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.

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.

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.

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.

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.

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.

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.

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.

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.

Association scan of the novel psoriasis susceptibility region on chromosome 19: evidence for both susceptible and protective loci.

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.

Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis.

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.

Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families.

HLA antigens are associated with psoriasis vulgaris across populations with different ethnic background. We have previously shown that in Caucasians this association is primarily based on the class I alleles of the extended HLA haplotype 57.1 (EH57.1/I), HLA-Cw6-HLA-B57. However, it remained unclear whether HLA-Cw6 itself or a closely linked locus predisposes to the disease. An interesting candidate for this presumed locus is corneodesmosin, which is exclusively synthesized in keratinocytes. The corneodesmosin gene locus (CDSN) is only 160 kb telomeric to HLA-C and tightly associated with psoriasis. In order to find out whether EH57.1/I or a corneodesmosin variant are the susceptibility determinants on 6p, HLA class I alleles and single-nucleotide polymorphisms (SNPs) of corneodesmosin were investigated at the sequence level and analyzed by comparative association tests. Transmission disequilibrium tests (TDT) were performed in 52 nuclear families, of which 36 were fully informative for a joint comparison of HLA and CDSN with regard to association to psoriasis. The extended TDT according to Wilson was employed to test for locus interaction. Using the HLA haplotype EH57.1/I and the CDSN haplotype formed by three intragenic variant sites at nt=619 (T), 1236 (T), and 1243 (C), we obtained the best resolution of parental transmission to index cases in the trio families. On direct comparison of the contributions of the HLA and the CDSN haplotypes, there was a markedly stronger association of the corneodesmosin TTC haplotype, which is not apparent in single locus analysis. We show furthermore that there is no higher order interaction between psoriasis, HLA, and CDSN. This lack of three-locus interaction is suggestive of two independent genetic contributions to psoriasis within the major histocompatibility complex (MHC).

Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13.

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.

PERB11 (MIC): a polymorphic MHC gene is expressed in skin and single nucleotide polymorphisms are associated with psoriasis.

The susceptibility genes for psoriasis remain to be identified. At least one of these must be in the major histocompatibility complex (MHC) to explain associations with alleles at human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and C4. In fact, most of these alleles are components of just two ancestral haplotypes (AHs) designated 13.1 and 57.1. Although relevant MHC gene(s) could be within a region of at least 4 Mb, most studies have favoured the area near HLA-B and -C. This region contains a large number of non-HLA genes, many of which are duplicated and polymorphic. Members of one such gene family, PERB11.1 and PERB11.2, are expressed in the skin and are encoded in the region between tumour necrosis factor and HLA-B. To investigate the relationship of PERB11.1 alleles to psoriasis, sequence based typing was performed on 97 patients classified according to age of onset and family history. The frequency of the PERB11.1*06 allele is 44% in type I psoriasis but only 7% in controls (Pc = 0.003 by Fisher's exact test, two-tailed). The major determinant of this association is a single nucleotide polymorphism (SNP) within intron 4. In normal and affected skin, expression of PERB11 is mainly in the basal layer of the epidermis including ducts and follicles. PERB11 is also present in the upper keratin layers but there is relative deficiency in the intermediate layers. These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis.