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  • 1.
    Anderson, K S
    et al.
    Harvard Medical School, Boston, MA 02115, USA.
    Wong, J
    Harvard Medical School, Boston, MA 02115, USA.
    Polyak, K
    Harvard Medical School, Boston, MA 02115, USA.
    Aronzon, D
    Harvard Medical School, Boston, MA 02115, USA.
    Enerbäck, Charlotta
    Sahlgrenska University Hospital.
    Detection of psoriasin/S100A7 in the sera of patients with psoriasis2009In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 160, no 2, p. 325-332Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Psoriasis is a disease of dysregulated inflammation and epithelial hyperproliferation in the skin, involving both the innate and adaptive immune system. Psoriatic keratinocytes express high levels of psoriasin (S100A7), a small calcium-binding protein. OBJECTIVES: To determine if patients with active psoriasis have elevated serum levels of psoriasin and psoriasin-specific autoantibodies. METHODS: Blood was collected from 14 patients with psoriasis vulgaris at the start of narrowband ultraviolet (UV) B therapy and from 11 of these patients every 2 weeks during the course of the UVB treatment. Patient and control sera were tested for psoriasin antigen levels by sandwich enzyme-linked immunosorbent assay, and for psoriasin autoantibody titres using recombinant purified psoriasin and overlapping peptides. RESULTS: We confirmed strong and specific expression of psoriasin in psoriatic epidermis by immunohistochemistry. Systemic psoriasin antigen levels tended to be lower in patients (mean 213 ng mL(-1)) than in controls (mean 331 ng mL(-1), P = 0.308) and decreased with increasing disease severity. Psoriasin-specific autoantibodies were detected in a subset of patients with psoriasis and healthy normal donors (mean 0.347 vs. 0.255 units, P = 0.246). The epitopes recognized by the autoantibodies were mapped to an external loop domain of the molecule but did not show corresponding T-cell immunogenicity. CONCLUSIONS: Although psoriasin is overexpressed in psoriatic skin lesions, systemic levels of psoriasin tended to be lower with increasing disease severity, which may be due to the presence of psoriasin-specific autoantibodies. Neither psoriasin nor psoriasin-specific autoantibodies appear to be promising serum biomarkers for clinical psoriasis.

  • 2.
    Arnetz, B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Fjellner, B
    Stress responsiveness in patients with psoriasis2007In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, ISSN 0007-0963, Vol. 156, no 2, p. 388-Article in journal (Refereed)
  • 3. Asplund, A.
    et al.
    Bjorklund, M. Gry
    Sundquist, C.
    Stromberg, S.
    Edlund, K.
    Oestman, A.
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics.
    Ponten, F.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology.
    Expression profiling of microdissected cell populations selected from basal cells in normal epidermis and basal cell carcinoma2008In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 158, no 3, p. 527-538Article in journal (Refereed)
    Abstract [en]

    Background Basal cell carcinomas (BCCs) are prevalent tumours with uniform histology that develop without any known precursor lesion. Alterations in the sonic hedgehog-patched1 signalling pathway are accepted as necessary events for tumorigenesis, and mutations in the patched1 gene are frequently present in tumours. Objectives To analyse transcript profiles in BCC. Methods We used laser-assisted microdissection to isolate and collect cell populations defined under the microscope. Peripheral cells from nests of BCC were selected to represent tumour cells, and normal keratinocytes from epidermis basal layer were used as control. Extracted RNA was amplified and hybridized on to a cDNA microarray. Results Our results show that BCC cells express a transcript signature that is significantly different from that of normal keratinocytes, and over 350 genes with various functions were identified as differentially expressed. The compiled data suggest an upregulation of the Wnt signalling pathway as a major event in BCC cells. Furthermore, tumour cells appear to have an increased sensitivity to oxygen radicals and dysregulated genes involved in antigen presentation. Results were validated at both the transcriptional level using real-time polymerase chain reaction and at the protein level using immunohistochemistry. Conclusions We show that microdissection in combination with robust strategies for RNA extraction, amplification and cDNA microarray analysis allow for reliable transcript profiling and that antibody-based proteomics provides an advantageous strategy for the analysis of corresponding differentially expressed proteins. We found that expression patterns were significantly altered in BCC cells compared with basal keratinocytes and that the Wnt signalling pathway was upregulated in tumour cells.

  • 4. Asplund, A.
    et al.
    Gustafsson, A. C.
    Wikonkal, N. M.
    Sela, A.
    Leffell, D. J.
    Kidd, K.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology.
    Brash, D. E.
    Ponten, F.
    PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer2005In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 152, no 5, p. 868-873Article in journal (Refereed)
    Abstract [en]

    Background The PTCH tumour suppressor gene is involved in the development of nearly all basal cell carcinomas (BCCs) of the skin and a fraction of squamous cell carcinomas (SCCs). A nonconservative Pro/Leu nucleotide polymorphism within PTCH exon 23 at codon 1315 was recently reported to be potentially important for the development of breast epithelial cell cancers. Objectives Accordingly, the status of PTCH codon 1315 was analysed for a possible association with the development of nonmelanoma skin cancers (NMSCs) in a pilot study. Because skin cancer risk is affected by specific population-dependent phenotypes such as skin and hair colour, codon 1315 was also analysed for normal allele frequency variation in human populations having differing extents of eumelanin vs. phaeomelanin. Methods The single nucleotide polymorphism in codon 1315 of the human PTCH gene was analysed in genomic DNA from six different populations comprising 472 blood samples and from 170 patients in four different categories with NMSC. Polymerase chain reaction and pyrosequencing were used to determine the allele frequencies. Allelic loss was furthermore determined in tumours following microdissection. Results The Pro/Pro genotype frequency ranged from 30% to 65% between populations, with a significant trend for a reduced frequency of the Pro/Pro genotype in populations having lighter pigmentation (P = 0.020). Pro/Pro frequency showed an increasing trend with increasing tumour case severity (P = 0.027). In 260 samples from 180 Swedish patients with NMSC and a control group of 96 healthy ethnically matched volunteers, no statistically significant pairwise differences between groups were detected in the PTCH codon 1315 allelic distribution, neither was a difference seen for multiple or early onset cases of BCC in the Swedish population. In Swedish patients with single tumours, allelic loss (loss of heterozygosity) was observed in 20 of 30 (67%) patients with BCC and four of 22 (18%) patients with SCC, with no preference in the allele lost. In contrast, the Pro/Pro genotype was frequent in seven U.S. patients having multiple independent BCCs. One of these patients was heterozygous, enabling allelic loss studies. Of 20 independent tumours, 11 had lost an allele; 10 of the 11 had lost Leu, suggesting nonrandom loss that favoured retention of Pro (P = 0.0059). Conclusions Our results indicate an association between the eumelanin-to-phaeomelanin shift and a shift from the Pro/Pro genotype to Leu-containing genotypes. Failure to lose Pro during the shift to phaeomelanin may be associated with an increased population risk for BCC and increased individual risk for multiple BCC. During development of a tumour, the effect of Pro may be magnified by loss of the Leu allele.

  • 5.
    Asplund, A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gustafsson, A
    Wikonkal, N
    Seli, A
    Leffell, DJ
    Kidd, K
    Lundeberg, J
    Brash, DE
    Pontén, F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer2005In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 152, no 5, p. 868-873Article in journal (Refereed)
    Abstract [en]

    Background  The PTCH tumour suppressor gene is involved in the development of nearly all basal cell carcinomas (BCCs) of the skin and a fraction of squamous cell carcinomas (SCCs). A nonconservative Pro/Leu nucleotide polymorphism within PTCH exon 23 at codon 1315 was recently reported to be potentially important for the development of breast epithelial cell cancers.

    Objectives  Accordingly, the status of PTCH codon 1315 was analysed for a possible association with the development of nonmelanoma skin cancers (NMSCs) in a pilot study. Because skin cancer risk is affected by specific population-dependent phenotypes such as skin and hair colour, codon 1315 was also analysed for normal allele frequency variation in human populations having differing extents of eumelanin vs. phaeomelanin.

    Methods  The single nucleotide polymorphism in codon 1315 of the human PTCH gene was analysed in genomic DNA from six different populations comprising 472 blood samples and from 170 patients in four different categories with NMSC. Polymerase chain reaction and pyrosequencing were used to determine the allele frequencies. Allelic loss was furthermore determined in tumours following microdissection.

    Results  The Pro/Pro genotype frequency ranged from 30% to 65% between populations, with a significant trend for a reduced frequency of the Pro/Pro genotype in populations having lighter pigmentation (P = 0·020). Pro/Pro frequency showed an increasing trend with increasing tumour case severity (P = 0·027). In 260 samples from 180 Swedish patients with NMSC and a control group of 96 healthy ethnically matched volunteers, no statistically significant pairwise differences between groups were detected in the PTCH codon 1315 allelic distribution, neither was a difference seen for multiple or early onset cases of BCC in the Swedish population. In Swedish patients with single tumours, allelic loss (loss of heterozygosity) was observed in 20 of 30 (67%) patients with BCC and four of 22 (18%) patients with SCC, with no preference in the allele lost. In contrast, the Pro/Pro genotype was frequent in seven U.S. patients having multiple independent BCCs. One of these patients was heterozygous, enabling allelic loss studies. Of 20 independent tumours, 11 had lost an allele; 10 of the 11 had lost Leu, suggesting nonrandom loss that favoured retention of Pro (P = 0·0059).

    Conclusions  Our results indicate an association between the eumelanin-to-phaeomelanin shift and a shift from the Pro/Pro genotype to Leu-containing genotypes. Failure to lose Pro during the shift to phaeomelanin may be associated with an increased population risk for BCC and increased individual risk for multiple BCC. During development of a tumour, the effect of Pro may be magnified by loss of the Leu allele.

