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  • 1. 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.

  • 2. 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.

  • 3. 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.

  • 4.
    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, ISSN 1471-2350, 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.

  • 5.
    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. 

  • 6.
    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)
  • 7.
    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.

  • 8.
    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.

  • 9.
    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.

  • 10.
    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.

  • 11.
    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.

  • 12. 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.

  • 13. 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.

  • 14. 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.

  • 15.
    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.

  • 16.
    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)
  • 17.
    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, ISSN 1932-6203, 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.

  • 18.
    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.

  • 19.
    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.

  • 20. 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)
  • 21. 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.

  • 22. 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.

  • 23. 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.

  • 24.
    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, ISSN 1471-2350, 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.

  • 25. 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.

  • 26. 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.

  • 27. 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.

  • 28.
    Norlin, Jenny M
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Steen Carlsson, K
    Persson, U
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Analysis of three outcome measures in moderate to severe psoriasis: a registry-based study of 2450 patients2012In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 166, no 4, p. 797-802Article in journal (Refereed)
    Abstract [en]

    Background: As moderate to severe psoriasis is a systemic disease with large effects on health related quality of life (HRQOL) generic measures that include overall health, not only skin involvement, are necessary. The knowledge about the relationship between the generic preference-based EQ-5D and dermatology-specific measures in psoriasis is limited.

    Objective: The objective was to analyse EQ-5D, the Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) in patients with moderate to severe psoriasis in Swedish clinical practice by demographic characteristics, to compare EQ-5D among patients to Swedish population values, and to analyse the relationships between EQ-5D, DLQI and PASI.

    Methods: This observational cohort study was based on PsoReg, the Swedish National Registry for Systemic Treatment of Psoriasis. EQ-5D among psoriasis patients was compared to a defined general population in Sweden, retrieved from a previous study. Relationships between measures were examined with correlation tests and regression analysis.

    Results: 2450 patients (men n=1479, women n=971) were included. Median EQ-5D, DLQI and PASI was 0.769, 4 and 4.7, respectively. Psoriasis patients had a significantly lower EQ-5D compared to the defined general population. EQ-5D correlated moderately with DLQI (-0.55) and weakly with PASI (-0.25) (p<0.001).

    Conclusions: When assessing psoriasis treatments and making decisions about treatment guidelines and resource allocation, EQ-5D, DLQI and PASI provide a useful set of complementary tools, answering to different needs. If EQ-5D is not included in the original trial the second best option in cost-effectiveness studies is to use mapping between DLQI and EQ-5D.

  • 29.
    Norlin, Jenny M.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. The Swedish Institute for Health Economics (IHE), Lund, Sweden.
    Steen Carlsson, Katarina
    Department of Clinical Sciences, Skåne University Hospital, Clinical Research, Lund University, Malmö, Sweden.
    Persson, Ulf
    Institute for Economic Research, School of Economics, Lund University, Lund, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Register-Based Evaluation of Relative Effectiveness of New Therapies: Biologics Versus Conventional Agents in Treatment of Psoriasis in Sweden2015In: BioDrugs, ISSN 1173-8804, E-ISSN 1179-190X, Vol. 29, no 6, p. 389-398Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) was established in 2006. This article analyzes the implementation phase of biologics in the treatment of moderate to severe psoriasis in Sweden in the period 2006-2012. Clinical studies have shown efficacy of biologic agents in psoriasis, but their relative effectiveness in real-world clinical practice has rarely been studied.

    OBJECTIVE: To estimate the incremental changes in clinical health-related quality-of-life measures in patients receiving biologics versus conventional systemic agents.

    METHODS: Patients fulfilling the clinical criteria for moderate to severe psoriasis were included. Average treatment effects were estimated from longitudinal data as incremental changes in: (1) the Psoriasis Area and Severity Index (PASI) score, (2) the Dermatology Life Quality Index (DLQI) score, and (3) the EQ-5D score, by matching patients switching to biologics with patients remaining on conventional systemic agents.

    RESULTS: The study included 239 biologic-treated patients and 378 conventionally treated patients. The matched patient groups were essentially equivalent in terms of important patient characteristics. The average treatment effects of biologics versus conventional systemic agents were 2.2 for PASI, 3.5 for DLQI, and 0.11 for EQ-5D. The estimated incremental benefits of biologics for the subgroup of patients not responding to their conventional systemic agent were even greater.

