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  • 1.
    Abdelhadi, Saly
    et al.
    Karolinska Inst, Sweden.
    Nordlind, Klas
    Karolinska Inst, Sweden.
    Johansson, Bjoern
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Theodorsson, Elvar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Holst, Mikael
    Karolinska Inst, Sweden.
    Loenndahl, Louise
    Karolinska Inst, Sweden.
    Expression of calcitonin gene-related peptide in atopic dermatitis and correlation with distress2024In: Immunopharmacology and immunotoxicology, ISSN 0892-3973, E-ISSN 1532-2513, Vol. 46, no 1, p. 67-72Article in journal (Refereed)
    Abstract [en]

    BackgroundAtopic dermatitis (AD) is a chronic, inflammatory, often severely itching skin disorder. It may worsen due to stress, depression, or anxiety. Calcitonin gene-related peptide (CGRP) may be involved in inflammation signaling. CGRP has also been suggested in relation to stress, depression, and anxiety. This study aimed to investigate the expression of CGRP in the skin of patients with AD.MethodsTwenty-seven adult patients with AD, characterized with clinical and psychodemographic parameters, were investigated regarding CGRP expression in skin biopsies, using an immunohistochemical technique.ResultsThe total number of CGRP-positive nerve-like fibers was found to be higher in lesional skin than in non-lesional skin. Moreover, more inflammatory cells of dendritic shape intruded into the epidermis in lesional skin compared to non-lesional skin. Keratinocytes showing expression of CGRP were also found in lesional skin. Interestingly, the number of CGRP-positive nerve-like fibers in lesional skin correlated with depressive and anxiety scores. Correlation with depressive score was also found for round CGRP-positive inflammatory cells in the epidermis.ConclusionsCGRP may have a role in both the inflammatory process and distress, in AD.

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  • 2.
    Albadri, Zeyad
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    AL Bayati, Doua
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Habel, Henrike
    Karolinska Inst, Sweden.
    Jerkovic Gulin, Sandra
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Div Dermatol & Venereol, Sweden.
    Groenhagen, Carina
    Lund Univ, Sweden.
    Seifert, Oliver
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Incidence of Dermatitis Herpetiformis in Sweden 2005 to 2018: A Nationwide Retrospective Cohort Study2023In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 103, article id adv13210Article in journal (Refereed)
    Abstract [en]

    Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79-1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.

  • 3.
    Alsterholm, Mikael
    et al.
    Univ Gothenburg, Sweden; Karolinska Inst, Sweden; Univ Goth enburg, Sweden.
    Svedbom, Axel
    Karolinska Inst, Sweden.
    Anderson, Chris
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Sommar, Lena Holm
    Stockholm Hud, Sweden.
    Ivert, Lina U.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Josefson, Anna
    Orebro Univ, Sweden; Univ Hosp Orebro, Sweden.
    Von Kobyletzki, Laura
    Orebro Univ, Sweden; Lund Univ, Sweden.
    Lindberg, Magnus
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lundeberg, Lena
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Lundqvist, Maria
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden; Orebro Univ, Sweden.
    Nylander, Elisabet
    Umea Univ, Sweden.
    Falk, Marihelen Sandstroem
    Capio Skin, Carlanderska Hospital, Gothenburg, Sweden .
    Shayesteh, Alexander
    Umea Univ, Sweden.
    Sigurdardottir, Gunnthorunn
    Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Sonesson, Andreas
    Department of Dermatology and Venereology, Skåne University Hospital, Lund, Sweden.
    Svensson, Ake
    Department of Occupational and Environmental Dermatology, Lund University, Skåne University Hospital, Malmö, Sweden.
    Virtanen, Marie
    Department of Medical Sciences, Section of Dermatology, Uppsala University, Uppsala, Sweden.
    Vrang, Sophie
    Patients’ organization Atopikerna, The Swedish Asthma and Allergy Association, Stockholm, Sweden.
    Wahlgren, Carl-fredrik
    Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Bradley, Maria
    Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Emma K.
    Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Establishment and Utility of SwedAD: A Nationwide Swedish Registry for Patients with Atopic Dermatitis Receiving Systemic Pharmacotherapy2023In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 103, article id adv7312Article in journal (Refereed)
    Abstract [en]

    SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharma-cotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly re-gistry to the benefit of patients with atopic dermati-tis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approxi-mate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Seve-rity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were im-proved. Regional coverage varied, reflecting the distri-bution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.

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  • 4.
    Andersson, Rolf
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Quirk, Chris
    Royal Perth Hospital, WA Australien.
    Sullivan, John
    Liverpool Hospital, NSW Australien.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Cutaneous manifestations of internal disease2008In: Drug Discovery Today : Disease Mechanisms, E-ISSN 1740-6765, Vol. 5, no 1, p. e113-e123Article in journal (Refereed)
    Abstract [en]

    The skin mirrors the individual's well being. Visible for both the patient and the attending physician, it can be a source of information for the diagnosis of multi-system diseases and diseases of internal organs. Therapy is usually directed at the primary disease. Pharmaco-therapeutic options for internal diseases are at present not always optimal and specific management of side effects of drugs with vital indication may be necessary. Better understanding of the mechanisms of the cutaneous manifestations may help develop more efficacious, better tolerated therapy and improve the patient's situation.

  • 5.
    Assarsson, Malin
    et al.
    Div Dermatol and Venereol, Sweden.
    Duvetorp, Albert
    Div Dermatol and Venereol, Sweden.
    Dienus, Olaf
    Div Med Diagnost, Sweden.
    Söderman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Div Med Diagnost, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Div Dermatol and Venereol, Sweden.
    Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B2018In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 98, no 4, p. 428-436Article in journal (Refereed)
    Abstract [en]

    Changes in the skin microbiome have been shown to promote cutaneous inflammation. The skin microbiome of patients with chronic plaque type psoriasis was analysed before and after treatment with narrowband ultraviolet B (UVB). Swab samples of the microbiome were taken from lesional and non-lesional skin of 26 patients. Microbiotas were characterized by sequencing 16S rRNA bacterial genes on the Illumina MiSeq platform. Lesional skin microbiome diversity correlated with psoriasis severity (measured with the Psoriasis Area and Severity Index; PASI). There was a significantly lower abundance of the phylum Firmicutes and the genus Staphylococcus in lesional skin compared with non-lesional skin before UVB treatment. Responders (amp;gt; 75% target Psoriasis Severity Index (PSI) improvement) had significantly lower abundance of the phyla Firmicutes in lesional and non-lesional skin and lower abundance of the genera Staphylococcus, Finegoldia, Anaerococcus, Peptoniphilus, Gardnerella, Prevotella and Clostridium in lesional skin after UVB treatment. Pseudomonas significantly decreased in lesional and non-lesional skin of treatment responders. These results suggest that skin microbiome alterations after UVB treatment could be related to treatment and treatment response.

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  • 6.
    Assarsson, Malin
    et al.
    Ryhov Hosp, Sweden.
    Soderman, Jan
    Ryhov Hosp, Sweden.
    Duvetorp, Albert
    Skanes Univ Hosp, Sweden.
    Mrowietz, Ulrich
    Univ Med Ctr Schleswig Holstein, Germany.
    Skarstedt, Marita
    Ryhov Hosp, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Narrowband UVB treatment induces expression of WNT7B, WNT10B and TCF7L2 in psoriasis skin2019In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 311, no 7, p. 535-544Article in journal (Refereed)
    Abstract [en]

    WNT/beta-catenin signaling pathways play a pivotal role in the human immune defense against infections and in chronic inflammatory conditions as psoriasis. Wnt gene alterations are linked to known comorbidities of psoriasis as obesity, diabetes and Crohns disease. The objective of this study was to investigate WNT7B, WNT10B, WNT16 and TCF7L2 gene and protein expression in lesional and non-lesional skin and in the peripheral blood of patients with chronic plaque psoriasis compared with healthy individuals. To investigate the effect of narrowband UVB radiation, expression of these genes were analyzed before and after narrowband UVB treatment. Associations between single nucleotide polymorphisms for WNT7B, WNT10B, WNT16 and TCF7L2 genes and psoriasis were tested. Our results show significantly decreased WNT7B, WNT10B and TCF7L2 gene expression in lesional skin compared with non-lesional skin and healthy controls. Narrowband UVB treatment significantly increased expression of these genes in lesional skin. Immunohistochemistry shows increased WNT16 expression in lesional skin. No significant differences in allele or genotype frequencies for Wnt or TCF7L2 gene polymorphisms were found between patient and control group. This study shows for the first time significant UVB induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis.

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  • 7.
    Assarsson, Malin
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Division of Dermatology and Venereology, Region Jönköping County, Sweden.
    Söderman, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Division of Medical Diagnostics, Region Jönköping County, Jönköping, Sweden.
    Dienus, Olaf
    Division of Medical Diagnostics, Region Jönköping County, Jönköping, Sweden.
    Seifert, Oliver
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Division of Dermatology and Venereology, Region Jönköping County, Sweden.
    Significant Differences in the Bacterial Microbiome of the Pharynx and Skin in Patients with Psoriasis Compared with Healthy Controls2020In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 100, article id adv00273Article in journal (Refereed)
    Abstract [en]

    Studies have shown differences in the skin and gut bacterial microbiomes in patients with psoriasis, but the pharyngeal microbiome has not been studied previously. The aim of this study was to investigate differences in the bacterial microbiome of the pharynx and skin of patients with psoriasis compared with healthy controls. Swabs were taken from the pharynx and el-bow skin of 39 patients with psoriasis and 70 controls. Microbiomes were characterized by sequencing 16S rRNA genes on the Illumina MiSeq platform. Significant differences were found in alpha and beta diversity in the skin, but not in the pharynx. Significant differences were also found between several phyla and genera in both skin and pharynx. The severity of psoriasis did not correlate with any genera in the pharynx, but with Capnocytophaga, Leptotrichia, Abiotrophia and Tannerella in the skin. The composition of the pharyngeal and skin microbiome may be of importance in the pathogenesis of psoriasis.

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  • 8.
    Bergfors, Elisabet
    et al.
    Univ Gothenburg, Sweden.
    Inerot, Annica
    Univ Gothenburg, Sweden.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Nyström Kronander, Ulla
    Region Östergötland, Heart and Medicine Center, Allergy Center.
    Trollfors, Birger
    Sahlgrens Univ Hosp, Sweden.
    Patch testing children with aluminium chloride hexahydrate in petrolatum: A review and a recommendation2019In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 81, no 2, p. 81-88Article, review/survey (Refereed)
    Abstract [en]

    Background: According to studies on adults, patch testing with aluminium chloride hexahydrate 2% pet. is insufficient to detect aluminium allergy, and a 10% preparation is recommended. Other studies suggest that a 2% preparation is sufficient for testing children. Objectives: To review three previously published Swedish studies on patch testing children with aluminium chloride hexahydrate 2% pet. Patients/Methods: Altogether, 601 children with persistent itching subcutaneous nodules (granulomas) induced by aluminium-adsorbed vaccines were patch tested with aluminium chloride hexahydrate 2% pet. and metallic aluminium in (a) a pertussis vaccine trial, (b) clinical practice, and (ca) prospective study. Results: Overall, 459 children had positive reactions to the 2% pet. preparation. Another 10 reacted positively only to metallic aluminium. An extreme positive reaction (+++) was seen in 65% of children aged 1 to 2 years as compared with 22% of children aged 7 years. From 8 years onwards, extreme positive reactions were scarce. Conclusions: Aluminium chloride hexahydrate 2% pet. is sufficient to trace aluminium allergy in children. Small children are at risk of extreme reactions. We thus suggest that aluminium chloride hexahydrate 10% pet. should not be used routinely in children before the age of 7 to 8 years.