  • 6.
    Asplund, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Gry Björklund, M.
    Sundquist, C.
    Strömberg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Edlund, K.
    Östman, A.
    Nilsson, P.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Lundeberg, J.
    Expression profiling of microdissected cell populations selected from basal cells in normal epidermis and basal cell carcinoma2008In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 158, no 3, p. 527-38Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Basal cell carcinomas (BCCs) are prevalent tumours with uniform histology that develop without any known precursor lesion. Alterations in the sonic hedgehog-patched1 signalling pathway are accepted as necessary events for tumorigenesis, and mutations in the patched1 gene are frequently present in tumours. OBJECTIVES: To analyse transcript profiles in BCC. METHODS: We used laser-assisted microdissection to isolate and collect cell populations defined under the microscope. Peripheral cells from nests of BCC were selected to represent tumour cells, and normal keratinocytes from epidermis basal layer were used as control. Extracted RNA was amplified and hybridized on to a cDNA microarray. Results Our results show that BCC cells express a transcript signature that is significantly different from that of normal keratinocytes, and over 350 genes with various functions were identified as differentially expressed. The compiled data suggest an upregulation of the Wnt signalling pathway as a major event in BCC cells. Furthermore, tumour cells appear to have an increased sensitivity to oxygen radicals and dysregulated genes involved in antigen presentation. RESULTS: were validated at both the transcriptional level using real-time polymerase chain reaction and at the protein level using immunohistochemistry. CONCLUSIONS: We show that microdissection in combination with robust strategies for RNA extraction, amplification and cDNA microarray analysis allow for reliable transcript profiling and that antibody-based proteomics provides an advantageous strategy for the analysis of corresponding differentially expressed proteins. We found that expression patterns were significantly altered in BCC cells compared with basal keratinocytes and that the Wnt signalling pathway was upregulated in tumour cells.

  • 7. Aushev, M.
    et al.
    Mussolino, C.
    Cathomen, T.
    Törmä, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Reichelt, J.
    Molecular surgery for epidermolysis bullosa simplex2014In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 170, no 4, p. E35-E35Article in journal (Other academic)
  • 8. Basset-Seguin, N
    et al.
    Ibbotson, S
    Emtestam, L
    Tarstedt, M
    Morton, C
    Maroti, M
    Cazavara-Pinton, P
    Varma, S
    Roelandts, R
    Wolf, P
    Saksela, O
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Photodynamic therapy using methyl aminolaevulinate is as efficacious as cryotherapy in basal cell carcinoma, with better cosmetic results2003In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 149, p. 46-46Conference paper (Other academic)
  • 9.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Missing factors in human skin equivalent models?2017In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 176, no 1, p. 11-12Article in journal (Refereed)
  • 10.
    Buraczewska, Izabela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Berne, Berit
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Lindberg, Magnus
    Törmä, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Lodén, Marie
    Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial2007In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 156, no 3, p. 492-498Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Moisturizers are commonly used by patients with dry skin conditions as well as people with healthy skin. Previous studies on short-term treatment have shown that moisturizers can weaken or strengthen skin barrier function and also influence skin barrier recovery. However, knowledge of the effects on skin barrier function of long-term treatment with moisturizers is still scarce. OBJECTIVES: To investigate the impact of long-term treatment with moisturizers on the barrier function of normal skin, as measured by transepidermal water loss (TEWL) and susceptibility to an irritant, and to relate those effects to the composition of the designed experimental moisturizers. METHODS: Volunteers (n = 78) were randomized into five groups. Each group treated one volar forearm for 7 weeks with one of the following preparations: (i) one of three simplified creams, containing only a few ingredients in order to minimize the complexity of the system; (ii) a lipid-free gel; (iii) one ordinary cream, containing 5% urea, which has previously been shown to decrease TEWL. The lipids in the simplified creams were either hydrocarbons or vegetable triglyceride oil, and one of them also contained 5% urea. After 7 weeks, treated and control forearms were exposed for 24 h to sodium lauryl sulfate (SLS) using a patch test. TEWL, blood flow and skin capacitance of both SLS-exposed and undamaged skin were evaluated 24 h after removal of patches. Additionally, a 24-h irritancy patch test of all test preparations was performed on 11 volunteers in order to check their possible acute irritancy potential. RESULTS: Changes were found in the barrier function of normal skin after 7 weeks of treatment with the test preparations. The simplified creams and the lipid-free gel increased TEWL and skin response to SLS, while the ordinary cream had the opposite effect. One of the simplified creams also decreased skin capacitance. All test preparations were shown to be nonirritant, both by short-term irritancy patch test and by measurement of blood flow after long-term treatment. CONCLUSIONS: Moisturizers influence the skin barrier function of normal skin, as measured by TEWL and susceptibility to SLS. Moreover, the effect on skin barrier function is determined by the composition of the moisturizer. The ingredients which influence the skin barrier function need to be identified, and the mechanism clarified at the molecular level.

  • 11. Carlsson, A
    et al.
    Gånemo, A
    Anderson, C D
    Meding, Birgitta
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Svensson, Åke
    Scoring of hand eczema: good agreement between patients and dermatological staff2011In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, ISSN 0007-0963, Vol. 165, no 1, p. 123-128Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Assessment of hand eczema in a clinical study has been achieved using a scoring system which documents extent of eczema on different areas of the hand.

    OBJECTIVES: To investigate whether the same scoring system could be used by patients to communicate current status of hand eczema.

    METHODS: In a study of 62 patients (36 women and 26 men, age range 19-75 years), the patient's own assessment was compared with the assessment by a dermatologist and a dermatological nurse. Standardized information was given to the patient and the form was filled in independently by the patient, the nurse and the dermatologist, during the patient's visit to the clinic. Individual area scores were summed to a total score.

    RESULTS: The overall agreement was good, with an interclass correlation (ICC) of 0·61 between patient and dermatologist for the total score. The ICC between nurse and dermatologist was 0·78. Differences between observers were more pronounced for the more severe cases - those with higher numerical scores as assessed by the dermatologist. There was a tendency for women and for patients over the median age of 44 years to set a lower point score than the dermatologist. The concordance of observations from individual anatomical areas was higher for fingertips and nails and lower for the palm and dorsum of the hand.

    CONCLUSIONS: Patients are able to report the extent of hand eczema with good accuracy. Self-assessment protocols for hand eczema may well have a place in the monitoring of hand eczema extent over time.

  • 12.
    Carlsson, Annica
    et al.
    Department of Dermatology, Institute of Clinical Research in Malmö, Skåne University Hospital, Lund University, Malmö.
    Gånemo, Agneta
    Department of Dermatology, Institute of Clinical Research in Malmö, Skåne University Hospital, Lund University, Malmö.
    Anderson, Chris
    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.
    Meding, Birgitta
    Unit of Occupational and Environmental Dermatology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm.
    Stenberg, Berndt
    Department of Public Health and Clinical Medicine, Umeå University, Umeå.
    Svensson, Åke
    Department of Dermatology, Institute of Clinical Research in Malmö, Skåne University Hospital, Lund University, Malmö.
    Scoring of hand eczema: good agreement between patients and dermatological staff2011In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 165, no 1, p. 123-128Article in journal (Refereed)
    Abstract [en]

    Background Assessment of hand eczema in a clinical study has been achieved using a scoring system which documents extent of eczema on different areas of the hand. Objectives To investigate whether the same scoring system could be used by patients to communicate current status of hand eczema. Methods In a study of 62 patients (36 women and 26 men, age range 1975 years), the patients own assessment was compared with the assessment by a dermatologist and a dermatological nurse. Standardized information was given to the patient and the form was filled in independently by the patient, the nurse and the dermatologist, during the patients visit to the clinic. Individual area scores were summed to a total score. Results The overall agreement was good, with an interclass correlation (ICC) of 0.61 between patient and dermatologist for the total score. The ICC between nurse and dermatologist was 0.78. Differences between observers were more pronounced for the more severe cases - those with higher numerical scores as assessed by the dermatologist. There was a tendency for women and for patients over the median age of 44 years to set a lower point score than the dermatologist. The concordance of observations from individual anatomical areas was higher for fingertips and nails and lower for the palm and dorsum of the hand. Conclusions Patients are able to report the extent of hand eczema with good accuracy. Self-assessment protocols for hand eczema may well have a place in the monitoring of hand eczema extent over time.

  • 13.
    Cederlöf, M.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Karlsson, R.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, C.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Lung and Allergy Unit, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Magnusson, P. K. E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Nordlind, K.
    Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Landén, M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
    Lichtenstein, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Intellectual disability and cognitive ability in Darier disease: Swedish nation-wide study2015In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 173, no 1, p. 155-158Article in journal (Refereed)
    Abstract [en]

    Background: Darier disease is an autosomal dominant skin disorder caused by mutations in the ATP2A2 gene. Anecdotal reports suggest a relationship between Darier disease and intellectual disabilities, but these reports are based on small clinical samples and limited by absence of control populations.

    Objectives: To examine the risk of intellectual disability and subclinical impairments in cognitive ability in Darier disease.

    Methods: We conducted a matched cohort study based on Swedish Population-, Patient- and Conscript Registers. The risk of being diagnosed with intellectual disability was estimated in 770 individuals with Darier disease, compared with matched comparison individuals without Darier disease. Associations were examined with risk ratios from conditional logistic regressions. In addition, we analysed test-based cognitive ability data (i.e. IQ data) from the Swedish conscript examination, for a subset of patients without diagnosed intellectual disability.

