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  • 1. Arana, Alejandro
    et al.
    Pottegard, Anton
    Kuiper, Josephina G.
    Crellin, Elizabeth
    Reutfors, Johan
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Lund, Lars Christian
    Houben, Eline
    Booth, Helen
    Calingaert, Brian
    Kaye, James A.
    Gembert, Karin
    Rothman, Kenneth J.
    Dedman, Daniel
    Kieler, Helle
    Gutierrez, Lia
    Hallas, Jesper
    Perez-Gutthann, Susana
    To what extent are topical tacrolimus or pimecrolimus associated with increased risk of skin cancer and lymphoma?: Longterm results from Joelle study2020In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 29, p. 568-569Article in journal (Other academic)
  • 2. Arana, Alejandro
    et al.
    Pottegård, Anton
    Kuiper, Josephina G.
    Booth, Helen
    Reutfors, Johan
    Calingaert, Brian
    Lund, Lars Christian
    Crellin, Elizabeth
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Kaye, James A.
    Gembert, Karin
    Rothman, Kenneth J.
    Kieler, Helle
    Dedman, Daniel
    Houben, Eline
    Gutiérrez, Lia
    Hallas, Jesper
    Perez-Gutthann, Susana
    Long-Term Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus and Pimecrolimus: Final Results from the Extension of the Cohort Study Protopic Joint European Longitudinal Lymphoma and Skin Cancer Evaluation (JOELLE)2021In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 13, p. 1141-1153Article in journal (Refereed)
    Abstract [en]

    Purpose: Evidence is insufficient to infer whether topical calcineurin inhibitors (TCIs; tacrolimus and pimecrolimus) cause malignancy. The study objective was to estimate the long-term risk of skin cancer and lymphoma associated with topical TCI use in adults and children, separately.

    Patients and Methods: A cohort study in Denmark, Sweden, UK, and the Netherlands was conducted. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for nonmelanoma skin cancer (NMSC), melanoma, cutaneous T-cell lymphoma (CTCL), non-Hodgkin lymphoma (NHL) excluding CTCL, and Hodgkin lymphoma (HL) in new users of TCIs versus users of moderate/high-potency topical corticosteroids.

    Results: The study included 126,908/61,841 adults and 32,605/27,961 children initiating treatment with tacrolimus/pimecrolimus, respectively. Follow-up was ≥10 years for 19% of adults and 32% of children. Incidence rate ratios and (95% confidence intervals) for tacrolimus versus corticosteroid users in adults were <1 for melanoma, non-Hodgkin lymphoma, and Hodgkin lymphoma; and 1.80 (1.25-2.58) for cutaneous T-cell lymphoma. For pimecrolimus, IRRs in adults were <1 for non-Hodgkin lymphoma, cutaneous T-cell lymphoma, and Hodgkin's lymphoma; and 1.21 (1.03-1.41) for melanoma; and 1.28 (1.20-1.35) for nonmelanoma skin cancer. In children, results were inconclusive due to few events. In adults, incidence rate ratios ≥5 years after first topical calcineurin inhibitor exposure were not higher than in overall analyses.

    Conclusion: Overall, we found little evidence associating use of topical calcineurin inhibitors with skin cancer and lymphoma; confounding by indication, surveillance bias, and reverse causation may have influenced these results. Even if causal, the public health impact of these excess risks would be low and confined to the first years of exposure.

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  • 3.
    Blauvelt, Andrew
    et al.
    Oregon Medical Research Center, OR, Portland, United States.
    Gondo, George C.
    National Psoriasis Foundation, OR, Portland, United States.
    Bell, Stacie
    National Psoriasis Foundation, OR, Portland, United States.
    Echeverría, Cristina
    Instituto de Rehabilitación Psicofísica (IREP), Buenos Aires, Argentina.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Skov, Lone
    Department of Dermatology and Allergy, University of Copenhagen, Copenhagen, Denmark.
    van de Kerkhof, Peter
    Nijmegen Medical Centre, Radboud University, Nijmegen, Netherlands.
    McCormick Howard, Leah
    National Psoriasis Foundation, OR, Portland, United States.
    Strober, Bruce
    Yale University School of Medicine, CT, New Haven, United States.
    Psoriasis involving special areas is associated with worse quality of life, depression, and limitations in the ability to participate in social roles and activities2023In: Journal of Psoriasis and Psoriatic Arthritis, ISSN 2475-5303, Vol. 8, no 3, p. 100-106Article in journal (Refereed)
    Abstract [en]

    Background: Psoriasis severity has traditionally been categorized as mild, moderate, and severe. Commonly, cut-offs for severe disease require a body surface area (BSA) involvement of ≥10% or a Psoriasis Area Severity Index (PASI) > 10. However, clinical experience challenges these traditional measures and requirements, as patients with less extensive psoriasis may have disease that severely impacts quality of life.

    Objective: The objective of the present study was to further explore the extent of patient burden when psoriasis affects special locations.

    Methods: A total of 69,190 individuals living in the U.S were invited to participate in a patient advocacy survey by telephone and or web interviews over the course of 3 years (2019-2021). The survey instrument consisted of validated patient-reported outcome measures, measuring disease-specific quality of life (Dermatology Life Quality Index, DLQI), depression (Patient Health Questionnaire (PHQ)-2 and (PHQ)-9), and the ability to participate in social roles and activities (PROMIS Ability to Participate in Social Roles and Activities (SF-4a). Chi-square tests were performed to explore association between psoriasis involvement on special locations and patient outcomes and multivariate logistic regression models were then constructed, to assess impact of having psoriasis on special locations patient outcomes, controlling for potential confounding factors.

    Results: A total of 4129 individuals completed the survey. 3594 (84.4%) of patients surveyed reported psoriasis involving special areas of the bodysuch as the scalp, face, hands, feet, or genitalia. Involvement of special areas is associated with worse quality of life and depression. 35-71% of patients with 10% or less total BSA involvement experienced a moderate-to-extremely large effect on these life function domains. When adjusting for age, sex, and body surface area, psoriasis involvement of a special location was associated with poorer patient reported outcomes. including a 46% less likelihood of reporting their skin disease ass having “no or only a small effect on QoL,” a 30% less likelihood of having a “normal l ability to participate in social roles and activities,” and a 126% higher likelihood of f having depression.

    Conclusion: Real-world data presented here demonstrate that psoriasis involving special areas is associated with adverse life consequences, including poor quality of life and depression.

  • 4. Broms, Gabriella
    et al.
    Kieler, Helle
    Ekbom, Anders
    Gissler, Mika
    Hellgren, Karin
    Lahesmaa-Korpinen, Anna-Maria
    Pedersen, Lars
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sorensen, Henrik T.
    Granath, Fredrik
    Anti-TNF treatment during pregnancy and birth outcomes: Apopulation-based study from Denmark, Finland, and Sweden2020In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 29, no 3, p. 316-327Article in journal (Refereed)
    Abstract [en]

    Purpose: To study the risk of preterm birth, caesarean section, and small for gestational age after anti-tumor necrosis factor agent treatment (anti-TNF) in pregnancy.

    Methods: Population-based study including women with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, and their infants born 2006 to 2013 from the national health registers in Denmark, Finland, and Sweden. Women treated with anti-TNF were compared with women with nonbiologic systemic treatment. Adalimumab, etanercept, and infliximab were compared pairwise. Continuation of treatment in early pregnancy was compared with discontinuation. Odds ratios with 95% confidence intervals were calculated in logistic regression models adjusted for country and maternal characteristics.

    Results: Among 1 633 909 births, 1027 infants were to women treated with anti-TNF and 9399 to women with nonbiologic systemic treatment. Compared with non-biologic systemic treatment, women with anti-TNF treatment had a higher risk of preterm birth, odds ratio 1.61 (1.29-2.02) and caesarean section, 1.57 (1.35-1.82). The odds ratio for small for gestational age was 1.36 (0.96-1.92). In pairwise comparisons, infliximab was associated with a higher risk of severely small for gestational age for inflammatory joint and skin diseases but not for inflammatory bowel disease. Discontinuation of anti-TNF had opposite effects on preterm birth for inflammatory bowel disease and inflammatory joint and skin diseases.

    Conclusions: Anti-TNF agents were associated with increased risks of preterm birth, caesarean section, and small for gestational age. However, the diverse findings across disease groups may indicate an association related to the underlying disease activity, rather than to agent-specific effects.