  • 9.
    Bergfors, Elisabet
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Lundmark, Katarzyna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nyström Kronander, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    A child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines2013In: BMJ Case Reports, E-ISSN 1757-790XArticle in journal (Refereed)
    Abstract [en]

    A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.

  • 10.
    Bhattarai, Sabina
    et al.
    Department of Dermatology and Venereology, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.
    Pandey, Arti S
    Department of Biochemistry, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.
    Bastakoti, Sherya
    Department of Dermatology and Venereology, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.
    Söderkvist, Peter
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Bhusal, Mohan
    Department of Dermatology and Venereology, Kathmandu Medical College and Teaching Hospital, Kathmandu, Nepal.
    A case of keratitis, ichthyosis, and deafness syndrome with rickets2020In: JAAD case reports, ISSN 2352-5126, Vol. 6, no 1, p. 9-12Article in journal (Refereed)
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  • 11. Order onlineBuy this publication >>
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Regulation of UV induced apoptosis in human melanocytes2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Malignant melanoma arises from the pigment producing melanocytes in epidermis and is the most aggressive type of skin cancer. The incidence of malignant melanoma is increasing faster than any other type of cancer in white population worldwide, with a doubling rate every 10-20 years. So far, the only identified external risk factor for malignant melanoma is UV exposure. Elimination of photodamaged cells by apoptosis (programmed cell death) is essential to prevent tumor formation. Melanocytes are considered relatively resistant to apoptosis, however, the regulation of apoptosis in melanocytes is still unknown.

    The aim of this thesis was to investigate the apoptotic process following ultraviolet (UV) irradiation in primary cultures of human melanocytes. Focus was on regulation of mitochondrial stability by Bcl-2 family proteins and the possible participation of lysosomal proteases, cathepsins. UV irradiation activated the mitochondrial pathway of apoptosis, leading to cytochrome c release, caspase activation, and nuclear fragmentation. No change in protein expression of Bax and Bcl-2 was observed in response to UV. Instead, translocation of the Bcl-2 family proteins from cytosol to mitochondia was important in the regulation of survival and death of melanocytes. The findings further demonstrated permeabilization of the lysosomal membrane to occur early in the apoptotic process, resulting in cathepsin release into the cytosol. The cathepsins were potent pro-apoptotic mediators and triggered apoptosis upstream of Bax translocation and mitochondrial membrane permeabilization. In response to both heat and UV irradiation, there was a marked increase in expression of stress-induced heat shock protein 70 (Hsp70), which inhibited apoptosis by binding lysosomal and mitochondrial membranes and counteracting the release of cathepsins and cytochrome c. Furthermore, UV irradiation activated c-jun N-terminal kinase (JNK), which triggered apoptosis upstream of cathepsins release from the lysosomes. In addition, JNK mediated apoptosis through phosphorylation of pro-apoptotic Bim, which was released from anti-apoptotic Mcl-1, by UV induced Mcl-1 depletion.

    This thesis illustrates that permeabilization of mitochondria and lysosomes and release of their constituents to the cytosol participates in UV induced apoptosis signaling in human melanocytes in vitro. The process is regulated by a complex network of pro- and anti-apoptotic proteins, exerting their effects through intracellular translocation and alteration of protein expression.

    List of papers
    1. Wavelength specific effects on UVB induced apoptosis in melanocytes. A study of the Bcl-2/Bax expression and keratinocyte rescue effects
    Open this publication in new window or tab >>Wavelength specific effects on UVB induced apoptosis in melanocytes. A study of the Bcl-2/Bax expression and keratinocyte rescue effects
    2005 (English)In: Melanoma Research, ISSN 0960-8931, Vol. 15, no 1, p. 7-13Article in journal (Refereed) Published
    Abstract [en]

    Apoptosis and alterations in Bcl-2 and Bax messenger RNA (mRNA) and protein expression were examined in cultured human epidermal melanocytes following UVB irradiation (50 mJ/cm2). The effects of various spectral ranges within UVB were investigated. A co-culture system was set up to study the interplay between melanocytes and keratinocytes in response to UVB. Melanocytes expressed high basal levels of the anti-apoptotic protein Bcl-2 compared with keratinocytes. Different wavelengths within the UVB spectrum induced diverse response patterns of Bcl-2 and Bax mRNA and had different apoptotic power. Both Bcl-2 and Bax mRNA were upregulated to preserve protein levels and only a slight increase in apoptosis was noted 24 h after UVB ([lambda]>305 nm). Increasing UVB between 280 and 305 nm enhanced apoptosis and upregulated Bcl-2, whilst Bax mRNA was unaltered. However, no change in protein levels was detected. A redistribution of Bax protein from different compartments within the cell may be more important than direct upregulation for the acceleration of apoptosis, but it cannot be excluded that other apoptotic pathways may be induced by shorter UVB wavelengths. The increase in apoptosis was significantly lower in melanocytes co-cultured with irradiated matched keratinocytes than in melanocytes from pure cultures, indicating that melanocytes are protected from UVB-induced apoptosis by the release of substance(s) from keratinocytes. This rescue response concurred with a fast and significant increase in Bcl-2 mRNA level in melanocytes.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14399 (URN)10.1097/00008390-200502000-00003 (DOI)
    Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2021-12-28
    2. UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members
    Open this publication in new window or tab >>UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members
    Show others...
    2006 (English)In: Journal of Investigative Dermatology, ISSN 0022-202X, Vol. 126, no 5, p. 1119-1127Article in journal (Refereed) Published
    Abstract [en]

    We demonstrate UVA/B to induce apoptosis in human melanocytes through the mitochondrial pathway, displaying cytochrome c release, caspase-3 activation, and fragmentation of nuclei. The outcome of a death signal depends on the balance between positive and negative apoptotic regulators, such as members of the Bcl-2 protein family. Apoptotic melanocytes, containing fragmented nucleus, show translocation of the proapoptotic proteins Bax and Bid from the cytosol to punctate mitochondrial-like structures. Bcl-2, generally thought to be attached only to membranes, was in melanocytes localized in the cytosol as well. In the fraction of surviving melanocytes, that is, cells with morphologically unchanged nucleus, the antiapoptotic proteins Bcl-2 and Bcl-XL were translocated to mitochondria following UVA/B. The lysosomal proteases, cathepsin B and D, which may act as proapoptotic mediators, were released from lysosomes to the cytosol after UVA/B exposure. Proapoptotic action of the cytosolic cathepsins was confirmed by microinjection of cathepsin B, which induced nuclear fragmentation. Bax translocation and apoptosis were markedly reduced in melanocytes after pretreatment with either cysteine or aspartic cathepsin inhibitors. No initial caspase-8 activity was detected, excluding involvement of the death receptor pathway. Altogether, our results emphasize translocation of Bcl-2 family proteins to have central regulatory functions of UV-induced apoptosis in melanocytes and suggest cathepsins to be proapoptotic mediators operating upstream of Bax.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14400 (URN)10.1038/sj.jid.5700124 (DOI)
    Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2021-12-28
    3. Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes
    Open this publication in new window or tab >>Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes
    2007 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 28, no 3, p. 537-544Article in journal (Refereed) Published
    Abstract [en]

    Stress-induced heat shock protein 70 (Hsp70) effectively protects cells against apoptosis, although the anti-apoptotic mechanism is still undefined. Exposure of human melanocytes to heat and subsequent UVB irradiation increased the level of Hsp70 and pre-heating reduced UVB induced apoptosis. Immunofluorescence staining of Hsp70 in combination with staining of lysosomes (Lamp2) or mitochondria (Mitotracker®) in pre-heated UVB exposed cells showed co-localization of Hsp70 with both lysosomes and mitochondria in the surviving cell population. Furthermore, UVB induced apoptosis was accompanied by lysosomal and mitochondrial membrane permeabilization, detected as release of cathepsin D and cytochrome c, respectively, which were prevented by heat pre-treatment. In purified fractions of lysosomes and mitochondria, recombinant Hsp70 attached to both lysosomal and mitochondrial membranes. Moreover, in apoptotic cells Bax was translocated from a diffuse cytosolic location into punctate mitochondrial-like structures, which was inhibited by Hsp70 induction. Such inhibition of Bax translocation was abolished by transfection with Hsp70 siRNA. Furthermore, Hsp70 siRNA eliminated the apoptosis preventive effect observed after pre-heating. These findings show Hsp70 to rescue melanocytes from UVB induced apoptosis by preventing release of cathepsins from lysosomes, Bax translocation and cytochrome c release from mitochondria.

     

    Abbreviations: AIF, apoptosis-inducing factor; Hsp, heat shock protein; NAG, ß-N-acetylglucosaminidase; tBid, truncated Bid; UV, ultraviolet

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14401 (URN)10.1093/carcin/bgl152 (DOI)
    Available from: 2007-05-14 Created: 2007-05-14 Last updated: 2021-12-28
    4. JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins
    Open this publication in new window or tab >>JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins
    2008 (English)In: Apoptosis (London), ISSN 1360-8185, E-ISSN 1573-675X, Vol. 13, no 9, p. 1111-1120Article in journal (Refereed) Published
    Abstract [en]

    UVB irradiation induced phosphorylation of JNK and subsequent apoptosis in human melanocytes. Depletion of both JNK1 and JNK2 expression using siRNA transfection, protected against apoptosis, as detected by decreased nuclear fragmentation and caspase-3 activity, as well as reduced translocation of Bax to mitochondria. Moreover, release of cathepsin B and D from lysosomes to the cytosol was reduced when JNK expression was suppressed by siRNA, demonstrating a JNK dependent regulation of lysosomal membrane permeabilization. In unirradiated control melanocytes, coimmunoprecipitation showed that Bim was sequestered by Mcl-1, which had a pro-survival function. After UVB irradiation, a significant decrease in Mcl-1 protein level was found, which was prevented by addition of a proteasome inhibitor. The interaction between Bim and Mcl-1 was reduced in response to UVB irradiation and Bim was phosphorylated in a JNK dependent manner. In conclusion, these findings Suggest JNK to have an important pro-apoptotic function following UVB irradiation in human melanocytes, by acting upstream of lysosomal membrane permeabilization and Bim phosphorylation.

    Keywords
    UV, Cathepsin, JNK, Mcl-1, Bim
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-16886 (URN)10.1007/s10495-008-0240-7 (DOI)
    Note
    The original publication is available at www.springerlink.com: Cecilia Bivik and Karin Öllinger, JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins, 2008, Apoptosis (London), (13), 9, 1111-1120. http://dx.doi.org/10.1007/s10495-008-0240-7 Copyright: Springer Science Business Media http://www.springerlink.com/ Available from: 2009-04-29 Created: 2009-02-20 Last updated: 2021-12-28Bibliographically approved
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  • 12.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Regulation of UV-induced apoptosis in human melanocytes2009In: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, no 1, p. 25-26Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 13.
    Bivik Eding, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Domer, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wäster, Petra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jerhammar, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rosdahl, Inger
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 7, p. 792-797Article in journal (Refereed)
    Abstract [en]

    Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melanocyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.

