The association between serum 25-hydroxyvitamin D levels and psoriasis in a large population-based cohort: a cross-sectional analysis of The Tromsø Study 2015-16.

BACKGROUND: Case-control studies indicate an association between lower serum 25-hydroxyvitamin D [25(OH)D] levels and psoriasis. Data from larger population-based cohorts including mild cases are sparse. OBJECTIVES: To investigate the association between 25(OH)D and psoriasis in a large population-based cohort, and assess possible effect modification by overweight. METHODS: Data from the Tromsø Study 2015-16 (Tromsø7), which included 19 520 participants from the general population aged 40-79 years, were subjected to a cross-sectional analysis. We assessed the shapes of the relationships between 25(OH)D and psoriasis using fractional polynomials. Odds ratios (ORs) for lifetime and active psoriasis were estimated using logistic regression. Adjusted models included month of blood sampling, body mass index (BMI), age and sex. Two-way and additive interaction between BMI and 25(OH)D were explored. RESULTS: From a total of 19 520 participants [10 203 women (52.3%); mean age 56.3 years (SD 10.4); mean 25[OH]D, 63.4 nmol L-1 (SD 21.9)], 2088 (10.7%) reported lifetime psoriasis and 1179 (6.0%) reported active psoriasis the past 12 months. There was no association between 25(OH)D and lifetime psoriasis [OR per 10 nmol L-1 increase in 25(OH)D 1.02, 95% confidence interval (CI) 0.99-1.04]. The relationship between 25(OH)D and active psoriasis was suggested to be nonlinear, but the model was not significant (P = 0.098). There was evidence for a superadditive effect (i.e. larger than the sum of the factors) of BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1 on the odds for active psoriasis (OR 1.92, 95% CI 1.18-3.12), but not for lifetime psoriasis (OR 1.41, 95% CI 0.93-2.15). There was no evidence for two-way interaction between BMI and 25(OH)D. CONCLUSIONS: This large population-based study found no significant relationship between 25(OH)D and psoriasis. The analysis may have been underpowered to detect a threshold effect in the lower 25(OH)D spectrum. Interaction analysis indicates that high BMI and vitamin D deficiency combined increase the odds of active psoriasis more than the sum of these factors, with an estimated 92% higher odds for active psoriasis in participants with BMI > 27.5 kg m-2 and 25(OH)D < 25 nmol L-1. Providing advice to prevent vitamin D deficiency may be considered in the follow-up of overweight patients with psoriasis.

MicroRNA profiling of psoriatic skin identifies 11 miRNAs associated with disease severity.

MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as central regulators of gene expression and powerful biomarkers of disease. Much is yet unknown about their role in psoriasis pathology. To globally characterize the miRNAome of psoriatic skin, skin biopsies were collected from psoriatic cases (n = 75) and non-psoriatic controls (n = 46) and RNA sequenced. Count data were meta-analysed with a previously published dataset (cases, n = 24, controls, n = 20), increasing the number of psoriatic cases fourfold from previously published studies. Differential gene expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell-specific analyses were performed. Across all contrasts, we identified 439 significantly differentially expressed miRNAs (DEMs), of which 85 were novel for psoriasis and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in the constitution of all skin in psoriasis. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including "thyroid hormone signalling," "insulin resistance" and various infectious diseases. Cell-specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells. This study provides the most comprehensive overview of the miRNAome in psoriatic skin to date and identifies a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.

Effect of Vitamin D Supplementation on Psoriasis Severity in Patients With Lower-Range Serum 25-Hydroxyvitamin D Levels: A Randomized Clinical Trial.