  • 5. Broms, Gabriella
    et al.
    Kieler, Helle
    Ekbom, Anders
    Gissler, Mika
    Hellgren, Karin
    Leinonen, Maarit K.
    Pedersen, Lars
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sorensen, Henrik Toft
    Granath, Fredrik
    Infant Infections after Maternal Anti-TNF Treatment in Pregnancy2019In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 28, p. 10-10Article in journal (Other academic)
  • 6. Bröms, Gabriella
    et al.
    Kieler, Helle
    Ekbom, Anders
    Gissler, Mika
    Hellgren, Karin
    Leinonen, Maarit K.
    Pedersen, Lars
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Centre for Pharmacoepidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Sorensen, Henrik Toft
    Granath, Fredrik
    Paediatric infections in the first 3 years of life after maternal anti-TNF treatment during pregnancy2020In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 52, no 5, p. 843-854Article in journal (Refereed)
    Abstract [en]

    Background: Most anti‐tumour necrosis factor (anti‐TNF) agents are transferred across the placenta and may increase paediatric susceptibility to infections.

    Aims: To assess the risk of paediatric infections after maternal anti‐TNF treatment.

    Methods: Population‐based cohort study in Denmark, Finland and Sweden 2006‐2013 in which 1027 children born to women with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis or inflammatory bowel disease, treated with anti‐TNF, and 9346 children to women with nonbiologic systemic treatment, were compared to 1 617 886 children of the general population. Children were followed for 3 years.

    Results: Adjusted by maternal age, parity, smoking, body mass index, country and calendar year, the incidence rate ratios with 95% confidence interval (CI) for hospital admissions for infection in the first year were 1.43 (1.23‐1.67) for anti‐TNF and 1.14 (1.07‐1.21) for non‐biologic systemic treatment, and 1.29 (1.11‐1.50) and 1.09 (1.02‐1.15), respectively, when additionally adjusting for adverse birth outcomes. There was a slight increase in antibiotic prescriptions in the second year for anti‐TNF, 1.19 (1.11‐1.29), and for non‐biologic systemic treatment, 1.10 (1.07‐1.13). There was no difference among anti‐TNF agents, treatment in the third trimester, or between mono/combination therapy with non‐biologic systemic treatment.

    Conclusions: Both anti‐TNF and non‐biologic systemic treatment were associated with an increased risk of paediatric infections. However, reassuringly, the increased risks were present regardless of treatment in the third trimester, with combination of treatments, and were not persistent across the first 3 years of life. Our findings may indicate a true risk, but could also be due to unadjusted confounding by disease severity and healthcare‐seeking behaviour. This may in turn shift the risk‐benefit equation towards continuation of treatment even in the third trimester.

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  • 7. Bröms, Gabriella
    et al.
    Kieler, Helle
    Ekbom, Anders
    Hellgren, Karin
    Gissler, Mika
    Lahesmaa-Korpinen, Anna-Maria
    Pedersen, Lars
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sorensen, Henrik T.
    Granath, Fredrik
    Tnf inhibitor treatment during pregnancy and risk of preterm birth2018In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 27, p. 30-31, article id 60Article in journal (Other academic)
  • 8. Calara, Paul S
    et al.
    Althin, Rikard
    Carlsson, Katarina Steen
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Regional Differences in the Prescription of Biologics for Psoriasis in Sweden: a Register-Based Study of 4168 Patients2017In: BioDrugs, ISSN 1173-8804, E-ISSN 1179-190X, Vol. 31, no 1, p. 75-82Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Observational studies suggest an inequitable prescription of biologics in psoriasis care, which may be attributed to geographical differences in treatment access. Sweden regularly ranks high in international comparisons of equitable healthcare, and is, in connection with established national registries, an ideal country to investigate potential inequitable access.

    OBJECTIVE: The aim was to determine whether the opportunity for patients to receive biologics depends on where they receive care.

    METHODS: Biologic-naïve patients enrolled in the Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) from 2008 to 2015 (n = 4168) were included. The association between the likelihood of initiating a biologic and the region where patients received care was analyzed. The strength of the association was adjusted for patient and clinical characteristics, as well as disease severity using logistic regression analysis. The proportion of patients that switched to a biologic (switch rate) and the probability of switch to a biologic was calculated in 2-year periods.

    RESULTS: The national switch rate increased marginally over time from 9.7 to 11.0%, though the uptake varied across regions. Adjusted odds ratios for at least one region were significantly different from the reference region in every 2-year period. During the latest period (2014-2015), the average patient in the lowest prescribing region was nearly 2.5 times less likely to switch as a similar patient in the highest prescribing region.

    CONCLUSIONS: Geographical differences in biologics prescription persist after adjusting for patient characteristics and disease severity. The Swedish example calls for further improvements in delivering equitable psoriasis care.

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  • 9. Calara, Paul S.
    et al.
    Norlin, Jenny M.
    Althin, Rikard
    Steen Carlsson, Katarina
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Healthcare Provider Type and Switch to Biologics in Psoriasis: Evidence from Real-World Practice2016In: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, ISSN 1173-8804, Vol. 30, no 2, p. 145-151Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous research indicates an uneven uptake of biologics in patients with moderate-to-severe psoriasis in Sweden. Therefore, it is essential to scrutinise variations in treatment patterns.

    OBJECTIVE: The aim of this study was to evaluate the extent to which the uptake of biologics for psoriasis differs between types of healthcare provider.

    METHODS: Three types of provider were identified within 52 units participating in the Swedish National Registry for Systemic Psoriasis Treatment (PsoReg): university hospitals, non-university hospitals and individual practices. Biologics-naïve patients (n = 3165) were included in analyses to investigate the probability of switch to biologics. The numbers of patients fulfilling the criteria for moderate-to-severe psoriasis [Psoriasis Area and Severity Index (PASI) ≥10 and Dermatology Life Quality Index (DLQI) ≥10] among patients who switched to biologics and patients who did not switch were reported. A logistic regression model was used to calculate how healthcare provider type influenced the probability of switch to biologics whilst adjusting for patient characteristics and disease severity.

    RESULTS: During registration, 16 % of patients switched to biologics while 84 % remained on conventional systemic treatment. In 7 % of patients, the criteria PASI ≥10 and DLQI ≥10 was fulfilled at their last visit without switching to biologics, whereas in 10 % of patients the criteria was not fulfilled prior to switch. After controlling for patient characteristics and disease severity, small or no difference in the probability of switch was observed between provider types.

    CONCLUSIONS: Disease severity does not explain the decision to switch or not to switch to biologics for a disproportionate number of patients. There seems to be an uneven uptake of biologics in Swedish clinical practice, but the type of healthcare provider cannot explain this variation. More research is needed on what factors influence the prescription of biologics.

  • 10.
    Ericson, Oskar
    et al.
    The Swedish Institute for Health Economics, Lund, Sweden.
    Löfvendahl, Sofia
    The Swedish Institute for Health Economics, Lund, Sweden; Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Lund, Sweden.
    Norlin, Jenny M.
    The Swedish Institute for Health Economics, Lund, Sweden.
    Gyllensvärd, Harald
    Boehringer Ingelheim AB, Stockholm, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mortality in generalized pustular psoriasis: a population-based national register study2023In: The Journal of American Academy of Dermatology, ISSN 0190-9622, E-ISSN 1097-6787, Vol. 89, no 3, p. 616-619Article in journal (Other academic)
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  • 11. Fakler, JW
    et al.
    Schmitt-Egenolf, Marcus
    Department of Dermatology, University of Ulm, Ulm, Germany.
    Vejbaesya, S
    Boehncke, WH
    Sterry, W
    Eiermann, TH
    Analysis of TAP2 and HLA-DP gene polymorphism in psoriasis1994In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 40, no 4, p. 299-302Article in journal (Refereed)
    Abstract [en]

    TAP2 is a gene, located between HLA-DP and HLA-DQ, whose products form a transporter molecule involved in endogenous antigen processing. Polymorphic residues have been described in this gene. TAP2 is of particular interest because its involvement in antigen presentation makes it a candidate for a disease susceptibility gene. In psoriasis, two clinical subtypes analogous to the situation in diabetes type I with early onset and family history and type II with later onset and without family history have been described. We have previously shown that type I but not type II psoriasis is associated with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 haplotype. To investigate whether this haplotype extends to include particular TAP2 and/or DP alleles, we tested the TAP2 and HLA-DP alleles of a control group (n = 199), patients with psoriasis type I (n = 66), and patients with psoriasis type II (n = 35) by hybridization with SSOs. Our data show that there is no significant correlation between TAP2 and/or HLA-DP gene polymorphism and psoriasis type I and/or type II. We conclude that disease association in type I psoriasis is associated with the extended haplotype HLA-B57, -Cw6, -DRB1*0701/2, -DQA1*0201, -DQB1*0303.

