Caring for young people with moderate to severe psoriasis: an interpretive description of parental perspectives.

Introduction: Psoriasis often sets on during childhood or adolescence, when parents have great importance for the young people's self-management, well-being, and quality of life. The aim of this study was to understand parents' perspectives on young people's daily life with psoriasis in order to improve adolescents' self-management.Method: Adopting interpretive, description methodology (ID), focus group discussion, and interviews were conducted with eight parents of adolescents with psoriasis. The analysis was inductive with an iterative comparative approach. Main themes conveying participants' perceptions were identified for constructing a coherent narrative of parents' perspectives on their young people's transition with psoriasis through adolescence.Results: Parents initially perceived psoriasis mainly a physical and treatment-related burden and not until late realized its socio-emotional impact. They eventually found themselves balancing between declining treatment due to fear of side effects and acknowledging the impact on their young people's quality of life and their desire for effective treatment.Conclusions: Caring for young people with psoriasis is a stressful process involving experimental learning to understand and manage the complexity of psoriasis and its impact on adolescents' emotional and social life. Future research should consider integration of shared decision-making and self-management support interventions in routine daily care as focus points.

Experience of Being Young With Psoriasis: Self-Management Support Needs.

Psoriasis is a long-term condition with a possibly cumulative life course impairment. Young people struggle to minimize its effects on appearance and functioning. To date, the self-management needs of adolescents suffering from psoriasis have been underinvestigated. Using focus groups and individual interviews, we present an interpretive description of young people's experiences of living with psoriasis, the challenges they face, and the support they need to relieve suffering and come to terms with their condition. This process is characterized by loneliness, the self-imposition of limitations, and the lack of personalized knowledge and communication skills to manage the impact of disease and society's reactions. Our study provides insight into needs of early interventions tailored to address condition, role, and emotional management, involving parent education, peer support, storytelling, and roles for professionals. We argue that further research should involve young people, their parents, and professionals in the development and evaluation of interventions.

Association Between Changes in Coronary Artery Disease Progression and Treatment With Biologic Agents for Severe Psoriasis.

Importance: Inflammatory pathways of psoriasis share similarities with the mechanisms identified in atherosclerosis, and the association between psoriasis and cardiovascular disease due to accelerated coronary artery disease is well established. The effect of anti-inflammatory drugs on the development of coronary atherosclerosis remains essentially unknown. Objective: To investigate the association of biological therapy with changes in coronary artery disease progression, measured by repeated coronary computed tomography (CT). Design, Setting, and Participants: This single-center prospective, controlled, observer-blinded clinical study at a tertiary dermatology university hospital clinic enrolled patients with severe psoriasis initiating biological therapy and matched controls not receiving systemic therapy from April 11, 2011, through June 30, 2014. Interventions: Biological therapy approved for psoriasis (adalimumab, etanercept, infliximab, ustekinumab) with the possibility to switch between treatments to ensure tight control of inflammation. Main Outcomes and Measures: Patients underwent noncontrast coronary artery calcium (CAC) CT and contrast-enhanced coronary CT angiography at baseline and after 13 months of follow-up. Changes in CAC score, number of coronary plaques, severity of narrowing, composition, and vessel wall volume were measured. Results: There were 28 treated patients (mean [SD] age, 49.2 [10.2] years; 71% men; mean [SD] Psoriasis Area Severity Index [PASI], 15.4 [4.3]) and 28 controls (mean [SD] age, 52.8 [10.6] years; 71% men; mean [SD] PASI, 12.4 [3.9]). The CAC scores remained stable in the intervention group (mean [SD] yearly CAC change, -16 [56]; P = .15) and progressed in the control group (14 [29]; P = .02) (intervention vs controls: P = .02). The number of segments with luminal abnormalities remained unchanged in both groups. The severity of luminal narrowing in the diseased segments was unchanged in the intervention group (Wilcoxon W = 76, n = 483, P = .39) but increased at follow-up in the control group (Wilcoxon W = 281, n = 414, P = .02). Automated vessel wall volume index remained unchanged from baseline to follow-up in the intervention group (mean [SD] baseline, 7.1 [1.5], follow-up, 7.1 [1.7]; P = .91), while controls demonstrated statistically nonsignificant progression (baseline, 8.3 [1.6], follow-up, 8.9 [2.2]; P = .06). Conclusions and Relevance: Clinically effective treatment with biologic agents was associated with reduced coronary artery disease progression in patients with severe psoriasis. These findings support a beneficial effect of biologic anti-inflammatory agents in preventing cardiovascular disease progression in addition to disease control in inflammatory diseases.

