Elisabet Nylander

Effect of narrow-band ultraviolet B phototherapy on p63 and microRNA (miR-21 and miR-125b) expression in psoriatic epidermis.

Psoriasis is an inflammatory skin disease in which dysregulation of p63, a member of the p53 family that is crucial for skin development and maintenance, has been demonstrated. Involvement of miR-203, miR-21 and miR-125b, small non-coding RNAs implicated in the regulation of p63 or p53, has been suggested in the patho-genesis of psoriasis. To elucidate the roles of p63 and p63-related microRNAs in psoriasis and to increase our understanding of the mechanisms of narrow-band ultraviolet B (NB-UVB) phototherapy, we studied the effects of NB-UVB treatment on the expression of these molecules. Skin biopsies from 12 psoriasis patients were collected before, during and after NB-UVB therapy. Real-time PCR and immunohistochemistry showed that p63 expression was not significantly affected, whereas NB-UVB phototherapy significantly decreased expression of miR-21 (p = 0.003) and increased miR-125b levels (p = 0.003). The results indicate that the unresolved p63 abnormality in treated epidermis may play a role in maintenance of this disease.

Improved contact tracing for Chlamydia trachomatis with experienced tracers, tracing for one year back in time and interviewing by phone in remote areas

Objectives: To evaluate the Swedish model for contact tracing and especially the “Västerbotten model” with centralised, extended contact interview periods, sometimes by telephone. Methods: Using questionnaires, the contact tracing and interview procedure was evaluated during 2002, followed by an evaluation of contact interviewing by phone in 2005–6. Results: Patients with diagnosed Chlamydia trachomatis infection reported on average 2.5 sexual contacts, 3.0 contacts when contact interviewing was performed at the clinic, and 2.3 contacts when performed by phone. 65% of the sexual contacts with a known test result were infected. Conclusion: Centralised contact tracing, exploring the sexual history for at least 12 months back in time, shows good results. Combined with screening of certain risk groups it is probably one effective way of preventing C trachomatis infections. Preventing C trachomatis by primary prevention such as information and counselling is, however, still of great importance.

Mucosal lichen planus, a systemic disease requiring multidisciplinary care : a cross-sectional clinical review from a multidisciplinary perspective

Objective This study aimed to emphasize the importance of seeing mucosal lichen planus (LP) as a systemic disease and not an isolated oral or genital disease and to analyze the proportion of thyroid antibodies among patients with multimucosal LP. Materials and Methods All patients examined by the authors and diagnosed with mucosal LP within 1 year were consecutively included. Full medical histories were collected with special emphasis on autoimmune and thyroid diseases. Sera were analyzed for thyroid antibodies and underwent serologic test for herpes virus. The control group comprised 83 healthy volunteers matched regarding sex and age. Results Of the patients, 120 were included, 89 (74%) of whom were women and 31 (26%) were men. The vast majority of the patients had multifocal lesions, whereas oral lesions solely were found in 28% of women and 36% of men. Of the patients, 28% had at least 1 additional autoimmune disease. Approximately half of the women were treated with levothyroxine owing to thyroid disease. Antibodies against herpes simplex virus were found in 60% of the patients and 44% of the controls (p < .03). Conclusions Lichen planus with mucosal involvement should be considered and taken care of as a systemic disease and not as an isolated oral and/or genital lichen. Contradictory to many former reports, most of our patients have a multimucosal disease that emphasizes the need for a multidisciplinary clinic to get optimal care and treatment.

The use of a novel ELISA method for detection of antibodies against p63 in sera from patients diagnosed with oral and/or genital and skin lichen planus.

Lichen planus is a chronic inflammatory disease of mucosa and skin affecting approximately 1-2% of the adult population. Autoimmunity has been implicated in the etiology of this disease, and recently we detected antibodies directed against all six p63 isoforms in sera from 2 out of 20 patients diagnosed with oral lichen planus (OLP) using Western blot analysis. Here we have developed an ELISA method for screening sera for presence of autoantibodies directed against p63. Using the same sera as previously analysed, we show that the optical density ratios for sera from the two patients with known autoantibodies was considerably higher compared to mean optical density ratios for all samples as well as controls analysed. Applying this novel ELISA technique for screening of sera from an additional group of 46 patients with oral and/or genital or skin lichen and 43 matched controls, we detected another three patients with autoantibodies against the p63 proteins. These data are discussed together with the observation that all five patients with detectable p63 autoantibodies from our two studies had clinically severe disease symptoms.