    Results: Individuals with Darier disease had a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6.2, 95% confidence interval 3.1-12.4). For conscripted individuals with Darier disease but no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than for comparison subjects.

    Conclusions: Darier disease is associated with intellectual disability and subclinical impairments in cognitive ability. The Darier-causing mutations merit further attention in molecular genetic research on intellectual disability and cognitive ability.

  • 14.
    Chalmers, J. R.
    et al.
    Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham, England..
    Simpson, E.
    Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA..
    Apfelbacher, C. J.
    Univ Regensburg, Inst Epidemiol & Prevent Med, Med Sociol, D-93053 Regensburg, Germany..
    Thomas, K. S.
    Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham, England..
    von Kobyletzki, Laura B.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013). Lund Univ, Skane Univ Hospital, Dept Dermatol, Malmo, Sweden.
    Schmitt, J.
    Univ Dresden, Ctr Lvidence Based Hlthcare, Dresden, Germany.;Tech Univ Dresden, Dept Occupat & Social Med, D-01062 Dresden, Germany..
    Singh, J. A.
    Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.;Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA..
    Svensson, A.
    Malmo Univ Hosp, Dept Dermatol & Venerol, Malmo, Sweden..
    Williams, H. C.
    Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham, England..
    Abuabara, K.
    Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA..
    Aoki, V.
    Univ Sao Paulo, Sch Med, Dept Dermatol, Sao Paulo, Brazil..
    Ardeleanu, M.
    Regeneron Pharmaceut Inc, Immunol & Inflammat, New York, NY USA..
    Awici-Rasmussen, M.
    Psoriasis & Eczema Assoc Norway, Oslo, Norway..
    Barbarot, S.
    CHU Nantes, Dept Dermatol, F-44035 Nantes 01, France..
    Berents, T. L.
    Univ Oslo, Inst Clin Med, Oslo 3, Norway.;Oslo Univ Hosp, Dept Dermatol, Oslo, Norway..
    Block, J.
    Natl Eczema Assoc, Natl Eczema Org, San Rafael, CA USA..
    Bragg, A.
    Chugai Pharma Europe Ltd, London, England..
    Burton, T.
    Clemmensen, K. K. Bjerring
    Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, Copenhagen, Denmark..
    Creswell-Melville, A.
    Soc Canadienne IEczema, Keswick, ON, Canada..
    Dinesen, M.
    LEO Pharma AS, Industriparken 55, Ballerup, Denmark..
    Drucker, A.
    Univ Hlth Nem ork, Div Dermatol, Toronto, ON, Canada..
    Eckert, L.
    Hlth Econ & Outcomes Res, Sanofi, France..
    Flohr, C.
    Guys & St Thomas Hosp NHS Fdn Trust, St Johns Inst Dermatol, London, England.;Kings Coll London, London, England..
    Garg, M.
    LEO Pharma, Copenhagen, Denmark..
    Gerbens, L. A. A.
    Univ Amsterdam, Acad Med Ctr, Dept Dermatol, Amsterdam, Netherlands..
    Graff, A. L. B.
    Natl Eczema Soc, London, England..
    Hanifin, J.
    Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA..
    Heinl, D.
    Univ Regensburg, Inst Epidemiol & Prevent Med, Med Sociol, D-93053 Regensburg, Germany..
    Humphreys, R.
    Natl Eczema Soc, London, England..
    Ishii, H. A.
    Brazilian Atop Dermatitis Assoc AADA, Sao Paulo, Brazil..
    Kataoka, Y.
    Osaka Prefectural Med Ctr Resp & Allerg Dis, Osaka, Japan..
    Leshem, Y. A.
    Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA..
    Marquort, B.
    Massuel, M. -A
    Merhand, S.
    Assoc Francaise Eczema, Redon, France..
    Mizutani, H.
    Mie Univ, Grad Sch Med, Tsu, Mie, Japan.;Mie Univ, Hosp Tsu, Tsu, Mie, Japan..
    Murota, H.
    Osaka Univ, Dept Dermatol, Osaka, Japan..
    Murrell, D. F.
    St George Hosp, Dept Dermatol, Sydney, NSW, Australia.;Univ New S Wales, Sydney, NSW, Australia..
    Nakahara, T.
    Kyushu Univ, Grad Sch Med Sci, Dept Dermatol, Fukuoka, Japan..
    Nasr, I.
    Nograles, K.
    Greater New York City Area Pharmaceut, Celgene Corp, New York, NY USA..
    Ohya, Y.
    Natl Ctr Child Hlth & Dev, Dept Med Subspecialties, Div Allergy, Tokyo, Japan..
    Osterloh, I.
    Ostermed Ltd, Kent, OH USA..
    Pander, J.
    Celgene BV, Utrecht, Netherlands..
    Prinsen, C.
    Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Amsterdam, Netherlands..
    Purkins, L.
    Ziarco Pharma Ltd, Canterbury, Kent, England..
    Ridd, M.
    Univ Bristol, Sch Social & Community Med, Bristol, Avon, England..
    Sach, T.
    Univ E Anglia, Hlth Econ Grp, Norwich, Norfolk, England..
    Schuttelaar, M. -LA.
    Shindo, S.
    Osaka Univ, Dept Dermatol, Osaka, Japan..
    Smirnova, J.
    Karlstad Univ, Dept Publ Hlth Sci, Karlstad, Sweden..
    Sulzer, A.
    Sanofi Aventis, Montpellier, France..
    Gjerde, E. Synnove
    Psoriasis & Eczema Assoc Norway, Oslo, Norway..
    Takaoka, R.
    Univ Sao Paulo, Sch Med, Dept Dermatol, Sao Paulo, Brazil..
    Talmo, H. Vestby
    Sanofi Aventis, Montpellier, France..
    Tauber, M.
    Toulouse Univ, Toulouse, France..
    Torchet, F.
    Mie Univ, Grad Sch Med, Tsu, Mie, Japan.;Mie Univ, Hosp Tsu, Tsu, Mie, Japan..
    Volke, A.
    Univ Tartu, Dept Dermatol, Tartu, Estonia..
    Wahlgren, C. -F
    Weidinger, S.
    Venereol & Allergy Univ Hosp Schleswig Holstein, Dept Dermatol, Kiel, Germany..
    Weisshaar, E.
    Heidelberg Univ, Dept Social Med, Occupat & Environm Dermatol, Heidelberg, Germany..
    Wollenberg, A.
    Univ Munich, Dept Dermatol & Allergy, Munich, Germany..
    Yamaga, K.
    Osaka Univ, Dept Dermatol, Osaka, Japan..
    Zhao, C. Y.
    St George Hosp, Dept Dermatol, Sydney, NSW, Australia.;Univ New S Wales, Sydney, NSW, Australia..
    Spuls, P. I.
    Univ Amsterdam, Acad Med Ctr, Dept Dermatol, Amsterdam, Netherlands..
    Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 175, no 1, p. 69-79Article in journal (Refereed)
    Abstract [en]

    This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmo, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [ including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

  • 15. Chalmers, J. R.
    et al.
    Thomas, K. S.
    Apfelbacher, C.
    Williams, H. C.
    Prinsen, C. A.
    Spuls, P. I.
    Simpson, E.
    Gerbens, L. A. A.
    Boers, M.
    Barbarot, S.
    Stalder, J. F.
    Abuabara, K.
    Aoki, V.
    Ardeleanu, M.
    Armstrong, J.
    Bang, B.
    Berents, T. L.
    Burton, T.
    Butler, L.
    Chubachi, T.
    Cresswell-Melville, A.
    DeLozier, A.
    Eckert, L.
    Eichenfield, L.
    Flohr, C.
    Futamura, M.
    Gadkari, A.
    Gjerde, E. S.
    van Halewijn, K. F.
    Hawkes, C.
    Howells, L.
    Howie, L.
    Humphreys, R.
    Ishii, H. A.
    Kataoka, Y.
    Katayama, I.
    Kouwenhoven, W.
    Langan, S. M.
    Leshem, Y. A.
    Merhand, S.
    Mina-Osorio, P.
    Murota, H.
    Nakahara, T.
    Nunes, F. P.
    Nygaard, U.
    Nygardas, M.
    Ohya, Y.
    Ono, E.
    Rehbinder, E.
    Rogers, N. K.
    Romeijn, G. L. E.
    Schuttelaar, M. L. A.
    Sears, A. V.
    Simpson, M. A.
    Singh, J. A.
    Srour, J.
    Stuart, B.
    Svensson, A.
    Talmo, G.
    Talmo, H.
    Teixeira, H. D.
    Thyssen, J. P.
    Todd, G.
    Torchet, F.
    Volke, A.
    von Kobyletzki, Laura B.
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013).
    Weisshaar, E.
    Wollenberg, A.
    Zaniboni, M.
    Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 5, p. E332-E341Article in journal (Refereed)
    Abstract [en]

    This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to pre-defined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

  • 16.
    Chamcheu, Jean Christopher
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Pihl-Lundin, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Eteti Mouyobo, Cedrique
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Gester, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Virtanen, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Moustakas, Aristidis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Navsaria, Harshad
    Centre for Cutaneous Research, Queen Mary’s School of Medicine and Dentistry, London E1 2AT, U.K..
    Vahlquist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Törmä, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Immortalized keratinocytes derived from patients with epidermolytic ichthyosis reproduce the disease phenotype: A useful in vitro model for testing new treatments2011In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 164, no 2, p. 263-272Article in journal (Refereed)
    Abstract [en]