Interleukin 20 regulates dendritic cell migration and expression of co-stimulatory molecules.

BACKGROUND: Psoriasis is an inflammatory disease characterized by leukocyte skin infiltration. Interestingly, recent works suggest that the migration of dendritic cells (DCs) is abnormal in psoriatic skin. DCs have significant role in regulating the function of T lymphocytes, at least in part influenced by the local environment of cytokines. In psoriatic skin lesions the expression of IL-20 is highly up-regulated. It is unclear if this cytokine has any influence on DCs. METHODS: Here, we investigated the influence of IL-20 in monocyte-derived dendritic cell (MDDCs) in vitro. This work addressed IL-20 effects on DC maturation, receptor expression and signaling. By use of extra cellular matrix components mimicking the skin environment, we also studied the functional effects of IL-20 on the chemotactic migration of DCs. Based on the recent finding that CD18 integrin are shed during migration of myeloid leukocytes, the concentration of these adhesion molecules was measured in MDDCs culture supernatants post migration. RESULTS: Following stimulation with IL-20, immature human MDDCs enhanced the expression of the co-stimulatory molecule CD86, further enabling activation of the p38 MAPK, but not the STAT3, pathway. IL-20 increased the migration of MDDCs in a biphasic response narrowly controlled by the interleukin concentration. A concomitant change in the shedding of CD18 integrins suggested that these adhesion molecules play a role in the migration of the MDDCs through the extracellular matrix layer. CONCLUSION: Taken together, our findings points to a possible, yet subtle, role of IL-20 in DCs migration. The biphasic response suggests that the aberrant IL-20 expression in psoriasis impedes DC migration, which could be a part of the processes that precipitates the dysregulated inflammatory response associated with this disease.

Increased Prevalence of Coronary Artery Disease in Severe Psoriasis and Severe Atopic Dermatitis.

BACKGROUND: Psoriasis and atopic dermatitis (AD) are immuno-inflammatory diseases that can result in lifelong systemic inflammation. Unlike AD, psoriasis has been associated with cardiovascular disease. The aim of this study was to examine the prevalence, severity, and subtype of coronary artery disease (CAD) in psoriasis and AD patients without known cardiovascular disease. METHODS: Consecutively enrolled patients (psoriasis n = 58, AD n = 31) and retrospectively matched controls (n = 33) were examined using cardiac computed tomography angiography (CCTA) and assessed using an 18-segment model of the coronary tree. RESULTS: The prevalence of a coronary artery calcium score >0 was 29.8% in psoriasis and 45.2% in AD, vs 15.2% in controls (P = .09 and P = .01, respectively). More patients with psoriasis had a coronary artery calcium score ≥100 (psoriasis 19.3%, controls 2.9%; P = .02). CCTA showed the presence of plaques in 38.2% of psoriasis patients and 48.1% of AD patients, vs 21.2% of controls (P = .08 and P = .03, respectively). Psoriasis was associated with an increased prevalence of significant coronary stenosis (stenosis >70%) (psoriasis 14.6%, controls 0%; P = .02) and 3-vessel coronary affection or left main artery disease (psoriasis 20%, controls 3%; P = .02), whereas AD was associated with mild (AD 40.7%, controls 9.1%; P = .005) single-vessel affection. CONCLUSIONS: These findings suggest that psoriasis and AD are associated with an increased prevalence of CAD. Patients with psoriasis have an increased prevalence of severe CAD.

Unmet needs in the treatment of psoriasis.