    CONCLUSION: Register-based research complements knowledge from randomized controlled trials regarding relative effectiveness in clinical practice. This information can be used to support health care decision making. This research suggests that there is both under- and overtreatment with biologics in Swedish clinical practice. Reallocation of biologics to more severe cases of psoriasis could improve overall health in the total patient population.

  • 30.
    Norlin, Jenny M.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. The Swedish Institute for Health Economics, Lund.
    Steen Carlsson, Katarina
    Department of Clinical Sciences, Skåne University Hospital, Clinical Research, Lund University, Malmö, Sweden.
    Persson, Ulf
    Institute for Economic Research, School of Economics, Lund University, Lund, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Resource use in patients with psoriasis after the introduction of biologics in Sweden2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 2, p. 156-161Article in journal (Refereed)
    Abstract [en]

    The introduction of biologics has changed treatment patterns as well as costs in patients with psoriasis. To estimate direct and indirect costs of the psoriasis population in Sweden, and to analyse changes in costs between 2006 and 2009. The study population was identified in national registers. Direct costs included health care visits with primary psoriasis diagnoses in specialist care and drugs relevant for treating psoriasis. Productivity loss, including long-term sick leave and disability pension, was estimated as the difference compared to matched controls from the general population. Total direct cost (in SEK 2009 price level) increased from SEK 348 million in 2006 to SEK 459 million in 2009, whereas the total productivity loss decreased from SEK 1,646 to 1,618 million between 2006 and 2009. Although direct costs, especially for biologic agents, have increased for patients with psoriasis over time, this study indicates that costs related to productivity loss are still more substantial.

  • 31.
    Norlin, Jenny M
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Steen Carlsson, Katarina
    Department of Clinical Sciences, Skåne University Hospital, Clinical Research, Lund University, Malmö, Sweden.
    Persson, Ulf
    Institute for Economic Research, School of Economics, Lund University, Lund, Sweden.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Switch to biological agent in psoriasis significantly improved clinical and patient-reported outcomes in real-world practice2012In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 225, no 4, p. 326-332Article in journal (Refereed)
    Abstract [en]

    Background: Although clinical studies have shown efficacy of biological agents in moderate to severe psoriasis, observational studies of real-world effectiveness are rare.

    Objective: To analyse the psoriasis area and severity index (PASI) and quality of life by the EQ-5D questionnaire and dermatology quality of life index (DLQI) in psoriasis patients who switched from conventional systemic treatment to biological agents in clinical practice. Furthermore, to analyse patient groups with the highest benefit of biological agents.

    Methods: Longitudinal, observational study based on the Swedish National Registry for Systemic Treatment of Pso-riasis, PsoReg. Outcomes of biological-naïve patients who switched to a biological agent (n = 267) were analysed before switch and at the first follow-up.

    Results: Patients significantly improved in EQ-5D, DLQI and PASI (p < 0.001). Patients with DLQI ≥10 and/or PASI ≥10 had the greatest benefits from biological agents in terms of EQ-5D.

    Conclusions: Patients with moderate to severe psoriasis benefit from biological agents in clinical practice; the patients with the highest benefits were those with high pretreatment PASI and DLQI scores.

  • 32.
    Norlin, Jenny
    et al.
    Umeå University. Leo Pharma AS Köpenhamn, Institutet för hälso och sjukvårdsekonomi (IHE).
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Steen Carlsson, Katarina
    Persson, Ulf
    Registerstudier mäter effektivitet av läkemedel i klinisk praxis: Exemplet PsoReg – omfördelning av systemisk terapi kan ge ökad effektivitet2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 24, p. 1061-3Article in journal (Refereed)
    Abstract [en]

    Pharmaceuticals and medical technologies may have different outcomes in randomized controlled trials and observational studies. Register-based research can provide complementary information about the effectiveness of new medical technologies in clinical practice. Studies based on PsoReg, the Swedish register for systemic treatment of psoriasis, indicate that there is both an over- and under-treatment with biologics in patients with psoriasis in clinical practice. By optimizing the allocation of biologic systemic treatments for psoriasis the overall health level would increase without increas­ing the budget.