  • 12.
    Falk Kieri, Catarina
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Bergendal, Birgitta
    Lind, Lisbet K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Stecksén-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology.
    EDAR-induced hypohidrotic ectodermal dysplasia: a clinical study on signs and symptoms in individuals with a heterozygous c.1072C > T mutation2014In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 15, p. 57-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mutations in the EDAR-gene cause hypohidrotic ectodermal dysplasia, however, the oral phenotype has been described in a limited number of cases. The aim of the present study was to clinically describe individuals with the c.1072C > T mutation (p. Arg358X) in the EDAR gene with respect to dental signs and saliva secretion, symptoms from other ectodermal structures and to assess orofacial function.

    METHODS: Individuals in three families living in Sweden, where some members had a known c.1072C > T mutation in the EDAR gene with an autosomal dominant inheritance (AD), were included in a clinical investigation on oral signs and symptoms and self-reported symptoms from other ectodermal structures (n = 37). Confirmation of the c.1072C > T mutation in the EDAR gene were performed by genomic sequencing. Orofacial function was evaluated with NOT-S.

    RESULTS: The mutation was identified in 17 of 37 family members. The mean number of missing teeth due to agenesis was 10.3 ± 4.1, (range 4-17) in the mutation group and 0.1 ± 0.3, (range 0-1) in the non-mutation group (p < 0.01). All individuals with the mutation were missing the maxillary lateral incisors and one or more of the mandibular incisors; and 81.3% were missing all four. Stimulated saliva secretion was 0.9 ± 0.5 ml/min in the mutation group vs 1.7 ± 0.6 ml/min in the non-mutation group (p < 0.01). Reduced ability to sweat was reported by 82% in the mutation group and by 20% in the non-mutation group (p < 0.01). The mean NOT-S score was 3.0 ± 1.9 (range 0-6) in the mutation group and 1.5 ± 1.1 (range 0-5) in the non-mutation group (p < 0.01). Lisping was present in 56% of individuals in the mutation group.

    CONCLUSIONS: Individuals with a c.1072C > T mutation in the EDAR-gene displayed a typical pattern of congenitally missing teeth in the frontal area with functional consequences. They therefore have a need for special attention in dental care, both with reference to tooth agenesis and low salivary secretion with an increased risk for caries. Sweating problems were the most frequently reported symptom from other ectodermal structures.

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  • 13.
    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. 

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  • 14.
    Geale, Kirk
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henriksson, M.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    The Relationship Between Disease Severity and Quality of Life In Patients With Moderate to Severe Psoriasis2015In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 18, no 7, p. A675-A675Article in journal (Refereed)
  • 15.
    Geale, Kirk
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Quantify Research, Stockholm, Sweden.
    Henriksson, Martin
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Association of Skin Psoriasis and Somatic Comorbidity With the Development of Psychiatric Illness in a Nationwide Swedish Study2020In: JAMA dermatology, ISSN 2168-6068, E-ISSN 2168-6084, Vol. 156, no 7, p. 795-804Article in journal (Refereed)
    Abstract [en]

    Importance: Psoriasis is a complex systemic disease with skin involvement, somatic comorbidity, and psychiatric illness (PI). Although this view of psoriasis is widely accepted, potential synergies within this triad of symptoms have not been adequately investigated.

    Objectives: To investigate the independent association of skin psoriasis and somatic comorbidity with the development of PI and to assess whether skin psoriasis and somatic comorbidity act synergistically to produce a risk of PI that is greater than the additive associations.

    Design, Setting, and Participants: Participants were enrolled between January 2005 and December 2010, in this retrospective matched case-control study using secondary (ie, administrative), population-based registry data from Swedish patients in routine clinical care. The dates of analysis were March 2017 to December 2019. Participants were patients with skin psoriasis and control participants without psoriasis matched on age, sex, and municipality, who were all free of preexisting PI.

    Exposures: Presence of skin psoriasis and somatic comorbidity (captured through the Charlson Comorbidity Index and the Elixhauser Comorbidity Index).

    Main Outcomes and Measures: Risk of PI onset (composite of depression, anxiety, and suicidality) is shown using Kaplan-Meier curves stratified by the presence of skin psoriasis and somatic comorbidity. Adjusted associations of skin psoriasis and somatic comorbidity with the development of PI were analyzed using Cox proportional hazards regression models, including interactions to assess synergistic associations. The 3 components of PI were also assessed individually.a

    Results: A total of 93 239 patients with skin psoriasis (mean [SD] age, 54 [17] years; 47 475 men [51%]) and 1 387 495 control participants (mean [SD] age, 54 [16] years; 702 332 men [51%]) were included in the study. As expected, patients with skin psoriasis were more likely to have somatic comorbidity and PI than control participants. Compared with those without skin psoriasis or somatic comorbidity, patients with psoriasis without somatic comorbidity had a 1.32 times higher risk of PI onset (hazard ratio [HR], 1.32; 95% CI, 1.27-1.36; P < .001), whereas patients with psoriasis with somatic comorbidity had a 2.56 times higher risk of PI onset (HR, 2.56; 95% CI, 2.46-2.66; P < .001). No synergistic associations of skin psoriasis and somatic comorbidity with the development of PI were found (HR, 0.93; 95% CI, 0.81-1.04; P = .21).

    Conclusions and Relevance: This study found that somatic comorbidity appeared to alter PI onset even more than skin psoriasis. The observed association of skin psoriasis and somatic comorbidity with the development of PI reinforces the need for proactive, holistic treatment of patients with psoriasis.

  • 16.
    Geale, Kirk
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. PAREXEL Int, Stockholm, Sweden.
    Henriksson, Martin
    Linköping Univ, Dept Med & Hlth Sci, Linköping, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    How is disease severity associated with quality of life in psoriasis patients?: Evidence from a longitudinal population-based study in Sweden2017In: Health and Quality of Life Outcomes, ISSN 1477-7525, E-ISSN 1477-7525, Vol. 15, no 1, article id 151Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Assessing the impact of disease severity on generic quality of life (QOL) is a critical step in outcomes research and in the development of decision-analytic models structured around health states defined by clinical measures. While data from routine clinical practice found in healthcare registers are increasingly used for research, more attention should be paid to understanding the relationship between clinical measures of disease severity and QOL. The purpose of this work was therefore to investigate this relationship in psoriasis using a population-based dataset.

    METHODS: Severity was measured by the Psoriasis Area and Severity Index (PASI), which combines severity of erythema, induration, and desquamation into a single value ranging from 0 to 72. The generic EQ-5D-3L utility instrument, under the UK tariff, was used to measure QOL. The association between PASI and EQ-5D-3L was estimated using a population-based dataset of 2674 patients with moderate to severe psoriasis enrolled over ten years in the Swedish psoriasis register (PsoReg). Given the repeated measurement of patients in the register data, a longitudinal fixed-effects model was employed to control for unobserved patient-level heterogeneity.

    RESULTS: Marginal changes in PASI are associated with a non-linear response in EQ-5D-3L: Moving from PASI 10 to 9 (1 to 0) is associated with an increase of 0.0135 (0.0174) in EQ-5D-3L. Furthermore, unobserved patient-level heterogeneity appears to be an important source of confounding when estimating the relationship between QOL and PASI.

    CONCLUSIONS: Using register data to estimate the impact of disease severity on QOL while controlling for unobserved patient-level heterogeneity shows that PASI appears to have a larger impact on QOL than previously estimated. Routine collection of generic QOL data in registers should be encouraged to enable similar applications in other disease areas.

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  • 17.
    Geale, Kirk
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Quantify Research, Stockholm, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Severity of psoriasis: time to disentangle severity from symptom control2022In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 186, no 6, p. 1033-1034Article in journal (Other academic)
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  • 18. Gutierrez, Lia
    et al.
    Booth, Helen
    Dedman, Daniel
    Crellin, Elizabeth
    Kaye, James A.
    Franzoni, Carla
    Arana, Alejandro
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sundström, Anders
    Byström, Camilla
    Case validation of cutaneous lymphoma to minimize protopathic bias2019In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 28, no S2, p. 315-315Article in journal (Other academic)
  • 19.
    Hajdarevic, Senada
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Hörnsten, Åsa
    Umeå University, Faculty of Medicine, Department of Nursing.
    Sundbom, Elisabet
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Patients' decision making in seeking care for suspected malignant melanoma2010In: Journal of Nursing and Healthcare of Chronic Illness, ISSN 1752-9816, E-ISSN 1752-9824, Vol. 2, no 2, p. 164-173Article in journal (Refereed)
    Abstract [en]

    Aim. To explore patients' decision making about seeking care for malignant melanoma (MM).