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  • 14.
    Brohede, Sabina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Wyon, Yvonne
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Wingren, Gun
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wijma, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Wijma, Klaas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Body dysmorphic disorder in female Swedish dermatology patients2017In: International Journal of Dermatology, ISSN 0011-9059, E-ISSN 1365-4632, Vol. 56, no 12, p. 1387-1394Article in journal (Refereed)
    Abstract [en]

    BackgroundIndividuals with body dysmorphic disorder (BDD) are highly distressed and impaired owing to perceived defects in their physical appearance that are not noticeable to others. They are frequently concerned about their skin and often present to dermatologists rather than psychiatrists. However, BDD patients attending dermatology clinics may be at risk of not receiving an appropriate assessment and beneficial treatment. The aims of this study were to estimate the BDD prevalence rate among Swedish female dermatology patients and to assess the psychological condition of BDD patients compared to that of other dermatology patients. MethodsThe occurrence of BDD was estimated using the Body Dysmorphic Disorder Questionnaire (BDDQ), a validated self-report measure for BDD. Symptoms of depression and anxiety were measured by the Hospital Anxiety and Depression Scale (HADS), and quality of life was assessed using the Dermatology Life Quality Index (DLQI). ResultsThe prevalence rate of BDD among female Swedish dermatology patients was 4.9% (95% CI 3.2-7.4). Anxiety (HADS A11) was 4-fold more commonly reported by patients with positive BDD screening (48% vs. 11%), and depression (HADS D11) was over 10-fold more common in patients with positive BDD screening (19% vs. 1.8%) (Pamp;lt;0.001). The median DLQI score was 18 in the BDD group, compared to a score of 4 in the non-BDD group (Pamp;lt;0.001). ConclusionsOur results indicate that BDD is fairly common among female Swedish dermatology patients (4.9%) and that BDD patients have high levels of depression and anxiety and severely impaired quality of life.

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  • 15.
    Carlsson, Annica
    et al.
    Lund University, Sweden; Ängelholm Hospital, Sweden.
    Svensson, Åke
    Lund University, Sweden.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Baranovskaya, Irina
    Lund University, Sweden.
    Hindsen-Stenstrom, Monica
    Lund University, Sweden.
    Holt, Ingebjorg
    Angelholm Hospital, Sweden.
    Meding, Birgitta
    Karolinska Institute, Sweden.
    Stenberg, Berndt
    Umeå University, Sweden.
    Stenlund, Hans
    Umeå University, Sweden.
    Ganemo, Agneta
    Lund University, Sweden.
    Scoring of Hand Eczema: Good Reliability of the Hand Eczema Extent Score (HEES)2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 2, p. 193-197Article in journal (Refereed)
    Abstract [en]

    There is good agreement between dermatological staff and patients using the Hand Eczema Extent Score (HEES). The aim of this study was to assess inter-and intra-observer reliability of the HEES in dermatologists and intra-observer reliability of the HEES in patients with hand eczema. Six dermatologists assessed 18 patients twice. Only the hands of the patients were visible to the assessors. Patients performed a selfassessment twice. Inter-and intra-observer reliability was tested with intraclass correlation coefficient (ICC). The mean HEES score for all dermatologists assessments was 21.0 (range 3.6-46.3). The corresponding mean scores for all patients own assessments were 24.9 (range 4.0-54.0). Inter-observer reliability in the dermatologists observations ICC classification was very good, median value 0.82 (range 0.56-0.92). The overall intra-observer reliability for the 6 dermatologists ICC classification was very good (range 0.88-0.94). Intra-observer reliability in the patients 2 self-assessments ICC classification was very good (ICC 0.95). In conclusion, HEES is a reliable tool for both dermatologists and patients to grade the extent of hand eczema.

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  • 16.
    Cengiz, Cigdem
    et al.
    Linköping University, Department of Mathematics. Linköping University, Faculty of Science & Engineering. Swedish Univ Agr Sci, Sweden.
    von Rosen, Dietrich
    Linköping University, Department of Mathematics, Mathematical Statistics. Linköping University, Faculty of Science & Engineering. Swedish Univ Agr Sci, Sweden.
    Singull, Martin
    Linköping University, Department of Mathematics, Mathematical Statistics. Linköping University, Faculty of Science & Engineering.
    Profile Analysis in High Dimensions2021In: Journal of Statistical Theory and Practice, ISSN 1559-8608, E-ISSN 1559-8616, Vol. 15, no 1, article id 15Article in journal (Refereed)
    Abstract [en]

    The three tests in profile analysis: test of parallelism, test of level and test of flatness are modified so that high-dimensional data can be analysed. Using specific scores, dimension reduction is performed and the exact null distributions are derived for the three hypotheses.

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  • 17. Order onlineBuy this publication >>
    Clifford, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences.
    Gold allergy: In vitro studies using peripheralblood mononuclear cells2009Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Positive patch test reactions to gold are commonly seen in dermatology clinics, but it is veryunusual for the patients to actually have any clinical symptoms. It is also common with irritantreactions that are not linked to adaptive immunity. Therefore, a deeper understanding of themechanisms underlying allergic contact dermatitis (ACD) reaction, and the search for acomplementing diagnostic tool, is important.

    In paper I we included three subject groups; one with morphologically positive patch testreactions to gold sodium thiosulphate (GSTS, the gold salt used in patch testing), one withnegative patch tests, and one with irritant reactions to gold. Blood samples were collected andexamined regarding the proliferation rate and which cytokines were secreted after culturingwith GSTS. We saw that the cultured lymphocytes from the allergic donors proliferated at asignificantly higher rate than the two other subject groups, and that the cells secreted cytokinesof both Th1 (Interferon (IFN) -g and Interleukin (IL) -2) and Th2 (IL-13 and IL-10) types. Theallergic donors secreted significantly higher levels of IFN-g, IL-2 and IL-13 than the two othersubject groups. Both the negative and irritant subject groups showed suppressed levels of thecytokines as compared with the unstimulated cultures, demonstrating the immunosuppressingeffects of gold.

    We also examined whether any of the analyzed markers, alone or combined, could be usedas an aid for diagnosing ACD to gold. We found that the IFN-g assay yielded the highestsensitivity (81.8 %) and specificity (82.1 %), and also identified 87.5 % of the irritant group asnon-allergic.

    In paper II we decided to investigate what cell types and subsets that reacted to the goldstimulation. We analyzed proliferation rate and expression of CD45RA, CD45R0, cutaneouslymphocyte-associated antigen (CLA) and the chemokine receptors CXCR3, CCR4 andCCR10. Similar to what has previously been published about nickel (Ni) allergy, the cells fromthe gold-allergic subjects that reacted to the GSTS stimulation expressedCD3+CD4+CD45R0+CLA+. However, contrary to findings in studies on Ni-reactive cells, wesaw no differences between allergic and non-allergic subjects regarding any of the chemokine receptors studied.

    In conclusion, we found that analysis of IFN-g might be a useful complement to patchtesting, possibly of interest in avoiding the need for repeated tests to rule out irritant reactions.We also saw that the cells that proliferated in response to gold were memory T-cells expressingCD4 and CLA, the marker for skin-homing. However, these cells did not express elevatedlevels of any of the chemokine receptors analyzed, showing that there are both similarities anddifferences between the mechanisms for Ni allergy and gold allergy.

    List of papers
    1. Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold
    Open this publication in new window or tab >>Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold
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    2006 (English)In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 55, no 2, p. 101-112Article in journal (Refereed) Published
    Abstract [en]

    10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

    Keywords
    Allergic contact dermatitis, cytokines, gold, interferon-γ, lymphocyte transformation test, multibead assay
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20564 (URN)10.1111/j.1600-0536.2006.00908.x (DOI)16930235 (PubMedID)
    Available from: 2009-09-14 Created: 2009-09-14 Last updated: 2017-12-13Bibliographically approved
    2. T-cells expressing CD4, CD45RO and CLA from gold-allergic but not healthy subjects react to gold sodium thiosufate in vitro
    Open this publication in new window or tab >>T-cells expressing CD4, CD45RO and CLA from gold-allergic but not healthy subjects react to gold sodium thiosufate in vitro
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Patch test positivity to gold is common in western societies, but in contrast to nickel (Ni) allergy it is uncommon that the patch test positive patient shows any clinical symptoms. In this study we investigated cytotoxic effects of gold sodium thiosulphate (GSTS) on peripheral blood mononuclear cells (PBMC), including different T-cell subsets. We also separated lymphocytes from allergic and non-allergic subjects into CD45RA and CD45R0 cell fractions. We also expressed CLA. The fraction of analyzed the effects of GSTS using lymphocyte transformation test, propidium iodide staining and flow cytometry to determine lymphocyte memory status, expression of chemokine receptors and cutaneous lymphocyte-associated antigen (CLA), and compared the results to what has previously been reported on Ni allergy. We found that only the cells from the allergic subjects proliferated in the lymphocyte transformation test (LTT), and in the CD45R0 fraction there was a dose-dependent increase in the fraction of CD3/CD4 cells. Similar to Ni-allergy, these CD3/CD4/CD45R0 cells also expressed CLA. The fraction of CD3/CD8 in the CD45R0 enriched fraction decreased with GSTS exposure. In contrast to Ni allergy, however, we found no differences between the allergic and non-allergic subjects regarding the chemokine receptors CCR4, CXCR3 and CCR10.

    Keywords
    contact dermatitis t-cell CD45RA CD45R0 CLA gold
    National Category
    Dermatology and Venereal Diseases
    Identifiers
    urn:nbn:se:liu:diva-19965 (URN)
    Available from: 2009-09-14 Created: 2009-08-21 Last updated: 2010-01-14Bibliographically approved
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  • 18.
    Clifford, Jenny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Dermatology and Venerology UHL.
    Karin, Cederbrant
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences.
    T-cells expressing CD4, CD45RO and CLA from gold-allergic but not healthy subjects react to gold sodium thiosufate in vitroManuscript (preprint) (Other academic)
    Abstract [en]

    Patch test positivity to gold is common in western societies, but in contrast to nickel (Ni) allergy it is uncommon that the patch test positive patient shows any clinical symptoms. In this study we investigated cytotoxic effects of gold sodium thiosulphate (GSTS) on peripheral blood mononuclear cells (PBMC), including different T-cell subsets. We also separated lymphocytes from allergic and non-allergic subjects into CD45RA and CD45R0 cell fractions. We also expressed CLA. The fraction of analyzed the effects of GSTS using lymphocyte transformation test, propidium iodide staining and flow cytometry to determine lymphocyte memory status, expression of chemokine receptors and cutaneous lymphocyte-associated antigen (CLA), and compared the results to what has previously been reported on Ni allergy. We found that only the cells from the allergic subjects proliferated in the lymphocyte transformation test (LTT), and in the CD45R0 fraction there was a dose-dependent increase in the fraction of CD3/CD4 cells. Similar to Ni-allergy, these CD3/CD4/CD45R0 cells also expressed CLA. The fraction of CD3/CD8 in the CD45R0 enriched fraction decreased with GSTS exposure. In contrast to Ni allergy, however, we found no differences between the allergic and non-allergic subjects regarding the chemokine receptors CCR4, CXCR3 and CCR10.

  • 19.
    Cuijpers, Pim
    et al.
    Linköping University, Faculty of Arts and Sciences. Vrije University of Amsterdam, Netherlands; EMGO Institute Health and Care Research, Netherlands; Karolinska Institute, Sweden.
    De Wit, Leonore
    Vrije University of Amsterdam, Netherlands; EMGO Institute Health and Care Research, Netherlands.
    Weitz, Erica
    Vrije University of Amsterdam, Netherlands; EMGO Institute Health and Care Research, Netherlands.
    Andersson, Gerhard
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Karolinska Institute, Sweden.
    Huibers, Marcus J. H.
    Vrije University of Amsterdam, Netherlands; EMGO Institute Health and Care Research, Netherlands.
    THE COMBINATION OF PSYCHOTHERAPY AND PHARMACOTHERAPY IN THE TREATMENT OF ADULT DEPRESSION: A COMPREHENSIVE META-ANALYSIS2015In: JOURNAL OF EVIDENCE-BASED PSYCHOTHERAPIES, ISSN 2360-0853, Vol. 15, no 2, p. 147-168Article in journal (Refereed)
    Abstract [en]

    No meta-analysis in the field of depression has examined the effects of combined treatment compared with pill placebo, nor has any meta-analysis integrated the comparison of combined treatment against pharmacotherapy alone and psychotherapy alone (i.e., mono treatments). In this comprehensive meta-analysis, we found that combined treatment had a moderate effect on depression compared with pill placebo (g=0.46), and small to moderate effects compared against pharmacotherapy (g=0.38) alone, psychotherapy (g=0.34) alone, and psychotherapy plus placebo (g=0.23). There were some indications for publication bias when combined therapy was compared against placebo (adjusted effect size g=0.31). In multivariate metaregression analyses we found no significant differential predictors for the four comparisons. There were some indications that the use of interpersonal psychotherapy in the combined treatment was associated with a smaller effect size, but this has to be considered with caution, because of the correlational nature of this association. Despite limitations (small number of studies; suboptimal quality of studies) this meta-analysis suggests that combined treatment of depression may be the best treatment available for adult depression, and that it is significantly more effective than placebo, pharmacotherapy alone, psychotherapy alone and the combination of psychotherapy and placebo.

