Incontinentia pigmenti Stage 1 is not simply vesiculo-bullous but vesiculo-pustular.

Incontinentia pigmenti (IP) is a rare X-linked dominant, male-lethal disorder characterized by pathognomic skin lesions. As described in the literature the typical cutaneous changes follow the pattern of Blaschko's lines and develop in four stages that usually start at birth. Stage 1 is called vesicular, bullous or inflammatory. The vesicles are rapidly filled with eosinophils and thus turn into pustules. Thus, the term "pustular" is relevant to the first phase of IP, and the stage can be considered as "vesiculopustular/inflammatory" to be more precise than "vesicular" or "bullous."

Four cases of Chanarin-Dorfman syndrome presenting with different types of erythrokeratoderma.

Chanarin-Dorfman syndrome (CDS) is a multisystem autosomal recessive disorder due to variants of the ABHD5 gene, characterized by lipid vacuoles in the liver and leukocytes, and possible involvement of eyes, ears, skeletal muscle, and central nervous system. CDS may present with skin changes, most commonly congenital non- bullous ichthyosiform erythroderma, however erythrokeratoderma-like findings have been rarely reported in CDS patients. Herein, we report clinical, histopathological and genetic findings of four patients with CDS presenting with different clinical forms of erythrokeratoderma (three with progressive symmetric erythrokeratoderma-like features and one with erythrokeratoderma variabilis (EKV)-like features), including one patient with a novel mutation in ABHD5. Although the typical skin finding of CDS syndrome is reported as non-bullous congenital ichthyosiform erythroderma, CDS should also be in the differential diagnosis in patients with EKV-like lesions.

S3 Guideline Atopic dermatitis: Part 1 - General aspects, topical and non-drug therapies, special patient groups.

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.

S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.

Short anagen hair syndrome: association with mono- and biallelic variants in WNT10A and a genetic overlap with male pattern hair loss.

BACKGROUND: Short anagen hair (SAH) is a rare paediatric hair disorder characterized by a short anagen phase, an inability to grow long scalp hair and a negative psychological impact. The genetic basis of SAH is currently unknown. OBJECTIVES: To perform molecular genetic investigations in 48 individuals with a clinical phenotype suggestive of SAH to identify, if any, the genetic basis of this condition. METHODS: Exome sequencing was performed in 27 patients diagnosed with SAH or with a complaint of short, nongrowing hair. The cohort was screened for variants with a minor allele frequency (MAF) < 5% in the general population and a Combined Annotation Dependent Depletion (CADD) score > 15, to identify genes whose variants were enriched in this cohort. Sanger sequencing was used for variant validation and screening of 21 additional individuals with the same clinical diagnosis and their relatives. Genetic association testing of SAH-related variants for male pattern hair loss (MPHL) was performed using UK Biobank data. RESULTS: Analyses revealed that 20 individuals (42%) carried mono- or biallelic pathogenic variants in WNT10A. Rare WNT10A variants are associated with a phenotypic spectrum ranging from no clinical signs to severe ectodermal dysplasia. A significant association was found between WNT10A and SAH, and this was mostly observed in individuals with light-coloured hair and regression of the frontoparietal hairline. Notably, the most frequent variant in the cohort [c.682T>A;p.(Phe228Ile)] was in linkage disequilibrium with four common WNT10A variants, all of which have a known association with MPHL. Using UK Biobank data, our analyses showed that c.682T>A;p.(Phe228Ile) and one other variant identified in the SAH cohort are also associated with MPHL, and partially explain the known associations between WNT10A and MPHL. CONCLUSIONS: Our results suggest that WNT10A is associated with SAH and that SAH has a genetic overlap with the common phenotype MPHL. The presumed shared biologic effect of WNT10A variants in SAH and MPHL is a shortening of the anagen phase. Other factors, such as modifier genes and sex, may also play a role in the clinical manifestation of hair phenotypes associated with the WNT10A locus.

Effects of Early Emollient Use in Children at High Risk of Atopic Dermatitis: A German Pilot Study.