    Background: Epidermolytic ichthyosis (EI) is a skin fragility disorder caused by mutations in genes encoding suprabasal keratins 1 and 10. While the aetiology of EI is known, model systems are needed for pathophysiological studies and development of novel therapies. Objectives To generate immortalized keratinocyte lines from patients with EI for studies of EI cell pathology and the effects of chemical chaperones as putative therapies. Methods We derived keratinocytes from three patients with EI and one healthy control and established immortalized keratinocytes using human papillomavirus 16-E6/E7. Growth and differentiation characteristics, ability to regenerate organotypic epidermis, keratin expression, formation of cytoskeletal aggregates, and responses to heat shock and chemical chaperones were assessed. Results The cell lines EH11 (K1-p.Val176-Lys197del), EH21 (K10-p.156Arg>Gly), EH31 (K10-p.Leu161-Asp162del) and NKc21 (wild-type) currently exceed 160 population doublings and differentiate when exposed to calcium. At resting state, keratin aggregates were detected in 9% of calcium-differentiated EH31 cells, but not in any other cell line. Heat stress further increased this proportion to 30% and also induced aggregates in 3% of EH11 cultures. Treatment with trimethylamine N-oxide and 4-phenylbutyrate (4-PBA) reduced the fraction of aggregate-containing cells and affected the mRNA expression of keratins 1 and 10 while 4-PBA also modified heat shock protein 70 (HSP70) expression. Furthermore, in situ proximity ligation assay suggested a colocalization between HSP70 and keratins 1 and 10. Reconstituted epidermis from EI cells cornified but EH21 and EH31 cells produced suprabasal cytolysis, closely resembling the in vivo phenotype. Conclusions These immortalized cell lines represent a useful model for studying EI biology and novel therapies.

     

  • 17.
    Chamcheu, Jean Christopher
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Virtanen, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Navsaria, Harshad
    Centre for Cutaneous Research, ICMS, Bart’s and London School of Medicine and Dentistry, Queen Mary University of London.
    Bowden, Paul E.
    Cardiff University, School of Medicine, Department of Dermatology.
    Vahlquist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Törmä, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Epidermolysis bullosa simplex due to KRT5 mutations: mutation-related differences in cellular fragility and the protective effects of trimethylamine N-oxide in cultured primary keratinocytes2010In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 162, no 5, p. 980-989Article in journal (Refereed)
    Abstract [en]

    Summary Background Epidermolysis bullosa simplex (EBS) is a mechanobullous skin fragility disease characterized by cytolysis of basal keratinocytes and intraepidermal blistering often caused by mutations in keratin genes (KRT5 or KRT14). No remedies exist for these disorders presenting a need for development of novel therapies. Objectives To identify new genotype-phenotype relationships in vivo and in cultured primary EBS keratinocytes in vitro, and to study the cytoskeletal stabilizing effects of trimethylamine N-oxide (TMAO) in heat-stressed EBS cells. Methods Genomic DNA and cDNA samples from three Swedish patients with EBS were analysed for keratin mutations. Primary EBS keratinocyte cultures were established, heat stressed with and without added TMAO, followed by evaluation of cellular fragility. Results In addition to the previously reported KRT5 mutation (V186L) in one patient, two patients were found to have a novel I183M and recurrent E475G replacements in KRT5. Cultured EBS keratinocytes did not exhibit keratin aggregates or cell loss, except in the patient with the p.I183M mutation who showed 3% aggregates and 2% cell loss. Upon transient heat stress the number of aggregate-containing cells increased to 21%, 27% and 13%, respectively, in the p.I183M, p.E475G and p.V186L mutant cells. Interestingly, pretreatment with TMAO prior to heat stress, dose dependently reduced the number of aggregate-containing cells and cell loss. Conclusion These results revealed a genotype-phenotype correlation in EBS keratinocytes upon heat stress and suggest protein stabilization as a new therapeutic strategy.

  • 18. Charlesworth, A.
    et al.
    Chiaverini, C.
    Chevrant-Breton, J.
    DelRio, M.
    Diociaiuti, A.
    Dupuis, R. P.
    El Hachem, M.
    Le Fiblec, B.
    Sankari-Ho, A. M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Valhquist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Wierzbicka, E.
    Lacour, J. P.
    Meneguzzi, G.
    Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations2013In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 168, no 4, p. 808-814Article in journal (Refereed)
    Abstract [en]

    Background Genetic mutations in the plectin gene (PLEC) cause autosomal recessive forms of epidermolysis bullosa simplex (EBS) associated with either muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA). Phenotype-genotype analysis has suggested that EBS-MD is due mostly to genetic mutations affecting the central rod domain of plectin, and EBS-PA to mutations outside this domain. Objectives This study aimed to describe new phenotypes of patients with EBS-MD and EBS-PA, to identify novel PLEC mutations and to establish genotype-phenotype correlations. Methods Seven patients with a suspicion of EBS linked to PLEC mutations were included. A standardized clinical questionnaire was sent to the physicians in charge of each patient. Immunofluorescence studies of skin biopsies followed by molecular analysis of PLEC were performed in all patients. Results We report the first case of nonlethal EBS-PA improving with age, the first multisystemic involvement in a patient with lethal EBS-PA, and the first patients with EBS-MD with involvement of either the bladder or oesophagus. Eleven novel PLEC mutations are also reported. Conclusions Our results confirm that EBS-PA is linked to mutations in the distal exons 1-30 and 32 of PLEC. Long-term survival is possible, with skin improvement, but a delayed onset of MD is probable. While EBS-MD is linked to PLEC mutations in all exons, in most cases one of the mutations affects exon 31. The precocity of MD seems to be linked to the type and localization of the PLEC mutation(s), but no correlation with mucosal involvement has been found.

  • 19. Coast, J
    et al.
    Salisbury, C
    de Berker, D
    Noble, A
    Horrocks, S
    Peters, T J
    Flynn, T N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Preferences for aspects of a dermatology consultation.2006In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 155, no 2, p. 387-92Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: General practitioners with special interests (GPSIs) are increasingly being used to provide dermatology services in the U.K. Little is known about U.K. dermatology patient attitudes to proposed variations in secondary care service delivery or the values they attach to aspects of the care they receive.

    OBJECTIVES: To quantify preferences for different attributes of care within dermatology secondary care services.

    METHODS: Attributes of care that are important to dermatology patients were derived using in-depth qualitative interviews with 19 patients at different points in the care pathway. A discrete choice experiment using 'best-worst scaling' was sent by post to 119 patients referred to secondary care dermatology services and suitable for GPSI care who had agreed to participate in research.

    RESULTS: Four attributes were derived from the qualitative work: waiting, expertise, thorough care and convenience. For the discrete choice experiment, 99 patients returned questionnaires, 93 of which contained sufficient data for analysis. All attributes were found to be quantitatively important. The attribute of greatest importance was expertise of the doctor, while waiting time was of least importance. Respondents were willing to wait longer than the current 3 months maximum to receive care that was thorough, 2.1 months to see a team led by an expert and 1.3 months to attend a consultation that is easy to get to.

    CONCLUSIONS: Although the need to reduce outpatient waiting times is a key policy driver behind the expansion of GPSI services, this does not appear to be the most important issue for patients. The thoroughness with which the consultation is provided and the expertise of the clinician seen are higher priorities.

  • 20.
    Davila-Seijo, P.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Academia Espanola de Dermatologıa Venereolog Fundacion Piel Sana, Madrid, Spain.
    Descalzo, M. A.
    Registries as real-world cohort studies that are useful and necessary in the pyramid of evidence2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 1, p. 300-301Article in journal (Refereed)
  • 21. Dréno, B
    et al.
    Kaufmann, R
    Talarico, S
    Torres Lozada, V
    Rodríguez-Castellanos, M A
    Gómez-Flores, M
    De Maubeuge, J
    Berg, M
    Department of Dermatology Sörmland, Mälar Hospital, Eskilstuna, Sweden.
    Foley, P
    Sysa-Jedrzejowska, A
    Kerrouche, N
    Paliargues, F
    Bettoli, V
    Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study2011In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 165, no 2, p. 383-390Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first-line option in the treatment of moderate to severe acne vulgaris.

    OBJECTIVES:

    To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%-BPO 2·5% (A/BPO) fixed-dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris.

    METHODS:

    A total of 378 subjects were randomized in a double-blind, controlled trial to receive once-daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects 'clear' or 'almost clear'), skin tolerability, adverse events and patients' satisfaction.

    RESULTS:

    The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (-74·1%) than in the lymecycline with vehicle group (-56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P < 0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were 'very satisfied' was significantly greater (P = 0·031).

    CONCLUSION:

    These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris.

  • 22.
    Egelrud, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Dermatology and Venerology.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Dermatology and Venerology.
    Kreutzmann, P
    Walden, M
    Vitzithum, K
    Marx, U C
    Forssmann, W G
    Mägert, H J
    hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6.2005In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 153, no 6, p. 1200-1203Article in journal (Refereed)
  • 23.
    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)
  • 24.
    Ekman, Anna-Karin
    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.
    Verma, Deepti
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Enerbäck, Charlotta
    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.
    Genetic variations of NLRP1: susceptibility in psoriasis2014In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, no 6, p. 1517-1520Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the inflammasome multiprotein complex involved in the production of interleukin (IL)-1β and IL-18, two cytokines strongly implicated in psoriasis pathogenesis. Genetic variations in NLRP1 are associated with a predisposition for chronic inflammatory conditions.

    OBJECTIVES: The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.

    MATERIAL AND METHODS: Four haplotype-tagging single-nucleotide polymorphisms (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by TaqMan allelic discrimination in a patient sample comprising 1847 individuals from 478 families and 802 healthy controls.

