Practical management of epidermolysis bullosa: consensus clinical position statement from the European Reference Network for Rare Skin Diseases.

Inherited epidermolysis bullosa (EB) comprises rare disorders that manifest with fragility and blistering of the skin and mucous membranes, with variable clinical severity. Management of EB is challenging due to disease rarity and complexity, the wide range of extracutaneous manifestations and a profound impact on daily life for the patient and family members. Although reference centres providing multidisciplinary care for EB exist in each European country, it is common for healthcare professionals that are not specialized in this rare disorder to treat EB patients. Here, experts of the European Reference Network for Rare and Undiagnosed Skin Diseases (ERN-Skin, https://ern-skin.eu) propose practical recommendations for the diagnosis and management of the commonest clinical issues, skin blisters and wounds, oral manifestations, pain and itch.

Surgical treatment and management of cutaneous squamous cell carcinoma in patients with dystrophic epidermolysis bullosa - a case report.

Epidermolysis bullosa (EB) is a rare inherited disease which is characterized by blisters on the skin and mucous membranes. Some forms of EB are associated with a risk of squamous cell carcinoma (SCC) development, which, unlike in the general population, is formed at a young age. SCC is the most common cause of death in patients with a dystrophic form. It is necessary to examine chronic and non-healing wounds for an increased risk of SCC. The basic treatment consists of surgical excision of the tumor site with a wide margin into healthy tissue. The surgical wound can be healed by secondary intention to prevent further trauma of the patient. The radicality of the excision is influenced by the location of the tumor. On the body, it is considerably limited by the surrounding tissue; on the limb, it is necessary to consider its amputation. In case of dissemination of the disease, it is important to approach patients individually and discuss other treatment options, including palliative care, within the national EB Center. The therapy is focused on pain treatment, remedial surgical dressings and psychological support with an emphasis on maintaining the quality of life.

Keratin mutations in patients with epidermolysis bullosa simplex: correlations between phenotype severity and disturbance of intermediate filament molecular structure.

BACKGROUND: Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in the keratin 5 (KRT5) and keratin 14 (KRT14) genes, with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. OBJECTIVES: In this study, we characterized mutations in KRT5 and KRT14 genes in patients with EBS and investigated their possible structure-function correlations. MATERIALS AND METHODS: Mutations were characterized using polymerase chain reaction (PCR) and DNA sequencing. Further, to explore possible correlations with function, the structural effects of the mutations in segment 2B of KRT5 and KRT14 and associated with EBS in our patients, as well as those reported previously, were modelled by molecular dynamics with the aid of the known crystal structure of the analogous segment of human vimentin. RESULTS: We have identified mutations in the KRT5 and KRT14 genes in 16 of 23 families affected by EBS in the Czech Republic. Eleven different sequence variants were found, of which four have not been reported previously. Novel mutations were found in two patients with the EBS-Dowling-Meara variant (EBS-DM) [KRT14-p.Ser128Pro and KRT14-p.Gln374_Leu387dup(14)] and in three patients with localized EBS (KRT14-p.Leu136Pro and KRT5-p.Val143Ala). Molecular dynamics studies show that the mutations p.Glu411del and p.Ile467Thr perturb the secondary alpha-helical structure of the mutated polypeptide chain, the deletion p.Glu411del in KRT14 has a strong but only local influence on the secondary structure of KRT14, and the structural impact of the mutation p.Ile467Thr in KRT5 is spread along the helix to the C-terminus. In all the other point mutations studied, the direct structural impact was significantly weaker and did not destroy the alpha-helical pattern of the secondary protein structure. The changes of 3-D structure of the KRT5/KRT14 dimer induced by the steric structural impact of the single point mutations, and the resulting altered inter- and intramolecular contacts, are spread along the protein helices to the protein C-terminus, but the overall alpha-helical character of the secondary structure is not destroyed and the atomic displacements induced by mutations cause only limited-scale changes of the quaternary structure of the dimer. CONCLUSIONS: The results of molecular modelling show relationships between patients' phenotypes and the structural effects of individual mutations.

Proactive disease management with 0.03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study.

BACKGROUND: Long-term treatment for atopic dermatitis (AD) using low-dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent exacerbations. OBJECTIVES: This 12-month, European, multicentre, randomized study investigated if proactive, twice-weekly application of 0.03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children. PATIENTS AND METHODS: During the initial open-label period, 267 children with AD applied 0.03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of

[Ultrastructural findings in the so-called minimal glomerular changes]. / Ultrastrukturální nálezy u takzvaných minimálních glomerulárních zmen.

Fifty-eight needle biopsies of the kidneys with the light microscopical diagnosis of so-called minimal glomerular lesions were subjected to ultrastructural evaluation. The series contained children and adults under 25 years of age with the mean age of 16.9 years. The most frequent findings were those of the glomerular epithelia: vacuolation and swelling of their cytoplasm in 72.8%, microvilloustransformation in 13.6%. Endothelial lesions were less frequent: swelling and vacuolation of their cytoplasm occurred in 46.6%. The most important ultrastructural lesions appeared to be the mesangial ones. Focal increase in the mesangial matrix was seen in 44.8% and small intralobular scars in 13.6%. True focal increase in mesangial cells was rare (6.9%). The formation of duplicatures of the basement membranes in the glomeruli was exceptional (3.6%). Another important ultrastructural finding was a focal thickening of the basement membrane in a larger number of cases (32.3%). Deposits were found rarely (7 cases, 12.1%) most of them occurring in the mesangium. The cellularity of the glomeruli did not exceed the normal range.

A concurrent occurrence of cutis laxa, Dandy-Walker syndrome and immunodeficiency in a girl.

UNLABELLED: We report on a 17-y-old girl with inherited cutis laxa, immunodeficiency and Dandy-Walker syndrome. Immunodeficiency manifested itself by decreased and fluctuating levels of IgG, IgA and IgM and intermittent leucopenia causing increased susceptibility to respiratory tract infections. Dandy-Walker syndrome (agenesis of the cerebellar vermis with a large posterior fossa cyst communicating with an enlarged 4th ventricle) was shown on a CT scan but with the exception of macrocrania, no typical signs or symptoms were observed at the age of 17. Loose hyperextensible skin with pendulous skinfolds as a manifestation of cutis laxa was observed from birth. Anomalies of the right pulmonary artery, abnormal branching of the left arteria subclavia (arteria lusoria) from the left aortic arch and bicuspidal aortic valve were also present. CONCLUSION: The combination of the rare disorders cutis laxa, Dandy-Walker syndrome and immunodeficiency is reported here for the first time.