  • 20.
    Dahlen Gyllencreutz, J.
    et al.
    Skaraborg Hospital, Sweden.
    Paoli, J.
    University of Gothenburg, Sweden.
    Bjellerup, M.
    Lund University, Sweden.
    Bucharbajeva, Z.
    Umeå University, Sweden.
    Gonzalez, H.
    University of Gothenburg, Sweden.
    Nielsen, K.
    Lund University, Sweden.
    Sandberg, C.
    University of Gothenburg, Sweden.
    Synnerstad, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Faculty of Medicine and Health Sciences.
    Terstappen, K.
    Skaraborg Hospital, Sweden.
    Wennberg Larko, A. -M.
    University of Gothenburg, Sweden.
    Diagnostic agreement and interobserver concordance with teledermoscopy referrals2017In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 31, no 5, p. 898-903Article in journal (Refereed)
    Abstract [en]

    BackgroundMalignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. ObjectiveTo evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. MethodsThe referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. ResultsTeledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. ConclusionBy adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.

  • 21.
    Danielsen, Kjersti
    et al.
    UiT, Norway; Univ Hosp North Norway, Norway.
    Duvetorp, Albert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Skanes Univ Sjukhus, Sweden.
    Iversen, Lars
    Aarhus Univ Hosp, Denmark.
    Ostergaard, Mikkel
    Univ Copenhagen, Denmark.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Steinar Tveit, Kare
    Haukeland Hosp, Norway.
    Skov, Lone
    Univ Copenhagen, Denmark.
    Prevalence of Psoriasis and Psoriatic Arthritis and Patient Perceptions of Severity in Sweden, Norway and Denmark: Results from the Nordic Patient Survey of Psoriasis and Psoriatic Arthritis2019In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 99, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    Optimal clinical management of psoriasis and psoriatic arthritis (PsA) requires understanding of the impact on patients. The NORdic PAtient survey of Psoriasis and PsA (NORPAPP) aimed to obtain current data on disease prevalence and patient perceptions in Sweden, Denmark and Norway. Among 22,050 individuals questioned, the reported prevalence of psoriasis and/or PsA was 9.7% (5.7% physician-diagnosed plus 4.0% self-diagnosed only); prevalence was similar in Sweden (9.4%) and Denmark (9.2%) but significantly higher in Norway (11.9%). Of those reporting a physicians diagnosis, 74.6% reported psoriasis alone, 10.3% PsA alone and 15.1% both. Patients with PsA perceived their disease to be more severe than those with psoriasis; patients with PsA and psoriasis reported greater disease severity than those with each condition alone. Patients perceptions of psoriasis severity correlated weakly (Spearmans rho 0.42) with clinical severity; both patient perceptions and clinical measures are important in the assessment and management of psoriasis.

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  • 22. Order onlineBuy this publication >>
    Duvetorp, Albert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Different Aspects of Psoriasis: Comorbidity, Comedication and Disease Biomarkers2021Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Psoriasis is a common heterogeneous inflammatory disease with its predominant manifestation occurring in the skin. The impact of this disease, however, extends far beyond the skin surface. During the last decades, mounting scientific evidence of psoriasis disease impact on quality of life, stigmatization and comorbidity has led to the predominant view that psoriasis care needs a holistic approach. Epidemiological research is needed to visualize the greater picture whereas research on disease pathomechanisms can provide answers to disease evaluation challenges, facilitate development of new treatments, and provide insights into mechanistical bridges explaining comorbidity occurrence. 

    In study I of this thesis, serum S100A8/A9 was evaluated as a possible biomarker of psoriasis skin disease activity. Dramatic reductions in S100A8 and S100A9 and S100A8/A9 heterocomplex levels were found in lesional psoriasis skin after NB-UVB treatment without any significant reduction occurring in serum. 

    Study II was designed as a retrospective, cross-sectional population study including the adult population of the county of Jönköping. The odds of having pharmacologically treated depression among individuals with psoriasis was compared to the odds of the background population. Psoriasis was associated with an elevated depression risk. Depression was more prevalent among women (both in the background population and among individuals with psoriasis). Young age was associated with higher odds for depression among individuals with psoriasis. 

    Study III was based on the same study population as study II. In this study the comedication burden of individuals with psoriasis was compared to the background population. Comedication assessed were prescription drugs used to treat comorbidity associated with psoriasis in previous scientific publications. Patients with psoriasis were found to have a high comedication burden. Patients receiving systemic treatment for psoriasis had a higher number of different dispensed drugs suggesting that severe disease implies a higher risk of comorbid disease. 

    Study IV was an exploratory study assessing numerous potential biomarkers for psoriasis disease activity. Extensive Luminex analysis of skin and serum samples collected during study I was performed. No serum mediator (potential biomarker of disease activity) showed a significant change after NB-UVB (following correction for multiple testing). In skin, NB-UVB had effects on mediators of the Th17 pathway and multiple chemokines but also previously undescribed or less explored disease mediators. 

    Study II and III suggest that comorbidity and its comedication is common among Swedish psoriasis patients in contact with the health care system. This research reinforces the perception that a holistic approach is needed when treating patients with psoriasis. Behind the failure to identify a biomarker for skin disease activity in study I and IV lurks the questions to how, if or when inflammation in the skin affects systemic inflammation and in extension comorbid disease. 

    List of papers
    1. Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum
    Open this publication in new window or tab >>Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum
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    2019 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 3, article id e0213344Article in journal (Refereed) Published
    Abstract [en]

    S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity.

    Place, publisher, year, edition, pages
    PUBLIC LIBRARY SCIENCE, 2019
    National Category
    Dermatology and Venereal Diseases
    Identifiers
    urn:nbn:se:liu:diva-155895 (URN)10.1371/journal.pone.0213344 (DOI)000461048900062 ()30865695 (PubMedID)
    Note

    Funding Agencies|Futurum - Academy for Health and Care [657091, 416821, 383521]

    Available from: 2019-04-03 Created: 2019-04-03 Last updated: 2023-12-28
    2. Sex and Age Influence the Associated Risk of Depression in Patients with Psoriasis: A Retrospective Population Study Based on Diagnosis and Drug-Use
    Open this publication in new window or tab >>Sex and Age Influence the Associated Risk of Depression in Patients with Psoriasis: A Retrospective Population Study Based on Diagnosis and Drug-Use
    2021 (English)In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 237, no 4, p. 595-602Article in journal (Refereed) Published
    Abstract [en]

    Background:The reported prevalence of depression among individuals with psoriasis varies substantially, and the effect of gender on depression distribution has revealed conflicting results. In addition, using medication to identify cases is uncommon. Objective: To study the prevalence of pharmacologically treated depression among individuals with and without psoriasis in a Swedish population using ICD-10 codes and data from the Swedish Prescribed Drug Register. Methods: A retrospective case-control population-based study was performed including all living individuals (age ≥18 years) in Region Jönköping, southern Sweden (n = 273,536). ICD-10 codes for the diagnosis of psoriasis (L40.*) and depression (F32.* and F33.*), and data on pharmacological treatment from the Swedish Prescribed Drug Register, were extracted from electronic medical records between April 9, 2008 and January 1, 2016. The extraction date was January 1, 2016. Results: The risk of pharmacologically treated depression was increased in individuals with psoriasis (age- and sex-adjusted OR 1.55; CI 1.43–1.68); 21.1% of women with psoriasis received pharmacological treatment for depression during the study period compared to 14.2% in the control population. Prevalence figures for depression were significantly higher in women with psoriasis compared to men. The risk of suffering from depression was highest among male and female patients with psoriasis under the age of 31 years. Conclusions: Depression is common among patients with psoriasis. The results of the current study underline the need for dermatologists to adopt a holistic approach, looking beyond the skin, when handling patients with psoriasis in every-day clinical practice.

    Place, publisher, year, edition, pages
    KARGER, 2021
    Keywords
    Psoriasis, Depression, Sex, Age, Comorbidity
    National Category
    Psychiatry
    Identifiers
    urn:nbn:se:liu:diva-178321 (URN)10.1159/000509732 (DOI)000668636300015 ()32927456 (PubMedID)
    Note

    Funding agencies: The present study was funded by grants from the Swedish Psoriasis Association and FUTURUM Research Council County Jönköping. These funding sources were not involved in the preparation of data or the manuscript.

    Available from: 2021-08-18 Created: 2021-08-18 Last updated: 2023-12-28Bibliographically approved
    3. Psoriasis is Associated with a High Comedication Burden: A Population Based Register Study
    Open this publication in new window or tab >>Psoriasis is Associated with a High Comedication Burden: A Population Based Register Study
    2020 (English)In: Dermatology and Therapy, ISSN 2193-8210, Vol. 10, p. 1285-1298Article in journal (Refereed) Published
    Abstract [en]

    Introduction A large body of evidence supports the association between psoriasis and concomitant diseases. However, the study of comedication for these diseases in patients with psoriasis is limited. The current study aimed to investigate the prescription and drug dispensation for comorbidity associated with psoriasis. Methods We conducted a retrospective case-control study from 9 April 2008 until 1 January 2016 using an electronic medical records database covering the entire population of the County of Jonkoping and the Swedish Prescribed Drug Register. ICD-10 and Anatomical Therapeutic Chemical codes were used to identify patients with psoriasis and dispensed pharmaceutical prescriptions. Individuals without psoriasis were selected as controls. Patients receiving systemic treatment for psoriasis were considered as having moderate-severe psoriasis. Odds ratios for being dispensed pharmaceutical prescriptions and differences in mean number of dispensed prescriptions were explored. Results A total of 4587 patients with psoriasis were identified in the medical records, and 268,949 individuals served as controls. Patients with psoriasis had a significantly higher number of different drug dispensations compared to controls. Only 1.3% of all patients with psoriasis were without any prescription (excluding medication for psoriasis) during the study period while the number in the general population was 9.3%. Sex- and age-adjusted odds ratios for dispensation of drug groups related to comorbid disease were significantly higher among patients with psoriasis including drug groups such as anxiolytics and sedatives as well as drugs targeting COPD, migraine and erectile dysfunction. The most frequently dispensed comedications were oral antibiotics and analgesics including an increased risk for dispensation of opioids. Sex predisposed dispensation frequency for a variety of drug groups. Drugs targeting obesity, osteoporosis, psychiatric disease and anti-mycotics/-fungals were more frequent among women. Conclusion Patients with psoriasis have significantly increased numbers of different dispensed prescriptions than those without psoriasis. This underlines previous findings on increased comorbidity and health care costs for patients with psoriasis.