Correlation between Reversal of DNA Methylation and Clinical Symptoms in Psoriatic Epidermis Following Narrow-Band UVB Phototherapy

Epigenetic modifications by DNA methylation are associated with a wide range of diseases. Previous studies in psoriasis have concentrated on epigenetic changes in immune cells or in total skin biopsies that include stromal-associated changes. In order to improve our understanding of the role of DNA methylation in psoriasis, we sought to obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy. Genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls revealed a distinct DNA methylation pattern in psoriasis compared with controls. A total of 3,665 methylation variable positions (MVPs) were identified with an overall hypomethylation in psoriasis patient samples. DNA methylation pattern was reversed at the end of phototherapy in patients showing excellent clinical improvement. Only 7% of phototherapy-affected MVPs (150 out of 2,108) correlate with nearby gene expression. Enrichment of MVPs in enhancers indicates tissue-specific modulation of the transcriptional regulatory machinery in psoriasis. Our study identified key epigenetic events associated with psoriasis pathogenesis and helps understand the dynamic DNA methylation landscape in the human genome.

Oxidation Reduction is a Key Process for Successful Treatment of Psoriasis by Narrow-band UVB Phototherapy

Narrow-band UVB (NB-UVB) phototherapy is commonly used for treatment of psoriasis, though the mechanisms underlying its efficacy have not been completely elucidated. We used gene expression profiling to characterise gene expression in lesional epidermis from psoriasis patients in the middle and late stages of NB-UVB photo-therapy. Increased melanogenesis gene expression was the earliest response to phototherapy. At the end of treatment, genes responding to phototherapy and correlated to treatment outcome were involved in oxidation reduction, growth and mitochondria organisation. Particularly, SPATA18, a key regulator of mitochondrial quality, was significantly down-regulated in psoriasis (p < 0.05). Poly(dA:dT) and poly(I:C) stimulation increased SPATA18 level in primary keratinocytes, indicating the importance of mitochondria quality control under innate immune induced oxidative stress. Normalised SPATA18 expression after phototherapy indicates improved mitochondrial quality control and restored cellular redox status. Our data suggest that oxidation reduction is critical for the resolution of psoriatic plaques following NB-UVB phototherapy.

Autoantibodies and decreased expression of the transcription factor ELF-3 together with increased chemokine pathways support an autoimmune phenotype and altered differentiation in lichen planus located in oral mucosa

Background  The pathogenesis of oral lichen planus (OLP), a chronic inflammatory disease, is not fully understood. It is known that OLP has autoimmune features, and it is suggested to be an autoimmune disease. ELF‐3 is involved in differentiation of keratinocytes and deregulated in different tumours and inflammatory diseases. CXCR‐3 and its ligands CXCL‐10 and CXCL‐11 are increased in autoimmune diseases and linked to Th‐1 immune response.

Genes involved in epithelial differentiation and development are differentially expressed in oral and genital lichen planus epithelium compared to normal epithelium.

Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

Genital Graft-versus-host Disease in a Male Following Allogeneic Stem Cell Transplantation

Chronic graft-versus-host disease (GVHD) involving the vulva or vagina has been reported in 15% of fema-les receiving allogeneic peripheral stem cells (1–3). We have, however, been unable to find any reports of genital GVHD in men. Here we describe the case of a man who developed chronic GVHD with severe genital involvement. CASE REPORT

Asking about condom use : a key to individualized care when screening for chlamydia.

Chlamydia trachomatis (CT) infection has been a target for both selective and national screening programmes, and Sweden has an opportunistic approach. A national plan of action states that risk groups should be identified and offered risk reduction counselling. Patients attending a drop-in sexually transmitted infection (STI) clinic reception at the University Hospital, Umeå, Sweden, were invited to complete a questionnaire regarding sociodemographic characteristics, symptoms and sexual risk behaviour; all had a CT test taken. A total of 1305 patients were included, 58% men, mean age 27.8 years. CT prevalence was 11%; 51% of those with CT were ≥25 years old. Only 5% used a condom during the entire sexual intercourse with their last new/temporary partner. Sexually active inconsistent condom users comprised 62% of the study population and contributed to 81% of the chlamydia infections. Asking whether a condom was used could quickly triage patients into groups with a ‘higher risk’ (none or inconsistent use of condoms and at least one new/temporary partners), and ‘lower risk’ (with more consistent condom use, although not always accurate) allowing for individualized care and counselling when screening for chlamydia. Evaluating whether a condom was used throughout the sexual intercourse did not add any useful information.