has been known to increase the health risks of patients with psoriasis owing to patients immune dysregulation, comorbidities, and immunosuppressive drug use. A total of 423 psoriasis patients not infected with COVID-19 was recruited from the Department of Dermatology, National Taiwan University Hospital Hsin-Chu Branch, Chang Gung Memorial Hospital, and China Medical University Hospital from May 2020 to July 2020. A self-administered questionnaire was used to evaluate the perceived threat, mental health, and psychological impact on psoriasis patients using the Perceived COVID-19-Related Risk Scale score for Psoriasis (PCRSP), depression, anxiety, insomnia, and stress-associated symptoms (DAISS) scales, and Impact of Event Scale-Revised (IES-R), respectively. Over 94% of 423 patients with psoriasis perceived threat to be 1 due to COVID-19; 18% of the patients experienced psychological symptoms more frequently 1, and 22% perceived psychological impact during the pandemic to be 1. Multivariable linear regression showed that the higher psoriasis severity and comorbidities were significantly associated with higher PCRSP, DAISS, and IES-R scores. The requirement for a prolonged prescription and canceling or deferring clinic visits for psoriasis treatment among patients are the two most common healthcare-seeking behavior changes during the COVID-19 pandemic. Psoriasis patients who perceived a higher COVID-19 threat were more likely to require a prolonged prescription and have their clinic visits canceled or deferred. Surveillance of the psychological consequences in psoriasis patients due to COVID-19 must be implemented to avoid psychological consequences and inappropriate treatment delays or withdrawal.

PMID:34882690 | DOI:10.1371/journal.pone.0259852

Link:
Perception of the threat, mental health burden, and healthcare-seeking behavior change among psoriasis patients during the COVID-19 pandemic - DocWire...

At U.S. Dermatology Partners, our board-certified dermatologists utilize a range of treatment options to help our clients achieve healthier, more beautiful skin. Among these are dermal fillers, a great option to improve the appearance of fine lines, wrinkles, and sagging skin. There are many different dermal fillers available, and each has its own, unique advantages. RADIESSE dermal filler injections from U.S. Dermatology Partners are an innovative treatment option. Due to the long-lasting results, RADIESSE has quickly become one of the most popular filler options available. You can learn more on this page, and dont hesitate to call the U.S. Dermatology Partners team near your home or office to schedule a cosmetic dermatology consultation. Book your appointment today to find the best cosmetic dermatology treatment for you and your skin.

RADIESSE is an injectable dermal filler used to plump the skin. When age or scarring causes fine lines, wrinkles, or sagging, RADIESSE dermal fillers can be injected below the skin to restore volume and smooth, youthful fullness. Each type of dermal filler is uniquely formulated to address specific concerns. RADIESSEs formula uses a water-based gel with calcium-based microspheres to recreate lost volume, with non-toxic and non-allergenic ingredients. Because the components of RADIESSEs formula are very similar to naturally-occurring minerals, people are much less likely to experience an allergic response. Over time, the body absorbs the filler material, but unlike traditional dermal fillers that need to be immediately readministered to maintain the desired results after theyre absorbed, RADIESSE dermal filler treatment is also designed to spark the production of your bodys natural collagen, meaning youll retain your improved appearance for even longer before you need retreatment.

While most people select RADIESSE for use improving the appearance of the face, specifically the skin around the nose and mouth, it is also used to restore volume on the backs of hands, and it can sometimes be administered as an alternative to implant surgery in the nose, cheeks, or chin.

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Evans Dermatology Austin | U.S. Dermatology Partners

LOVE Island's Olivia Bowen "hid" her painful psoriasis from husband Alex and told how her mental health suffered as she battled the chronic skin condition.

The reality TV star bravely spoke after showing fans red and itchy "angry" patches all over her body earlier this year.

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In an exclusive interview with The Sun Olivia, 27, revealed she couldn't bring herself to take off her clothes in front of her husband during aggressive flare-ups.