    Place, publisher, year, edition, pages
    ADIS INT LTD, 2020
    Keywords
    Comorbidity; Drug therapy; Polypharmacy; Psoriasis; Psoriatic arthritis
    National Category
    Social and Clinical Pharmacy
    Identifiers
    urn:nbn:se:liu:diva-170055 (URN)10.1007/s13555-020-00442-3 (DOI)000566052000001 ()32888181 (PubMedID)
    Note

    Funding Agencies|Psoriasisforbundet (The Swedish Psoriasis Association); Region Skane; Futurum Academy for Health and Care

    Available from: 2020-09-28 Created: 2020-09-28 Last updated: 2023-12-28
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  • 23.
    Duvetorp, Albert
    et al.
    Skane Univ Hosp, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Engerstedt Mattsson, Emma
    LEO Pharma AS, Denmark.
    Ryttig, Lasse
    LEO Pharma AS, Denmark.
    A Cost-utility Analysis of Calcipotriol/Betamethasone Dipropionate Aerosol Foam versus Ointment for the Topical Treatment of Psoriasis Vulgaris in Sweden2019In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 99, no 4, p. 393-399Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a chronic inflammatory disorder that imposes a substantial economic burden. We conducted a cost-utility analysis from a Swedish healthcare payers perspective using a decision-tree model with a 12-week time horizon. Patients with psoriasis vulgaris could have two 4-week cycles of topical treatment with calcipotriol 50 mu g/g and betamethasone 0.5 mg/g as dipropionate (Cal/BD) foam or Cal/BD ointment before progressing to phototherapy/methotrexate. In the base-case analysis, Cal/BD foam dominated over Cal/BD ointment. The increased efficacy of Cal/BD foam resulted in fewer consultations and a decreased risk of progressing to phototherapy/methotrexate. Although Cal/BD foam costs more than Cal/BD ointment, this was offset by lower costs for phototherapy/methotrexate or consultation visits. Sensitivity analyses revealed that the base-case net monetary benefit was robust to plausible variations in key parameters. In conclusion, Cal/BD foam was predicted to be more cost-effective than Cal/BD ointment in the treatment of psoriasis vulgaris.

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  • 24.
    Duvetorp, Albert
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Skanes Univ Sjukhus, Sweden.
    Ostergaard, M.
    Univ Copenhagen, Denmark.
    Skov, L.
    Univ Copenhagen, Denmark.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Hosp, Sweden.
    Tveit, K. S.
    Haukeland Hosp, Norway.
    Danielsen, K.
    UiT Arctic Univ Norway, Norway; Univ Hosp North Norway, Norway.
    Iversen, Lars
    Aarhus Univ Hosp, Denmark.
    Quality of life and contact with healthcare systems among patients with psoriasis and psoriatic arthritis: results from the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP)2019In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 311, no 5, p. 351-360Article in journal (Refereed)
    Abstract [en]

    Psoriasis (skin psoriasis, PsO) is a chronic inflammatory condition. In about one-third of cases, the joints are affected (psoriatic arthritis, PsA). Both conditions, especially PsA, profoundly impact patients health-related quality of life (HRQoL). To describe the impact of psoriasis on HRQoL and patients contact with the healthcare system in Sweden, Denmark, and Norway, the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP) asked 22,050 adults randomly selected in Sweden, Denmark and Norway if they had psoriasis. 1264 individuals who reported physician-diagnosed PsO/PsA were invited to the full survey; 1221 responded (74.6% diagnosed with PsO alone; 25.4% with PsA +/- PsO). Respondents with PsA most frequently consulted a rheumatologist; however, 14.3% had never seen a rheumatologist. Respondents with PsO alone most frequently consulted a general practitioner and 10.7% had never seen a dermatologist (although those with severe symptoms visited dermatologists more often). Negative impacts on HRQoL were reported by 38.1% of respondents with PsO [mostly limitations on clothing (22.6%), sleep disorders (16%), and depression/anxiety (16%)] and by 73% of respondents with PsA [mostly limitations on clothing (41.8%), sports/leisure (44.0%), or daily routine (45.1%) and sleeping disorders]. Absence from work/education was more common with PsA +/- PsO (51.9%) than PsO alone (15.1%). In this survey in Sweden, Denmark, and Norway, the impact of psoriasis on the respondents HRQoL was profound and was greater for PsA than for PsO, as was sickness absence. Sleeping disorders and depression were common and should not be overlooked.

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  • 25.
    Duvetorp, Albert
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Skanes Univ Sjukhus, Sweden.
    Pettersson, Kjellina
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Soderman, Jan
    Lanssjukhuset Ryhov, Sweden.
    Assarsson, Malin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Lanssjukhuset Ryhov, Sweden.
    Seifert, Oliver
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Lanssjukhuset Ryhov, Sweden.
    Narrowband-UVB treatment reduces levels of mediators of the Th17 pathway and chemotaxis in psoriatic skin without any concurring effect on mediator levels in serum2022In: EJD. European journal of dermatology, ISSN 1167-1122, E-ISSN 1952-4013, Vol. 32, no 2, p. 250-259Article in journal (Refereed)
    Abstract [en]

    Background: Narrowband-UVB (NB-UVB) is a common and effective psoriasis treatment. It exerts its effect locally and is therefore a better model for exploring dynamics of serum biomarkers reflecting psoriasis skin disease activity compared to other treatments with systemic uptake. Objectives: To perform an exploratory study to assess potential roles of multiple disease mediators as biomarkers for psoriasis disease activity, and increase understanding of NB-UVB treatment effects in psoriatic skin. Materials & Methods: Patients with plaque psoriasis were sampled (lesional, non-lesional skin, serum) before and after full NB-UVB treatment. Samples were assessed for 78 different mediators using Luminex assays. Correlation networks were analysed to explore interactions between lesional skin mediators before and after NB-UVB treatment. Results: None of the studied serum mediators were significantly affected by NB-UVB treatment after correction for multiple testing. Thirty mediators revealed a significant difference in lesional skin compared to non-lesional skin before treatment including interleukin 23 (IL-23) and C-C motif chemokine ligand 20 (CCL20), but also novel mediators such as angiopoietin-like 4 (ANGPTL4) and pentraxin 3 (PTX3). The levels of 25 mediators in skin decreased significantly, and network analysis revealed markedly reduced cluster formations and correlations after NB-UVB. Conclusion: NB-UVB treatment reduced the concentration of mediators of the Th17 inflammatory pathway and chemotaxis in psoriatic lesional skin, but also affected less studied and novel mediators. Although the treatment affected the levels of a majority of mediators in skin, no corresponding effect was observed in serum, thus challenging the possibility of a serum biomarker reflecting skin disease activity.

  • 26.
    Duvetorp, Albert
    et al.
    Regional Jönköping County, Sweden.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Nyström, Helena
    Regional Jonköping County, Sweden.
    Skarstedt, Marita
    Regional Jonköping County, Sweden.
    Dienus, Olaf
    Regional Jonköping County, Sweden.
    Mrowietz, Ulrich
    University of Medical Centre Schleswig Holstein, Germany.
    Soederman, Jan
    Regional Jonköping County, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in psoriasis skin2017In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 26, no 11, p. 1033-1038Article in journal (Refereed)
    Abstract [en]

    Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signalling. Wnt ligands are thought to play an important role in innate immunity and psoriasis, and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV-B radiation, LRP5/6 skin gene expression was analysed before and after narrowband UV-B treatment. Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non-lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in psoriasis.

  • 27.
    Duvetorp, Albert
    et al.
    Regional Jönköping County, Sweden.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Skarstedt, Marita
    Regional Jonköping County, Sweden.
    Söderman, Jan
    Regional Jonköping County, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 8, p. 916-921Article in journal (Refereed)
    Abstract [en]

    CD93 is involved in angiogenesis and inflammation, both of which are key processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral blood mononuclear cells and skin of patients with psoriasis and controls. Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms rs2749812 and rs2749817 were assessed in patients with psoriasis compared with controls and the effect of narrow-band ultraviolet B (NB-UVB) treatment on CD93 gene expression was evaluated in the skin of patients with psoriasis. CD93 gene expression was significantly increased in lesional and non-lesional skin from patients with psoriasis compared with controls. Immunohistochemistry revealed CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment of patients with psoriasis did not alter skin CD93 gene expression. Increased protein expression of CD93 psoriatic skin and association with the rs2749817 polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.

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  • 28.
    Duvetorp, Albert
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Skane Univ Hosp, Sweden.
    Söderman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Assarsson, Malin
    Ryhov Cty Hosp, Sweden.
    Skarstedt, Marita
    Ryhov Cty Hosp, Sweden.
    Svensson, Ake
    Skane Univ Hosp, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 3, article id e0213344Article in journal (Refereed)
    Abstract [en]

    S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity.

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  • 29.
    Egeberg, Alexander
    et al.
    Univ Copenhagen, Denmark.
    Freilich, Jonatan
    Umea Univ, Sweden; Parexel Int, Sweden.
    Stelmaszuk, M. Natalia
    Parexel Int, Sweden.
    Kongerslev, Rikke
    LEO Pharma AS, Denmark.
    Apol, Eydna
    LEO Pharma AS, Denmark.
    Hansen, Jes Birger
    LEO Pharma AS, Denmark.
    Levin, Lars-Åke
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Real-world dose adjustments of biologic treatments in psoriasis and their economic impact: a Swedish national population study2022In: Clincal and Experimental Dermatology, ISSN 0307-6938, E-ISSN 1365-2230, Vol. 47, no 11, p. 1968-1975Article in journal (Refereed)
    Abstract [en]

    Background To date, evidence on the dose adjustments of biologics in the real-world treatment of psoriasis is limited. However, dose adjustments may have important clinical and economic implications. Aims To study the dose adjustments of individual biologics over time in real-world practice in Sweden. Methods A retrospective observational study of adults with moderate to severe psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Treatment episodes were identified for individual patients from the date of drug dispensation to the end of the supply of the drug. Dosing data were expressed as the proportion of treatment episodes with accumulated syringes/vials equal to, above or below the recommended guidelines. Real-world costs were calculated and compared with costs predicted from dosing guidelines. Results The mean dose was above recommended levels for all biologics investigated. Weighted mean dose adjustments for adalimumab, etanercept, secukinumab and ustekinumab were 13%, 23%, 8% and 3%, respectively, over the entire treatment period. Higher doses translate to higher costs, including notable increases over time vs. expected costs for secukinumab. Conclusions Dose adjustments of biologics are frequent in clinical practice but differ for the various biologics. The mean observed increases in dose above guideline recommendations might indicate perceptions of suboptimal efficacy for biologics, with implications for the cost and cost-effectiveness of these treatments. Further research is warranted to understand the reasons for dose adjustments in clinical practice.

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  • 30.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Ingrid Asp Psoriasis Research Center.
    Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis.2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 2, p. 424-426Article in journal (Refereed)
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  • 31.
    Ekman, Anna-Karin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Vegfors, Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Overexpression of Psoriasin (S100A7) Contributes to Dysregulated Differentiation in Psoriasis.2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 4, p. 441-448Article in journal (Refereed)
    Abstract [en]

    Psoriasin, which is highly expressed in psoriasis, is encoded by a gene located within the epidermal differentiation complex. The aim of this study was to investigate the effect of endogenous psoriasin on disturbed keratinocyte differentiation in psoriasis. Immunohistochemical staining revealed a gradient of psoriasin expression in the psoriatic epidermis with highest expression in the suprabasal, differentiated layers. Induction of keratinocyte differentiation caused concurrent expression of psoriasin and the differentiation marker involucrin. The differentiation-induced psoriasin expression was found to be mediated by the protein kinase C pathway. The downregulation of psoriasin expression by small interfering RNA revealed that psoriasin mediates the expression of involucrin, desmoglein 1, transglutaminase 1 and CD24 in normal differentiation. The lentivirus-mediated overexpression of psoriasin, mimicking the psoriatic milieu, gave rise to an altered regulation of differentiation genes and an expression pattern reminiscent of that in psoriatic epidermis. These findings suggest that psoriasin contributes to the dysregulated differentiation process in the psoriasis epidermis.