    RESULTS: Using the transmission disequilibrium test, a significant increase in the transmission of the NLRP1 rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P = 0·006 and P = 0·033, respectively). Furthermore, homozygosity for the rs878329C allele correlated with a younger age of onset. We also observed an increase in the expression of NLRP1 mRNA in the peripheral blood cells of patients with psoriasis. This was accompanied by a higher level of circulating IL-18 and appeared to be associated with the rs878329C allele.

    CONCLUSIONS: Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.

  • 25. Ericson, MB
    et al.
    Sandberg, C
    Stenquist, B
    Gudmundson, F
    Karlsson, M
    Ros, A-M
    Rosén, A
    Larkö, O
    Wennberg, A-M
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Photodynamic therapy of actinic keratosis at varying fluence rates: Assessment of photobleaching, pain and primary clinical outcome2004In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 151, no 6, p. 1204-1212Article in journal (Refereed)
    Abstract [en]

    Background: Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans. Objectives: The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment. Patients/methods Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580-650 nm) and fluence rates of 30 or 45 mW cm-2, and two groups with broad filter (580-690 nm) and fluence rates of 50 or 75 mW cm-2. The total cumulative light dose was 100 J cm-2 in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks. Results: Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photo-bleaching dose (1/e) was found to be related to fluence rate, ranging from 4.5 ± 1.0 J cm -2 at 30 mW cm-2, to 7.3 ± 0.7 J cm-2 at 75 mW cm-2, indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm-2 no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm-2. However, the pain was found to be most intense up to a cumulative light dose of 20 J cm-2. Conclusions: Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm-2) seems preferable when performing PDT of AK using noncoherent light sources.

  • 26. Eriksson, M.O.
    et al.
    Hagforsen, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lundin, Inger Phil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Palmoplantar pustulosis: a clinical and immunohistological study1998In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 138, no 3, p. 390-398Article in journal (Refereed)
    Abstract [en]

    Pustulosis palmoplantaris (PPP) is a common chronic skin disease, which is very resistant to treatment. It is not known why the lesions are located in the palms and soles. There are few studies of the disease and in particular studies of the histology. Fifty-nine patients with PPP answered a questionnaire concerning their medical history and 39 of them were clinically examined. Biopsy specimens were taken from involved skin in 22 of the 39 patients and studied immunohistologically for tryptase+ mast cells, EG2+ eosinophils, lipocalin+ neutrophils and CD3+ T lymphocytes. The sweat gland and sweat duct were visualized with AE1/AE3 antibody (cytokeratins 1-8, 10, 14/15, 16, 19). In addition to neutrophils in the pustule and lymphocytes in the upper dermis, there were also large numbers of mast cells and eosinophils in the subpustular area. Numerous eosinophils were present in the pustule. The epidermal part of the eccrine duct was not detectable in any of the specimens from patients with PPP but was present in all of the nine control persons (including two smokers). The results indicate that the acrosyringium is involved in the inflammation and also that mast cells and eosinophils participate in a hitherto unknown way. Of the 39 patients clinically examined, two had previously diagnosed thyroid disease and two had gluten hypersensitivity. Seventeen had one or several abnormal serum concentrations of thyroid-stimulating hormone, thyroxin, antibodies against thyroglobulin or thyroperoxidase and 10 had immunoglobulin (Ig) A antibodies to gliadin. The mean +/- SD for serum IgA and for eosinophil cationic protein was increased. From the questionnaire the most notable finding was that 56 of the 59 patients had been or still were smokers, all of whom had started smoking before the first signs of PPP. We hypothesize that the acrosyringium might be the target for the inflammation and that PPP is linked to autoimmune thyroid disease and smoking.

  • 27.
    Gaele, Kirk
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Henriksson, Martin
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Evaluating equality in psoriasis healthcare: a cohort study of the impact of age on prescription biologics2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 3, p. 579-587Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Inequality in healthcare has been identified in many contexts. To the best of our knowledge, this is the first study investigating age inequity in the form of prescription patterns of biologics in psoriasis care.

    OBJECTIVE:

    To determine whether psoriasis patients have equitable opportunities to receive biologic medications as they age. If patients do not receive equitable treatment, a subsequent objective is to determine the magnitude of the disparity.

    METHODS:

    A cohort of biologic-naïve psoriasis patients were analysed using Cox proportional hazard models to measure the impact of each additional year of life on the likelihood of initiating biologic treatment, after controlling for sex, body mass index, comorbidities, disease activity, and education level. A supporting analysis used a non-parametric graphical method to study the proportion of patients initiating biologic treatment as age increases, after controlling for the same covariates.

    RESULTS:

    The Cox proportional hazards model results in a hazard ratio of a one year increase in age of 0.963 to 0.969 depending on calendar year stratification, which implies that an increase in age of 30 years corresponds to a reduced likelihood of initiating biologic treatment by 61.3-67.6%. The estimated proportion of patients initiating biologic medication is always decreasing as age increases, at a statistically significant level.

    CONCLUSIONS:

    Psoriasis patients have fewer opportunities to access biologic medications as they age. This result was shown to be applicable at all stages in a patient's life course and was not only restricted to the elderly, although it implies greater disparities as the age difference between patients increases. These results show that inequity in access to biologic treatments due to age is prevalent in clinical practice today. Further research is needed to investigate the extent to which this result is influenced by patient preferences. 

  • 28.
    Geale, K.
    et al.
    Umeå University, Sweden; PAREXEL Int, Sweden.
    Henriksson, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Schmitt-Egenolf, M.
    Umeå University, Sweden.
    Evaluating equality in psoriasis healthcare: a cohort study of the impact of age on prescription of biologics2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 3, p. 579-587Article in journal (Refereed)
    Abstract [en]

    Background Inequality in healthcare has been identified in many contexts. To the best of our knowledge, this is the first study investigating age inequality in the form of prescription patterns of biologics in psoriasis care. Objectives To determine whether patients with psoriasis have equal opportunities to receive biological medications as they age. If patients did not receive equal treatment, a subsequent objective was to determine the magnitude of the disparity. Methods A cohort of biologic-naive patients with psoriasis was analysed using Cox proportional hazards models to measure the impact of each additional year of life on the likelihood of initiating biological treatment, after controlling for sex, body mass index, comorbidities, disease activity and educational level. A supporting analysis used a nonparametric graphical method to study the proportion of patients initiating biological treatment as age increased, after controlling for the same covariates. Results The Cox proportional hazards model resulted in hazard ratios of a 1-year increase in age of 0.96-0.97 depending on calendar-year stratification, which implies that an increase in age of 30 years corresponds to a reduced likelihood of initiating biological treatment by 61.3-67.6%. The estimated proportion of patients initiating biological medication always decreased as age increased, at a statistically significant level. Conclusions Patients with psoriasis have fewer opportunities to access biological medications as they age. This result was shown to be applicable at all stages in a patients life course and was not only restricted to the elderly, although it implies greater disparities as the age difference between patients increases. These results show that inequality in access to biological treatments due to age is prevalent in clinical practice today. Further research is needed to investigate the extent to which this result is influenced by patient preferences.

  • 29. Gronhagen, C. M.
    et al.
    Fored, C. M.
    Granath, F.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Increased risk of cancer among 3663 patients with cutaneous lupus erythematosus: a Swedish nationwide cohort study2012In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 166, no 5, p. 1053-1059Article in journal (Refereed)
    Abstract [en]

    Background: Other autoimmune diseases have been associated with higher risks for cancer, and numerous case reports of cutaneous lupus erythematosus (CLE) and different cancer types are available.

    Objectives: To estimate the overall and specific cancer risks in a nationwide cohort study of patients diagnosed with CLE in Sweden and compare that risk with that in a control cohort without CLE.

    Methods: A cohort of 3663 individuals with CLE and a matched control cohort from the general population (three controls to each CLE case) without a diagnosis of CLE were derived from the Swedish National Patient Register, 1997-2007, and were electronically linked to the Swedish Cancer Register and the Swedish Cause of Death Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to compare the observed vs. the expected numbers of cancers.

    Results: A total of 183 incident cancers occurred within the observation interval, yielding a HR of 1.8 (95% CI 1.5-2.2) for cancer overall. Median follow-up was 4.1 years. About a fourfold risk increase was seen for buccal cancer, lymphomas, respiratory cancer and nonmelanoma skin cancer.

    Conclusions: Patients with CLE appear to have an elevated risk for certain cancer types, an increase that remains when excluding patients also diagnosed with systemic lupus erythematosus. Our findings point to the importance of counselling about not smoking and sun avoidance, and underscore the need for specialized monitoring of this patient group along with bench-to-bedside research efforts to clarify pathogenesis.

  • 30. Gronhagen, C. M.
    et al.
    Fored, C. M.
    Linder, M.
    Granath, F.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Subacute cutaneous lupus erythematosus and its association with drugs: a population-based matched case-control study of 234 patients in Sweden2012In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 167, no 2, p. 296-305Article in journal (Refereed)
    Abstract [en]

    Background Numerous case reports about drug-induced (DI) subacute cutaneous lupus erythematosus (SCLE) have been published. Various drug types with different latencies has been proposed as triggers for this autoimmune skin disease.

    Objectives To evaluate the association between exposure to certain suspected drugs (previously implicated to induce SCLE) and a subsequent diagnosis of SCLE.

    Methods We performed a population-based matched case-control study in which all incident cases of SCLE (n = 234) from 2006 to 2009 were derived from the National Patient Register. The control group was selected from the general population, matched (1 : 10) for gender, age and county of residence. The data were linked to the Prescribed Drug Register. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the association between exposures to certain suspected drugs and the development of SCLE.