The star said: "Im shocked when I say it out loud but I used to turn away when trying to put my T-shirt on without him seeing my back and front because it was really bad, and he was like what are you doing? Why are you hiding? I dont care.

"That was such a struggle for me to understand that he was accepting of it.

"Back in the day Id be bullied for it, boys would laugh at me and think its disgusting - so having this guy that fully accepted me was quite shocking.

"Your mind runs away with you, but he is so supportive."

Olivia said she has come to terms with her skin thanks to encouragement from her fans and fellow sufferers after speaking out.

She added: "I dont feel 100 per-cent confident in myself. I'm not sure I ever will. Ive learned to accept that.

"I am gonna have my down days. I am gonna feel crap sometimes, thats completely human. Sharing it with everyone else has helped me so much.

"I remember when I was taping on Instagram, I had psoriasis and it really flared up. Id been itching and scratching all day. I was having a breakdown. I had a panic attack and I was so scared to share it.

"When I was 17 no one accepted it. No one was there for me to look up to. When I put it out there I was so scared, but the support - people I dont personally know - its overwhelming. It really helped my confidence.

"I have had so many inboxes about my psoriasis recently. Girls and guys saying Ive struggled with this for so long. 'You helped me so much you make me feel comfortable in my skin.'

"It makes you feel like youre doing a lot which is nice."

Olivia has partnered with fair online casino and Bingo site, PlayOJO to launch a sex-education-style campaign to promote its latest safer gambling campaign, Safe Bets.

The campaign has been designed to help people understand that although Gambling is fun, it should be safe fun and this video explains how it can be made safer, by drawing parallels with another area of life we have fun and the idea of protection is already well established - safe sex.

She said: "When we filmed it I struggled to keep a straight face, the whole thing I was just laughing through it.

"It was such a nice way to get such an important message across. Ive had people in my past and present who have struggled with gambling problems and I think its something thats really hard to talk about for people my age.

"I thought the way the idea of sex education back in the 80s might grab peoples attention and take on board some of the safer gambling messages.

"It starts out as fun, it's obviously quite addictive, having tools in place to cut playing short or cap your spend is really useful."

To view the full video please and for further details on the campaign please visit PlayOJO.

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I hid my body from husband Alex after psoriasis gave me panic attacks and drove me to breakdowns, says... - The Sun

PN-235 (JNJ-77242113) now expected to advance into multiple Phase 2 clinical studies in 2022, for indications including psoriasis and inflammatory bowel diseases

NEWARK, Calif., Dec. 2, 2021 /PRNewswire/ -- Protagonist Therapeutics (Nasdaq: PTGX) ("Protagonist" or "the Company") today announced the selection of PN-235 (JNJ-77242113) as the final candidate for all clinical studies in multiple indications based on intervention of the Interleukin-23 (IL-23) pathway, under the Company's collaboration with Janssen Biotech, Inc. (Janssen). In addition to the previously announced Phase 2 clinical study of PN-235 in psoriasis, new Phase 2 clinical studies of PN-235 in inflammatory bowel diseases (IBD) are expected to commence in late 2022. Further development of PN-232 (JNJ-7510586) will be discontinued in favor of PN-235 based on its superior potency, and overall pharmacokinetic and pharmacodynamic profile.

"We are delighted to see PN-235 emerge as the clear focal point going forward, after over four-plus years of a highly productive and ongoing collaboration with Janssen," said Dinesh V. Patel, PhD, President and CEO of Protagonist. "We look forward to exploring the full potential of a highly differentiated, oral targeted therapy like PN-235, thereby potentially addressing persistent unmet needs of patients with immune-mediated diseases like psoriasis and IBD."

Protagonist will earn a $25 million milestone in connection with the initiation of the first Phase 2 study of PN-235 in psoriasis in early 2022. Protagonist is also eligible for a $10 million milestone in connection with the start of the second indication-based Phase 2 study. Protagonist is eligible for up to approximately $900 million in development-related milestone payments, in addition to the $87.5M in milestones already earned. Under the terms of the collaboration, Janssen will conduct all future clinical studies, including these anticipated Phase 2 studies, and will be solely financially responsible for any such studies.