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  • 32.
    Eldh, Maria
    et al.
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Olofsson Bagge, Roger
    1.Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Lässer, Cecilia
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Svanvik, Joar
    Sahlgrenska universitetssjukhuset, Göteborg.
    Sjöstrand, Margareta
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    Mattsson, Jan
    1.Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Lindnér, Per
    1.Transplant Institute, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital.
    Choi, Dong-Sic
    1.Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology (POSTECH).
    Gho, Yong Song
    1.Division of Molecular and Life Sciences, Department of Life Science, Pohang University of Science and Technology (POSTECH).
    Lötvall, Jan
    1.Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma2014In: BMC Cancer, ISSN 1471-2407, Vol. 14, no 962, p. 1-10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.

    METHODS:

    Exosomes were isolated from the liver perfusate of twelve patients with liver metastases from uveal melanoma undergoing IHP. Exosomes were visualised by electron microscopy, and characterised by flow cytometry, Western blot and real-time PCR. Furthermore, the concentration of peripheral blood exosomes were measured and compared to healthy controls.

    RESULTS:

    The liver perfusate contained Melan-A positive and RNA containing exosomes, with similar miRNA profiles among patients, but dissimilar miRNA compared to exosomes isolated from tumor cell cultures. Patients with metastatic uveal melanoma had a higher concentration of exosomes in their peripheral venous blood compared to healthy controls.

    CONCLUSIONS:

    Melanoma exosomes are released into the liver circulation in metastatic uveal melanoma, and is associated with higher concentrations of exosomes in the systemic circulation. The exosomes isolated directly from liver circulation contain miRNA clusters that are different from exosomes from other cellular sources.

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  • 33.
    Eriksson, Hanna
    et al.
    Department of Oncology-Pathology, Karolinska Institutet, and Deptartment of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Andersson, Therese M-L
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    The proportion cured of patients diagnosed with Stage III-IV cutaneous malignant melanoma in Sweden 1990-2007: A population-based study.2016In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 12Article in journal (Refereed)
    Abstract [en]

    The survival in cutaneous malignant melanoma (CMM) is highly dependent on the stage of the disease. Stage III-IV CMM patients are at high risk of relapse with a heterogeneous outcome, but not all experience excess mortality due to their disease. This group is referred to as the cure proportion representing the proportion of patients who experience the same mortality rate as the general population. The aim of this study was to estimate the cure proportion of patients diagnosed with Stage III-IV CMM in Sweden. From the population-based Swedish Melanoma Register, we included 856 patients diagnosed with primary Stage III-IV CMM, 1990-2007, followed-up through 2013. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by sex, age, tumor site, ulceration status (in Stage III patients) and disease stage. The standardized (over sex, age and site) cure proportion was lower in Stage IV CMMs (0.15, 95% CI 0.09-0.22) than non-ulcerated Stage III CMMs (0.48, 95% CI 0.41-0.55) with a statistically significant difference of 0.33 (95% CI = 0.24-0.41). Ulcerated Stage III CMMs had a cure proportion of 0.27 (95% CI 0.21-0.32) with a statistically significant difference compared to non-ulcerated Stage III CMMs (difference 0.21; 95% CI = 0.13-0.30). The standardized MST of uncured was approximately 9-10 months longer for non-ulcerated versus ulcerated Stage III CMMs. We could demonstrate a significantly better outcome in patients diagnosed with non-ulcerated Stage III CMMs compared to ulcerated Stage III CMMs and Stage IV disease after adjusting for age, sex and tumor site.

  • 34.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Anogenital Chlamydia trachomatis Infection Including Lympho­granuloma Venereum: Clinical Guidelines, Sweden2009In: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, no 4, p. 101-103Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 35.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Challenges of treatment for urethritis and cervicitis, (SY06:5)2012Conference paper (Other academic)
    Abstract [en]

    Challenges of treatment for urethritis and cervicitis

     

    Urethritis in men caused by gonorrhoea is symptomatic. Non-gonorrhoic-urethritis (NGU) i.e. caused by Chlamydia trachomatis, Mycoplasma genitalium and occasionally other bacteria is in most cases an asymptomatic infection. Swartz’ definition of microscopic urethritis > 4 polymorphonucleated leucocytes (PML) per high power field (HPF) in > 4 HPF is the general accepted, but has limitations and is dependant on the sampling, microscope, the physician and the patient as well. Cervicitis is even more cumbersome since it is even more often asymptomatic. Other factors such as which contraception method is used, concurrent infections (bacterial vaginosis, candidosis), the microscope and the physician, may have a great impact. Brunham proposed as definition observed mucopurulent discharge from the cervix orifice combined with > 10 PML per HPF in stained endocervical smear. Lindner proposed sign of friability of the portio cervicis. Weström found a correlation of more PML than vaginal epithelial cells in wet mount. The variety of definitions causes problem in comparing scientific studies and at the clinic as well. The intention to treat also means testing and treatment of a current sexual partner as well.

     

    The ever emerging decreased susceptibility of various antibiotics especially against Neisseria gonorrhoeae and M. genitalium makes it even more important to choose whether to treat immediately without having positive tests or to miss a treatment of a potential serious infection. N. gonorrhoeae is visible microscopically in urethral stains from men, but can be missed in smears from endocervix and urethra in women. Cefixim 400 mg stat is the recommended first line antibiotic treatment. Ceftriaxone 500 mg is under consideration to become the first treatment of choice due to emerging decreased susceptibility. M.genitalium will be discussed in another speech by Jørgen Skov Jensen. There are some few reports of antibiotic resistance of Chlamydia trachomatis but this infection is generally still eradicated by tetracycline and macrolide treatment. In an NGU and or unspecific cervicitis doxycycline 100 mg bid for one week is the first treatment of choice. Azithromycin 1 g stat should be used with precaution. If there are persisting signs and or symptoms after doxycycline treatment, azithromycin 500 mg day 1 and 250 mg following four days should be prescribed. Bacterial vaginosis may give symptoms and signs of cervicitis and is also a very common concurrent infection in women with C. trachomatis and M.genitalium as well and treatment with metronidazole or clindamycin should be considered. The fast ways of communication via the Internet and the easy accessible and legal way of an individual to buy antibiotics just for safe or to avoid attending a clinic is a big threat now and even more in the future because of the potential rapid increasing antibiotic resistance of many bacterial infections including STIs

  • 36.
    Falk, Lars
    Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Clinical Guidelines in Sweden - Anogenital Chlamydia trachomatis Infection Including Lymphogranuloma Venereum2009In: Forum for Nordic Dermato-Venerology, Vol. 14, no 4, p. 101-103Article in journal (Other academic)
  • 37.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    The overall agreement of proposed definitions of mucopurulent cervicitis in women at high risk of chlamydia infection2010In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, ISSN 0001-5555, Vol. 90, p. 506-511Article in journal (Refereed)
    Abstract [en]

    The overall agreement between different criteria for cervicitis in women infected with Chlamydia trachomatis and/or Mycoplasma genitalium, and in women who tested negative was examined. Women attending a clinic for sexually transmitted diseases were enrolled because of sexual partners’ suspected chlamydia infection. M. genitalium was tested in a sample of first-catch urine and an endocervical specimen, whereas specimens from four different sites were used for detection of C. trachomatis. Signs of friability and purulent endocervical discharge were documented at gynaecological examination. Specimens for microscopy were taken from the endocervix and urethra as well as the vaginal discharge, and bacterial vaginosis was examined for. The criteria being evaluated included cervical friability and/or pus; polymorphonuclear leukocytes (PMNL)/epithelium cell ratio in the vaginal discharge; and more than 30 PMNL per high-power field in the endocervical smear. The overall agreement of the indicators of cervicitis in women infected with C. trachomatis and/or M. genitalium was 40.5% (15/37), and for those women with negative tests 35.3% (12/34). The criteria for cervicitis require further evaluation, including study of a control group of women at low risk of having a sexually transmitted infection.

  • 38.
    Falk, Lars
    et al.
    Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland. Linköping University, Faculty of Health Sciences.
    Coble, Britt-Inger
    Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Mjörnberg, Per-Anders
    Ryhov County Hospital, Jönköping.
    Fredlund, Hans
    Örebro Universitet.
    Sampling for Chlamydia trachomatis infection – a comparison of vaginal, first-catch urine, combined vaginal and first-catch urine and endocervical sampling2010In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, ISSN 0956-4624, Vol. 21, no 4, p. 283-287Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to evaluate the sensitivity of patients' self-sampled vaginal specimens, first-catch urine (FCU), combined vaginal/FCU specimens and endocervical specimens for detecting chlamydial infection in women. Women attending sexually transmitted disease clinics, youth clinics and a women's health clinic were enrolled. They self-collected a vaginal specimen with two swabs, which were placed into a sterile tube and into a tube containing a buffer medium, respectively. An FCU sample was collected and aliquoted into both an empty tube and the tube containing the vaginal swab. A clinician collected an endocervical swab. The samples were sent to laboratories for analysis using polymerase chain reaction testing and strand displacement amplification testing, respectively. The sensitivities calculated in all 171 Chlamydia trachomatis-infected women were equal for endocervical specimens (97.1%), vaginal specimens (96.5%) and combined vaginal/FCU specimens (95.3%), whereas the sensitivity for FCU was significantly lower (87.7%). The sensitivity of vaginal specimens for the detection of C. trachomatis is as high as that of combined vaginal/FCU specimens.

  • 39.
    Falk, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Faculty of Medicine and Health Sciences.
    Enger, Martin
    Vastervik Hosp, Vastervik, Sweden.
    Jensen, Jorgen Skov
    Statens Serum Institut Köpenhamn.
    Time to eradication of Mycoplasma genitalium after antibiotic treatment in men and women.2015In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 70, no 11, p. 3134-3140Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The objectives of this study were to evaluate the time to a Mycoplasma genitalium-negative test after start of treatment and to monitor if and when antibiotic resistance developed.

    METHODS:

    Sexually transmitted disease (STD) clinic attendees with suspected or verified M. genitalium infection were treated with azithromycin (5 days, 1.5 g; n = 85) or moxifloxacin (n = 5). Subjects with symptomatic urethritis or cervicitis of unknown aetiology were randomized to either doxycycline (n = 49) or 1 g of azithromycin as a single dose (n = 51). Women collected vaginal specimens and men collected first-catch urine 12 times during 4 weeks. Specimens were tested for M. genitalium with a quantitative MgPa PCR and for macrolide resistance-mediating mutations with a PCR targeting 23S rRNA.

    CLINICAL TRIALS REGISTRATION:

    NCT01661985.

    RESULTS:

    Ninety M. genitalium cases were enrolled. Of 56 patients with macrolide-susceptible strains before treatment with azithromycin (1.5 g, n = 46; 1 g single oral dose, n = 10), 54 (96%) had a negative PCR test within 8 days. In four patients, M. genitalium converted from macrolide susceptible to resistant after a 10 day lag time with negative tests (azithromycin 1.5 g, n = 3; 1 g single oral dose, n = 1). Moxifloxacin-treated subjects (n = 4) were PCR negative within 1 week. Six of eight (75%) remained positive despite doxycycline treatment.

    CONCLUSIONS:

    PCR for M. genitalium rapidly became negative after azithromycin treatment. Macrolide-resistant strains were detected after initially negative tests. Test of cure should be recommended no earlier than 3-4 weeks.

  • 40.
    Falk, Lars
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Fredlund, Hans
    Örebro University Hospital.
    Letter: Re: Sampling for Chlamydia trachomatis infection2010In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 21, no 12, p. 847-847Article in journal (Other academic)
  • 41.
    Falk, Lars
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Hegic, Sabina
    Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Wilson, Daniel
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Home-sampling as a Tool in the Context of Chlamydia trachomatis Partner Notification: A Randomized Controlled Trial2014In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 94, no 1, p. 72-74Article in journal (Other academic)
    Download full text (pdf)
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  • 42.
    Falk, Lars
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Skov Jensen, Jorgen
    Microbiology and Infection Control, Sexually Transmitted Infections, Research and Development, Statens Serum Institut, Copenhagen, Denmark.
    Successful outcome of macrolide-resistant Mycoplasma genitalium urethritis after spectinomycin treatment: a case report2017In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 72, no 2, p. 624-625Article in journal (Refereed)
  • 43.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Self-estimation or Phototest Measurement of Skin UV Sensitivity and its Association with Peoples Attitudes Towards Sun Exposure2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 2, p. 797-803Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Fitzpatrick's classification is the most common way of assessing skin UV sensitivity. The study aim was to investigate how self-estimated and actual UV sensitivity, as measured by phototest, are associated with attitudes towards sunbathing and the propensity to increase sun protection, as well as the correlation between self-estimated and actual UV sensitivity.

