Prevalence and incidence of palmoplantar pustulosis in Sweden: a population-based register study.

BACKGROUND: Palmoplantar 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 population with PPP. METHODS: The Swedish National Patient Register was used, covering all inpatient and outpatient nonprimary care for the Swedish population. We identified cases (2004-2015) with one International Classification of Diseases 10th Revision 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 definitions: (i) requiring two visits and (ii) requiring two visits, one of which was within dermatology or internal medicine. RESULTS: The base case prevalence of PPP was estimated to be 147 per 100 000 (women 227, men 68) and the annual prevalence was estimated to 26 per 100 000 in 2015. Among the population of people with PPP, 17% were registered with a diagnostic code for psoriasis vulgaris. The incidence of PPP in 2015 was estimated to be 12·7 per 100 000 (women 18·7, men 6·6). The criteria used had an impact on the prevalence and incidence estimates: strict case 1 gave an overall prevalence of 72 per 100 000 and an incidence of 5·4 per 100 000. CONCLUSIONS: The results indicate that the population-based prevalence of PPP may be larger than previously estimated. However, the estimates were sensitive to the employed PPP case criteria. The findings enhance demands for studies using validated diagnostic algorithms potentially also including data from primary care.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

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.

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 goals.

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 naïve 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 < 0·001). The magnitude of improvements in DLQI (P = 0·02) 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 9·9 (7·4), 11·5 (7·0) and 8·0 (6·1), 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. What's already known about this topic? Randomized clinical trials of biologics as well as treatment guidelines include treatment goals based on a percentage improvement compared with baseline Psoriasis Area and Severity Index (PASI), such as PASI 75 or PASI 90. Few studies have assessed which factors are associated with high skin clearance rates, or health-related quality of life (HRQoL) improvements associated with different levels of skin clearance in clinical practice. What does this study add? A high absolute PASI before switch to biologics and low body mass index are associated with higher PASI percentage response. Few patients with baseline PASI >30 achieved complete skin clearance (CSC). All responder groups achieved significant HRQoL improvements. Patients achieving CSC (PASI 100) had lower absolute PASI before switch and lower improvements in absolute PASI and HRQoL than patients with almost cleared skin. What are the clinical implications of this work? Relative measures based on PASI percentage, such as PASI 75 or PASI 90, are not suitable for treatment guidelines or for follow-up in clinical practice.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 1: treatment and monitoring recommendations.

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.

Sustained Psoriasis Area and Severity Index, Dermatology Life Quality Index and EuroQol-5D response of biological treatment in psoriasis: 10 years of real-world data in the Swedish National Psoriasis Register.

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 now includes 10 years of real-world data on the effectiveness of biological treatment. OBJECTIVES: To analyse the long-term real-world outcome data of patients who are biologically naïve with moderate-to-severe psoriasis after switching to biological treatment. METHODS: An observational study of patients who are biologically naïve with at least one registration of outcome before switching to biological treatment while included in PsoReg and at least one follow-up visit. Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and EuroQol-5D (EQ-5D) values were analysed at 3-5 months, 6-11 months and at least once after ≥ 1 year, up to 9 years after the switch to biological treatment. RESULTS: In total, 583 patients fulfilled the inclusion criteria. Of these, 399, 395 and 373 patients had observed outcome data beyond 1 year on the PASI, DLQI and EQ-5D, respectively, and 164, 168 and 152, respectively, were observed in at least three time periods after the switch. Significant (P < 0·01) improvement in PASI, DLQI and EQ-5D scores was observed 3-5 months after the switch and sustained under the whole observation period. The mean PASI, DLQI and EQ-5D changed from 13·5 ± 9·1, 9·0 ± 8·1 and 0·74 ± 0·22, respectively, before the switch, to 4·0 ± 3·5, 3·7 ± 4·7 and 0·79 ± 0·21, respectively, 1-5 years after the switch. CONCLUSIONS: Biological treatment, as used in clinical practice, shows a stable long-term effectiveness in all the measured dimensions, PASI, DLQI and EQ-5D.

[Subpectoral tenodesis of the long head of the biceps tendon with an interference screw and a cortical button : Clinical and cosmetic results after 1 year]. / Subpektorale Tenodese der langen Bizepssehne mittels Interferenzschraube und Cortical-Button : Klinische und kosmetische Ergebnisse nach einem Jahr.

BACKGROUND: Pathologies of the long head of biceps tendon (LHB) can cause anterior shoulder pain. Surgical treatment includes tenotomy and tenodesis (TD), however TD causes fewer cosmetic deformities and less cramping of the biceps muscle. To date, numerous techniques for TD have been described but the "gold standard" has not yet been established. OBJECTIVES: The purpose of this study is to evaluate the functional and cosmetic outcome following subpectoral biceps TD with an interference screw and a cortical-button (STLHB-IC) after 1 year. MATERIALS AND METHODS: 35 patients (10 female, 25 male) with an average age of 57.4 ± 7 years were examined after STLHB-IC with a follow up of 12.8 ± 1.2 months. The constant score (CS), the long head of biceps score (LHBS) and the subjective shoulder value (SSV) were assessed. Furthermore, the cosmetic result was evaluated by the patient and the examiner, and the elbow flexion strength (EFS) was measured. RESULTS: The CS (82.5 ± 17.2), LHBS (90.1 ± 11.5) and SSV (83.2 ± 17.7) showed good and excellent results. The SSV increased significantly pre vs. postoperatively (40.6 ± 19.7 vs. 83.2 ± 17.7). The CS (82.5 ± 17.2) and the LHBS (90.1 ± 11.5), as well as the EFS (17.5 ± 4.8 kg) of the affected shoulder revealed no significant differences compared with the non-affected shoulder (CS: 91.8 ± 11.3, LHBS: 99.1 ± 11.5; EFS: 19.7 ± 4.8). Severe Popeye deformities (measured by LHBS) were found in 6% of the cases, however if they occurred patients (13.4 ± 3.8) evaluated them as significantly less disadvantageous than the examiners (11.9 ± 4.7). There were no neurovascular injuries, infections or fractures. CONCLUSION: STLHB-IC is a safe, reproducible technique with convincing functional and cosmetic results that provides high patient satisfaction.