Story continues

About Protagonist

Protagonist Therapeutics is a biopharmaceutical company with multiple peptide-based investigational new chemical entities in different stages of development, all derived from the Company's proprietary technology platform.

Protagonist's pipeline includes rusfertide (PTG-300), an investigational, injectable hepcidin mimetic currently in a Phase 2 proof-of-concept clinical trial for polycythemia vera (PV), a Phase 2 study in PV subjects with high hematocrit levels, and a recently completed Phase 2a study for hereditary hemochromatosis. The Company plans to initiate a single, global Phase 3 randomized, placebo-controlled trial evaluating the efficacy and safety of a once weekly, subcutaneously self-administered dose of rusfertide.

The Company is also evaluating an orally delivered, gut-restricted alpha-4-beta-7 integrin specific antagonist peptide (PN-943) currently in a Phase 2 study in adults with moderate to severe active ulcerative colitis (UC). The Company is targeting ulcerative colitis as the initial indication.

The Company has a worldwide license and collaboration agreement with Janssen Biotech, Inc., for the development of oral peptide IL-23 receptor antagonists. Compounds in development include PN-235, a second-generation oral interleukin-23 receptor antagonist candidate. Under the collaboration with Janssen, PN-235 is expected to advance into Phase 2 studies in psoriasis and new Phase 2 clinical studies in inflammatory bowel diseases.

Cautionary Note on Forward-Looking Statements

This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding our intentions or current expectations concerning, among other things, the Company's collaboration with Janssen, the timing of Janssen's PN-235 trials and the potential benefits of PN-235. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreements, the impact of the current COVID-19 pandemic on our discovery and development efforts, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release.

Protagonist Therapeutics, Inc. (PRNewsFoto/Protagonist Therapeutics, Inc.)

Cision

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SOURCE Protagonist Therapeutics, Inc.

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Protagonist Therapeutics Announces the Selection of Oral Peptide PN-235 into Phase 2 Clinical Development Program for Multiple Indications - Yahoo...

Most of us might not think twice about using a hand sanitiser, especially since it's an essential item during the pandemic.

However, things aren't as easyfor17-year-old Monissha Nath Kaushal.Kaushal suffers from psoriasis, a skin disorder that causes one's skin cells to multiply up to 10 times faster than normal.

In October, she posted a TikTok recounting an incident in school where she was forced to use hand sanitiser, despite indicatingthat she has a skin condition.

why did you do that ##fyp ##sgtiktok ##skin ##foryoupage ##psoriasis ##psoriasisawareness ##eczema ##pain ##trending ##shopping ##xyzbca

The video has over 5.4 million views and received many comments from other TikTokers with similar experiences.

Speaking with AsiaOne last Saturday (Nov 20), Kaushal saidshe was diagnosed with psoriasis and twenty-nail dystrophy when she was five.

Psoriasiscauses her skin to appear bumpy and covered in white scales. Sometimes,patches ofdry skin appear on her soles and palms and they maytear and bleed.

Her initial motivationfor creating a TikTok account, she shared, was so that she could keep track of her skin's recovery.

"I'm turning17 this year, I wanted to learn how to treat my psoriasis on my own. I made my first TikTok so that I could be committed to tending to my skin every day."

Judgmentalgazes and opinionsdon't seem to faze Kaushal that much anymore, as she's had a fair share of them growing up.

"I've heard plenty insensitive things said to me but thats just how life is. [There are people] who really don't care about what their words do to someone," she said.

"Ive been through so much discrimination in my life, so it'seasy to ignore someones opinion on the internet."

ouch#psoriasis #fyp #psoriasisawareness #foryoupage #fyp #what #eczema #skin #skintok #skincare #ouch #shook #sgtiktok #skincondition #trending #m

That said, she still vividly remembers an incident that happened when she attended a friend's birthday party in primary school.

"When I entered my friend's place, I kept my socks on. Every two minutes, my palms bled and I needed to be taken care of. I remember other kids' parents seeing itand keeping their children away from me. I ended up leavingearly."