Biologics have greatly improved the treatment of moderate-to-severe plaque psoriasis, as most patients are now able to achieve an initial improvement of 75% in the Psoriasis Area and Severity Index. However, only ∼20%-57% reach a 90% improvement in this measurement and responses may be lost over time. In addition, there are potential safety issues as TNF-inhibitor biologics have been associated with infections or non-melanoma skin malignancies. Here we review unmet needs with current therapies for psoriasis. We researched the medical literature to discuss new therapies in development and assess their potential to meet these needs. Several new classes of anti-psoriatic drugs are currently undergoing clinical development and potential improvements with these new therapies include attaining earlier and higher-level responses that are durable, more specific targeting of cytokines involved directly in psoriatic inflammation, and new therapies offering convenient administration. Additionally, based on results from clinical trials evaluating these new agents, it may be possible to find predictive markers that identify patients best treated with certain drug classes, those prone to lose treatment responses and patients who can discontinue treatment and remain in remission. It remains to be determined whether the promising results seen in early studies of therapies in development for psoriasis will translate into actual improvements over currently available treatment options.

Interleukin 20 protein locates to distinct mononuclear cells in psoriatic skin.

We previously demonstrated that mRNA for the pro-inflammatory cytokine interleukin 20 (IL-20) is expressed in suprapapillary keratinocytes of lesional psoriatic skin (LS). Here, we describe the distribution of IL-20 protein and the identity of the IL-20-positive cells in LS. We found that the main part of IL-20 immunoreactivity is present in mononuclear cells of the dermal papillae, and that the IL-20-positive cells located in the papillae were langerin+, CD1a+, CD4+ and CD303+. These cells might be immature dendritic cell. In situ hybridization for IL-20 mRNA on non-LS, ex vivo stimulated with IL-1ß revealed a colocalization between IL-20 mRNA and the keratinocyte marker CK14. No IL-20 mRNA was detected in the dermal mononuclear cells. Our results suggest that IL-20 is produced by keratinocytes, released into the epidermis and then possibly taken up by papillary mononuclear cells. Our study supports that IL-20 is involved in the pathogenesis of psoriasis.

Implementing best practice in psoriasis: a Nordic expert group consensus.

In the absence of Nordic-wide guidelines on the best practice management of psoriasis, this paper aims to provide Nordic recommendations for treatment goals, evaluation of quality of life impact and assessment/management of co-morbidities. This Delphi approach consisted of telephone interviews, local Nordic face-to-face meetings, and a Nordic-wide meeting, in which questions on treatment goals, quality of life impact and assessment/management of co-morbidities were posed to 17 dermatologists with psoriasis-treatment experience to gain consensus (≥ 90% agreement). The dermatologists agreed on the individualisation of treatment goals using Psoriasis Area and Severity Index and Dermatology Life Quality Index, which should be measured at the same frequency. Training of healthcare professionals on the use of these tools and psychological assessments were considered important, along with the referral of psoriasis patients with cardio-metabolic risk factors to their general practitioner. In order to achieve the best practice management of psoriasis, Nordic dermatologists should be trained and adhere to these recommendations in conjunction with available treatment guidelines.

National and multinational guidelines in Europe: results from an online survey on awareness of different national and European psoriasis guidelines.

Guidelines can be developed on a national or multinational level. There are discussions concerning the relevance of different guidelines at different regional levels. Guidelines' evaluation can be approached by looking at the items "awareness", "agreement", "adoption" and "adherence". To assess the awareness of national and European (EDF/EADV) guidelines as a means of guidelines' evaluation. Online survey in five selected European countries (Germany [D], Spain [E], France [F], Italy [I], and the United Kingdom [UK]) among 257 dermatologists assessing awareness of different guidelines (European [EDF/EADV], German, Spanish, French, British). Participants were volunteers registered with a field market research company database. Mean awareness of EDF/EADV guidelines in all countries was 54 %, with lower results in the UK (33 %) and Germany (37 %) and higher awareness in Spain (63 %) and Italy (79 %). Awareness of the national guidelines was very high within the respective countries (mean 92 %). The European guidelines where always the best known guidelines after the respective national guidelines. The most important tools for dissemination of all guidelines were the original publication (63 %) and scientific presentations (46 %).This study identified widespread interest in guidelines as assessed by the grade of awareness. Awareness of European guidelines was higher in countries with late development of national guidelines (i.e. Spain and Italy) compared to countries with early development of own national guidelines such as Germany and the UK. National guidelines can reach almost complete awareness within their respective countries. The original publication is still the most important dissemination tool for guidelines.

