Summary
Background In the pathogenesis of psoriasis, proinflammatory T cells are strongly involved in the inflammatory process, where regulatory T‐cell (Treg) function is impaired.
Objectives As ...effective Treg function is associated with a numerical balance between Treg and effector T cells, we wondered whether Treg/T‐helper cell ratios may be associated with certain stages of the inflammatory process. We opted for the margin zone model as a dynamic approach.
Methods From nine patients with chronic plaque psoriasis, 3‐mm punch biopsies were obtained from the centre and margin of the lesion, perilesional skin and distant uninvolved skin. Skin biopsies of 10 healthy volunteers were included as a control. Samples were analysed using immunohistochemistry and immunofluorescence.
Results In the transition from symptomless to lesional skin, a significant increase of CD3+, CD4+ and Foxp3+ cells was found. In seven of nine patients the ratio of Treg (Foxp3+) vs. CD4+ T cells was higher in the distant uninvolved skin than in the perilesional and lesional skin. Interestingly, the Foxp3/CD4 ratio in the distant uninvolved skin was even higher than in the skin of healthy controls. Notably, we found that most of the interleukin (IL)‐17 expression was not related to CD4+ cells, but to mast cells.
Conclusions The relatively high Foxp3/CD4 ratio in symptomless skin of patients with psoriasis suggests an active immune controlling mechanism distant from the psoriatic plaque. In the margin and centre of the plaque the ratio appears skewed towards effector cells associated with inflammation. IL‐17, an important driver of the psoriatic process, is mostly related to mast cells, and only sporadically to T cells.
What’s already known about this topic?
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T‐helper cells play an important role in the pathogenesis of psoriasis.
What does this study add?
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The present study lends support for a critical role of the regulatory T cell (Treg) vs. T‐helper cell balance in the transition from symptomless to lesional psoriatic skin. Foxp3/CD4 ratios were higher in symptomless skin than in lesional psoriatic skin, and even higher than in healthy skin. This may suggest activated and functional immune controlling mechanisms in the skin of patients with psoriasis.
Background
Available literature on psoriasis and psoriatic arthritis (PsA) demonstrates a tremendous burden of disease and suggests underdiagnosis and undertreatment.
Objective
To obtain real‐world ...physician perspectives on the impact of psoriasis and PsA and its treatment on patients' daily lives, including perceptions of, and satisfaction with, current therapies.
Methods
The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) surveyed dermatologists (n = 391) and rheumatologists (n = 390) in North America (Canada and the United States) and Europe (France, Germany, Italy, Spain and United Kingdom).
Results
Dermatologists classified 20.3% and 25.7% of their patients as having severe psoriasis and severe PsA respectively; rheumatologists indicated that 48.4% of their PsA patients had active disease. Of the psoriasis patients complaining of joint pain, only 33.0% had a diagnosis of PsA. An impact on daily activities or social/emotional well‐being was recognized by 57.2% to 79.3% of physicians. In patients with moderate‐to‐severe psoriasis, dermatologists reported 74.9% were receiving topical therapy, 19.5% conventional oral therapy and 19.6% biologics. Dermatologists and rheumatologists reported similar rates of topical (≈45%) and biologic (≈30%) therapy utilization for their PsA patients; conventional oral therapy was more often prescribed by rheumatologists (63.4%) vs. dermatologists (35.2%). Reasons for not initiating or maintaining systemic therapies were related to concerns about long‐term safety, tolerability, efficacy and costs (biologics).
Conclusion
Physicians in North America and Europe caring for patients with psoriasis and PsA acknowledge unmet treatment needs, largely concerning long‐term safety/tolerability and efficacy of currently available therapies; evidence suggests underdiagnosis of PsA and undertreatment of psoriasis among dermatologists.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder that affects one or two individuals per 100,000. The disease is caused by an extended CAG repeat in exon 8 of ...the
gene and is characterized mostly by a profound loss of cerebellar Purkinje cells, leading to disturbances in coordination, balance, and gait. At present, no curative treatment is available for SCA1. However, increasing knowledge on the cellular and molecular mechanisms of SCA1 has led the way towards several therapeutic strategies that can potentially slow disease progression. SCA1 therapeutics can be classified as genetic, pharmacological, and cell replacement therapies. These different therapeutic strategies target either the (mutant)
RNA or the ataxin-1 protein, pathways that play an important role in downstream SCA1 disease mechanisms or which help restore cells that are lost due to SCA1 pathology. In this review, we will provide a summary of the different therapeutic strategies that are currently being investigated for SCA1.
Summary
Background
Balancing treatment decisions in frail older adults with nonmelanoma skin cancer (NMSC) can be challenging. Clinical practice guidelines (CPGs) could provide assistance.
Objectives
...To collect and prioritize items related to frail older adults with NMSC for integration into CPGs and to assess the current extent of this integration.