  • 33. Ormerod, AD
    et al.
    Augustin, M
    Baker, C
    Chosidow, O
    Cohen, AD
    Dam, TN
    Garcia-Doval, I
    Lecluse, LL
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Spuls, PI
    Watson, KD
    Naldi, L
    Challenges for synthesising data in a network of registries for systemic Psoriasis therapies2012In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 224, no 3, p. 236-243Article in journal (Refereed)
    Abstract [en]

    Background: Large disease registries are the preferred method to assess long-term treatment safety. If psoriasis registries collaborate in a network, their power to assess safety is increased.

    Objective: To identify heterogeneity in psoriasis registries and methodological challenges for synthesising the data they provide.

    Methods: We surveyed the registries in PSONET and identified and addressed the challenges to collaborative analysis for the network in several round table meetings.

    Results: Eight out of 10 registries had a prospective comparator cohort with similar disease characteristics but not on biologics. Registries differed in the coding and validation or follow-up of adverse events and in the way they sampled their population. Fifteen challenges to registries collaborating were identified in the areas of operational governance, structural conduct, bias and analysis.

    Conclusions: Participation in PSONET, a network of psoriasis registries, helps identify and solve common issues, enhancing the individual registries, and provides larger sets of more powerful safety data in a diverse population. Challenges to interpreting data collectively include heterogeneity in sampling, variable penetration of biologics and compatibility of different datasets.

    Copyright (c) 2012 S. Karger AG, Basel

  • 34.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    How dermatologists can evaluate systemic psoriasis treatments2009In: Forum for nordic dermato-venereology, ISSN 1402-2915, Vol. 14, no 2, p. 38-40Article in journal (Refereed)
  • 35.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Physical activity and lifestyle improvement in the management of psoriasis2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 175, no 3, p. 452-453Article in journal (Refereed)
  • 36.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Pso-Reg: the quality register for systemic psoriasis treatment2004In: Forum for Nordic dermato-venereology, Vol. 9, no 4, p. 94-97Article in journal (Refereed)
  • 37.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    PsoReg: the Swedish registry for systemic psoriasis treatment. The registry's design and objectives.2007In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 214, no 2, p. 112-117Article in journal (Refereed)
  • 38.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Psoriasis therapy in real life: the need for registries2006In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 213, no 4, p. 327-330Article in journal (Refereed)
    Abstract [en]

    The introduction of new therapeutic options for the management of psoriasis is a challenge for the dermatology community, and new tools are needed to face this challenge. This article argues for the establishment of profession-based registries to collect solid, long-term data on the safety and effectiveness of different psoriasis treatment regimens. Managed by health care professionals, registries will be most successful if they enroll patients based on indications for treatment rather than on drugs given. This protects the evaluation process from commercial influences and allows a fair comparison of old- versus new-generation psoriasis treatments. In contrast to the patients in a registry who receive care in the natural clinical setting, subjects in randomized clinical trials (RCTs) are selected according to study criteria and may therefore not reflect the experience of patients in clinical practice. It is possible that particular risks and opportunities in the real patient population may therefore go undetected in RCTs.

    Copyright © 2006 S. Karger AG, Basel

  • 39.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Switching biologicals: switching TNFalpha antagonists in psoriasis treatment2008In: Dermatology, ISSN 1018-8665, E-ISSN 1421-9832, Vol. 216, no 4, p. 281-282Article in journal (Refereed)
  • 40.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    What can we learn from 'dropouts' in clinical trials?2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 2, p. 318-319Article in journal (Other academic)
  • 41.
    Schmitt-Egenolf, Marcus
    et al.
    Department of Dermatology, University of Kiel, Germany.
    Boehncke, WH
    Christophers, E
    Ständer, M
    Sterry, W
    Type I and type II psoriasis show a similar usage of T-cell receptor variable regions1991In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 97, no 6, p. 1053-1056Article in journal (Refereed)
    Abstract [en]