    Background. Unlike other cancers, MM is generally visible and can be easily and cheaply cured if treated in time. It is the delay in diagnosis, most often attributable to the patient rather than to care providers, that results in mortality. Self-examination of suspicious lesions is important, but it is not a guarantee of immediate care-seeking, nor is early detection and increased melanoma awareness associated with early care-seeking.

    Method. During 2009, men (n = 10) and women (n = 11) diagnosed with malignant melanoma were interviewed within two years after excision and the text was analysed according to Grounded Theory.

    Results. The perception of a critical level of severity, feelings of fear and threat were found to be a key motivator for patients to seek care for suspected melanomas; as soon as sufficient insight into the severity of the disease was achieved, the patient reached a turning point and sought care immediately.

    Conclusions. Most of the participants described the process from the discovery of the lesion to the decision to seek care as a time-consuming inner negotiation about the severity of the disease, personal and social considerations, and interactions with the healthcare system.

    Relevance to clinical practice. We analysed the complex reasoning of the patients leading up to the turning point when they sought care. This study illustrates for caregivers the importance of simplifying the pathways to care, emphasising the seriousness of MM, and taking worried patients seriously from their first contact with health care. Health professionals, through their attitudes in contact with patients, can either facilitate or obstruct the patient's decision making process.

  • 20.
    Hajdarevic, Senada
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hörnsten, Åsa
    Umeå University, Faculty of Medicine, Department of Nursing.
    Sundbom, Elisabet
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Isaksson, Ulf
    Umeå University, Faculty of Medicine, Department of Nursing.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Health care delay in malignant melanoma: various pathways to diagnosis and treatment2014In: Dermatology Research and Practice, ISSN 1687-6105, E-ISSN 1687-6113, p. 294287-Article in journal (Refereed)
    Abstract [en]

    We aimed to describe and compare patients diagnosed with malignant melanoma (MM), depending on their initial contact with care andwith regard to age, sex, andMMtype and thickness, and to explore pathways and time intervals (lead times) between clinics from the initial contact to diagnosis and treatment.The sample from northern Sweden was identified via the Swedish melanoma register. Data regarding pathways in health care were retrieved from patient records. In our unselected population of 71 people diagnosedwith skinmelanoma of SSMandNMtypes, 75%of patients were primarily treated by primary health-care centres (PHCs). The time interval (delay) from primary excision until registration of the histopathological assessment in the medical records was significantly longer in PHCs than in hospital-based and dermatological clinics (Derm). Thicker tumors were more common in the PHC group. Older patients waited longer times for wide excision. Most MM are excised rapidly at PHCs, but some patients may not be diagnosed and treated in time. Delay of registration of results from histopathological assessments within PHCs seems to be an important issue for future improvement. Exploring shortcomings inMMpatients’ clinical pathways is important to improve the quality of care and patient safety.

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  • 21.
    Hajdarevic, Senada
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Sundbom, Elisabet
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Hörnsten, Asa
    Umeå University, Faculty of Medicine, Department of Nursing.
    Malignant melanoma: gender patterns in care seeking for suspect marks2011In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 20, no 17-18, p. 2676-2684Article in journal (Refereed)
    Abstract [en]

    Aims and objectives. Gender patterns in self-detection of melanoma are not sufficiently highlighted in the literature. The aim of the study was to identify specific patterns in the decision-making process to seek care for suspect melanoma, as narrated by women and men.

    Background. Females have a more favourable prognosis than males and also a higher level of perceived susceptibility and a higher level of knowledge about melanoma. Women are, furthermore, more prone to participate in screening.

    Method. Thirty patients (15 women and 15 men) with a mean age of 55.5 years and diagnosed with malignant melanoma were interviewed about their decisions to seek care for suspect skin marks. The interviews were transcribed and analysed with qualitative content analysis.

    Results. Care-seeking behaviour for suspect melanoma was influenced by gender constructions. Men seldom or never acknowledged interest in attention to bodily changes, but when they became aware of changes, they often took a quick decision and sought an expert's assessment. Men were compliant with wives' and relatives' advice about seeking care. All women reported that they paid attention to bodily changes, but they often delayed care seeking, due to family responsibilities and emotional struggles. The women also attempted self-care remedies, such as applying ointment, before seeking professional care.

    Conclusions. There are gender-specific patterns that may influence decision making in the care-seeking process. Such patterns are important to identify, since health care professionals must take these factors into account in communicating with men and women.

    Relevance to clinical practice. Nurses and in particular those working in telephone counselling, are often at the frontlines, deciding who can have access to health services. They are ideally placed to tackle the issue of gender constructions in the development of effective health care services.

  • 22.
    Hajdarevic, Senada
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Umeå University, Faculty of Medicine, Department of Nursing.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sundbom, Elisabet
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Isaksson, Ulf
    Umeå University, Faculty of Medicine, Department of Nursing.
    Hörnsten, Åsa
    Umeå University, Faculty of Medicine, Department of Nursing.
    Coping styles in decision making among men and women diagnosed with malignant melanoma2013In: Journal of Health Psychology, ISSN 1359-1053, E-ISSN 1461-7277, Vol. 18, no 11, p. 1445-1455Article in journal (Refereed)
    Abstract [en]

    Early care seeking is important for prognosis of malignant melanoma. Coping styles in decision-making to seek care can relate to prognosis since avoidant strategies could delay care seeking. The aim of this study was to compare self-reported coping styles in decision-making between men and women diagnosed with malignant melanoma. We used the Swedish version of the Melbourne Decision-Making Questionnaire to assess coping styles. Men generally scored higher in buck-passing while women and those living without a partner scored higher in hypervigilance. This knowledge could be used in the development of preventive programmes with intention to reach those who delay care seeking.

  • 23. 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.

  • 24. Hensen, P
    et al.
    Windemuth, C
    Hüffmeier, U
    Rüschendorf, F
    Stadelmann, A
    Hoppe, V
    Fenneker, D
    Ständer, M
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wienker, TF
    Traupe, H
    Reis, A
    Association scan of the novel psoriasis susceptibility region on chromosome 19: evidence for both susceptible and protective loci2003In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 12, no 4, p. 490-496Article in journal (Refereed)
    Abstract [en]

    To follow up the novel psoriasis susceptibility region on chromosome 19 (PSORS6), we performed an association scan for psoriasis vulgaris using 45 evenly spaced DNA microsatellite markers. For this study, a new independent sample of 210 nuclear psoriasis families (trio design) from Northern Germany was recruited. We used the family based association test (FBAT) for an association scan over the chromosome 19 region encompassing 50.8 cM. We obtained a positive association for the markers D19S922 (allele 5, P = 0.008) and D19S916 (allele 13, P = 0.016), which correspond to the peak of the region identified in a previously performed scan. We identified two novel regions by a single marker, each showing negative association at D19S917 on 19p13.1 (allele 8, P = 0.0034) and at D19S425 (allele 9, P = 0.0005), compatible with the hypothesis of protective loci. These two novel regions were explored in more detail using novel microsatellite markers at an average distance of 100 kb. A separate analysis distinguishing between familial (n = 137) and sporadic (n = 73) psoriasis families showed that the familial trios contribute strongly in the region around D19S425 (P = 0.004), while the comparably small subset of 73 sporadic trios has a stronger effect at the locus around D19S917 (P = 0.026). These studies confirm the existence of a psoriasis susceptibility locus on chromosome 19 and give first evidence for the existence of both susceptible and protective loci in this region. Analysis of a dense marker set from these refined regions will eventually allow identification of the underlying susceptibility alleles.

  • 25. 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.

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  • 26.
    Hjalte, Frida
    et al.
    Swedish Institute for Health Economics, Lund.
    Steen Carlsson, Katarina
    Swedish Institute for Health Economics, Lund; Department of Clinical Sciences, Lund University, Malmö.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Real-world outcome analysis of continuously and intermittently treated patients with moderate to severe psoriasis after switching to a biologic agent2015In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 230, no 4, p. 347-353Article in journal (Refereed)
    Abstract [en]

    Background: Clinical studies of continuous versus intermittent biologic therapy for moderate to severe psoriasis demonstrate improved efficacy with continuous treatment. Objective: To analyse Swedish real-world data of continuously and intermittently treated biologic-naive patients after switching to a biologic agent. Methods: This is an observational study based on PsoReg, the Swedish registry for systemic psoriasis treatment. Outcome effects in biologic-naive patients who switched to a biologic agent (n = 351) were analysed in groups of continuous, intermittent and terminated treatment. Results: Intermittently treated patients (n = 50) reported higher Psoriasis Area and Severity Index and Dermatology Life Quality Index values after switching than patients with continuous (n = 260) or terminated treatment (n = 41). Study Limitations:The reason for intermittent treatment was not recorded. The intermittently treated patients may be a heterogeneous group and a limitation is that it cannot be determined whether less than continuous use was offered to handle negative aspects. Conclusion: Patients with continuous biologic treatment tend to achieve better outcomes compared to intermittently treated patients.