Studies of Jak/STAT3 expression and signalling in psoriasis identifies STAT3-Ser727 phosphorylation as a modulator of transcriptional activity.

Jak/Tyk proteins have recently aroused as possible therapeutic targets for the treatment of psoriasis. In psoriasis, these proteins signal through STAT molecules including STAT3, and STAT3 expression and activation has been shown augmented in psoriatic lesions. Here, we characterized the expression of Jak/Tyk proteins in lesional compared with non-lesional psoriatic skin. Jak1, Jak2 mRNA and protein and Tyk2 mRNA appeared to be downregulated, whereas Jak3 mRNA expression was increased. Moreover, STAT3 expression and activation was examined in psoriasis. STAT3 is activated at two phosphorylation sites: Tyr705 and Ser727. Both phosphorylation sites were phosphorylated in lesional psoriatic skin. The activation of STAT3 by Jak/Tyk proteins was studied in cultured normal human keratinocytes. Tyr705 phosphorylation was induced by IL-6 and IL-20 in a Jak2-dependent manner, and moreover, phosphorylation of Tyr705 produced a strong increase in STAT3 transcriptional activity. TNFα, 12-O-Tetradecanoylphorbol 13-acetate (TPA) and UVB irradiation induced Ser727 phosphorylation of STAT3 in an ERK1/2- and p38 MAPK-dependent manner, which resulted in a modulatory effect on STAT3 transcriptional activity. Our results demonstrate how different signalling pathways can integrate and lead to regulation of STAT3 transcriptional activity.

Long-term management of scalp psoriasis: perspectives from the International Psoriasis Council.

The scalp is a well-known predilection site for psoriasis. Epidemiological data on the various manifestations of scalp psoriasis as well as on its therapeutic management are sparse. The understanding of the natural course of scalp psoriasis is relevant for its therapeutic management. In over 25% of patients, scalp psoriasis is the first signal of the psoriatic condition. Nevertheless, few of the therapies currently used for the treatment of scalp psoriasis have been evaluated for efficacy in the setting of well-designed, well-controlled clinical studies. The lack of comparative data impedes the interpretation of the results from studies of scalp psoriasis. Long-term studies of the efficacy and safety of scalp treatments are lacking. Moreover, clinical studies generally do not incorporate quality of life impact or mechanisms to enhance adherence thus hindering the optimal management of the patient over the long-term. Consequently, this report will evaluate the available data and the associated factors to be considered in the development of a treatment paradigm for the long-term management of the scalp psoriasis patient.

IL-20, IL-21 and p40: potential biomarkers of treatment response for ustekinumab.

Although biological drugs in psoriasis treatment show clinical efficacy, there are still a proportion of patients in whom little treatment response is obtained. The aim of this study was to identify molecular biomarkers for treatment response and to investigate the molecular effects of ustekinumab treatment of psoriasis. The mRNA expression of various genes in skin biopsies was analysed by quantitative polymerase chain reaction (qPCR). At baseline, there was no significant clinical difference be-tween responders and non-responders. Ten patients were clinical responders, with a mean baseline Psoriasis Area and Severity Index (PASI) score of 15.4 and a mean percentage improvement of 89.6%. No significant reduction in PASI during treatment was seen among the 5 non-responders. In the responder group, ustekinumab therapy reduced the mRNA expression of the majority of the studied genes in lesional psoriatic skin. IL-20, IL-21 and p40 mRNA expression in lesional psoriatic skin at baseline were significantly upregulated by factors of 2.7, 2.4 and 2.3, respectively, among non-responders compared with responders. The mRNA levels of p40, IL-20 and IL-21 at baseline may serve as potential predictors of treatment response to ustekinumab treatment.

Treatment patterns, treatment satisfaction, severity of disease problems, and quality of life in patients with psoriasis in three Nordic countries.