    In nonpustular psoriasis, principally two forms can be distinguished [Christophers E. Henseler T: Patient subgroups and the inflammatory pattern in psoriasis. Acta Dermatol Venereol 69(suppl 151):88-92, 1989): Type I frequently shows positive family history, linkage disequilibrium for human leucocyte antigens (HLAs) Cw6, B13 and Bw57 as well as an early onset. Type II manifests itself around the 5th decade, it is more frequently than normal associated with Cw2 and B27. In the light of this association with HLAs an autoimmune pathogenesis has been discussed. In order to investigate the pathogenetic function of T cells we obtained biopsies from patients with type I (n = 10) and type II (n = 10) psoriasis. Three-step peroxidase staining was performed using a panel of monoclonal antibodies directed against five variable (V) regions of the beta chain (V beta 5a, V beta 5b, V beta 6, V beta 8, V beta 12) and one of the alpha chain (V alpha 2) of the T cell receptor (TCR). Positive or negative selection of a particular TCR V region could not be detected in the demonstrable repertoire. Furthermore, the usage of the V regions under investigation revealed a similar pattern in the two forms of psoriasis.

  • 42.
    Schmitt-Egenolf, Marcus
    et al.
    Department of Dermatology, University of Ulm, Ulm, Germany.
    Boehncke, WH
    Ständer, M
    Eiermann, TH
    Sterry, W
    Oligonucleotide typing reveals association of type I psoriasis with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype1993In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 100, no 6, p. 749-752Article in journal (Refereed)
    Abstract [en]

    Although the pathogenesis of psoriasis is still a matter of debate, there are several lines of evidence supporting the concept of this disease being immunologically mediated with T cells playing a crucial role. Because a considerable portion of the cellular infiltrate in psoriasis consists of activated T-helper cells, expression of HLA class II antigens might be of particular importance for the understanding of its pathogenesis. Therefore, we investigated the HLA type of patients with type I (early onset, positive family history) and type II (late onset, no family history) psoriasis by means of serology (n = 89) and genotyping using sequence-specific oligonucleotide probes (n = 64). Serologic analysis of class I documented the association of type I psoriasis with HLA-Cw6, -B13, and -B57, whereas type II psoriasis showed a weaker correlation with HLA-Cw2 and -B27. Genotyping using SSO for class II detected the elevation of the HLA-DRB1*0701/2 allele frequency from 13% in normal population to 36% in type I, but only to 15% in type II psoriatics. Moreover, positive correlations with type I psoriasis were detected for HLA-DQA1*0201 and HLA-DQB1*0303. The HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype was found exclusively in type I psoriasis. This is the first report documenting the association of distinct HLA class II alleles with type I psoriasis as detected on the DNA level, an approach both more specific and more sensitive when compared to serology.

  • 43.
    Schmitt-Egenolf, Marcus
    et al.
    Department of Dermatology, School of Medicine (Charité), Humboldt University, Berlin, Germany & Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, Vienna, Austria.
    Eiermann, TH
    Boehncke, WH
    Ständer, M
    Sterry, W
    Familial juvenile onset psoriasis is associated with the human leukocyte antigen (HLA) class I side of the extended haplotype Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303: a population- and family-based study1996In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 106, no 4, p. 711-714Article in journal (Refereed)
    Abstract [en]

    To further evaluate the nature of the HLA association with psoriasis, HLA haplotypes of 60 patients with type 1 (early onset, positive family history) and 30 patients with type II (late onset, no family history) psoriasis were investigated by polymerase chain reaction sequence-specific oligonucleotide hybridization (HLA class II) and serology (HLA class I). Ethnically matched blood donors (146) served as controls. In type I, but not type II psoriasis, the Caucasian HLA extended haplotype (EH) Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303 named according to the B allele EH-57.1 was highly significantly overrepresented (p cor= 0.00021). This particular EH was present in 35% of type I psoriatics but only 2% of controls. EH-57.1+ individuals therefore carry a 26 times higher risk of developing type I psoriasis than individuals who are EH-57.1-negative Further analysis of individual HLA alleles revealed that within EH-57.1, HLA class I antigens (Cw6-B57) were associated to a much higher extent with type I psoriasis than the HLA class II alleles (DRB1*0701-DQA1*0201-DQB1* 0303). Pedigree analysis of three multiply affected families over three generations revealed a cosegregation of disease with EH-57.1. These results strongly suggest that a gene for familial psoriasis is associated with the class I side of the extended haplotype Cw6-B57-DRB1*0701-DQA1*0201-DQB1*0303.

  • 44.
    Schmitt-Egenolf, Marcus