Evaluating equality in psoriasis healthcare: a cohort study of the impact of age on prescription of biologics.

BACKGROUND: Inequality in healthcare has been identified in many contexts. To the best of our knowledge, this is the first study investigating age inequality in the form of prescription patterns of biologics in psoriasis care. OBJECTIVES: To determine whether patients with psoriasis have equal opportunities to receive biological medications as they age. If patients did not receive equal treatment, a subsequent objective was to determine the magnitude of the disparity. METHODS: A cohort of biologic-naive patients with psoriasis was analysed using Cox proportional hazards models to measure the impact of each additional year of life on the likelihood of initiating biological treatment, after controlling for sex, body mass index, comorbidities, disease activity and educational level. A supporting analysis used a nonparametric graphical method to study the proportion of patients initiating biological treatment as age increased, after controlling for the same covariates. RESULTS: The Cox proportional hazards model resulted in hazard ratios of a 1-year increase in age of 0·96-0·97 depending on calendar-year stratification, which implies that an increase in age of 30 years corresponds to a reduced likelihood of initiating biological treatment by 61·3-67·6%. The estimated proportion of patients initiating biological medication always decreased as age increased, at a statistically significant level. CONCLUSIONS: Patients with psoriasis have fewer opportunities to access biological medications as they age. This result was shown to be applicable at all stages in a 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 inequality in access to biological treatments due to age is prevalent in clinical practice today. Further research is needed to investigate the extent to which this result is influenced by patient preferences.

[Reasons for proximal femoral fracture surgery delays : Analysis of the structured dialog in Rheinland-Pfalz]. / Verzögerte Versorgung hüftgelenknaher Femurfrakturen : Analyse des Strukturierten Dialogs Rheinland-Pfalz.

BACKGROUND: For the "preoperative stay" quality indicator , which is part of the external quality assurance for proximal femoral fractures (module 17/1), a tolerance range for surgery within 48 h after admission of ≤15 % is given. MATERIALS AND METHODS: The structured dialog (2014) in Rheinland-Pfalz was analyzed with respect to reasons for delaying surgery for more than 48 h after admission. RESULTS: A total of 331 cases were analyzed. In 60.7 % patient-related reasons and in 13.3 % administrative reasons were found. In 9.1 % the statements were not feasible. Due to a lack of software-related specifications in 7.3 % a wrong preoperative length of stay was generated. Wrong coding or a computer-related problem was found in 6.6 %. The most common reason for delay was the intake of an anticoagulant (25.7 %). CONCLUSION: The significance of the quality indicator "Preoperative stay" without division into whether this was administrative or patient-related must be considered critically.

Hair shaft structures in EDAR induced ectodermal dysplasia.

BACKGROUND: Mutations in the EDAR-gene cause hypohidrotic ectodermal dysplasia with defects in ectodermal appendage development including teeth, skin, exocrine glands and hair. Hair defects are sparsely described in genetically defined samples. The aim of this study was to investigate hair structures in three families with a heterozygous c.1072C > T mutation in the EDAR gene using scanning electron microscopy. METHODS: Three Swedish families, where some members had a known c.1072C > T mutation in the EDAR gene with an autosomal dominant inheritance (AD) were included (n = 37) of which 17 carried the mutation and 20 did not. Thirty-two age and gender matched not related individuals served as a reference group. Confirmation of the c.1072C > T mutation in the EDAR gene was performed by genomic sequencing. Hairs were subjected to blinded scanning electron microscopy examination and hair defects were categorized and scored. RESULTS: The minimum and maximum diameters of hairs were lower in the mutation group compared to the reference group. Subjects in the mutation group had to greater extent deep deformations in hair shafts compared to the non-mutation group and the reference group (p < 0.001). CONCLUSIONS: Individuals with a c.1072C > T mutation in the EDAR-gene displayed more hair shaft deformations confirming the role of EDAR for human hair follicle development and postnatal hair follicle cycling.

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).

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.

Analysis of three outcome measures in moderate to severe psoriasis: a registry-based study of 2450 patients.

BACKGROUND: As moderate to severe psoriasis is a systemic disease with large effects on health-related quality of life, generic measures that include overall health, not only skin involvement, are necessary. Knowledge about the relationship between the generic preference-based EuroQol 5D (EQ-5D) and dermatology-specific measures in psoriasis is limited. OBJECTIVES: To analyse EQ-5D, the Dermatology Life Quality Index (DLQI) and the 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 vs. 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 was compared among patients with psoriasis vs. a defined general population in Sweden, retrieved from a previous study. Relationships between measures were examined with correlation tests and regression analysis. RESULTS: In total, 2450 patients (1479 men and 971 women) were included. Median EQ-5D, DLQI and PASI scores were 0·769, 4 and 4·7, respectively. Patients with psoriasis had a significantly lower EQ-5D compared with 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.

Challenges for synthesising data in a network of registries for systemic psoriasis therapies.

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.

Real-world outcomes in 2646 psoriasis patients: one in five has PASI ≥10 and/or DLQI ≥10 under ongoing systemic therapy.

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 2646 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 with 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.

Type I and type II psoriasis show a similar usage of T-cell receptor variable regions.

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.

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 study.

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.

Oligonucleotide typing reveals association of type I psoriasis with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype.

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.