No abstract

Inherited ichthyoses belong to a large and heterogeneous group of mendelian disorders of cornification, and can be distinguished by the quality and distribution of scaling and hyperkeratosis, by other dermatologic and extracutaneous involvement, and by inheritance. We present the genetic analysis results of probands with X-linked ichthyosis, autosomal recessive congenital ichthyosis, keratinopathic ichthyosis, and a patient with Netherton syndrome. Genetic diagnostics was complemented by in silico missense variant analysis based on 3D protein structures and commonly used prediction programs to compare the yields of these two approaches to each other. This analysis revealed various structural defects in proteins coded by mutated genes while no defects were associated with known polymorphisms. Two patients with pathogenic variants in the ABCA12 gene have a premature termination codon mutation on one allele and a silent variant on the second. The silent variants c.69G > A and c.4977G > A are localised in the last nucleotide of exon 1 and exon 32, respectively, and probably affect mRNA splicing. The phenotype of both patients is very severe, including a picture harlequin foetus after birth; later (at 3 and 6 years of age, respectively) ectropin, eclabion, generalised large polygonal scaling and erythema. Electronic supplementary material The online version of this article (10.1186/s13023-019-1076-7) contains supplementary material, which is available to authorized users.

The IL-17 cytokine family encompasses six different homodimers and heterodimers referred to as IL-17A-F. Due to some differences in the mechanism of IL-17 inhibition, aninsufficient effect of one IL-17 inhibitor does not necessarily imply lack of efficacy of the other agent of the same class. Aim of study was analysis of the success rate of switches among IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) in patients treated in the Czech Republic. Data were obtained from the Czech nationwide registry of psoriatic patients receiving biological/targeted therapy (BIOREP). Our analysis involved data of a total of 90 patients with severe chronic plaque psoriasis and baseline PASI scores >10 both prior to first-line biological therapy initiation and after switch to another agent of the class of IL-17 inhibitors. The most effective switch was that from secukinumab to brodalumab, with PASI 90 reached by 64.7% and 73.3% of patients at weeks 12 and 24. Among patients switched from secukinumab to ixekizumab target PASI 90 responses were achieved (at weeks 12 and 24) by 41.2% and 55.2% of patients. Among patients switched from ixekizumab to brodalumab target PASI 90 responses were achieved, at the above time points, by 30.8% and 38.5% of patients. Our analysis showed a high success rate of switches from secukinumab to ixekizumab and brodalumab, followed by the ixekizumab-to-brodalumab switch. Importantly, the therapeutic response and success rates of individual switches are independent of the patient's body weight and presence of psoriatis arthritis.

Congenital ichthyoses are a very heterogeneous group of diseases manifested by dry, rough and scaling skin. In all forms of ichthyoses, the skin barrier is damaged to a certain degree. Congenital ichthyoses are caused by various gene mutations. Clinical manifestations of the individual types vary as the patient ages. Currently, the diagnosis of congenital ichthyoses is based on molecular analysis, which also allows a complete genetic counseling and genetic prevention. It is appropriate to refer the patients to specialized medical centers, where the cooperation of a neonatologist, a pediatric dermatologist, a geneticist and other specialists is ensured.