The importance of diet in psoriasis.

The impact of diet on psoriasis is not well studied but it is of interest to many patients. A hypocaloric diet with corresponding weight loss can reduce psoriasis severity in overweight or obese patients and should be considered an important supplement to conventional therapy, as argued in this review. Gluten-free diet might improve severity of psoriasis in patients with coeliac disease or merely presence of coeliac-specific antibodies. Mediterranean diet might also be beneficial. Overall, studies do not support a beneficial effect of micronutrient supplements (i.e., vitamin D, selenium, vitamin B12) in patients with normal serum levels.

Use of systemic and biological therapy in patients with moderate-to-severe psoriasis.

BACKGROUND: Patients with moderate-to-severe psoriasis are candidates for systemic treatment, but it is unknown how many receive such therapy at a national level in Denmark. OBJECTIVES: We aimed to determine the prevalence of conventional systemic therapy use in patients with moderate-to-severe psoriasis and, further, to investigate the time to discontinuation of conventional systemic therapy and initiation of biological therapy among biologic-naïve patients. METHODS: This registry-based study identified a cohort of patients with psoriasis in Denmark. We estimated the prevalence of moderate-to-severe psoriasis at a national level using registry data. Inverse probability weighting was used to mitigate potential selection bias in the prevalence estimate of moderate-to-severe psoriasis. Analyses were then performed on the weighted cohort. RESULTS: Of patients with psoriasis in Denmark, 10.9% were estimated to have moderate-to-severe psoriasis, of whom 62.3% received either conventional systemic or biological therapy, meaning 37.7% who were considered candidates for systemic therapy did not receive any systemic treatment. The study demonstrated that, comparing previous time periods with more recent years: (i) time on conventional systemic therapy for patients with moderate-to-severe psoriasis has become shorter, with a median (interquartile range) of 3.0 years (0.6-10.0) in 1985-1994 vs. 0.6 years (0.3-2.0) in 2014-2018; (ii) more patients initiated biologics as second-line therapy, with 69.5% in 2010-2013 vs. 71.2% in 2014-2018; and (iii) the median time from initiation of systemic therapy to initiation of biological therapy decreased from 13.3 years (11.5-16.8) in 2010-2013 to 1.9 years (1.7-2.4) in 2014-2018. CONCLUSIONS: This study found that nearly 37.7% of Danish patients with moderate-to-severe psoriasis do not receive systemic treatment even though they would qualify for this. Furthermore, for patients treated with conventional systemics, drug survival decreased during the observation period.

Multivariable Predictive Models to Identify the Optimal Biologic Therapy for Treatment of Patients With Psoriasis at the Individual Level.

Importance: Identifying the optimal long-term biologic therapy for patients with psoriasis is often done through trial and error. Objective: To identify the optimal biologic therapy for individual patients with psoriasis using predictive statistical and machine learning models. Design, Setting, and Participants: This population-based cohort study used data from Danish nationwide registries, primarily DERMBIO, and included adult patients treated for moderate-to-severe psoriasis with biologics. Data were processed and analyzed between spring 2021 and spring 2022. Main Outcomes and Measures: Patient clusters of clinical relevance were identified and their success rates estimated for each drug. Furthermore, predictive prognostic models to identify optimal biologic treatment at the individual level based on data from nationwide registries were evaluated. Results: Assuming a success criterion of 3 years of sustained treatment, this study included 2034 patients with a total of 3452 treatment series. Most treatment series involved male patients (2147 [62.2%]) originating from Denmark (3190 [92.4%]), and 2414 (69.9%) had finished an education longer than primary school. The average ages were 24.9 years at psoriasis diagnosis and 45.5 years at initiation of biologic therapy. Gradient-boosted decision trees and logistic regression were able to predict a specific cytokine target (eg, interleukin-17 inhibition) associated with a successful treatment with accuracies of 63.6% and 59.2%, and top 2 accuracies of 95.9% and 93.9%. When predicting specific drugs resulting in success, gradient boost and logistic regression had accuracies of 48.5% and 44.4%, top 2 accuracies of 77.6% and 75.9%, and top 3 accuracies of 89.9% and 89.0%. Conclusions and Relevance: Of the treatment prediction models used in this cohort study of patients with psoriasis, gradient-boosted decision trees performed significantly better than logistic regression when predicting specific biologic therapy (by drug as well as target) leading to a treatment duration of at least 3 years without discontinuation. Predicting the optimal biologic could benefit patients and clinicians by minimizing the number of failed treatment attempts.

Increase in Vitamin D but not Regulatory T Cells following Ultraviolet B Phototherapy of Patients with Atopic Dermatitis.