    PATIENTS AND METHODS:

    A total of 166 primary healthcare patients filled-out a questionnaire investigating attitudes towards sunbathing and the propensity to increase sun protection. They reported their skin type according to Fitzpatrick, and a UV sensitivity phototest was performed.

    RESULTS:

    Self-rated low UV sensitivity (skin type III-VI) was associated with a more positive attitude towards sunbathing and a lower propensity to increase sun protection, compared to high UV sensitivity. The correlation between the two methods was weak.

    CONCLUSION:

    The findings might indicate that individuals with a perceived low but in reality high UV sensitivity do not seek adequate sun protection with regard to skin cancer risk. Furthermore, the poor correlation between self-reported and actual UV sensitivity, measured by phototest, makes the clinical use of Fitzpatrick's classification questionable.

  • 44. Order onlineBuy this publication >>
    Falk, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Towards a broader use of phototesting: in research, clinical practice and skin cancer prevention2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In western societies, skin cancer incidence has increased dramatically over recent decades, due predominantly to increased sun exposure habits. Ultraviolet (UV) light exposure and individual light sensitivity of the skin constitute two important factors affecting the risk for skin cancer development. Individuals with a heightened propensity to get sunburnt have a higher risk for skin malignancies, and need to protect themselves more systematically from the sun. Individual UVlight sensitivity can be determined either by self-estimation of tendency to burn and tan, as in the Fitzpatrick’s classification, or by use of a phototest. Although phototesting constitutes a considerably more objective method, it is only sparsely used, chiefly due to financial and resource related factors, and is mainly limited to investigation of photodermatoses or dose-management in photo therapy.

    The general aim of this thesis was to develop and improve aspects of the phototest procedure in rder to broaden the utilisation of phototesting within the fields of research, clinical practice and skin cancer prevention. As a first step, a new phototesting technique, using a divergent UVB beam was evaluated. The principle of the method is to provoke a circular UVB-erythema in the skin, the diameter of which is related to the administered dose and thus the Minimal Erythema Dose (MED). In a test group of healthy subjects, naked eye reading by a trained observer resulted in a more exact, estimation of UVB-sensitivity, compared to traditional phototesting. Since the diffuse border of the provoked erythema was challenging for the untrained observer to read, the need for an objective, bio-engineering technique for test reading was clear. In this thesis, Laser Doppler perfusion imaging (LDPI) has been used. This data also enabled an objective description of doseresponse for the reaction, an outcome not possible in traditional testing. The divergent beam method was also shown to be useful as a model for evaluation of the effect of topically applied substances.

    In order to broaden the utilisation of phototests in general, a test procedure built on patient performed self-reading of skin tests (a traditional phototest and an irritant patch test) was evaluated. The reliability of these self-readings was shown to be substantial when compared to the control readings of a trained observer.

    Using the self-reporting procedure, phototesting was evaluated as a tool in primary prevention of skin cancer. The study focussed on sun habits and sun protection behaviour, and also on investigating the impact of different forms of presentation of the preventive information. Results showed significantly higher impact for a personally mediated preventive message than by letterform. For individuals with heightened UV-sensitivity the performance of a phototest led to a greater tendency to adopt sun protection behaviour than for subjects with a lower UV-sensitivity, suggesting that phototesting is a useful way to improve the outcome in terms of preventive behaviours for this group of susceptible, at-risk individuals.

    Divergent beam phototesting, patient-performed self-reading, and the application of phototesting in skin cancer prevention emerge as three novel, previously little investigated, aspects of phototesting, for which promising results could be demonstrated.

    List of papers
    1. Phototesting based on a divergent beam: a study on normal subjects
    Open this publication in new window or tab >>Phototesting based on a divergent beam: a study on normal subjects
    2001 (English)In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 17, no 4, p. 189-196Article in journal (Refereed) Published
    Abstract [en]

    In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P<0.05). The divergent beam provocation allowed a more detailed discrimination of MED compared to the collimated beam provocation. The MED values determined with the divergent beam were, however, generally higher, especially in the lower range of MED values. Technical factors related to the beam divergence and the correct measurement of erythemal effective irradiance are believed to be the explanation for this phenomenon, which is thus correctable. In conclusion, the results from this study support our belief that the phototesting protocol based on a divergent beam constitutes a good opportunity for improved phototesting, since MED and dose-response characteristics may be extracted in more detail from a single UV exposure.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12817 (URN)10.1034/j.1600-0781.2001.170409.x (DOI)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-12-14
    2. Inter-observer variability in reading of phototest reactions with sharply or diffusely delineated borders
    Open this publication in new window or tab >>Inter-observer variability in reading of phototest reactions with sharply or diffusely delineated borders
    2008 (English)In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 14, no 4, p. 397-402Article in journal (Refereed) Published
    Abstract [en]

    Background: In both clinical and experimental phototesting, naked eye assessment of erythema has been the main assessment parameter. As with all subjective assessment, variability in recorded results due to variable circumstances around the performance and reading of tests influences reliability and utility of data whether they be interpreted for an individual patient or for a group of research subjects.

    Methods: In the present study, variability in the reporting of diameter of ultraviolet B (UVB) erythema has been studied. The erythematous reactions were assessed by the naked eye and with the help of a millimetre-graded ruler by a group of dermatologists and dermatological trainees. Reaction size, objectively quantified by means of laser Doppler perfusion imaging (LDPI) using thresholding of the reaction perfusion, and known size of UVB provocation were used as yardsticks in order to quantify this variability.

    Results: Agreement between observers, against known size, was excellent for reactions with a sharp border, but for reactions with a diffuse or indistinct border there was a substantial inter-observer variability. This was also true for the comparison between naked-eye reading and LDPI assessment of the reaction size.

    Conclusion: It is concluded that if naked-eye readings are to be the outcome measurement, then provocations/protocols producing distinct borders are an advantage. If borders between provoked and unprovoked skin can be expected to be diffuse, i.e. part of a continuum of response, the use of objective, bioengineering techniques such as LDPI is required. Quantitative methods are also the basis for more detailed presentation and interpretation of test results including information on dose response above the minimal erythema dose.

    Keywords
    erythema, phototesting, UVB, LDPI, observer variability
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12818 (URN)10.1111/j.1600-0846.2008.00305.x (DOI)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-12-14
    3. Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
    Open this publication in new window or tab >>Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
    2003 (English)In: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 19, no 4, p. 195-202Article in journal (Refereed) Published
    Abstract [en]

    Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB.

    Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data.

    Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate.

    Conclusions:  The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seems to be applicable even in diagnostic testing of an individual patient's response to UVB.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2003
    Keywords
    acetone, anti-inflammatory effects, clobetasol diproprionate, erythema, gel vehicle, laser Doppler perfusion imaging, phototesting.
    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:liu:diva-12819 (URN)10.1034/j.1600-0781.2003.00037.x (DOI)000184575000006 ()2-s2.0-0042925506 (Scopus ID)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2018-01-13Bibliographically approved
    4. Can patients read their own UVB minimal erythema dose and irritant skin tests
    Open this publication in new window or tab >>Can patients read their own UVB minimal erythema dose and irritant skin tests
    2010 (English)Article in journal (Refereed) Submitted
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12820 (URN)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2012-03-27
    5. Prevention of skin cancer in primary health care: an evaluation of three different prevention effort levels and the applicability of a phototest
    Open this publication in new window or tab >>Prevention of skin cancer in primary health care: an evaluation of three different prevention effort levels and the applicability of a phototest
    2008 (English)In: European Journal of General Practice, ISSN 1381-4788, E-ISSN 1751-1402, Vol. 14, no 2, p. 68-75Article in journal (Refereed) Published
    Abstract [en]

    Background/objective: The high skin cancer incidence in western society, and its known association with sun exposure habits, makes the area an important target for prevention. We investigated, in a primary healthcare setting, differentiated levels of prevention efforts directed at the propensity of the patient to change his/her sun habits, sun protection behaviour, and attitudes, after information intervention. Additionally, the impact of the performance of a phototest to determine individual sun sensitivity was evaluated. Methods: 308 patients visiting a primary healthcare centre in southern Sweden completed a questionnaire concerning sun habits, sun protection behaviour, and attitudes, and were randomized into one of three groups, representing increasing levels of prevention effort in terms of resources. Feedback on their questionnaire and general preventive sun protection advice was given, in the first group by means of a letter, and in the second and third groups by a doctor's consultation. Group 3 also underwent a phototest, with a self-reading assessment and a written follow-up of the phototest result. Change of sun habits, behaviour, and attitudes, based on the Transtheoretical Model of Behaviour Change and on Likert scale scorings, was evaluated after 6 months, by a repeated questionnaire. Results: Prevention mediated by a doctor's consultation had a clearly better impact on the subjects. The addition of a phototest did not further reinforce this effect in the group as a whole, but it did for a subgroup of individuals with high ultraviolet (UV) sensitivity, as determined by the phototest itself, suggesting that this might actually be a tool to improve outcome in this high-risk group. Conclusion: A personal doctor's consultation is a valuable tool in the effective delivery of preventive information in the general practice setting. In individuals with high UV-sensitivity and thus high risk for skin cancer the performance of a photo-test reinforces a positive outcome in habits, behaviour and attitudes.

    Place, publisher, year, edition, pages
    London, UK: Informa Healthcare, 2008
    Keywords
    Skin cancer prevention; phototesting; behavioural change; self-assessment; questionnaire
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12821 (URN)10.1080/13814780802423430 (DOI)
    Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2017-12-14Bibliographically approved
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  • 45.
    Falk, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Primary Health Care Centres.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Measuring sun exposure habits and sun protection behaviour using a comprehensive scoring instrument: An illustration of a possible model based on Likert scale scorings and on estimation of readiness to increase sun protection2012In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 36, no 4, p. 265-269Article in journal (Refereed)
    Abstract [en]

    Background: Few attempts to present a comprehensive scoring instrument for sun exposure and protection have been made. The present paper aims to describe a possible set of questions suitable for such an instrument, comprising the most important aspects of sun exposure and protection. Methods: The material from a previously performed intervention study, using a questionnaire based on Likert scales and on the Transtheoretical Model of Behaviour Change (TTM), was utilised. 213 primary healthcare patients filled in the questionnaire and were randomised into two groups receiving sun protection advice, in Group 1 in letter-form, and in Group 2 orally during a doctor's consultation. In the original study, increased sun protection/readiness to increase sun protection was demonstrated for several items in Group 2, at six months. To compose a comprehensive scoring instrument, five questions concerning sun exposure/protection (intentional tanning, sunscreen use, choice of SPF, number of occasions with sunburn, and time spent in the sun at midday), were selected to give a 20 point behavioural score. Similarly, four TTM-based questions (giving up sunbathing, using clothes for sun protection, using sunscreens, and staying in the shade) gave a 16 point "propensity-to-change"-score. Results: At follow-up, increased sun protection reflected in the behavioural score occurred only in Group 2 (p<0.001). For the propensity-to-change-score, increased readiness to increase sun protection occurred in both groups, but the change was significantly higher in Group 2 (p<0.05). Categorisation of the 20 point behavioural score, into three risk levels, revealed a significantly higher shift of subjects moving to a lower risk level in Group 2 compared to Group 1 (p<0.05). Conclusions: In conclusion, twinning of a summarised Likert scale behavioural score with a TTM-based propensity-to-change-score seems promising for the creation of a questionnaire-based, comprehensive scoring instrument for sun exposure and protection.