    Results: During the 6 months preceding SCLE diagnosis, 166 (71%) of the patients with SCLE had at least one filled prescription of the suspected drugs. The most increased ORs were found for terbinafine (OR 52.9, 95% CI 6.6-infinity), tumour necrosis factor-alpha inhibitors (OR 8.0, 95% CI 1.6-37.2), antiepileptics (OR 3.4, 95% CI 1.9-5.8) and proton pump inhibitors (OR 2.9, 95% CI 2.0-4.0).

    Conclusions: We found an association between drug exposure and SCLE. More than one third of the SCLE cases could be attributed to drug exposure. No significant OR was found for thiazides, which might be due to longer latency and therefore missed with this study design. DI-SCLE is reversible once the drug is discontinued, indicating the importance of screening patients with SCLE for potentially triggering drugs. A causal relationship cannot be established from this study and the underlying pathogenesis remains unclear.

  • 31. Hagforsen, E
    et al.
    Lampinen, M
    Paivandy, A
    Weström, S
    Velin, H
    Öberg, S
    Pejler, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rollman, O
    Siramesine causes preferential apoptosis of mast cells in skin biopsies from psoriatic lesions.2017In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 177, no 1, p. 179-187Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Skin mast cells are implicated as detrimental effector cells in various inflammatory skin diseases such as contact eczema, atopic dermatitis and psoriasis. Selective reduction of cutaneous mast cells, e.g. by inducing targeted apoptosis, might prove a rational and efficient therapeutic strategy in dermatoses negatively influenced by mast cells.

    OBJECTIVES: The objective of the present study was to evaluate whether a lysosomotropic agent such as siramesine can cause apoptosis of mast cells present in psoriatic lesions.

    MATERIALS AND METHODS: Punch biopsies were obtained from lesional and uninvolved skin in 25 patients with chronic plaque psoriasis. After incubation with siramesine, the number of tryptase-positive mast cells and their expression of interleukin (IL)-6 and IL-17 was analysed. Skin biopsies were digested to allow flow cytometric analysis of the drug's effect on cutaneous fibroblasts and keratinocytes.

    RESULTS: Siramesine caused a profound reduction in the total number of mast cells in both lesional and uninvolved psoriatic skin biopsies without affecting the gross morphology of the tissue. The drug reduced the density of IL-6- and IL-17-positive mast cells, and showed antiproliferative effects on epidermal keratinocytes but had no apparent cytotoxic effect on keratinocytes or dermal fibroblasts.

    CONCLUSIONS: Considering the pathophysiology of psoriasis, the effects of siramesine on cutaneous mast cells may prove favourable from the therapeutic aspect. The results encourage further studies to assess the usefulness of siramesine and other lysosomotropic agents in the treatment of cutaneous mastocytoses and inflammatory skin diseases aggravated by dermal mast cells.

  • 32.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Edvinsson, M.
    Nordlind, K.
    Michaelsson, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Expression of nicotinic receptors in the skin of patients with palmoplanta pustulosis2002In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 146, no 3, p. 383-391Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions. OBJECTIVES: To study the alpha 3- and alpha 7-nAChR expression in palmar skin of patients with PPP in comparison with that in healthy smoking and non-smoking controls. METHODS: Biopsies from 20 patients with PPP, seven healthy smokers and eight healthy non-smokers were studied by immunohistochemistry with a monoclonal anti-alpha 3 and a polyclonal anti-alpha 7 antibody. RESULTS: In healthy controls both nAChR subtypes showed stronger immunoreactivity in the eccrine glands and ducts than in the epidermis. The papillary endothelium was positive for both subtypes. Epidermal alpha 3 staining was stronger and that of the coil and dermal ducts weaker in healthy smokers than in healthy non-smokers. In involved PPP skin, granulocytes displayed strong alpha 3 immunoreactivity. The normal epidermal alpha 7 staining pattern was abolished in PPP skin and was replaced by strong mesh-like surface staining, most markedly adjacent to the acrosyringium, which in controls was intensely alpha 7 positive at this level. Endothelial alpha 7 staining was stronger in PPP skin than in the controls. CONCLUSIONS: Smoking can influence nAChR expression. The altered nAChR staining pattern in PPP skin may indicate a possible role for nicotine in the pathogenesis of PPP. We hypothesize that there is an abnormal response to nicotine in patients with PPP, resulting in inflammation.

  • 33.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Einarsson, A.
    Aronsson, F.
    Nordlind, K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaelsson, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The distribution of choline acetyltransferase- and acetylcholinesterase-like immunoreactivity in the palmar skin of patients with palmoplantar pustulosis2000In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 142, no 2, p. 234-242Article in journal (Refereed)
    Abstract [en]

    The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and AChE-like immunoreactivity (LI) of varying intensity in all three groups and with stronger reactivity than in the epidermis. ChAT-LI was present in the coil and in the duct except in the corneal layer. Smokers and patients with PPP displayed significantly fewer ChAT+ acrosyringia than non-smokers. In the patients with PPP, the granulocytes in the pustules and in the papillary dermis displayed ChAT-LI. Western blot analysis of granulocytes from peripheral blood from healthy donors confirmed the presence of ChAT-like proteins in large amounts in neutrophils and small amounts in eosinophils. AChE-LI of varying intensity was found in all parts of the sweat gland apparatus in all three groups. The strongest AChE-LI in the acrosyringia was seen in the lowest part of the stratum corneum, where the PPP pustules are located. No significant differences in staining pattern or intensity were found between the coils, nerve fibres surrounding the coils or ducts. The number of mast cells in the papillary dermis was about four times larger in the patients with PPP than in the control subjects. AChE-LI was observed in about 25% of the mast cells in non-smoking control subjects and in patients with PPP, but only in 10% of those in the smoking control subjects. Our findings indicate that the (non-neuronal) cholinergic system may be involved in cutaneous inflammatory processes.

  • 34.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Hedstrand, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Nyberg, F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Michaelsson, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Novel findings of Langerhans cells and IL-17 expression in relation to the acrosyringium and pustule in palmoplantar pustulosis2010In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 163, no 3, p. 572-579Article in journal (Refereed)
    Abstract [en]

    Backgound Palmoplantar pustulosis (PPP) is a chronic and intensely inflammatory skin disease with pustules, erythema and scaling localized to the palms and soles. To date, no specific treatment is known. Earlier findings indicate the acrosyringium as the target for the inflammation.

    Objectives To identify specific features of the PPP inflammatory cell infiltrate and mediators of inflammation, which might provide insight into the pathogenesis and possible future treatment of the disease.

    Methods Skin biopsies were taken from 23 patients with typical PPP (23 from involved skin and seven from noninvolved skin) and from 18 healthy controls (10 nonsmokers, eight smokers). Cell infiltrates and inflammation mediators were studied with immunohistochemistry.

    Results A strong inflammation was observed in lesional skin of PPP. Our main findings of Langerhans cells and interleukin-17 close to or in the acrosyringium differs from findings in psoriasis vulgaris. Other inflammatory cells such as CD4+, CD8+, regulatory T cells and CD11a+ cells were also accumulated close to the sweat duct in epidermis and papillary dermis. More CD4+, CD8+, Langerhans cells, plasmacytoid dendritic cells and a higher proportion of regulatory T cells/CD3+ cells were seen in noninvolved palmar skin from patients with PPP compared with healthy controls.

    Conclusions Our novel findings indicate that the inflammation in PPP is initiated by the 'stand-by' innate immune system at the acrosyringium.

  • 35.
    Hagforsen, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Pihl-Lundin, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Calcium homeostasis and body composition in patients with palmoplantar pustulosis: a case-control study2012In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 166, no 1, p. 74-81Article in journal (Refereed)
    Abstract [en]

    Background

    Palmoplantar pustulosis (PPP) is a common disease strongly associated with smoking, autoimmune comorbidities and a deranged calcium homeostasis. It is unclear whether these changes in calcium homeostasis are a consequence of vitamin D status, abnormal dermal vitamin D synthesis or whether they are substantiated in effects on bone mineral density (BMD).

    Objectives

    To study the vitamin D status and BMD in patients with PPP.

    Methods

    In comparisons with two sets of controls (n = 101 for serum analyses and n = 5123 for BMD analyses), we therefore aimed to investigate whether PPP (59 cases) was associated with serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, whether patients with PPP had decreased BMD and finally if the dermal expression of 25-hydroxyvitamin D(3) -1α-hydroxylase (CYP27B1) and the vitamin D receptor (VDR) were affected in PPP skin lesions.

    Results

    We found no differences in mean serum 25-hydroxyvitamin D levels between cases and controls, whereas PPP cases displayed 17·8 pmol L(-1) lower (P = 0·04) values in 1,25-dihydroxyvitamin D. BMD at the hip, lumbar spine or of total body did not differ substantially between cases and controls. Finally, patients with PPP had lower dermal expression of CYP27B1 and VDR in affected skin lesions.

    Conclusions

    The increase in serum calcium levels and suppressed parathyroid hormone in patients with PPP were not attributable to derangements in vitamin D status and these patients did not have lower BMD.

  • 36. Hensen, P
    et al.
    Asadullah, K
    Windemuth, C
    Rüschendorf, F
    Hüffmeier, U
    Ständer, M
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wienker, TF
    Reis, A
    Traupe, H
    Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis2003In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 149, no 2, p. 381-385Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The anti-inflammatory cytokine interleukin (IL)-10 is considered to play a major role in the pathophysiology of psoriasis, which is characterized by an IL-10 deficiency. Systemic administration of IL-10 has been shown to be an effective therapy for psoriasis. The IL-10 promoter region contains a highly polymorphic microsatellite (IL10.G) and in a recent case-control study the IL10.G13 (144 bp) allele was found to be associated with familial early onset psoriasis (type 1 psoriasis) having a susceptible effect.