  • 27.
    Hägg, David
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sundström, Anders
    Psoriasis Patients New to Specialist Care in Sweden 2007-2009: A Two-Year Follow-Up of Treatment Allocation2016In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 25, p. 4-5Article in journal (Other academic)
  • 28.
    Hägg, David
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Sundström, Anders
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    The higher proportion of men with psoriasis treated with biologics may be explained by more severe disease in men2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 5, p. e63619-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Moderate to severe psoriasis, once regarded as merely a skin disease, is today seen as an inflammatory systemic disease. The sex ratio of the prevalence of psoriasis is balanced. In recent years several reports have documented that men receive more systemic or UV treatment than women, and different hypotheses were made. In PsoReg, the national registry for systemic treatment of psoriasis in Sweden, we have, like other European registries, observed a predominance of men (59%), especially of men treated with biologics (63%). Biologics are a relatively new group of very effective but high-priced drugs. The objective of this study was to analyse if women are discriminated by not having the same access to the high-priced biologics.

    DESIGN: Population based cohort study using data from a nationwide quality register of psoriasis patients.

    POPULATION: 2294 patients with moderate to severe psoriasis receiving systemic treatment from a specialist in dermatology.

    MAIN OUTCOME MEASURES: Time to initiation of biologic treatment. A multiple Cox proportional hazard's regression was performed, with time to initiating a biologic treatment as the outcome in order to assess the independent role of the patient's sex in initiating such therapy. The psoriasis severity was defined as a time-varying variable.

    RESULTS: Men had more severe psoriasis than women according to the Psoriasis Area and Severity Index (PASI), regardless of age at enrolment, and throughout the study period. The analysis in the multiple Cox regression show that age, psoriasis severity and psoriasis arthropathy were relevant factors for initiating biologic therapy, whereas sex is not.

    CONCLUSIONS: Although as many women as men are believed to suffer from psoriasis, men seem to be more severely affected by psoriasis. The asymmetry in allocation of biologic therapy thereby probably reflects the differing disease activity between the sexes, and is not a discrimination against women per se.

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  • 29.
    Hägg, David
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sundström, A
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Decision for biological treatment in real life is more strongly associated with the Psoriasis Area and Severity Index (PASI) than with the Dermatology Life Quality Index (DLQI)2015In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 29, no 3, p. 452-456Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Following the establishment of the National Quality Registry for systemic psoriasis treatment (PsoReg), the two psoriasis outcome measurements, Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), are now integrated in clinical practice in Sweden. According to current guidelines, the initiation of a biological treatment should depend on a combination of the physician's (PASI) and the patients' assessment of the disease impact on a health-related quality of life measure (DLQI).

    OBJECTIVE: To evaluate if either of the two measures, PASI or DLQI, is more strongly associated with initiation of biological therapy.

    METHODS: The study is based on 2216 patients suffering from moderate to severe psoriasis who were biological naïve at enrolment to PsoReg. The relationship between the two measures PASI and DLQI and initiation of biological treatment (as outcome) were estimated by a logistic regression and a Cox proportional hazard's model with combinations of PASI and DLQI as independent variables.

    RESULTS: The adjusted regression models showed that patients with high PASI score and low DLQI score had a higher chance to receive biological treatment compared to patients with low PASI score and high DLQI score.

    CONCLUSION: The decision to initiate biological treatment is more strongly associated with PASI than with DLQI. However, since the DLQI reflects both socio-economic costs and patient suffering better than PASI, the relevance of the DLQI may be underestimated in clinical practice.

  • 30.
    Hägg, David
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Centre for Pharmacoepidemiology (CPE), Karolinska Institutet, Karolinska University Hospital, T2, 171 76 Stockholm, Sweden.
    Sundström, Anders
    Centre for Pharmacoepidemiology (CPE), Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Severity of psoriasis differs between men and women: a registry based study of the clinical outcome measure Psoriasis Area and Severity Index (PASI) in 5438 patients2017In: American Journal of Clinical Dermatology, ISSN 1175-0561, E-ISSN 1179-1888, Vol. 18, p. 583-590Article in journal (Refereed)
    Abstract [en]

    Background: Psoriasis is a common skin disease and moderate to severe psoriasis is associated with a dose-dependent risk for metabolic and cardiovascular morbidity. It has previously been speculated that women have less severe psoriasis, as men are overrepresented in psoriasis registers and consume more care.

    Objective: The objective of this study was to investigate, for the first time, the sex differences in the severity of psoriasis using the gold standard of severity measurement, the Psoriasis Area and Severity Index (PASI), and the distinct elements of the PASI score.

    Design, Setting and Participants: This was a cross-sectional study based on the national registry for systemic treatment of psoriasis in Sweden (PsoReg), with 5438 patients experiencing moderate to severe psoriasis. Differences in the PASI score and its elements at enrolment were tested by multivariable ordinal logistic regressions.

    Main Outcome Measures: The different components of the PASI score were used to analyze the assessment of disease severity. For each body area (head, arms, trunk, and legs), the score of the plaque characteristics and degree of skin involvement were used as outcomes.

    Results: Women had statistically significantly lower median PASI scores (5.4) than men (7.3) [p < 0.001], which was consistent across all ages. The difference remained statistically significant in a multivariable linear regression. The itemized PASI analyses from the Mann–Whitney–Wilcoxon tests and the adjusted ordinal logistic regressions confirmed that women had significantly lower scores than men in all areas of the body, except for the head. No differences in the use of medications prior to enrolment could be found that may cause this difference between the sexes.

    Conclusions: As the PsoReg contains the detailed disease measurement PASI, which was traditionally used for selected participants in clinical studies only, a nationwide unselected population could be investigated. The fact that women have less severe psoriasis can explain the dominance of males in the systemic treatment of psoriasis. These findings motivate a gender perspective in the management of psoriasis and in the prevention and management of its comorbidities.

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  • 31. Jacob, N
    et al.
    Rüschendorf, F
    Schmitt-Egenolf, Marcus
    Department of Dermatology, Humboldt University, Charité, Berlin, Germany.
    Hennies, HC
    Friedl, G
    Ständer, M
    Wienker, TF
    Reis, A
    Traupe, H
    Promoter polymorphism at -238 of the tumor necrosis factor alpha gene is not associated with early onset psoriasis when tested by the transmission disequilibrium test1999In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 112, no 4, p. 513-514Article in journal (Refereed)
  • 32. Kapferer-Seebacher, Ines
    et al.
    Pepin, Melanie
    Werner, Roland
    Aitman, Timothy J
    Nordgren, Ann
    Stoiber, Heribert
    Thielens, Nicole
    Gaboriaud, Christine
    Amberger, Albert
    Schossig, Anna
    Gruber, Robert
    Giunta, Cecilia
    Bamshad, Michael
    Björck, Erik
    Chen, Christina
    Chitayat, David
    Dorschner, Michael
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Hale, Christopher J
    Hanna, David
    Hennies, Hans Christian
    Heiss-Kisielewsky, Irene
    Lindstrand, Anna
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Mitchell, Anna L
    Nickerson, Deborah A
    Reinstein, Eyal
    Rohrbach, Marianne
    Romani, Nikolaus
    Schmuth, Matthias
    Silver, Rachel
    Taylan, Fulya
    Vandersteen, Anthony
    Vandrovcova, Jana
    Weerakkody, Ruwan
    Yang, Margaret
    Pope, F Michael
    Byers, Peter H
    Zschocke, Johannes
    Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, no 5, p. 1005-1014Article in journal (Refereed)
    Abstract [en]

    Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.

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  • 33. Kohrgruber, N
    et al.
    Halanek, N
    Gröger, M
    Winter, D
    Rappersberger, K
    Schmitt-Egenolf, Marcus
    Stingl, G
    Maurer, D
    Survival, maturation, and function of CD11c- and CD11c+ peripheral blood dendritic cells are differentially regulated by cytokines1999In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 163, no 6, p. 3250-3259Article in journal (Refereed)
    Abstract [en]

    Two types of dendritic cells (DC) are circulating in human blood and can be identified by their differential expression of the myeloid Ag CD11c. In this study, we show that CD11c- peripheral blood (PB)-DC correspond to plasmacytoid DC of lymphoid tissue not only by their surface Ag expression profile but, more impressively, by their peculiar ultramorphology. We also demonstrate that CD11c- and CD11c+ DC differ in the quality of their response to and in their requirement for certain cytokines. Freshly isolated CD11c- cells depend on IL-3 for survival and use autocrine or exogenous TNF-alpha as maturation signal, leading to the appearance of a highly dendritic phenotype, the up-regulation and redistribution of MHC class II from lysosomal compartments to the plasma membrane, the increased expression of costimulatory molecules, and the switch from a high Ag-processing to a low Ag-processing/potent accessory cell mode. Surprisingly, IL-4 efficiently killed freshly isolated CD11c- PB-DC, but did not impair the viability of CD11c+ PB-DC and, together with GM-CSF, induced maturation of these cells. A direct functional comparison revealed that neo-Ag-modified and subsequently matured CD11c- but to a lesser extent CD11c+ DC were able to prime naive Ag-specific CD4+ T cells. Our findings show that two diverse DC types respond to certain T cell-derived cytokines in a differential manner and, thus, suggest that suppression or activation of functionally diverse DC types may be a novel mechanism for the regulation of the quantity and quality of immune responses.