Methods
Items were collected and prioritized by a multidisciplinary working group (29 members) using a modified Delphi procedure and a five‐point Likert scale. To assess current integration of these items in CPGs, a systematic review was subsequently performed by two independent reviewers using five medical databases (PubMed, Embase, Cochrane Library, SUMsearch and Trip Database), websites of guideline developers/databases, and (inter)national dermatological societies.
Results
Prioritization of a final 13‐item list showed that ‘limited life expectancy’ (4·5 ± 0·9) and ‘treatment goals other than cure’ (4·4 ± 0·7) were most desired to be integrated into CPGs; both were included in six (46%) of the CPGs found (n = 13). Attention to ‘tumour characteristics’ and ‘comorbidities’ were included in CPGs most often (100% and 77%, respectively).
Conclusions
More attention to items related to frail older adults in NMSC CPGs is broadly desired, but CPG integration of these items is currently limited. More integration might stimulate more holistic, personalized and patient‐centred care in frail older adults.
What's already known about this topic?
Nonmelanoma skin cancer is common among the growing population of frail older adults worldwide.
Treatment decisions in frail older adults with nonmelanoma skin cancer can be challenging.
Clinical practice guidelines are intended to assist healthcare providers to optimize patient care in daily clinical practice, but balancing the extensiveness and specificity of clinical practice guidelines might be a challenge.
What does this study add?
More attention to several frailty‐related items in clinical practice guidelines on nonmelanoma skin cancer is broadly desired.
Integration of these items into current clinical practice guidelines on nonmelanoma skin cancer is limited.
More integration is expected to optimize current nonmelanoma skin cancer care and might stimulate more holistic, personalized and patient‐centred care in frail older adults.
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Video Commentary
Summary
Background
Evidence on the effectiveness and safety of short‐contact dithranol therapy in paediatric psoriasis is sparse and based only on retrospective data. The best results are achieved in ...a time‐consuming day‐care setting.
Objectives
To study prospectively the effectiveness and safety of short‐contact dithranol therapy in paediatric psoriasis. In addition, the effectiveness, safety, duration of treatment and number of visits between regular day care and day care with telemedicine were compared.
Methods
Data were collected from the prospective observational Child‐CAPTURE registry of children with psoriasis. Effectiveness was measured as the mean percentage improvement in Psoriasis Area and Severity Index (PASI). Safety was assessed by recording adverse events. The number of visits and duration of treatment were reported.
Results
For all patients a mean percentage reduction in PASI score of −69·3% was found, with no significant differences between regular day care and day care with telemedicine. The only adverse event reported was irritation of the skin. Neither the frequency of irritation during treatment nor the mean duration of treatment significantly differed between the two groups. Patients with telemedicine had significantly fewer visits.
Conclusions
This first prospective observational study demonstrates that short‐contact dithranol therapy in paediatric psoriasis is effective and safe. Regular day care and day care with telemedicine are equally effective. Telemedicine can be of additional value as it is less time consuming. We hope it will therefore make dithranol treatment appropriate for a larger number of children with psoriasis.
What's already known about this topic?
Dithranol is a proven effective treatment for psoriasis in adults, without known long‐term side‐effects; in children only retrospective studies have been performed.
The best results with short‐contact dithranol therapy are achieved when it is administered in a day care centre.
What does this study add?
In this first prospective observational study, short‐contact dithranol therapy was demonstrated to be effective and safe in daily clinical practice in paediatric psoriasis.
Short‐contact dithranol therapy by day care with telemedicine has extra advantages for children and parents as it is less time consuming.
Background
A considerable disease period often precedes initiation of a biologic in patients with psoriasis. Little is known about this important period in patients’ lives. Evaluation of this ...‘journey’ can reveal important insights and opportunities for physicians and healthcare decision makers.
Objectives
(i) To describe patient and treatment characteristics until the start of biologic treatment in patients with severe psoriasis, (ii) to assess shifts in early (2005–2009) versus established (2010–2015) biologics prescription periods, (iii) to assess changes in hospital/day care admissions before vs. after starting biologics.
Methods
Explorative, retrospective study on the treatment characteristics of the disease period until first biologic, presented with descriptive statistics of patients included in the BioCAPTURE registry. Journeys of 2005–2009 and 2010–2015 were compared with statistical tests to identify important shifts.
Results
Median TUS (time until conventional systemic) was 11.0 years and median TUB (time until biologic) was 18.9 years for all patients treated from 2005 to 2015. Most patients received three different conventional antipsoriatic systemic therapies. We noticed a small trend towards a shorter journey (TUB) with only two conventional systemic agents instead of three before initiating a biologic in later years (2010–2015, vs. 2005–2009). We also noticed a significant decrease in (day care) admissions comparing the two years before, versus the first two years after the start of a biologic treatment (17.7 vs. 8.6 admissions/100 follow‐up years, P < 0.001). Cyclosporine, intensive topical treatment (dithranol), retinoids and PUVA therapy lost popularity in recent years.