  • 46.
    Fredriksson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Ilias, Michail
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    New mechanical device for effective removal of skin tags in routine health care2009In: Dermatologi Online, E-ISSN 1087-2108, Vol. 15, no 2, article id 9Article in journal (Refereed)
    Abstract [en]

    Skin tags (acrochordons) are exceedingly common benign skin lesions. A novel medical device in the form of a flat adhesive patch applies pressure to the base of a skin tag, leading to its removal within 3-6 days. The device was used in a clinical trial to treat and remove skin tags of the neck, upper torso, and axillae in volunteers. In this study, a total of 177 skin tags were treated in 32 individuals. One hundred seventy-two lesions fulfilled intention to treat (ITT) criteria. A majority of ITT lesions (90%) reached final assessment. Successful outcome was highest (90%) for lesions up to 1 mm in base. For lesions up to 2 mm, the rate of successful outcome was 76 percent. The desired outcome was seen in 65 percent of all ITT lesions. The cosmetic outcome after removal was excellent. Discomfort was assessed as minimal during all stages of the procedure. Analysis of data on blood flow in the skin tags during the treatment showed that the outcome was influenced by whether a decrease in blood flow was achieved immediately after application and at 2-3 days, but that the degree of occlusion was not critical. The results of this study illustrate that the device presents a new option for the management of unmet needs in the treatment of skin tags.

  • 47.
    Frölund, Maria
    et al.
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Falk, Lars
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology.
    Ahrens, Peter
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Jensen, Jorgen Skov
    Research Unit for Reproductive Microbiology, Statens Serum Institut, Copenhagen S, Denmark.
    Detection of ureaplasmas and bacterial vaginosis associated bacteria and their association with non-gonococcal urethritis in men2019In: PLOS ONE, E-ISSN 1932-6203Article in journal (Refereed)
    Abstract [en]

    No aetiology is found in up to 40% of men with symptomatic urethritis. Male partners of women with bacterial vaginosis (BV) may be at higher risk of non-gonococcal urethritis (NGU). The aim of this study was to examine the role of BV associated bacteria in first-void urine (FVU) in 97 asymptomatic men without urethritis (controls) and 44 men (cases) with NGU including 20 men with idiopathic urethritis (IU) attending a Swedish STD-clinic between January and October 2010. BV-associated bacteria and ureaplasmas were detected by quantitative PCR assays. All BV associated bacteria, except Megasphaera-like type 1, were strongly positively correlated with Uurealyticum p<0.005 and even stronger with the combined Uurealyticum and Uparvum load (p<0.0005) suggesting that ureaplasma induced elevated pH may stimulate the growth of BV associated bacteria. No statistically significant differences were found between IU cases and controls in the prevalence or load of BV associated bacteria or ureaplasmas. In multiple logistic regression, Megasphaera-like type 1 was associated with IU (p = 0.03), but most positive FVU samples contained very few bacteria and the finding may not be clinically relevant.

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  • 48.
    Geale, Kirk
    et al.
    Umea Univ, Sweden; Quantify Res, Sweden.
    Henriksson, Martin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Jokinen, Jussi
    Karolinska Inst, Sweden; Umea Univ, Sweden.
    Schmitt-Egenolf, Marcus
    Umea Univ, Sweden.
    Association of Skin Psoriasis and Somatic Comorbidity With the Development of Psychiatric Illness in a Nationwide Swedish Study2020In: JAMA dermatology, ISSN 2168-6068, E-ISSN 2168-6084, Vol. 156, no 7, p. 795-804Article in journal (Refereed)
    Abstract [en]

    Importance Psoriasis is a complex systemic disease with skin involvement, somatic comorbidity, and psychiatric illness (PI). Although this view of psoriasis is widely accepted, potential synergies within this triad of symptoms have not been adequately investigated. Objectives To investigate the independent association of skin psoriasis and somatic comorbidity with the development of PI and to assess whether skin psoriasis and somatic comorbidity act synergistically to produce a risk of PI that is greater than the additive associations. Design, Setting, and Participants Participants were enrolled between January 2005 and December 2010, in this retrospective matched case-control study using secondary (ie, administrative), population-based registry data from Swedish patients in routine clinical care. The dates of analysis were March 2017 to December 2019. Participants were patients with skin psoriasis and control participants without psoriasis matched on age, sex, and municipality, who were all free of preexisting PI. Exposures Presence of skin psoriasis and somatic comorbidity (captured through the Charlson Comorbidity Index and the Elixhauser Comorbidity Index). Main Outcomes and Measures Risk of PI onset (composite of depression, anxiety, and suicidality) is shown using Kaplan-Meier curves stratified by the presence of skin psoriasis and somatic comorbidity. Adjusted associations of skin psoriasis and somatic comorbidity with the development of PI were analyzed using Cox proportional hazards regression models, including interactions to assess synergistic associations. The 3 components of PI were also assessed individually. Results A total of 93 & x202f;239 patients with skin psoriasis (mean [SD] age, 54 [17] years; 47 475 men [51%]) and 1 & x202f;387 & x202f;495 control participants (mean [SD] age, 54 [16] years; 702 332 men [51%]) were included in the study. As expected, patients with skin psoriasis were more likely to have somatic comorbidity and PI than control participants. Compared with those without skin psoriasis or somatic comorbidity, patients with psoriasis without somatic comorbidity had a 1.32 times higher risk of PI onset (hazard ratio [HR], 1.32; 95% CI, 1.27-1.36; P &lt; .001), whereas patients with psoriasis with somatic comorbidity had a 2.56 times higher risk of PI onset (HR, 2.56; 95% CI, 2.46-2.66; P &lt; .001). No synergistic associations of skin psoriasis and somatic comorbidity with the development of PI were found (HR, 0.93; 95% CI, 0.81-1.04; P = .21). Conclusions and Relevance This study found that somatic comorbidity appeared to alter PI onset even more than skin psoriasis. The observed association of skin psoriasis and somatic comorbidity with the development of PI reinforces the need for proactive, holistic treatment of patients with psoriasis. This matched case-control study investigates the independent association of skin psoriasis and somatic comorbidity with the development of psychiatric illness and assesses whether skin psoriasis and somatic comorbidity act synergistically to produce a risk of psychiatric illness that is greater than the additive associations. Question How are skin psoriasis and somatic comorbidity associated with the development of psychiatric illness? Findings Among 93 & x202f;239 patients with skin psoriasis and 1 & x202f;387 & x202f;495 control participants in this matched case-control study, skin psoriasis and somatic comorbidity were independently associated with 1.32 and 2.09 times increased risk, respectively, of psychiatric illness onset compared with control participants without psoriasis and without somatic comorbidity. Skin psoriasis and somatic comorbidity acted additively but not synergistically. Meaning Proactive, holistic treatment of patients with psoriasis is recommended because treating skin symptoms alone cannot remedy the elevated risk for psychiatric comorbidity.

  • 49.
    Guenther, L.
    et al.
    Guenther Res Inc, Canada; Western Univ, Canada.
    Takhar, A.
    Wansford & Kings Cliffe Practice, England.
    Megna, M.
    Univ Federico II, Italy.
    Sebastian, M.
    Ctr Dermatol & Clin Trials, Germany.
    Nyholm, N.
    LEO Pharma AS, Denmark.
    Thoning, H.
    LEO Pharma AS, Denmark.
    Levin, Lars-Åke
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Impact of fixed-dose combination Cal/BD foam on the work productivity of patients with psoriasis: results from the 52-week randomized, double-blind, PSO-LONG trial2022In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 36, no 7, p. 1054-1063Article in journal (Refereed)
    Abstract [en]

    Background Psoriasis contributes to unemployment, work impairment, missed workdays and substantial indirect costs due to lost productivity. Combination Cal/BD foam is the only topical that is approved for long-term maintenance treatment of plaque psoriasis for 52 weeks. This is the first known investigation of the effect of topical psoriasis therapy on productivity. Objective To examine the change in work productivity and activity impairment after 4 weeks of treatment with fixed-dose combination calcipotriol 50 mu g/g/betamethasone dipropionate 0.5 mg/g (Cal/BD) foam and observe long-term changes after 52 weeks of long-term management (proactive or reactive treatment). Methods This is a post-hoc analysis of the PSO-LONG trial - a phase 3, randomized, double-blind, vehicle-controlled, parallel group, international multi-centre trial of treatment with combination Cal/BD foam. Work and activity impairment due to psoriasis were assessed by the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment Psoriasis (WPAI:PSO) questionnaire at baseline, week 4, week 28 and week 56. The improvement in hours of work productivity was translated into monthly and annual indirect cost savings estimates for patients in Italy, Sweden, United Kingdom, Canada and Germany. Results Using fixed-dose combination Cal/BD foam for four weeks significantly reduced psoriasis-related work presenteeism, total work productivity impairment (TWPI) and total activity impairment (TAI) over 56 weeks, with significant improvements observed as early as 4 weeks after the baseline visit. The proportion of patients reporting impact on work productivity (as measured by presenteeism and TWPI) and activity impairment (as measured by both DLQI-Q7b and TAI) also decreased. Conclusion Fixed-dose combination Cal/BD foam used for long-term management of psoriasis significantly reduces psoriasis-related work productivity and activity impairment which may result in substantial indirect cost savings.

  • 50.
    Hallberg, S.
    et al.
    Quantify Research, Sweden.
    Gandra, S. R.
    Amgen Inc, CA 91320 USA.
    Fox, K. M.
    Strateg Healthcare Solut LLC, MD USA.
    Mesterton, J.
    Quantify Research, Sweden; Karolinska Institute, Sweden.
    Banefelt, J.
    Quantify Research, Sweden.
    Johansson, G.
    Uppsala University, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Sobocki, P.
    Karolinska Institute, Sweden; IMS Heatlh, Sweden.
    Healthcare costs associated with cardiovascular events in patients with hyperlipidemia or prior cardiovascular events: estimates from Swedish population-based register data2016In: European Journal of Health Economics, ISSN 1618-7598, E-ISSN 1618-7601, Vol. 17, no 5, p. 591-601Article in journal (Refereed)
    Abstract [en]

    To estimate healthcare costs of new cardiovascular (CV) events (myocardial infarction, unstable angina, revascularization, ischemic stroke, transient ischemic attack, heart failure) in patients with hyperlipidemia or prior CV events. A retrospective population-based cohort study was conducted using Swedish national registers and electronic medical records. Patients with hyperlipidemia or prior CV events were stratified into three cohorts based on CV risk level: history of major cardiovascular disease (CVD), coronary heart disease (CHD) risk-equivalent, and low/unknown risk. Propensity score matching was applied to compare patients with new events to patients without new events for estimation of incremental costs of any event and by event type. A CV event resulted in increased costs over 3 years of follow-up, with the majority of costs occurring in the 1st year following the event. The mean incremental cost of patients with a history of major CVD (n = 6881) was a,not sign8588 during the 1st year following the event. This was similar to that of CHD risk-equivalent patients (n = 3226; a,not sign6663) and patients at low/unknown risk (n = 2497; a,not sign8346). Ischemic stroke resulted in the highest 1st-year cost for patients with a history of major CVD and CHD risk-equivalent patients (a,not sign10,194 and a,not sign9823, respectively); transient ischemic attack in the lowest (a,not sign3917 and a,not sign4140). Incremental costs remained elevated in all cohorts during all three follow-up years, with costs being highest in the major CVD history cohort. Healthcare costs of CV events are substantial and vary considerably by event type. Incremental costs remain elevated for several years after an event.

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