This study investigated serum 25-hydroxyvitamin D (25(OH)D) concentrations and circulating regulatory T cells in patients with atopic dermatitis receiving narrow-band ultraviolet B (nbUVB) phototherapy. Thirty adult patients with atopic dermatitis were included. Blood samples were collected at baseline and at weeks 2 and 4 of nbUVB phototherapy. Skin biopsies were taken at baseline and at week 4. Serum 25(OH)D concentrations increased significantly following nbUVB phototherapy (estimate of change from baseline to week 2: 32.00 nmol/l, confidence interval (CI) 20.48-43.52, p < 0.0001, n = 25; and from baseline to week 4: 50.30 nmol/l, CI 37.28-63.33, p < 0.0001, n = 18). This increase was independent of the filaggrin gene FLG loss-of-function mutation status. Flow cytometry showed no significant change in regulatory T cells or cytokine profiles of T cells in blood. Real-time quantitative PCR showed no change in skin cytokine levels. In conclusion, nbUVB phototherapy was associated with increased serum 25(OH)D concentrations, but not changes in circulating regulatory T cells in patients with atopic dermatitis.

Incidence and Prevalence of Psoriasis in Denmark.

The incidence and temporal trends of psoriasis in Denmark between 2003 and 2012 were examined. There was a female predominance ranging between 50.0% (2007) and 55.4% (2009), and the mean age at time of diagnosis was 47.7-58.7 years. A total of 126,055 patients with psoriasis (prevalence 2.2%) were identified. Incidence rates of psoriasis (per 100,000 person years) ranged from 107.5 in 2005 to a peak incidence of 199.5 in 2010. Incidence rates were higher for women, and patients aged 60-69 years, respectively. Use of systemic non-biologic agents, i.e. methotrexate, cyclosporine, retinoids, or psoralen plus ultraviolet A (PUVA) increased over the study course, and were used in 15.0% of all patients. Biologic agents (efalizumab, etanercept, infliximab, adalimumab, or ustekinumab) were utilized in 2.7% of patients. On a national level, incidence of psoriasis fluctuated during the 10-year study course. The relationship between psoriasis incidence and age appeared to be relatively linear, and disease prevalence was comparable to that in other European countries.

The effect of epidermal levels of urocanic acid on 25-hydroxyvitamin D synthesis and inflammatory mediators upon narrowband UVB irradiation.

BACKGROUND/PURPOSE: Urocanic acid (UCA) absorbs ultraviolet (UV)B radiation in the epidermis which may interfere with phototherapy. Therefore, the influence of individual levels of UCA on immune reactivity and vitamin D synthesis induced by narrowband UVB radiation was assessed. METHODS: Twenty-eight subjects with irritant contact dermatitis of the hands were irradiated with suberythemal doses of narrowband UVB radiation on their unaffected lower forearms on three consecutive days. Stratum corneum tape strips and epidermal interstitial fluid (ISF) as well as blood samples were analyzed. RESULTS: Narrowband UVB irradiation led to the conversion of trans-UCA into its cis-isomer in the epidermis. The observed increase in 25-hydroxyvitamin D serum concentrations was inversely correlated with the baseline levels of trans-UCA. Furthermore, UVB irradiation induced significant changes in the levels of CXCL10/IP-10, CCL2/MCP-1, CCL4/MIP-1ß, and the IL-1RA/IL-1α ratio. The levels of IL-1α and CXCL9/MIG showed a trend toward increase. The changes in the levels of inflammatory and immunomodulatory mediators did not depend on baseline levels of trans-UCA. CONCLUSION: The results suggest that epidermal levels of trans-UCA affect vitamin D synthesis, but not cutaneous immune reactivity upon repeated exposure to suberythemal doses of narrowband UVB radiation. However, this requires further exploration.

Neonatal risk factors of atopic dermatitis in Denmark - Results from a nationwide register-based study.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a multifactorial etiopathogenesis. Studies have suggested that several perinatal factors may influence the risk of AD in early childhood. We investigated possible neonatal risk factors such as jaundice, blue light phototherapy, birthweight, gestational age at birth, and season of birth on the risk of developing AD in the first 5 years of life. MATERIALS & METHODS: Data were collected through Danish nationwide administrative registers. All newborn children between 1997 and 2007 (n = 673,614) were included in the cohort. Incidence rate ratios (IRRs) were estimated with 95% confidence intervals (95% CIs) by multivariate Poisson regression analyses. RESULTS: We identified a total of 85,743 children with AD in the first 5 years of life. The risk of AD was slightly increased in children with neonatal jaundice (IRR 1.13 [95% CI 1.06-1.21]). Preterm birth was inversely associated with the risk of AD (IRR 0.74, [95% CI 0.68-0.81]) as well as low birthweight (IRR 0.68, [95% CI 0.61-0.75]). Children born in fall and winter seasons had an increased risk of AD compared to spring and summer. No association between neonatal blue light therapy and the risk of AD was found. CONCLUSIONS: Low birthweight and preterm birth were inversely associated with AD, while neonatal jaundice and cold seasons of birth were associated with an increased risk of AD.

Risk of Multiple Sclerosis in Patients with Psoriasis: A Danish Nationwide Cohort Study.