    OBJECTIVES: As it is essential in multifactorial diseases to replicate findings before definite conclusions can be drawn, we decided to perform a follow-up study and to follow a genetic approach analysing allele transmission in families with a positive family history of psoriasis.

    METHODS: We studied 137 nuclear families (trio-design) comprising 456 individuals and genotyped the IL10.G marker. For comparison we also genotyped the microsatellite tn62 as a reference marker of the major psoriasis susceptibility locus on chromosome 6p21 (PSORS1). In the present study allele transmission was evaluated using the family-based association test (FBAT) and GENEHUNTER 2.0 based on the transmission/disequilibrium test.

    RESULTS: The G13 allele (144 bp) had a frequency of 24%, was present in 88 families and clearly showed an even transmission (FBAT, P = 0.753). In contrast, allele 3 (IL10.G9) (136 bp) had a frequency of 39%, was present in 110 families and was transmitted in 43 trios and remained untransmitted in 67 trios (FBAT, P = 0.026), thus showing preferential nontransmission. For the HLA-linked tn62-marker we obtained a P-value of 0.00027 for allele 4 in the same study group.

    CONCLUSIONS: In conclusion, we failed to confirm the susceptible effect of the G13 allele, but provide the first data for a protective effect of allele 3 (IL10.G9) for familial psoriasis. Our results suggest that the IL10.G polymorphism is not a major locus, but acts as a minor locus.

  • 37. Hjalte, F.
    et al.
    Steen Carlsson, K.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sustained Psoriasis Area and Severity Index, DermatologyLife Quality Index and EuroQol-5D response of biologicaltreatment in psoriasis: 10 years of real-world data in theSwedish National Psoriasis Register2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 1, p. 245-252Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Few studies have analysed the long-term effects of biological treatment in psoriasis. PsoReg, the Swedish national register for systemic psoriasis treatment, started in 2006 and includes now ten years of real-world data on effectiveness of biological treatment.

    OBJECTIVE: To analyse long-term real-world outcome data on biological-naïve patients with moderate to severe psoriasis after switching to biological treatment.

    METHODS: Observational study including biological-naïve patients with at least one registration of outcome before switching to biological treatment while included in PsoReg and at least one follow-up visit. PASI, DLQI and EQ-5D values were analysed at 3-5 months, 6-11 months, and at least once 1 year and above, up to 9 years after switch to biological treatment.

    RESULTS: 583 patients fulfilled the inclusion criteria. Of these, 399/395/373 patients had observed outcome data beyond one year on PASI/DLQI/EQ-5D, respectively, and 164/168/152 were observed in at least three time periods after switch. Significant (p<0.01) improvement in PASI, DLQI and EQ-5D was observed 3-5 months after switch and sustained under the whole observation period. Mean PASI/DLQI/EQ-5D changed from 13.5 (SD 9.1)/9.0 (SD 8.1)/0.737 (SD 0.222), respectively, before switch, to 4.0 (SD 3.5)/3.7 (SD 4.7)/0.792 (SD 0.208), respectively, 1-5 years after switch.

    CONCLUSION: Biological treatment, as used in clinical practice, show a stable long term effectiveness in all measured dimensions: PASI, DLQI and EQ-5D.

  • 38.
    Hoppe, Torborg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Winge, Mårten C G
    Bradley, Maria
    Nordenskjöld, Magnus
    Vahlquist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Berne, Berit
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Törmä, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    X-linked recessive ichthyosis: an impaired barrier function evokes limited gene responses before and after moisturizing treatments2012In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 167, no 3, p. 514-522Article in journal (Refereed)
    Abstract [en]

    Background

    X-linked recessive ichthyosis (XLRI) is due to deletions or inactivating mutations in the steroid sulfatase (STS) gene. This results in an accumulation of cholesterol sulphate affecting the packing of intercorneocyte lipids. XLRI is characterized by dry, scaly skin and increased skin barrier permeability; patients are often dependent on daily use of moisturizers.

    Objectives

    To examine the biophysical and molecular changes in the skin of patients with XLRI compared with healthy volunteers, and to analyse the effects of moisturizers on the patients' barrier function.

    Methods 

    Patients with XLRI (= 14) and healthy controls (= 14) were included in the study. Skin dryness score, transepidermal water loss (TEWL) and skin surface pH were monitored at baseline, and punch biopsies were obtained for mRNA expression profiles determined by oligonucleotide arrays. Measurements were repeated in the patients with XLRI after a 4-week treatment with three different moisturizers on the volar forearms. Results  Patients with XLRI showed, compared with healthy controls, increased dryness and TEWL, equal skin pH and altered expression of 27 genes. There were no signs of activation of inflammation or repair pathways. Five selected genes were significantly altered also on quantitative polymerase chain reaction analysis. Treatment with the moisturizers showed similar effects: they improved skin dryness but had no effect on TEWL, pH or expression of selected genes.

    Conclusions 

    Despite a dysfunctional skin barrier, the limited number of genes altered in XLRI skin suggests that no inflammatory or repair mechanisms are triggered. Treatment with moisturizers does not have any major impact on the skin barrier properties of patients with XLRI.

  • 39.
    Hotz, A.
    et al.
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany..
    Fagerberg, C.
    Odense Univ Hosp, Dept Clin Genet, Odense, Denmark..
    Vahlquist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Bygum, A.
    Odense Univ Hosp, Dept Dermatol, Odense, Denmark.;Odense Univ Hosp, Allergy Ctr, Odense, Denmark..
    Törmä, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Rauschendorf, M-A
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany..
    Zhang, Hanqian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Heinz, L.
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany.;Univ Freiburg, Fac Biol, Freiburg, Germany..
    Bourrat, E.
    Hop St Louis, Ctr Reference Genodermatoses, Paris, France..
    Hausser, I.
    Univ Hosp Heidelberg, Inst Pathol, Heidelberg, Germany..
    Vestergaard, V.
    Odense Univ Hosp, Dept Clin Pathol, Odense, Denmark..
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Zimmer, A. D.
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany..
    Fischer, J.
    Univ Freiburg, Inst Human Genet, Fac Med, Med Ctr, Freiburg, Germany..
    Identification of mutations in SDR9C7 in six families with autosomal recessive congenital ichthyosis2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 3, p. E207-E209Article in journal (Other academic)
  • 40.
    Jahns, Anika C
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Eilers, Hinnerk
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ganceviciene, R.
    Alexeyev, Oleg A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Propionibacterium species and follicular keratinocyte activation in acneic and normal skin2015In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, no 4, p. 981-987Article in journal (Refereed)
    Abstract [en]

    Background The pathogenesis of acne vulgaris is multifactorial with increased sebum production, alteration in the quality of sebum lipids, dysregulation of the hormone microenvironment, follicular hyperkeratinization and Propionibacterium acnes-driven inflammation as major contributory factors. Hyperproliferation of keratinocytes is believed to contribute to hypercornification and eventually leads to comedone development. While the distribution of P. acnes is relatively well documented in acneic and healthy skin, little is known about P. granulosum and P. avidum.

    Objectives To visualize directly the three major Propionibacterium in 117 control and 26 acneic skin samples. In addition, keratinocyte proliferation was evaluated.

    Methods Propionibacteria were visualized by immunofluorescence microscopy, and keratinocyte proliferation was assessed by Ki67, keratin (K) 16 and p63 immunochemistry.

    Results P. acnes was identified in 68 samples (48%), while P. granulosum was identified in 12 (8%) samples; P. avidum was not detected at all. Unexpectedly, acne samples did not show higher keratinocyte proliferation than controls, nor was there any association between bacterial colonization and expression of Ki67/K16/p63.

    Conclusions Our findings do not support earlier notions of follicular keratinocyte hyperproliferation as a cause of ductal hypercornification in acneic facial skin. Further studies on the mechanisms underlying hypercornification in acne pathogenesis are needed.

  • 41.
    Jahns, Anika C
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundskog, Bertil
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ganceviciene, R
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Palmer, Ruth H
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Zouboulis, C C
    McDowell, A
    Patrick, S
    Alexeyev, Oleg A
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study2012In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 167, no 1, p. 50-58Article in journal (Refereed)
    Abstract [en]

    Summary Background  Acne vulgaris is a disorder of the sebaceous follicles. Propionibacterium acnes can be involved in inflammatory acne. Objectives  This case-control study aimed at investigating the occurrence and localization of P. acnes in facial biopsies in acne and to characterize the P. acnes phylotype in skin compartments. Methods  Specific monoclonal and polyclonal antibodies were applied to skin biopsies of 38 patients with acne and matching controls to localize and characterize P. acnes and to determine expression of co-haemolysin CAMP factor, a putative virulence determinant. Results  Follicular P. acnes was demonstrated in 18 (47%) samples from patients with acne and eight (21%) control samples [odds ratio (OR) 3·37, 95% confidence interval (CI) 1·23-9·23; P = 0·017]. In 14 (37%) samples from patients with acne, P. acnes was visualized in large macrocolonies/biofilms in sebaceous follicles compared with only five (13%) control samples (OR 3·85, 95% CI 1·22-12·14; P = 0·021). Macrocolonies/biofilms consisting of mixed P. acnes phylotypes expressing CAMP1 were detected in both case and control samples. Only four samples tested positive for the presence of Staphylococcus spp. and fungi were not observed. Conclusions  We have for the first time visualized different P. acnes phylotypes in macrocolonies/biofilms in sebaceous follicles of skin biopsies. Our results support the hypothesis that P. acnes can play a role in the pathogenesis of acne as acne samples showed a higher prevalence of follicular P. acnes colonization, both in terms of follicles containing P. acnes and the greater numbers of bacteria in macrocolonies/biofilms than in control samples.