Several small studies have indicated that daily emollient use from birth might delay, suppress or prevent atopic dermatitis (AD). Two larger trials did not confirm this; however, a recent smaller study indicated a protective effect if daily emollient use is used in the first 2 months of life. Further research is needed to evaluate the effect of emollient use on development of AD. The current study randomly assigned 50 newborns who were at high risk of developing AD (1:1) to receive general infant skin-care advice (control group), or skin-care advice plus emollient with advice to apply emollient at least once daily until 1 year of age (intervention group). Repeated skin examinations, skin physiology measurements and skin microbiome profiling were performed. Of the children in the intervention and control groups, 28% and 24%, respectively, developed AD (adjusted Relative Risk (RR) 1.19, p = 0.65, adjusted risk difference 0.05). Skin pH decreased and transepidermal water loss and stratum corneum hydration increased over time in both groups with no significant differences. In the intervention group skin microbiome alpha diversity increased earlier, and the abundance of Streptococcus and Staphylococcus species were significantly reduced at month 1. Daily early emollient use in children with high risk of AD was safe, but it did not significantly reduce the risk of developing AD or impact skin physiology development.

Epidemiology of inherited epidermolysis bullosa in Germany.

BACKGROUND: Epidermolysis bullosa (EB) is a rare genetic disorder manifesting with skin and mucosal membrane blistering in different degrees of severity. OBJECTIVE: Epidemiological data from different countries have been published, but none are available from Germany. METHODS: In this population-based cross-sectional study, people living with EB in Germany were identified using the following sources: academic hospitals, diagnostic laboratories and patient organization. RESULTS: Our study indicates an overall EB incidence of 45 per million live births in Germany. With 14.23 per million live births for junctional EB, the incidence is higher than in other countries, possibly reflecting the availability of early molecular genetic diagnostics in severely affected neonates. Dystrophic EB was assessed at 15.58 cases per million live births. The relatively low incidence found for EB simplex, 14.93 per million live births, could be explained by late or missed diagnosis, but also by 33% of cases remaining not otherwise specified. Using log-linear models, we estimated a prevalence of 54 per million for all EB types, 2.44 for junctional EB, 12.16 for dystrophic EB and 28.44 per million for EB simplex. These figures are comparable to previously reported data from other countries. CONCLUSIONS: Altogether, there are at least 2000 patients with EB in the German population. These results should support national policies and pharmaceutical companies in decision-making, allow more precise planning of drug development and clinical trials, and aid patient advocacy groups in their effort to improve quality of life of people with this orphan disease.

Characterization of Classical Flexural and Nummular Forms of Atopic Dermatitis in Childhood with Regard to Anamnestic, Clinical and Epidermal Barrier Aspects.

Nummular (coin-shaped) and classical (flexural) atopic dermatitis differ morphologically, but no other distinguishing features are known. The aim of this study was to determine differences and similarities of both variants in children. Detailed interviews, clinical examinations, biophysical measurements and electron microscopic analyses were performed on 10 children with nummular atopic dermatitis, 14 with classical atopic dermatitis and 10 healthy controls. Nummular atopic dermatitis affected more boys than girls and manifested less frequently within the first year of life than classical atopic dermatitis. Localization, distribution and morphology of the eczema varied more over time, and expression of keratosis pilaris was more severe in children with nummular atopic dermatitis. Both disease groups showed reduced hydration, increased transepidermal water loss and reduced intercellular lipid lamellae in lesional skin areas compared with non-lesional areas. These findings underline the separate classification of both variants. Further research is necessary to investigate the potential of diverging therapeutic approaches.

Prevalence of Itch in German Schoolchildren: A Population-based Study.

Itch is a common symptom, but there is limited evidence on the prevalence of itch in children. The aim of this study was to assess the prevalence of itch in schoolchildren. A questionnaire was developed by experts in the field and based on a literature search. The questionnaire was applied in a pilot study of 25 consecutively selected paediatric patients and their parents. It confirmed the high content validity of the questionnaire, and the questionnaire was comparable to hospital records regarding chronic itch (n = 19, mean consistency 89.47%). The questionnaire was distributed among German schoolchildren in 9/12 randomly selected primary schools in Kiel, Germany. Of 1,722 invited students, 443 schoolchildren aged 6-10 years participated, and 26.2% (n = 116) reported itch. The prevalence of acute itch was 20.0% (n = 87), and 14.7% (n = 65) reported chronic itch. Reduced sleep and mood were often related to chronic itch. This study demonstrated that itch is a common symptom in German schoolchildren.

Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly syndrome is caused by de novo mutations in protein kinase D1.