Psoriasis and multiple sclerosis (MS) are inflammatory disorders with similarities in genetic risk variants and inflammatory pathways. Limited evidence is available on the relationship between the two diseases. We therefore investigated the risk of incident (new-onset) MS in patients with mild and severe psoriasis, respectively. All Danish citizens aged ≥ 18 years from 1 January 1997 to 31 December 2011 were identified by linkage of nationwide registries at the individual level. We estimated incidence rate ratios (IRRs) adjusted for age, gender, socioeconomic status, smoking, medication, comorbidity, and UV phototherapy by Poisson regression. There were 58,628 and 9,952 cases of mild and severe psoriasis, respectively, and 9,713 cases of MS. Incidence rates of MS per 10,000 person-years for the reference population, mild psoriasis, and severe psoriasis were 1.78, 3.22, and 4.55, respectively. Adjusted IRRs of MS were 1.84 (95% confidence interval [CI], 1.46-2.30) and 2.61 (95% CI, 1.44-4.74) in mild and severe psoriasis, respectively. Similar results were observed when adjustment for family history of MS was included in the analyses. Psoriasis may confer a disease severity-dependent risk of MS. Further studies are warranted to establish the mechanisms underlying this relationship and its potential clinical consequences.

Treating Psoriasis During Pregnancy: Safety and Efficacy of Treatments.

Psoriasis is a chronic inflammatory disease with a well-documented negative effect on the quality of life of affected patients. Psoriasis often occurs in the reproductive years, during which the issue of pregnancy needs to be addressed. The course of psoriasis during pregnancy is unpredictable, and many patients face the challenge of needing treatment during pregnancy. In this review we provide an overview of the key considerations for managing psoriasis in pregnant women, covering the potential effects of active psoriasis and co-morbid conditions on the health of the mother and fetus, as well as the effects of psoriasis treatment options on the developing fetus. Although there are no robust data on the safety of systemic treatment of pregnant women, increasing evidence regarding the safety of cyclosporine (ciclosporin) treatment as well as anti-tumor necrosis factor-α is available and should be considered in pregnant women with moderate to severe psoriasis unresponsive to local corticosteroids and UVB light treatment.

miRNAs in inflammatory skin diseases and their clinical implications.

miRNAs are a class of non-coding RNA molecules that modulate gene expression post-transcriptionally. They have a major impact on several physiological and pathological cellular processes including modulation of the innate and the adaptive immune system. The role of miRNAs in skin biology is still incomplete; however, it is known that miRNAs are implicated in various cellular processes of both normal and diseased skin. Some miRNAs appear to be consistently deregulated in several different inflammatory skin diseases, including psoriasis and atopic dermatitis, indicating a common role in fundamental biological processes. The clinical implications of miRNAs are intriguing, both from a diagnostic and a therapeutic perspective. Accordingly, there is emerging evidence for the clinical potential of miRNAs as both biomarkers and possible therapeutic targets in skin diseases. Future studies will hopefully establish the biological significance of miRNAs in skin biology, paving the way for new miRNA-based diagnostic and therapeutic applications in dermatology.

Systemic combination treatment for psoriasis: a review.

Psoriasis is a chronic inflammatory skin disease, which affects approximately 2.6% of the population in Northern Europe and Scandinavia. In order to achieve disease control, combinations of systemic treatments are sometimes needed for variable time periods. However, no evidence-based guidelines exist for the use of systemic combination therapy. Therefore, our aim was to review the current literature on systemic anti-psoriatic combination regimens. We searched PubMed and identified 98 papers describing 116 studies (23 randomized) reporting on the effect of various systemic combination treatments. The most thoroughly investigated combination was retinoid and phototherapy. Further controlled research is needed to define the safest and most effective combination regimens.

Case-control study of gadodiamide-related nephrogenic systemic fibrosis.

BACKGROUND: Nephrogenic systemic fibrosis may be caused by gadolinium (Gd)-containing magnetic resonance imaging contrast agents. Most reported cases were associated with one particular agent, gadodiamide. Yet, unidentified cofactors might explain why only a minority of renal failure patients exposed to gadodiamide develop nephrogenic systemic fibrosis. METHODS: We conducted a case-control study of 19 histologically verified cases and 19 sex- and age-matched controls. All subjects had chronic renal failure when exposed to gadodiamide. Clinical, biochemical and pharmacological data were retrieved from medical records. RESULTS: Cases had been exposed to a mean gadodiamide dose of 0.29 mmol/kg (range 0.18-0.50) shortly before first signs of nephrogenic systemic fibrosis. Controls had been exposed to 0.28 mmol/kg (0.13-0.49). Cumulative gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls (0.41 vs 0.31 mmol/kg, P = 0.05) and among severe cases (n = 9) compared with non-severe cases (0.49 vs 0.33 mmol/kg, P = 0.02). Severe cases developed primarily among patients in regular haemodialysis therapy at exposure. Cases had higher serum concentrations of ionized calcium and phosphate than controls and tended to receive higher doses of epoietin-beta than controls at time of exposure. Severe cases were treated with higher doses of epoietin-beta than non-severe cases at exposure (10.8 vs 4.4 10(3) IU/week, P = 0.02). CONCLUSIONS: Increasing cumulative gadodiamide exposure, high-dose epoietin-beta treatment, and higher serum concentrations of ionized calcium and phosphate increase the risk of gadodiamide-related nephrogenic systemic fibrosis in renal failure patients. Severe cases seem to develop primarily among patients in regular haemodialysis therapy at exposure.