Importance: Topical vitamin D analogues are routine treatment for psoriasis, but the effect of oral supplementation has not been established. Objective: To examine the effect of vitamin D supplementation on psoriasis severity throughout the winter. Design, Setting, and Participants: This randomized, double-blind placebo-controlled clinical trial with 2 parallel groups was performed through 2 winter seasons (2017 to 2018 and 2018 to 2019). Randomization was computer generated. All participants, health care clinicians, and outcome assessors were masked to group assignment. Each participant was followed for 4 months. The presented analyses were conducted in May 2022. The trial was conducted at the clinical research unit of the University Hospital of North Norway (Tromsø; Norway). Adults from the general population in Tromsø with active plaque psoriasis and 25-hydroxyvitamin D (25[OH]D) levels of less than 24 ng/mL (to convert to nmol/L, multiply by 2.496) were included. Intervention: Vitamin D (cholecalciferol, 100 000 IU, loading dose, followed by 20 000 IU/week) or placebo for 4 months. Main outcomes and Measures: Psoriasis Area Severity Index (PASI) (primary outcome), Physician Global Assessment, self-administered PASI, and Dermatology Life Quality Index scores (secondary outcomes). Results: A total of 122 participants (46 women [37.7%]; mean [SD] age, 53.6 [10.0] years; mean [SD] PASI score, 3.1 [2.0]; mean [SD] serum 25(OH)D, 14.9 [3.9] ng/mL) were included. Of these, 60 (49.2%) were randomized to the vitamin D group and 62 (50.8%) to the placebo group. A total of 120 participants (59 vitamin D [49.2%]/61 placebo [51.8%]) completed the study. By completion, mean (SD) 25(OH)D levels were 29.7 (5.2) ng/mL (vitamin D) and 12.0 (3.8) ng/mL (placebo). There was no significant difference in change in PASI score between the groups (adjusted difference, 0.11; 95% CI, -0.23 to 0.45). There was no significant difference in change in Physician Global Assessment score (adjusted odds ratio, 0.66; 95% CI, 0.27-1.63), self-administered PASI (adjusted difference, -0.60; 95% CI, -1.76 to 0.55) or Dermatology Life Quality Index (adjusted difference, -0.86; 95% CI, -1.9 to 0.19) between the groups. No adverse effects of the intervention were registered. Conclusion and Relevance: The results of this randomized clinical trial showed that vitamin D supplementation did not affect psoriasis severity. Low baseline severity scores may explain the lack of measurable effect. Levels of 25(OH)D in the intervention group increased to a less-than-expected degree based on previous experimental data from the same source population, and this may have affected the results. Trial Registration: ClinicalTrials.gov Identifier: NCT03334136.

Life after a diagnosis with endometriosis - a 15 years follow-up study.

OBJECTIVE: Previous studies have elucidated the negative impact of endometriosis on life, but the patient selection may have contributed to a skewed picture. The aim of this study was to investigate longitudinally the consequences of the disease in women diagnosed with endometriosis 15 years ago. DESIGN: Retrospective descriptive. SETTING: Trondheim 2007. SAMPLE: One hundred thirty women diagnosed with endometriosis at St. Olav's Hospital in Trondheim between 1991 and 1993. METHODS: Questionnaires. Response rate of 60%. MAIN OUTCOME MEASURES: Consequences of living with endometriosis. RESULTS: Of the women, 19.2% never experienced pelvic pain and 21.8% did not have any further visits to the gynecological department after being diagnosed. Almost 70% had received pharmaceutical treatment and positive effect on pain was reported by 41% for NSAIDs and oral contraceptives, and by 62% for progestins and GnRH-analogues. Satisfactory effect on pain after surgical interventions at the time of diagnosis was reported by 60.9%, and by 89.9% after later surgeries. Of the infertile patients, 75.6% succeeded in delivering one or more biological children. Half of the women reported that endometriosis had some negative impact on their lives. After menopause, 96.9% were free from pain. CONCLUSION: This study confirms that endometriosis is a condition that often has considerable impact on a woman's life. However, the study also found that endometriosis does not always cause pain, that treatment in many cases is effective, that infertility may be overcome, and that almost all postmenopausal women were free from endometriosis-associated pain.