  • 34.
    Laskowski, Marta
    et al.
    Department of Dermatology and Venereology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Sweden.
    Schiöler, Linus
    Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Ottosson, Johan
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wennberg, Ann-Marie
    Department of Dermatology and Venereology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Sweden.
    Olbers, Torsten
    Department of Biomedical and Clinical Sciences, and Wallenberg Centre for Molecular Medicine, Linköping University, Linköping, Sweden; Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Torén, Kjell
    Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Sweden.
    Gustafsson, Helena
    Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Sweden; Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Impact of bariatric surgery on moderate to severe psoriasis: A retrospective nationwide registry study2021In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 101, no 6, article id adv00487Article in journal (Refereed)
    Abstract [en]

    Studies of the effects of bariatric surgery on psoriasis are few, with conflicting results. By linking the Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) with the Scandinavian Obesity Surgery Registry (SOReg), individuals with psoriasis who had undergone bariatric surgery in Sweden during 2008 to 2018 were identified, and matched with data for patients with psoriasis in PsoReg. Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were compared between the groups. Altogether, 50 operated individuals (median body mass index (BMI) 38.7 kg/m2) and 91 non-operated individuals (median BMI 33.0 kg/m2) were included. Control of disease at baseline was good in both groups. Linear mixed models showed no significant difference in psoriasis disease burden, measured as changes in mean PASI (ΔPASI) (–1.2, p = 0.43) and DLQI (ΔDLQI) (–2.2, p = 0.34). In summary, this study demonstrated no significant effect of bariatric surgery on psoriasis disease burden in patients with relatively well-controlled moderate to severe psoriasis.

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  • 35. Lee, YA
    et al.
    Rüschendorf, F
    Windemuth, C
    Schmitt-Egenolf, Marcus
    Department of Dermatology, Norwegian University of Science and Technology, Trondheim, Norway.
    Stadelmann, A
    Nürnberg, G
    Ständer, M
    Wienker, TF
    Reis, A
    Traupe, H
    Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p132000In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 67, no 4, p. 1020-1024Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a common chronic inflammatory skin disease with a strong genetic component. Few psoriasis-susceptibility loci have been reported, and only two have been confirmed in independent data sets. This article reports results of a genomewide scan that was performed, using 370 microsatellite markers, for psoriasis-susceptibility loci in 32 German extended families, comprising 162 affected and 195 unaffected individuals. Nonparametric linkage analysis of all families provided strong evidence for a novel psoriasis-susceptibility locus on chromosome 19p (Zlr=3.50; P=.0002). Parametric analysis revealed a heterogeneity LOD score of 4.06, corresponding to a genomewide significance level of.037, under the assumption of a recessive model with high disease-allele frequency and 66% as the proportion of linked families. This study confirms linkage of psoriasis to the HLA region on chromosome 6p and suggests additional regions on chromosomes 8q and 21q for further investigations.

  • 36.
    Lind, Lisbet K
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Stecksén-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology, Pediatric Dentistry.
    Lejon, Kristina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    EDAR mutation in autosomal dominant hypohidrotic ectodermal dysplasia in two Swedish families2006In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 7, p. 80-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by defective development of teeth, hair, nails and eccrine sweat glands. Both autosomal dominant and autosomal recessive forms of HED have previously been linked to mutations in the ectodysplasin 1 anhidrotic receptor (EDAR) protein that plays an important role during embryogenesis.

    METHODS: The coding DNA sequence of the EDAR gene was analyzed in two large Swedish three-generational families with autosomal dominant HED.

    RESULTS: A non-sense C to T mutation in exon 12 was identified in both families. This disease-specific mutation changes an arginine amino acid in position 358 of the EDAR protein into a stop codon (p.Arg358X), thereby truncating the protein. In addition to the causative mutation two polymorphisms, not associated with the HED disorder, were also found in the EDAR gene.

    CONCLUSION: The finding of the p.Arg358X mutation in the Swedish families is the first corroboration of a previously described observation in an American family. Thus, our study strengthens the role of this particular mutation in the aetiology of autosomal dominant HED and confirms the importance of EDAR for the development of HED.

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  • 37.
    Löfvendahl, Sofia
    et al.
    Swedish Institute for Health Economics (IHE), Sweden. Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Norlin, Jenny M.
    Swedish Institute for Health Economics (IHE), Lund, Sweden.
    Ericson, Oskar
    Swedish Institute for Health Economics (IHE), Lund, Sweden.
    Hanno, Malin
    Boehringer Ingelheim, Stockholm, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Prolonged sick leave before and after diagnosis of generalized pustular psoriasis: a swedish population-based register study2023In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 103, article id adv6497Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to analyse sick leave in generalized pustular psoriasis, the most severe form of pustular psoriasis. Prolonged sick leave of >14 days was analysed for 502 patients with generalized pustular psoriasis compared with controls with psoriasis vulgaris and matched controls from the general population. Using data from the Swedish National Patient Register, and the Longitudinal integrated database for health insurance and labour market studies, the study estimated the mean number of sick leave days in the year of first diagnosis of generalized pustular psoriasis (index year) and for 2 years before and after the index year. Patients with generalized pustular psoriasis were on sick leave to a larger extent than both control populations for all study years. The number of sick leave days peaked in the index year and then reduced. Compared with the control populations, sick leave in generalized pustular psoriasis was already higher prior to diagnosis, indicating delayed diagnosis and/or a comorbidity burden.

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  • 38.
    Löfvendahl, Sofia
    et al.
    Swedish Institute for Health Economics (IHE), Lund, Norway; Department of Laboratory Medicine, Lund University, Lund, Norway.
    Norlin, Jenny M.
    Swedish Institute for Health Economics (IHE), Lund, Norway.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Comorbidities in palmoplantar pustulosis: a Swedish population-based register study2023In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 189, no 2, p. 230-232Article in journal (Refereed)
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  • 39.
    Löfvendahl, Sofia
    et al.
    The Swedish Institute for Health Economics, Lund, Sweden; Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Norlin, Jenny M.
    The Swedish Institute for Health Economics, Lund, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Comorbidities in patients with generalized pustular psoriasis: a nationwide population-based register study2023In: The Journal of American Academy of Dermatology, ISSN 0190-9622, E-ISSN 1097-6787, Vol. 88, no 3, p. 736-738Article in journal (Refereed)
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  • 40. Löfvendahl, Sofia
    et al.
    Norlin, Jenny M.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Economic Burden of Generalized Pustular Psoriasis in Sweden: A Population-Based Register Study2022In: Psoriasis: Targets and Therapy, E-ISSN 2230-326X, Vol. 12, p. 89-98Article in journal (Refereed)
    Abstract [en]

    Background: Generalized pustular psoriasis (GPP), which can occur with or without psoriasis vulgaris (PV), is a severe form of pustular psoriasis with potentially life-threatening symptoms. GPP is also associated with several comorbidities, which further adds to the burden of disease. This study investigates the economic burden of disease in patients with GPP.

    Methods: All-cause and GPP-specific healthcare resource use (inpatient stays, physician visits and drug use), as well as associated costs, were compared for year 2015 between GPP patients (n = 914) and two matched control groups representing the general population (n = 4047) and patients with PV but no GPP (n = 2556). Information on resource use for 2015 was obtained from the Swedish National Patient Register and Swedish Prescribed Drug Register, respectively.

    Results: All-cause inpatient stays, physician visits, and use of psoriasis-related drugs were significantly more common among GPP patients compared to both control groups. This difference was reflected in total direct cost for GPP patients (5062 euros/year) which was 3.1 and 1.8 times higher (p < 0.001) compared to the general population and PV controls, respectively. For GPP patients, the share of total cost was 22% for all-cause physician outpatient visits and 40% for all-cause inpatient stays. However, only 6.3% and 11.3% of these costs, respectively, were due to GPP-specific problems. Psoriasis-related drugs constituted 27% of total costs for GPP patients of which a large fraction (86%) was represented by biologics.