Biological drugs are expensive, but can reduce symptoms and increase quality of life for patients with psoriasis. The aim of this study was to examine quality of life, disease severity and treatment satisfaction in Danish, Finnish and Swedish patients with psoriasis. Based on 12 months' data from patient surveys and chart reviews, 3 treatment groups were identified: topical, systemic and/or biological <12 months, and biological for 12 months. Regression analyses were performed to investigate influence on treatment satisfaction, disease problems and quality of life. Patients treated with biological drugs for 12 months showed the highest treatment satisfaction and the lowest Dermatology Life Quality Index score. A number of patients with topical treatment reported low quality of life, severe or very severe disease problems, and low treatment satisfaction. Some patients with psoriasis may be under-treated and might benefit from a more aggressive treatment strategy. It is important, however, that resource utilization is optimized and patients are not treated with more advanced agents than necessary.

Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment.

These national clinical guidelines outlining the screening, prophylaxis and critical information required prior to initiating anti-TNF-alpha treatment have been approved by the Danish Society for Gastroenterology. Anti-TNF-alpha therapy is widely used in gastroenterology (for inflammatory bowel disease), rheumatology (for rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies) and dermatology (for psoriasis). With this background, the Danish Society for Gastroenterology established a group of experts to assess evidence for actions recommended before treatment with anti-TNF-alpha agents. Screening should take place for both active tuberculosis and latent tuberculosis. Screening must evaluate the risk of hepatitis B exposure/infection and that of other viral infections such as human immunodeficiency virus (HIV) and varicella zoster virus (VZV). The assessment should include a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X-rays and laboratory tests, including an interferon gamma release assay, a hepatitis B test, an HIV test and, when prior VZV infection is uncertain, a VZV antibody test. Prophylaxis: Isoniazid should be administered in cases of suspected latent TB infection. Antiviral treatment is recommended in HBsAg-positive patients at the start of anti-TNF-alpha treatment. Before anti-TNF-alpha therapy, vaccination with 23-valent pneumococcal vaccine is recommended, and HBV vaccination may be considered in seronegative patients. Annual vaccination against seasonal influenza is recommended. Human papilloma virus vaccination should be administered in accordance with the guidelines of the National Board of Health of Denmark. In patients without a prior VZV infection, VZV vaccination may be considered. Information for patients: Anti-TNF-alpha treatment results in a generally increased risk of infection and latent tuberculosis flare-up. Women are advised to comply with the national guidelines for screening for cervical cancer, and their HPV immunisation status should be clarified. An increased risk of lymphoma with biological therapy in combination with thiopurines should be mentioned. Patients are advised to seek medical advice in case of herpes zoster infection.

Atopic dermatitis and risk of skin cancer: a Danish nationwide cohort study (1977-2006).

BACKGROUND: Recent data suggest a reduced risk of malignant melanoma (MM) among atopic dermatitis (AD) patients, but an increased risk of other skin cancers (including basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]). OBJECTIVE: We examined the association between AD and skin cancers in a large cohort study in Denmark from 1977 through 2006. METHODS: Our cohort consisted of 31 330 AD patients recorded in the Danish National Patient Registry, including AD patients admitted to hospitals and specialized outpatient clinics. Linkage to the Danish Cancer Registry allowed ascertainment of skin cancers. We calculated standardized incidence ratios (SIRs) and associated 95% confidence intervals (CIs) by comparing the incidence rate of skin cancers among AD patients with that among the general Danish population. RESULTS: The overall observed number of MM cases among AD patients was 12, with 21 expected, yielding a SIR of 0.59 (95% CI 0.30, 1.02), with the most pronounced protective effect among AD patients with more than 5 years of follow-up (SIR = 0.46; 95% CI 0.19, 0.95). The corresponding SIRs for BCC and SCC were increased among AD patients (1.41 [95% CI 1.07, 1.83] and 2.48 [95% CI 1.00, 5.11], respectively). CONCLUSIONS: Our findings support an inverse association between AD and MM, but an increased risk of BCC and SCC among AD patients.

Evaluation of recurrence after photodynamic therapy with topical methylaminolaevulinate for 157 basal cell carcinomas in 90 patients.

