Erna Snellman

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis

Background  Narrowband ultraviolet B (NB‐UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied.

Single nucleotide polymorphisms in the XPG gene: Determination of role in DNA repair and breast cancer risk

In this study we determined the effect of single nucleotide polymorphisms in the XPG gene on DNA repair and breast cancer susceptibility. Ninety individuals, with previously studied DNA repair rate at 24 hr of 2 types of UV‐specific cyclobutane pyrimidines dimers (CPDs) in skin were genotyped for XPG polymorphism at codon 1104 (exon 15 G>C; Asp > His). The repair rate of TT=C dimer was similar in both wild‐type GG homozygotes and GC heterozygotes, whereas, for TT=T, dimer repair was non‐significantly (Students t‐test, p = 0.34) lower in GC heterozygotes than wild‐type GG homozygotes. Genotyping of 220 breast cancer cases and 308 controls for the same single nucleotide polymorphism in exon 15 of the XPG gene exhibited marginally significant increased frequency of the variant allele (χ2 3.84, p = 0.05; OR 1.33, 95% CI 1.0–1.8) in cases (C‐allele 0.29) compared to controls (C‐allele 0.24). Combined heterozygote and variant homozygote genotype frequency was also higher in cases than controls (χ2 4.79, p = 0.03; OR 1.50, 95%CI 1.04–2.16).

Daylight photodynamic therapy for actinic keratoses: a randomized double-blinded nonsponsored prospective study comparing 5-aminolaevulinic acid nanoemulsion (BF-200) with methyl-5-aminolaevulinate

Daylight‐mediated photodynamic therapy (DL‐PDT) using methyl‐5‐aminolaevulinate (MAL) is effective for thin, grade I, actinic keratoses (AK). There are no published studies of other photosensitizers used in DL‐PDT.

Randomized half-side comparison of narrowband UVB and trimethylpsoralen bath plus UVA treatments for psoriasis.

The efficacy of trimethylpsoralen bath PUVA and UVB TL01 were compared in chronic plaque psoriasis. Patients were randomly assigned to receive UVB TL01 on one side and bath PUVA on the contra-lateral side. Altogether 17 patients received treatments and 15 completed the trial. The decrease in the PASI score was greater with UVB TL01 than PUVA. At the end of the treatment period, the difference was highly significant (p < 0.001). The difference was already significant at week 3 (p = 0.014). The relative median decrease in the PASI score was 77% (24-100%) with UVB and 45% (8-100%) with PUVA. The median cumulative UVB dose was 39.92 (range 13.95-81.56) J/cm2 and the corresponding UVA dose was 8.06 (range 3.31-12.51) J/cm2. All patients relapsed within 4 months. Narrowband UVB improved psoriasis clinically and statistically more efficiently than trimethylpsoralen bath PUVA, and UVB was better tolerated.

Matrix Metalloproteinase-19 is Expressed by Keratinocytes in Psoriasis

Keratinocyte hyperproliferation, inflammatory infiltrates, neoangiogenesis and alterations in cytokine levels are hallmarks of psoriatic skin. Matrix metalloproteinases (MMPs) have been associated with the remodeling of the extracellular matrix during inflammation, neovascularization, and malignant transformation. We have previously shown that particularly MMP-12 is abundantly expressed by macrophages and MMP-9 in macrophages and neutrophils of psoriatic lesions. In this work the expression of two novel metalloproteinases, MMP-19 and MMP-28, was investigated in psoriatic lesional and non-lesional skin. MMP-19 protein was detected by immunohistochemistry in 28/29 samples in keratinocytes in the same regions as Ki67 (marker of proliferating keratinocytes) and p63 (marker of keratinocyte stem cells). Immunosignaling was also seen in endothelial cells and fibroblasts. Furthermore, MMP-19 mRNA was upregulated in psoriatic keratinocytes and skin as assessed by quantitative real-time polymerase chain reaction. In lichen planus and lichenoid chronic dermatitis, MMP-19 staining was found in keratinocytes in areas where the basement membrane was abnormal. MMP-28 was not detected in psoriatic or non-lesional skin. Our results suggest that keratinocytes as well as the previously reported cell types (smooth muscle, endothelial and macrophages) can express MMP-19 in psoriasis and lichen planus. Upregulation of MMP-19 in keratinocytes may be influenced by changes in the architecture of the basement membrane zone.

In situ repair of cyclobutane pyrimidine dimers in skin and melanocytic nevi of cutaneous melanoma patients.