  • 42.
    Johannesson, Ulrika
    et al.
    Division of Obstetrics and Gynecology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm.
    Blomgren, Bo
    AstraZeneca, Södertälje, Sweden.
    Hilliges, Marita
    Halmstad University, School of Business and Engineering (SET), Biological and Environmental Systems (BLESS), Biomechanics and Biomedicine.
    Rylander, Eva
    Division of Obstetrics and Gynecology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm.
    Bohm-Starke, Nina
    Division of Obstetrics and Gynecology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm.
    The vulval vestibular mucosa - morphological effects of oral contraceptives and menstrual cycle2007In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 157, no 3, p. 487-493Article in journal (Refereed)
    Abstract [en]

    Background

    An erythematous and hypersensitive vestibular mucosa has been observed during the use of combined oral contraceptives (COC). Hormonal effects on the vestibular morphology have not been studied.

    Objectives

    Our aim was to evaluate the morphology of the vulval vestibular mucosa during the influence of COC and during the menstrual cycle.

    Methods

    Forty-five healthy women (20 using COC and 25 not using COC) were included. A 6-mm punch biopsy was obtained from the right posterior vestibule on days 7-11 of the menstrual cycle. A corresponding biopsy was taken 2 weeks later in 16 women without COC. The epithelial morphology was estimated by measuring interdermal papilla distance, dermal papilla to surface, from basal layer to surface and width of dermal papillae. A histopathological assessment was made.

    Results

    The vulval vestibular mucosa of women using COC displayed a larger distance between the dermal papillae (P = 0·04) and a larger space from the dermal papillae to the epithelial surface (P = 0·03) compared with controls in the follicular phase. Women without COC displayed a larger interdermal papilla distance in the luteal phase compared with the follicular phase, P = 0·02. Histopathology showed more superficial blood vessels in the COC users (P < 0·01).

    Conclusions

    The vulval vestibular mucosa of women with COC display an altered morphological pattern with shallow and sparse dermal papillae compared with the follicular phase. Similar findings are seen in women without COC during the luteal phase which indicate a gestagenic effect on the mucosa. Associations between the morphological pattern and changes in mucosal mechanical sensitivity require further studies.

  • 43.
    Josefson, A.
    et al.
    Örebro Univ, Dept Dermatol, Fac Med, SE-70185 Orebro, Sweden..
    Berg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    Ganemo, A.
    Inst Clin Res Malmo, Dept Dermatol, Malmo, Sweden.;Univ Malmo, Malmo, Sweden..
    Hallander, A.
    Orebro Univ, Dept Dermatol, Fac Med, SE-70185 Orebro, Sweden..
    Hindsen-Stenstrom, M.
    Inst Clin Res Malmo, Dept Dermatol, Malmo, Sweden.;Univ Malmo, Malmo, Sweden..
    Meding, B.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Svensson, A.
    Inst Clin Res Malmo, Dept Dermatol, Malmo, Sweden.;Univ Malmo, Malmo, Sweden..
    Lindberg, M.
    Orebro Univ, Dept Dermatol, Fac Med, SE-70185 Orebro, Sweden..
    Methodological aspects of assessing hand eczema: comparison of two tools and three different categories of evaluators2017In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 176, no 5, p. 1373-1375Article in journal (Other academic)
  • 44.
    Josefson, Anna
    et al.
    Örebro University Hospital. Department of Dermatology, Örebro University Hospital, Örebro, Sweden.
    Berg, Mats
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Gånemo, Agneta
    Department of Dermatology, Institute of Clinical Research in Malmö, Lund University, Malmö, Sweden.
    Hallander, Anna
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hindsén-Stenström, Monica
    Department of Dermatology, Institute of Clinical Research in Malmö, Lund University, Malmö, Sweden.
    Meding, Birgitta
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Svensson, Åke L.
    Department of Dermatology, Institute of Clinical Research in Malmö, Lund University, Malmö, Sweden.
    Lindberg, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Dermatology, Örebro University Hospital, Örebro, Sweden.
    Methodological aspects of assessing hand eczema: Comparison of two tools and three different categories of evaluators2017In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 176, no 5, p. 1373-1375Article in journal (Refereed)
  • 45.
    Josefson, Anna
    et al.
    Örebro University, School of Health and Medical Sciences.
    Färm, Gunilla
    Magnuson, A.
    Meding, Birgitta
    Nickel allergy as risk factor for hand eczema: a population-based study2009In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 160, no 4, p. 828-834Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In population-based studies using self-reported nickel allergy, a hand eczema prevalence of 30-43% has been reported in individuals with nickel allergy. In a previous Swedish study, 958 schoolgirls were patch tested for nickel. In a questionnaire follow up 20 years later no association was found between nickel allergy and hand eczema. OBJECTIVES: To investigate further the relation between nickel allergy and hand eczema. METHODS: Three hundred and sixty-nine women, still living in the same geographical area, now aged 30-40 years, were patch tested and clinically investigated regarding hand eczema. RESULTS: Patch testing showed 30.1% nickel-positive individuals. The adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 years in relation to nickel patch test results was 1.03 (95% confidence interval, CI 0.71-1.50). A history of childhood eczema was reported by 35.9%, and the PPR for hand eczema in relation to childhood eczema was 3.68 (95% CI 2.45-5.54). When analysing the relation separately in women with and without a history of childhood eczema a statistical interaction was found. The hand eczema risk was doubled in nickel-positive women without a history of childhood eczema, with a PPR of 2.23 (95% CI 1.10-4.49) for hand eczema after age 15 years. CONCLUSIONS: A doubled risk for hand eczema was found in nickel-positive women without a history of childhood eczema. When analysing all participants, there was no statistically significant difference between nickel-positive and nickel-negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. The risk for hand eczema in nickel-positive women may previously have been overestimated.

  • 46.
    Krynitz, B.
    et al.
    Karolinska University of Labs, Sweden; Karolinska Institute, Sweden.
    Olsson, H.
    Karolinska Institute, Sweden.
    Lundh Rozell, Barbro
    Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lindelof, B.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Edgren, G.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Smedby, K. E.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 1, p. 95-103Article in journal (Refereed)
    Abstract [en]

    Background Risk of basal cell carcinoma (BCC) has been reported to be several-fold increased among organ transplant recipients (OTRs). However, due to lack of reliable BCC registration, population-based risk estimates are scarce. Objectives To characterize risk of BCC among OTRs compared with the general population, and contrast with risk of cutaneous squamous cell carcinoma (SCC). Subjects and methods OTRs transplanted during 2004-2011 were identified through national healthcare registers and linked with the nationwide Swedish BCC Register initialized in 2004. Relative risk of BCC was expressed as standardized incidence ratios (SIR) with 95% confidence intervals (CI). Results Altogether, 4023 transplanted patients developed 341 BCCs during follow-up. Compared with the general population, the relative risk of BCC was increased sixfold (SIR 6.1, 95% CI 5.4-6.9). The risk was higher in kidney and heart/lung than in liver recipients (SIRkidney 7.2, 6.3-8.3; SIRheart/lung 5.8, 4.0-8.2; SIRliver 2.6, 1.7-4.0), and risk increased with time since transplantation (P-trend &lt; 0.01). The SCC to BCC ratio was 1 : 1.7 and BCC developed earlier after transplantation than SCC. Distribution of anatomical sites and histological types did not differ substantially between OTR- and population-BCCs. Conclusions Risk of BCC was strikingly elevated in OTRs compared with the general population. Risk was higher in kidney recipients and increased with follow-up time. These findings support a tumour-promoting effect of immunosuppressive drugs in BCC development. The low SCC to BCC ratio was possibly attributed to short follow-up time.

  • 47.
    Lindberg, Magnus
    Örebro University Hospital. Dept Dermatol, Örebro University Hospital, Örebro, Sweden.
    The hand eczema proteome: imbalance of epidermal barrier proteins2015In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, no 4, p. 852-853Article in journal (Refereed)
  • 48.
    Lindberg, Magnus
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Atopic dermatitis and gut microbiota2017In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 176, no 2, p. 297-298Article in journal (Refereed)
  • 49. Lindelöf, B
    et al.
    Sigurgeirsson, B
    Tegner, E
    Johannesson, A
    Berne, B
    Christensen, OB
    Andersson, T
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Törngren, M
    Molin, M
    Nylander-Lundqvist, E
    Emtestam, L
    PUVA and cancer risk: the Swedish follow-up study.1999In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 141, p. 108-112Article in journal (Refereed)
  • 50. Lyth, J.
    et al.
    Eriksson, H.
    Hansson, J.
    Ingvar, C.
    Jansson, M.
    Lapins, J.
    Mansson-Brahme, E.
    Naredi, P.
    Stierner, U.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Carstensen, J.
    Lindholm, C.
    Trends in cutaneous malignant melanoma in Sweden 1997-2011: thinner tumours and improved survival among men2015In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, no 3, p. 700-706Article in journal (Refereed)
    Abstract [en]

    Background Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most Western countries, although the rate of improvement in survival appears to have declined in Sweden at the end of the last millennium. Objectives To analyse the most recent trends in the distribution of tumour thickness (T category) as well as CMM-specific survival in Swedish patients diagnosed during 1997-2011. Methods This nationwide population-based study included 30 590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM during 1997-2011. The patients were followed through 2012 in the national Cause of Death Register. Results Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site and healthcare region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P < 0.001) and the CMM-specific survival significantly improved in men diagnosed during 2007-2011 compared with men diagnosed during 1997-2001 (hazard ratio = 0.81; 95% confidence interval 0.72-0.91; P < 0.001), while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared with those diagnosed earlier (during 1997-2001) and later (during 2007-2011). Conclusions In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men.

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