The aim of this study was to evaluate the effect of photodynamic therapy with topical methylaminolevulinate for the treatment of basal cell carcinomas in a single dermatological department. Ninety patients (34.4% men and 65.6% women) with a total of 157 basal cell carcinomas (111 superficial, 40 nodular, 6 unknown) were treated. Primary endpoint was clinically observed recurrence verified by biopsy 3, 6 and 12 months after treatment, then once a year. Estimated patient recurrence rates were 7% at 3 months, 19% at 6 months, 27% at 12 months and 31% at 24 months. Patients aged over 60 years had significantly higher estimated recurrence rates compared with patients aged 60 years or under (at 12 months, 35% vs. 19%, p?=?0.01). Estimated recurrence rates for tumours was 4% at 3 months, 11% at 6 months, 16% at 12 months and 19% at 24 months. There were significantly higher estimated recurrence rates for nodular basal cell carcinomas compared with superficial basal cell carcinomas (at 12 months, 28% vs. 13%, p?=?0.008). In conclusion, photodynamic therapy is only appropriate for treatment of superficial basal cell carcinoma, and, age above 60 years and histology showing nodular basal cell carcinoma are independent risk factors for developing a recurrent basal cell carcinoma.

CCL27 expression is regulated by both p38 MAPK and IKKß signalling pathways.

The skin-specific chemokine CCL27 is believed to play a pivotal role in establishing the inflammatory infiltrate characteristic for common inflammatory skin diseases. Through binding to the chemokine receptor 10 (CCR10), CCL27 mediates inflammation by promoting lymphocyte migration into the skin. Little is known about the regulation of CCL27 gene expression. The purpose of our study was to investigate the regulation of the IL-1ß-induced CCL27 gene expression in normal human keratinocytes (NHEK). Preincubation of NHEK with the inhibitory κB (IκB) kinase (IKK) inhibitor, SC-514, or the p38 mitogen-activated protein kinase (MAPK) inhibitor, SB202190, revealed a profound reduction in both CCL27 mRNA and CCL27 protein expression indicating the significance of these pathways in the regulation of CCL27 expression. Furthermore, the impact of inhibitors of mitogen- and stress-activated kinase 1 (MSK1) or the mitogen-activated protein kinase-interacting kinases (Mnk1+2), downstream kinases of p38 MAPK, on IL-1ß-induced CCL27 expression in NHEK were investigated. We identified seven NF-κB binding elements upstream from the CCL27 gene start codon using electrophoretic mobility shift assay (EMSA). Supershift analyses demonstrated the involvement of the p50/p65 NF-κB heterodimer. We conclude that IL-1ß-induced CCL27 gene expression in NHEK is regulated through the p38 MAPK/MSK1/Mnk1+2 as well as the IKKß/NF-κB signalling pathways.

Kinetics and differential expression of the skin-related chemokines CCL27 and CCL17 in psoriasis, atopic dermatitis and allergic contact dermatitis.

CCL27 and CCL17 are chemokines believed to be involved in the process of establishing the inflammatory infiltrate, characteristic for the various inflammatory skin diseases. The skin-specific CCL27 binds the chemokine receptor-10 (CCR10), and CCL17 is a chemokine receptor-4 (CCR4) ligand. The purpose of our study was to characterize the expression of CCL27 and CCL17 in the inflammatory skin diseases: psoriasis, atopic dermatitis (AD) and acute allergic contact dermatitis (ACD) induced in nickel-sensitive individuals. Surprisingly, our studies revealed a markedly decreased CCL27 mRNA and protein expression in psoriatic lesions compared with non-lesional psoriatic skin. A minor CCL17 mRNA increase was measured in lesional psoriatic skin. No alterations were found in AD. In ACD, we found a pronounced (90-fold) raise in CCL17 mRNA and a 50-fold increase in CCL17 protein compared with normal skin. A kinetic ACD study of CCL17 expression showed the highest mean value 24 h after hapten application. Furthermore, we found the mRNA levels of CCR10 and CCR4 paralleling the results of their corresponding ligands. Overall, our principal findings were a distinct decrease in CCL27 in lesional psoriatic skin and a marked upregulation of CCL17 in ACD. These findings underscore the differential cutaneous T-cell recruitment in different inflammatory diseases.