The development of cutaneous malignant melanoma (CMM) and its precursor lesions, melanocytic nevi, has been linked to sun exposure. Cyclobutane pyrimidine dimers (CPDs) are the majority of DNA lesions induced by sun exposure. In our study, we investigated if CMM patients have impaired ability to repair CPDs in skin as well as in melanocytic nevi. The repair kinetics were followed up to 3 weeks after exposure to 40 mJ/cm2 of solar simulating radiation. Altogether 12 CMM patients and 10 healthy controls were included in our study. Buttock skin biopsies were taken at 0 hr, 48 hr and 3 weeks after UV exposure, whereas melanocytic nevi and surrounding skin biopsies were taken only at 0 hr and 3 weeks. The CPD levels were measured by a 32P‐postlabeling method. The results showed that the repair rate of CPDs in neither the skin nor the nevi was significantly different between the CMM patients and the control group. For both groups, the repair rate of TT = C was faster than that for TT = T. The important finding is that about 10% of the initial TT = T damage remained unrepaired after 3 weeks, and was detectable in normal epidermis as well as in nevi of all subjects. We also found that the amount of TT = C and TT = T at 0 hr in nevi was significantly lower than that in surrounding skin (Wilcoxon rank sum test, p < 0.05).

Comparison of narrowband ultraviolet B exposure and oral vitamin D substitution on serum 25-hydroxyvitamin D concentration.

Summary Background  A short course of narrowband ultraviolet B (NB‐UVB) exposures increases the serum 25‐hydroxyvitamin D [25(OH)D] concentration in patients with psoriasis and healthy subjects.

Narrow-band Ultraviolet B Treatment Boosts Serum 25-hydroxyvitamin D in Patients with Psoriasis on Oral Vitamin D Supplementation

A course of treatment with narrow-band ultraviolet B (NB-UVB) improves psoriasis and increases serum 25-hydroxyvitamin D (25(OH)D). In this study 12 patients with psoriasis who were supplemented with oral cholecalciferol, 20 µg daily, were given a course of NB-UVB and their response measured. At baseline, serum 25(OH)D was 74.14 ± 22.9 nmol/l. At the 9th exposure to NB-UVB 25(OH)D had increased by 13.2 nmol/l (95% confidence interval (95% CI) 7.2-18.4) and at the 18th exposure by 49.4 nmol/l (95% CI 35.9-64.6) above baseline. Psoriasis Area Severity Index score improved from 8.7 ± 3.5 to 4.5 ± 2.0 (p < 0.001). At baseline, psoriasis lesions showed low vitamin D metabolizing enzyme (CYP27A1, CYP27B1) and high human β-defensin-2 mRNA expression levels compared with those of the healthy subjects. In conclusion, NB-UVB treatment significantly increases serum 25(OH)D in patients with psoriasis who are taking oral vitamin D supplementation, and the concentrations remain far from the toxicity level. Healing psoriasis lesions show similar mRNA expression of vitamin D metabolizing enzymes, but higher antimicrobial peptide levels than NB-UVB-treated skin in healthy subjects.

Detecting field cancerization using a hyperspectral imaging system

Field cancerization denotes subclinical abnormalities in a tissue chronically exposed to UV radiation. These abnormalities can be found surrounding the clinically visible actinic keratoses.

Clinical Associations of the Risk Alleles of HLA-Cw6 and CCHCR1*WWCC in Psoriasis

The PSORS1 locus is the consistently replicated genetic risk factor for psoriasis. Clinical associations with the main marker allele of PSORS1, HLA-Cw6, have been addressed in a number of studies, but clinical associations have not been used as a way to distinguish the effects of the neighbouring candidate genes in PSORS1. Our results show that HLA-Cw6 and CCHCR1 risk allele associations with clinical features of psoriasis are predictably highly similar in a Finnish nationwide cohort of 379 psoriasis patients. The clinical profiling of a small group of patients (n=34) who were HLA-Cw6- but CCHCR1*WWCC positive suggested that no great differences existed between them and HCR-Cw6- patients. HCR+ genotype (as well as Cw6+ genotype) correlated for the first time positively with female sex and, in contrast with previous studies, negatively with disease severity. Presence of psoriatic arthritis was more pronounced in HCR- psoriasis (as well as in Cw6- psoriasis). Clinical profiling may be a useful approach to distinguishing genetic effects of candidate genes even within a locus in sufficiently large cohorts.