Conclusion
The ‘journey’ of patients with psoriasis towards a biologic is still long and characterized by many different treatments. Shifts towards fewer conventional drugs before biologic initiation and a clear decrease in hospital and day care admissions before vs. after a biologic are seen. Improvement of this journey, especially in young or recently diagnosed patients, can decrease negative influences on patients’ lives and reduce societal impact.
Summary
Background
Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral ...Janus kinase inhibitor that has been investigated in patients with moderate‐to‐severe chronic plaque psoriasis.
Objectives
To consider the benefits and risks of tofacitinib in patients with moderate‐to‐severe psoriasis.
Methods
Data were pooled from one phase II, four phase III and one long‐term extension study comprising 5204 patient‐years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of ‘clear’ or ‘almost clear’, ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure.
Results
Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients’ quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID.
Conclusions
Tofacitinib has a benefit–risk profile in moderate‐to‐severe psoriasis consistent with that of other systemic treatments.
What's already known about this topic?
Psoriasis is a chronic, systemic inflammatory disease, which has a significant impact on patients’ health‐related quality of life.
Although several existing psoriasis treatments are efficacious and well tolerated in many patients, some patients require treatment switching, and a proportion of patients remain untreated or undertreated.
Potential challenges to the use of existing therapies include safety issues and limited efficacy in some patients with conventional oral psoriasis treatments, inconvenience of topical treatments and the requirement for parenteral administration of biologics.
What does this study add?
Consistent efficacy and a safety profile consistent with that seen in rheumatoid arthritis, psoriatic arthritis and ulcerative colitis were demonstrated for oral tofacitinib in patients with moderate‐to‐severe psoriasis.
Tofacitinib has a benefit–risk profile in patients with moderate‐to‐severe psoriasis that is consistent with that of other systemic psoriasis treatments.
Linked Comment: Fleming. Br J Dermatol 2019; 180:13–14.
Plain language summary available online
Respond to this article
We systematically reviewed all available literature concerning the prevalence of onychomycosis in patients with nail psoriasis and the distribution of pathogens causing onychomycosis in this specific ...group of patients. Databases searched were Pubmed, EMBASE and the Cochrane Controlled Clinical Trial Register. All studies reporting on the prevalence of onychomycosis in nail psoriasis were obtained, and quality assessment was determined by the STrengthening the Reporting of OBservational studies in Epidemiology checklist. Literature search revealed 720 studies, of which 10 studies met the inclusion criteria. The major limitation of the review was the heterogeneity of the included studies, which prevented the possibility to conduct a meta analysis. However, the average prevalence of 18.0% of onychomycosis in psoriatic patients seems to be increased when compared with control groups and literature on healthy population, even though the ultimate evidence remains lacking. As in the literature hypothesized shift in causative agents from dermatophytes to yeasts and/or moulds could not be confirmed. The clinical consequence of the relatively high prevalence of onychomycosis in psoriasis may be a general advice to rule out onychomycosis or concomitant onychomycosis in these patients with (suspected) nail psoriasis. This advice is stressed by the relative simplicity of treating the contribution of onychomycosis in the nail dystrophy but also the fact that nail psoriasis mostly is treated by immunosuppressive drugs, like steroids, methotrexate or biologics which may aggravate mycotic nail infections.
Summary
Background
Psychosocial stress can be a risk factor for the maintenance and exacerbation of chronic inflammatory diseases, such as psoriasis and rheumatoid arthritis (RA).
Objectives
To gain ...insight into the specificity of the psychophysiological stress response during chronic inflammation, we assessed autonomic and neuroendocrine responses to stress in different chronic inflammatory diseases.
Methods
Thirty patients with psoriasis (nine women, mean age 58·5 years ± 12·4), 34 patients with RA (16 women, mean age 60·8 years ± 9·2) and 25 healthy controls (16 women, mean age 55·6 years ± 8·7) underwent a standardized psychosocial stress task (Trier Social Stress Test). Salivary levels of α‐amylase and cortisol and self‐reported tension levels were measured before and after the stress test.
Results
The cortisol response to stress was heightened in patients with psoriasis compared with patients with RA and healthy controls, whereas there were no differences in the autonomic and self‐reported measures.
Conclusions
The altered neuroendocrine stress response in patients with psoriasis suggests that stressful events might have different physiological consequences for specific patient groups with chronic inflammatory conditions, possibly adversely affecting disease status.
What's already known about this topic?
Psychological stress can be a risk factor for maintenance and exacerbation of chronic inflammatory conditions, such as psoriasis and rheumatoid arthritis (RA).
It is not yet fully known whether patients with various chronic inflammatory conditions show distinct physiological stress response patterns.
What does this study add?
This is the first study to compare the psychophysiological stress response of patients with psoriasis, patients with RA and healthy controls.
Patients with psoriasis show a heightened cortisol response to an experimentally induced real‐life stressor compared with patients with RA and controls.
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