BACKGROUND: We describe two unrelated patients who display similar clinical features including telangiectasia, ectodermal dysplasia, brachydactyly and congenital heart disease. METHODS: We performed trio whole exome sequencing and functional analysis using in vitro kinase assays with recombinant proteins. RESULTS: We identified two different de novo mutations in protein kinase D1 (PRKD1, NM_002742.2): c.1774G>C, p.(Gly592Arg) and c.1808G>A, p.(Arg603His), one in each patient. PRKD1 (PKD1, HGNC:9407) encodes a kinase that is a member of the protein kinase D (PKD) family of serine/threonine protein kinases involved in diverse cellular processes such as cell differentiation and proliferation and cell migration as well as vesicle transport and angiogenesis. Functional analysis using in vitro kinase assays with recombinant proteins showed that the mutation c.1808G>A, p.(Arg603His) represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity. The mutation c.1774G>C, p.(Gly592Arg) in contrast shows a defect in substrate phosphorylation representing a loss-of-function mutation. CONCLUSION: The present cases represent a syndrome, which associates symptoms from several different organ systems: skin, teeth, bones and heart, caused by heterozygous de novo mutations in PRKD1 and expands the clinical spectrum of PRKD1 mutations, which have hitherto been linked to syndromic congenital heart disease and limb abnormalities.

Comparison of Lipid Foam Cream and Basic Cream on Epidermal Reconstruction in Mild Atopic Eczema.

INTRODUCTION: Basic therapy is of central importance in the treatment of atopic eczema. Using electron microscopic images, the morphology of epidermal skin barrier and its lipids was investigated after application of a lipid foam cream and basic cream. METHODS: Patients with two contralateral comparable atopic eczema (local SCORAD 1-10) on the forearms were tested. Eczema was treated with a lipid foam cream or basic cream twice daily for 28 days. At the beginning, after 14 days, and at the end of application, the local SCORAD, trans-epidermal water loss (TEWL), skin hydration, intercellular lipid length in the intercellular space of the stratum corneum (SC), and skin lipids were determined. RESULTS: After application of the foam cream, the epidermal skin barrier could be completely restored and corresponded to healthy skin, while the epidermal skin barrier could not reach this state after care with the basic cream. The content of lipids in the SC increases significantly by 31% after basic cream treatment, whereas they are significantly increased by 85% after application of the lipid foam cream. The local SCORAD improved for both treatments to about the same extent, and no significant results could be shown for TEWL and skin hydration. CONCLUSION: In subjects with mild atopic eczema, the lipid foam cream leads to a measurable recovery of the skin barrier which is much more pronounced in comparison to the basic cream.

[Viral exanthems in children]. / Virale Exantheme im Kindesalter.

Viral and paraviral exanthems are the most common exanthems in children and are often the reason for a medical evaluation, especially in pediatric primary care and emergency rooms. Familiarity with the various eruptions is important for early diagnosis and patient management as well as minimizing the risk of infection. In this review, we present the newly described entities reactive infectious mucocutaneous eruptions (RIME) and the pediatric inflammatory multisystem syndrome (PIMS). In addition, atypical manifestations of Gianotti-Crosti syndrome and hand, foot, and mouth disease are discussed.

The role of the skin microbiome in atopic dermatitis - correlations and consequences.

The physical barrier function of the skin is significantly supported by the (epi-)dermal immune system and the skin's own microbiome. Atopic dermatitis is characterized by an imbalance of all these three factors. The skin microbiome establishes itself immediately after birth and plays an important role in the development and maintenance of immune homeostasis. The clinical picture of atopic dermatitis shows, among other things, changes in the skin microbiome. Particularly during an acute phase, a strongly reduced bacterial diversity as well as the dominance of a single pathogen, Staphylococcus aureus, is observed. Staphylococcus aureus exacerbates the inflammatory process; furthermore, the bacteria produce proteases and toxins that further weaken the already severely compromised barrier function of the skin of patients with atopic dermatitis. However, knowledge of dermal dysbiosis also yields new treatment options for the therapy of the disease. In particular, the application of active bacteria represents a direct influence on the skin microbiome. Results of initial clinical studies on various approaches demonstrate promising results; this article provides an overview of work in this area.

Treatment Update of Port-Wine Stain: A Narrative Review.

BACKGROUND: Port-wine stain (PWS) is a congenital vascular malformation affecting 0.3–0.5% of normal population. These characteristic lesions arise due to the interplay of vascular, neural, and genetic factors. Treatment options include lasers, cosmetic tattooing, electrotherapy, cryosurgery, derma-abrasion, and skin grafting; however, none of these treatment alternatives appears to be satisfactory and is unable to provide consistent, satisfactory responses or even complete cures. Currently, laser is the treatment of choice, as it is comparatively safe and more effective than other procedures. The most commonly used modality is pulsed dye laser (PDL). The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) to January 2020 and reference lists of respective articles. Only articles published in English language were included. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5005.

Acral manifestations associated with infection.

Acral lesions are well-known physical findings in various infectious disorders. Although they are often overlooked, they can be the key to the diagnosis of the underlying disease. Considering this, we present an overview of various infectious causes of acral lesions in childhood. In addition, we discuss their characteristic presentation, evolution, and appropriate treatment. To our knowledge, this is the first review covering viral, bacterial and mycotic causes.

Update "Systemic treatment of atopic dermatitis" of the S2k-guideline on atopic dermatitis.

This guideline is an update from August 2020 the S2k-guideline "Atopic dermatitis" published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.

No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis.

BACKGROUND: Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis. OBJECTIVE: To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks. METHODS: Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries. RESULTS: There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred. LIMITATIONS: Observational prospective cohort study. CONCLUSION: The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.

Uncommon presentation of pigmented paraungual basal cell carcinoma on the first toe treated with total excision.

Basal cell carcinomas (BCCs) are the most common types of skin neoplasm. The finger, toe, and nail unit are uncommon and rare locations of BCC. Only a few patients with foot BCC have been reported, and ungual BCC is even less frequent. We present a patient with a BCC on the left first toe. Clinically, it appeared as a brown-colored plaque with an irregular border on the nail fold and dorsum of the left thumb. Histopathological findings were consistent with the pigmented type of BCC. Surgical approach with subsequent full thickness mesh graft led to a complete remission. Follow-up at 10 months revealed a functionally and cosmetically acceptable outcome. The clinical presentation of nail unit BCC is variable, and nonspecific manifestations occur more frequently. Our case stated the necessity of histopathologic examination in ulcerous lesions resistant to topical treatment.

Allergic contact dermatitis in patients with frontal fibrosing alopecia: An international multi-center study.

Frontal fibrosing alopecia (FFA) mainly affects the anterior hairline and eyebrows and its etiology and associated factors remain obscure. The aim of this study was to evaluate the allergic contact dermatitis with patch test in patients with FFA. In this prospective study, 20 patients with FFA and 24 age and sex-matched healthy individuals were evaluated with patch testing. Diagnosis was made histologically, clinically and based on dermoscopic findings. Demographic data, age of onset, disease duration and FFA severity index are evaluated in all patients. Positive patch test reaction to one or more allergen was observed in 65% of patients while it was 37.5% in control group (P = .003). There was a significant difference between age (P = .006) and positive patch test results. No statistical significant difference was observed in the results of patch testing and disease duration (P = .519), menopausal status (P = .085), and FFA severity index (P = .573). Our findings suggest an association between FFA and allergic contact dermatitis. The utility of patch testing in FFA patients can explore the role of allergic etiology and may have an enormous impact on the diagnostic potential and quality of life of these patients.

The OX40 Axis is Associated with Both Systemic and Local Involvement in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, or chronically relapsing, inflammatory skin disease associated with asthma and allergic rhinitis, and is dominated by Th2 cells. The co-stimulatory T-cell receptor OX40 and its ligand, OX40L, play a central role in the pathogenesis of AD, as their interactions are crucial for the generation of TH2 memory cells. Using enzyme-linked immunoassay (ELISA) and flow cytometry on blood samples from patients with AD and healthy volunteers, this study shows that the serum level of soluble (s) OX40 is decreased in patients with AD, and the expression of OX40 by activated skin-homing CD4+ T cells is increased. This study further shows, using immunofluorescence on skin biopsies, that OX40+ and OX40L+ cells are co-located within the dermis, indicating local activity of OX40/OX40L. Serum levels of sOX40 were associated with atopic diseases and, together, these results support that the OX40 system is important for chronic inflammation in AD skin.