It's no exaggeration, she said.

"When itfirst appeared on my skin, the soles of my feet were completely covered in dry, dead skin it was about four centimetres thick. My nails also looked like they were decaying; they curled inwards due to the nail dystrophy."

Physical pain wasn't the only problem.Kaushal also had many dietary restrictions no dairy, no gluten, no seafood and no meat.Even chocolate, a well-loved children's treat, was out of bounds.

The physical effects of her conditionweren't the only thing that Kaushal was struggling with.

"Many people think that psoriasis is just a skin condition, but it's more than that. It can alsoaffect one's mental health."

As a child, she never dared look at herself in a mirror. That only changed when she turned 14 andher skin started to show signs of improvement."I thought I was a monster," she said.

Without any peers she could turn to for advice or help, Kaushal spent a lot of time on her own. She confessed that she "didn't feel human" because she "didn't have similar experiences as people my age".

The pandemic in 2020 also brought along new fears and anxieties for the student, who was due to take her O'Level examinations the same year.

"I was incredibly stressed out. My skin started to flare up violently it got so bad I had an anxiety attack."

To protect herself physically and mentally,she took her exams as a private candidate. She said that she wanted to give herself "air to breathe".

With regard to her own journey towards self-acceptance, she said: "I saw myself and psoriasis as two different people, however, now I feel like it's a part of me, and so there's lessto worry about."

She also said that she "became less self-conscious" as time went by and she learntto "look at myself and see myself for who I was".

Addressing netizens' reactions to her TikToks so far, Kaushal saidthat sharing her story online has given her a sense of community, as others with similar conditions have begun reaching out to her.

One of the most memorable messages she received was from someone who had no idea they were suffering from a skin disorder until they came across her TikToks, and it prompted them to visit a dermatologist.

"I felt truly touched, knowing that Im a part of the reason why someone can feel better about their condition."

claudiatan@asiaone.com

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'I can't use hand sanitiser': Meet Monissha, a 17-year-old who suffers from psoriasis - AsiaOne

Dr Ophelia Veraitch, Consultant dermatologist and founder of Dr Ophelia Comsecutical Skin and hair, has shared her top tips to help you on your hair growth journey

Hair loss is completely normal, but when you start noticing more hair in your hair brush or clumps clogging up the shower drain, it can be quite concerning.

Genetics may play a part in hair loss, as can an underlying health condition.

But there are several other influences that may be a factor like stress, weight loss or an iron deficiency.

While we can't always prevent the cause of hair loss or thinning, there are things we can do to minimise it.

We spoke to Dr Ophelia Veraitch, Consultant dermatologist and founder of Dr Ophelia Comsecutical Skin and hair to find out what we could be doing wrong and how to things we can do to boss that hair growth.

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The state of your scalp can have a huge impact on the health of your hair.

A dry scalp or a scalp with a lot of product built up can lead to hair loss or thinning. This is because the build up slowly starts to suffocate the hair follicle, which can stunt growth or cause the hair to shed.

Dr Ophelia suggests massaging the scalp with oil, as she says "It's the best way to naturally hydrate your scalp and hair and help both to retain moisture."

"On the days I'm not going out I massage almond oil into my scalp and hair and onto my children's scalp and hair too.

"This ritual comes from my Sikh background where having uncut hair (which I havent stuck to!) and importantly looking after your hair is a sign of respect to personal attributes that are considered god given.

"Its common for Asian and Mediterranean cultures to put oil in the scalp and hair like this as a natural and effective way to moisturise our scalp and hair!"

Massaging almond oil into the scalp and hair like this helps to reduce frizziness of the hair and improve the condition of the scalp too.

"You can use coconut oil but I find this is smellier and harder," she says.

"Alternatively argan oil is thinner so it's better for people with finer hair."

Psoriasis is a skin condition that affects around 2 per cent of people in the UK and it can result in hair problems for women aged 45 and above.

