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.

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.

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.

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.

Polymorphism in an HLA linked proteasome gene influences phenotypic expression of disease in HLA-B27 positive individuals.

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.