    Conclusion: This study demonstrates a higher economic burden for GPP patients compared to both the general population and patients with PV, with inpatient visits and use of biologic drugs as major cost driving factors. Only fractions of the costs for physician visits and inpatient stays were attributable to specific GPP problems, indicating a higher economic burden of GPP-consequences and complications.

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  • 41.
    Löfvendahl, Sofia
    et al.
    The Swedish Institute for Health Economics (IHE), Lund, Sweden; Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Norlin, Jenny M.
    Swedish Institute for Health Economics (IHE), Lund, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Economic burden of palmoplantar pustulosis in Sweden: a population-based register study2023In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 103, article id adv00843Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to estimate the economic burden of palmoplantar pustulosis, a chronic relapsing skin condition commonly occurring in combination with psoriasis vulgaris. Using data from the Swedish National Patient Register and Swedish Prescribed Drug Register for 2015, the study estimated all-cause and palmoplantar pustulosis-specific healthcare resource use (inpatient stays, physician visits and drug use) for 14,715 patients with palmoplantar pustulosis, and compared these both with matched controls from the general population and with patients with psoriasis vulgaris (without palmoplantar pustulosis). Mean annual direct costs for a patient with palmoplantar pustulosis was higher compared with costs for the general population (3,000 vs 1,700 Euro, p < 0.001). Compared with psoriasis vulgaris, more patients with palmoplantar pustulosis had inpatient stays, but fewer had physician visits and psoriasis-related drugs; the overall costs were similar. Only a small fraction of the costs of physician visits and inpatient stays for patients with palmoplantar pustulosis were attributable to specific palmoplantar pustulosis problems, indicating a clear comorbidity burden in palmoplantar pustulosis.

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  • 42. Löfvendahl, Sofia
    et al.
    Norlin, Jenny M.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Prevalence and incidence of generalized pustular psoriasis in Sweden: a population-based register study2022In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 186, no 6, p. 970-976Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Generalized pustular psoriasis (GPP) is a severe form of pustular psoriasis with generalized eruption of sterile pustules, often along with systemic symptoms. There is a scarcity of population-based estimates of GPP prevalence and incidence.

    OBJECTIVES: To estimate (i) the prevalence and incidence of GPP in the Swedish general population and (ii) the prevalence of psoriasis vulgaris within the GPP population.

    METHODS: We identified cases (2004-2015) with one ICD-10 diagnostic code (base case) for GPP within the Swedish National Patient Register, which covers inpatient and outpatient secondary care. Cases were linked to the Swedish Total Population Register, and point prevalence was estimated as on 31 December 2015. In two alternative analyses we changed case definitions to: (i) requiring two visits (strict case 1) and (ii) requiring two visits of which one was within dermatology/internal medicine (strict case 2).

    RESULTS: The base case point prevalence of GPP was estimated at 9.1 per 100 000 (women, 11.2; men, 7.0) and the annual prevalence in 2015 was estimated at 1.53 per 100 000. Among the GPP population, 43% also had a psoriasis vulgaris code. The incidence of GPP in 2015 was estimated at 0.82 per 100 000 (women, 0.93; men, 0.74). The criteria used had an impact on prevalence and incidence estimates: prevalence strict case 1 gave 3.8 per 100 000 and incidence strict case 1 gave 0.42 per 100 000.

    CONCLUSIONS: Results indicate that the estimated GPP population in Sweden is within the range of previous published estimates. However, estimates were sensitive to the GPP case criteria used. The findings enhance demands for studies using validated diagnostic algorithms.

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  • 43. Löfvendahl, Sofia
    et al.
    Norlin, Jenny M.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Prevalence and incidence of palmoplantar pustulosis in Sweden: a population-based register study2021In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 185, no 5, p. 945-951Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Palmoplantaris pustulosis (PPP) is a chronic relapsing skin condition characterized by sterile pustules on the palm and soles. Population-based estimates of PPP incidence and prevalence are limited.

    OBJECTIVES: To estimate the prevalence and incidence of PPP in the Swedish general population and to estimate the prevalence of psoriasis vulgaris among the PPP population.

    METHODS: The Swedish National Patient Register, covering all inpatient and outpatient non-primary care for the Swedish population, was used. We identified cases (2004-2015) with one ICD-10 diagnostic code (base case) for PPP. The point prevalence estimates at the end of this period (31 December 2015) were obtained by linkage to the Swedish Total Population Register. In sensitivity analyses, we used alternative case defintions:1) requiring two visits, 2) requiring two visits of which one within dermatology/internal medicine.

    RESULTS: The base case prevalence of PPP was estimated to be 147/100 000 (women=227, men=68) and the annual prevalence was estimated to 26/100 000 in 2015. Among the PPP population, 17% were registered with a diagnostic code for psoriasis vulgaris. The incidence of PPP in 2015 was estimated to be 12.7/100 000 (women=18.7, men=6.6). The criteria used had an impact on prevalence and incidence estimates; strict case 1) 72/100 000 and 2) 5.4/100 000.

    CONCLUSIONS: Results indicate that the population-based prevalence of PPP may be larger than previous estimated. However, the estimates were sensitive to employed PPP case criteria. The findings enhance demands for studies using validated diagnostic algorithms potentially also including data from the primary care setting.

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  • 44. Maksymowych, WP
    et al.
    Wessler, A
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Suarez-Almazor, M
    Ritzel, G
    Von Borstel, RC
    Pazderka, F
    Russell, AS
    Polymorphism in an HLA linked proteasome gene influences phenotypic expression of disease in HLA-B27 positive individuals1994In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 21, no 4, p. 665-669Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the potential influence of the HLA-linked LMP (low molecular weight polypeptide) genes on disease susceptibility in HLA-B27 individuals with ankylosing spondylitis (AS).

    METHODS: A polymorphic CfoI restriction enzyme site in the coding region of one proteasome gene was evaluated in 125 genomic DNA samples from B27 individuals with well documented AS, 55 of whom had had acute iritis, and 42 samples from normal, ethnically matched B27 blood donors where AS was excluded.

    RESULTS: Analysis of individuals with B27 AS with iritis revealed significant differences in allelic distribution of this biallelic locus compared to patients with B27 AS without iritis. Furthermore, homozygosity for the disease associated allele was significantly more prevalent in patients with AS with iritis (72.7%) than in patients without iritis (38.6%) (p(uncorrected) = 0.0003) or B27 controls (45.2%) (p(uncorrected) = 0.01).

    CONCLUSION: Our findings support the involvement of additional HLA linked genes in the phenotypic expression of disease in B27 individuals and suggest a role for the non-B27 HLA haplotype in susceptibility to iritis.

  • 45. Maurer, D
    et al.
    Fiebiger, S
    Ebner, C
    Reininger, B
    Fischer, GF
    Wichlas, S
    Jouvin, MH
    Schmitt-Egenolf, Marcus
    Department of Dermatology, University of Vienna Medical School, Austria.
    Kraft, D
    Kinet, JP
    Stingl, G
    Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation1996In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 157, no 2, p. 607-616Article in journal (Refereed)
    Abstract [en]

    Originally limited to basophils and mast cells, the spectrum of high affinity IgE receptor (Fc epsilon RI-bearing cells has expanded recently to include Langerhans cells, dermal dendritic cells (DC), monocytes, and eosinophils. As a result of studies on the distribution, structure, and function of Fc epsilon RI on APCs, we discovered a minor nonbasophil, nonmonocyte PBMC population that can bind IgE via Fc epsilon RI. This receptor occurs on the surface of these cells as a multimeric structure containing Fc epsilon RI alpha- and Fc epsilon RI gamma-chains but, unlike its counterpart on basophils, lacking Fc epsilon RI beta. Further experiments revealed that these Fc epsilon RI alpha gamma-expressing cells closely resemble peripheral blood DC by immunophenotype (HLA-DRhigh, HLA-DQhhigh; CD4+, CD11a+, CD32+, CD33+, B7/2 (CD86)+; CD11blow, CD14low, CD40low, CD54low, CD64low) and cell morphology. These features allowed us to isolate Fc epsilon RI-expressing DC from the peripheral blood and to investigate their immunostimulatory properties. We found Fc epsilon RI-positive DC to be efficient stimulators of both primary (allogeneic MLR) and Fc epsilon RI/IgE-dependent, secondary T cell responses at low cell numbers. Thus, Fc epsilon RI-expressing DC may not only amplify established type I allergic immune reactions but, unlike Fc epsilon RI-positive semiprofessional APCs, may be able to prime naive T cells to common and/or cryptic epitopes of IgE-reactive Ags.

  • 46. Nast, A.
    et al.
    Smith, C.
    Spuls, P. I.
    Valle, G. Avila
    Bata-Csorgo, Z.
    Boonen, H.
    De Jong, E.
    Garcia-Doval, I.
    Gisondi, P.
    Kaur-Knudsen, D.
    Mahil, S.
    Malkonen, T.
    Maul, J. T.
    Mburu, S.
    Mrowietz, U.
    Reich, K.
    Remenyik, E.
    Ronholt, K. M.
    Sator, P. G.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sikora, M.
    Stroemer, K.
    Sundnes, O.
    Trigos, D.
    Van der Kraaij, G.
    Yawalkar, N.
    Dressler, C.
    EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris – Part 1: treatment and monitoring recommendations2020In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 34, no 11, p. 2461-2498Article in journal (Refereed)
    Abstract [en]

    This evidence‐ and consensus‐based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The first part of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline. Suggestions for disease severity grading and treatment goals are provided. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs. The treatment options discussed in this guideline are as follows: acitretin, ciclosporin, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab.

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  • 47.
    Nast, A.
    et al.
    Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Department of Dermatology, Venereology and Allergology, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
    Smith, C.
    St John's Institute of Dermatology, London, United Kingdom.
    Spuls, P.I.
    Academic Medical Centre Amsterdam, Amsterdam, Netherlands.
    Avila Valle, G.
    Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Department of Dermatology, Venereology and Allergology, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
    Bata-Csörgö, Z.
    University of Szeged, Szeged, Hungary.
    Boonen, H.
    Office-Based Dermatology Practice, Geel, Belgium.
    De Jong, E.
    Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands.
    Garcia-Doval, I.
    Unidad de Investigación. Fundación Piel Sana AEDV, Madrid, Spain.
    Gisondi, P.
    University of Verona, Verona, Italy.
    Kaur-Knudsen, D.
    University Hospital Copenhagen, Copenhagen, Denmark.
    Mahil, S.
    Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
    Mälkönen, T.
    Helsinki University Central Hospital, Helsinki, Finland.
    Maul, J.T.
    Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland.
    Mburu, S.
    International Federation of Psoriasis Associations (IFPA), Germany.
    Mrowietz, U.
    Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
    Reich, K.
    Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Remenyik, E.
    University of Debrecen, Debrecen, Hungary.
    Rønholt, K.M.
    Aarhus University Hospital, Aarhus, Denmark.
    Sator, P.G.
    Municipal Hospital Hietzing, Vienna, Austria.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sikora, M.
    Department of Dermatology, Medical University of Warsaw, Warsaw, Poland.
    Strömer, K.
    Office-Based Dermatology Practice, Mönchengladbach, Germany.
    Sundnes, O.
    Oslo University Hospital, Oslo, Norway.
    Trigos, D.
    International Federation of Psoriasis Associations (IFPA), Germany.
    Van Der Kraaij, G.
    Academic Medical Centre Amsterdam, Amsterdam, Netherlands.
    Yawalkar, N.
    Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
    Dressler, C.
    Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Department of Dermatology, Venereology and Allergology, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
    EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris – Part 2: specific clinical and comorbid situations2021In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 35, no 2, p. 281-317Article in journal (Refereed)
    Abstract [en]

    This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

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  • 48. Norlin, J. M.
    et al.
    Calara, P. S.
    Persson, U.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Real-world outcomes in 2,646 psoriasis patients: one in five has PASI ≥ 10 and/or DLQI ≥ 10 under ongoing systemic therapy2017In: Journal of dermatological treatment (Print), ISSN 0954-6634, E-ISSN 1471-1753, Vol. 28, no 6, p. 500-504Article in journal (Refereed)
    Abstract [en]

    Background: Although biologics introduced a new era in psoriasis care when available a decade ago, it is unclear to what extent the available systemic treatments treat patients adequately. Objective To analyse the clinical severity and quality of life of the psoriasis population in Sweden treated with systemics.

    Methods: Data included 2,646 patients from the Swedish Registry for Systemic Treatment of Psoriasis. Average Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and EQ-5D were reported. A subgroup of persisting moderate-to-severe psoriasis as defined by PASI≥10 and/or DLQI≥10 after >12 weeks treatment was analysed.

    Results: Mean (SD) PASI, DLQI, and EQ-5D were 4.12 (4.57), 4.11 (5.24) and 0.79 (0.22). Eighteen percent had persisting moderate-to-severe psoriasis (n = 472). These patients were younger, had higher BMI, had psoriasis arthritis and were smoking to a larger extent (p < 0.01) compared to lower-severity patients (n = 2174). Mean (SD) EQ-5D was also considerably lower 0.63 (0.29) vs. 0.82 (0.19) (p < 0.01).

    Conclusion: Almost one in every five patients had persisting moderate-to-severe psoriasis, despite ongoing systemic treatment. Both comorbidities and life style factors were associated with persisting moderate-to-severe psoriasis. The considerably lower generic quality of life in these patients demonstrates an unmet need. Subsequently, improved access to biologics and continuous drug development is needed in psoriasis.

  • 49. Norlin, J. M.
    et al.
    Nilsson, K.
    Persson, U.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Complete skin clearance and Psoriasis Area and Severity Index response rates in clinical practice: predictors, health-related quality of life improvements and implications for treatment goals2020In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 182, no 4, p. 965-973Article in journal (Refereed)
    Abstract [en]

    Background: Psoriasis Area and Severity Index (PASI) 90 is suggested to be the new standard endpoint for randomized controlled trials of biologics for psoriasis, whereas treatment guidelines often still refer to PASI 75.

    Objectives: To analyse in a real-world setting: firstly, what factors are associated with higher levels of treatment response to biologics; secondly, the health-related quality of life gains associated with different response levels in clinical practice.

    Methods: Biologically na€ıve patients with PASI, Dermatology Life Quality Index (DLQI) and EuroQol (EQ)-5D outcomes before (maximum 6 months) and after (3–12 months) switch to biologics during registration in the Swedish National Registry for Systemic Treatment of Psoriasis (PsoReg) were included (n = 515). Patient characteristics associated with higher treatment response were analysed by regression analyses. Improvements in absolute PASI, DLQI and EQ-5D were assessed in different PASI percentage response levels.

    Results: High PASI percentage response was associated with higher PASI before switch and lower body mass index. DLQI and EQ-5D improved within all responder groups (P < 0001). The magnitude of improvements in DLQI (P = 002) differed between responder groups. The mean (SD) DLQI improvements for PASI 75<90 responders, PASI 90<100 responders and patients achieving complete skin clearance (PASI 100) were 99 (74), 115 (70) and 80 (61), respectively.

    Conclusions: PASI percentage change is largely dependent on absolute PASI before switch. Patients in clinical practice lack ‘baseline’ PASI values as they may switch directly from one treatment to another or stay successfully treated for a longer time period. Treatment goals such as PASI 90 are thus not suitable for treatment guidelines or for follow-up in clinical practice.

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  • 50.
    Norlin, Jenny M.
    et al.
    The Swedish Institute for Health Economics (IHE), Lund, Sweden.
    Löfvendahl, Sofia
    The Swedish Institute for Health Economics (IHE), Lund, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    The influence of socioeconomic factors on access to biologics in psoriasis2023In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 12, no 23, article id 7234Article in journal (Refereed)
    Abstract [en]

    Background: Since the introduction of biologics for psoriasis, uptake has been uneven and limited. Few studies have investigated the influence of socioeconomic factors on access to biologics.

    Objective: To investigate how socioeconomic factors influenced access to biologics.

    Methods: Biologic-naïve patients in the Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) for the years 2006–2014 were included. For patients who remained on nonbiologic treatments during their entire registration (n = 1851), the most recent registration was analyzed. For patients who began treatment with biologics during registration in PsoReg (n = 665), the last observation before initiation of biologics was analyzed. A logistic regression model was used to investigate whether education and income influenced the probability of a switch to biologics, whilst adjusting for demographic and individual factors such as age, sex, disease severity, and clinical characteristics.

    Results: The odds ratio of access to biologics was 1.8 (CI = 1.3–2.6) in the group with a high level of disposable income, compared with the middle-income group. No differences were found concerning educational levels. The odds ratios of access to biologics decreased with age. Patients with psoriatic arthritis had odds ratios of access to biologics which were more than 50 percent higher, controlling for other variables. High disease severity, in terms of physician- and patient-reported severity, increased the odds ratios of access to biologics.

    Conclusions: The higher-income group had better access to biologics than the middle-income group when adjusting for disease severity and lifestyle factors. This may not only be an equity problem, as a better allocation of society’s resources might have resulted in a higher overall effectiveness of biologics.

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