It causes flaky patches of skin that are usually red and crusty with silvery scales and can occur in the scalp, resulting in fine scaling that looks like dandruff, a thick crust, or crusted plaques that cover the entire scalp.

Psoriasis is a chronic disease, this means that it's long-lasting and usually involves periods when you have symptoms and then periods where you don't have any. Whilst there's no cure as such, there are a number of safe and effective treatments that can improve the symptoms and the appearance of the skin and reduce the severity and size of the patches.

Lifestyle measures such as loosing weight, exercise, healthy eating, stopping smoking and reducing alcohol intake can all help psoriasis.

Soaking your scalp in olive oil can help to ease the symptoms of psoriasis, says Dr Ophelia.

Simply cover the scalp in the oil, wrap it in cling film and leave it for several hours or even overnight.

Another option is to use hair products that target hair thinning and loss that contain ingredients which can help promote hair growth.

For example, the sleep hormone melatonin isn't just to regulate the circadian rhythms, it's also a great antioxidant synthesised in hair follicles.

The expert recommends finding a hair growth tonic like Dr Ophelia Hair Growth Elixirs, to optimise luscious and beautiful looking hair.

A common mistake people make is drying their hair with a cotton towel.

The hair shaft is made of keratin. The outermost layer of the hair shaft is known as the cuticle, and is made of overlapping keratin cells.

The hair cuticle works as a protective layer, but if not looked after, damage to the hair cuticle can make the hair look and feel dry and unhealthy.

Towel drying wet hair can cause damage to the keratin cells in the cuticle.

Instead, either pat your hair dry or use a microfibre cloth or a t-shirt.

There's a common misconception that towel drying your hair before using conditioner makes the product absorb into the hair shaft more easily.

But Dr Ophelia warns against it.

"This argument to me is that it's a bit like using sand paper on your skin to make active ingredients absorb better into the skin.... I don't know why anyone would purposefully damage the cuticle of the hair shaft in order for the conditioner to be 'absorbed'."

If your hair loss is causing your distress, contact your GP for further advice.

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(WFXR) With the holidays closing in, it also means enduring the colder and drier months. These months can disrupt your skins barrier during the winter.

The American Academy of Dermatology (AAD) Association says that it is especially bad for those who deal with conditions like eczema and psoriasis.

To help make sure your skin is winter-ready, the AAD put together a survival kit to help you get through the winter blues.

You want to look for products that say gentle and moisturizing on the label and avoid products that contain alcohol. The alcohol can dry out your skin.

You want to look for cleansers that are liquid, gel, or mousse. Health officials say that the creamier the body cleanser is the better it is for your skin. If you suffer from eczema, you want to look for products that contain petrolatum, shea butter, and silicones.

When browsing the shelves for a facial moisturizer you want to keep in mind that lighter lotions may not protect your skin from the colder and drier elements.

Instead, doctors suggest you look for products that contain creams, oils, or balms. Doctors say that products containing lactic acid moisturizers can help exfoliate dry, flaky skin while locking in sky hydration.

Doctors suggest that you apply moisturizers to your skin when it is still damp after a shower or bath. They say it will help trap moisture in the skin.

When looking for a body moisturizer you want to find ointments and creams that you squeeze from a tube or scoop from a tub. Doctors suggest that the thicker the formula the more moisture it packs. Other ingredients to look for are glycerin, lanolin, mineral oil, petrolatum, and shea butter.

If you are looking for a rejuvenating product, doctors suggest that you stay away from products containing anti-aging ingredients. Instead, look for products that have a lower concentration of harsh ingredients.

Sunscreen is a product many dermatologists say we should be wearing year-round on areas that are not covered by the sun such as the face, neck, ears, and hands.

When thinking about what products to buy, look for creams instead of lotions or sprays. You also want to make sure your sunscreen has an SPF of at least 30. When you are out and about, always look for shade and wear gloves and sunglasses with UV protection.

Get breaking news, weather, and sports delivered to your smartphone with the WFXR News app available on Apple and Android.

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What to pack in your skins winter survival kit - WFXRtv.com