Transient infantile lingual leukoplakia: An underrecognized cause of white tongues in infancy.

We have observed a distinct phenomenon of transient oral lingual leukoplakia in infancy and report 22 healthy infants with gray-white plaques on the dorsal tongue with sparing of the tip from four medical centers in three countries. The onset of the eruption ranged from 1 week to 7 months of life and resolved in 19 patients (86%, with 3 patients lost to follow-up). None of the eight patients examined at 1 year of age had residual findings. We believe this is a common entity that can be distinguished from oral candidiasis on clinical and/or laboratory examination and name this entity "transient infantile lingual leukoplakia."

Psychometric Properties of the Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa patient score (iscorEB-p): a patient-reported outcome measure.

BACKGROUND: In contrast to clinical diagnosis via external examination, patient-related outcome measures (PROMs) allow access to patients' internal perceptions. In the case of epidermolysis bullosa (EB) - a rare disease characterized by a wide variety of symptoms and individual disease courses - it is important to integrate the patient's perspective into diagnostic processes. The Instrument for Scoring Clinical Outcomes of Research for EB (iscorEB) is an EB-specific measurement tool, combining a clinician score (iscorEB-c) and a patient questionnaire (iscorEB-p). OBJECTIVES: The aim of this study is to establish the iscorEB-p as an independent PROM tool by exploring its psychometric properties. METHODS: Sample-based psychometric testing and evaluation were performed on data collected via a multinational online cross-sectional study. RESULTS: Data analysis was performed with n = 95 participants across all EB types. The reliability and internal consistency of the iscorEB-p was excellent (α = 0.90). Principal component analysis with a varimax rotation resulted in a two-factor solution, explaining 55.6% of the total variance, with the distinct factors 'everyday life functioning' and 'specific EB symptoms'. Convergent validity was shown by high correlations to the Satisfaction With Life Scale (r = -0.52, P < 0.001), the Quality of Life in Epidermolysis Bullosa questionnaire (r = 0.72, P < 0.001) and the Epidermolysis Bullosa Family Burden of Disease questionnaire (r = -0.73, P < 0.001). CONCLUSIONS: The iscorEB-p is a reliable and valid instrument to assess patient-reported health status of people with EB.

Epidermolysis bullosa (EB) is a rare chronic condition characterized by fragility of the skin. Even minimal friction leads to the formation of blisters and wounds. People with EB are often called 'butterfly children' because their skin is as fragile as a butterfly's wings. EB affects about 500,000 people worldwide and there is currently no cure. As EB is a chronic disease, it is associated with constantly changing periods of better and worse health. To monitor the impact of EB on patients, it is important to record a range of relevant possible symptoms using a valid questionnaire. The Instrument for Scoring Clinical Outcomes of Research for EB (iscorEB) is such a measurement tool, combining a clinician score (iscorEB-c) and a patient questionnaire (iscorEB-p). However, until now, the patient questionnaire could only be used in addition to the clinician score. In this study, we aimed to emphasize patients' perspectives and strengthen the patient questionnaire so that it can be used independently. The questionnaire can support patients to assess even minimal changes over a period of the last 4 weeks. We collected data from 95 patients with EB from all over the world. Through statistical analysis, we found that the questionnaire is a useful new standalone instrument to obtain a patient-based view of their health status. Overall, our study findings suggest that the iscorEB-p is a reliable and valid tool and could be usefully applied in clinical practice, as an addition to quality-of-service monitoring and in future research studies.

Corticosteroid fear in parents of children with atopic dermatitis.

Background: Topical corticosteroids (TCS) are the mainstay of therapy for paediatric atopic dermatitis (AD). The use of TCS is often met with fear by parents. Assessing this parental TCS fear in clinical practice is still lacking. Aim: The aim was to assess parental fear and beliefs about TCS. Furthermore, we evaluated the quality of life (QoL) of the family and the disease severity of affected children. Methods: We conducted an observational study with a cross-sectional design. Inclusion criteria were children aged 0 to 5 years with a diagnosis of AD and outpatient treatment. The outcome measures were parental fears and beliefs about TCS, assessed with the "Topical Corticosteroid Phobia Score" (TOPICOP), parental QoL evaluated with the "Family Dermatology Life Quality Index", and disease severity, assessed with the "Scoring atopic dermatitis" (SCORAD). Descriptive statistic was used to analyse the data. Results: The current study found that in 40 affected children, 25 (62.5%), suffered from mild AD, 12 (30%) children had moderate AD, and 3 (7.5%) children had severe AD. TCS fear among parents was notable (mean TOPICOP score 18.1, standard deviation (SD) 7.1). The QoL was moderately affected (mean FDLQI score 6.5, SD 2.8). Conclusions: Our study indicates that fear of TCS is prevalent. Furthermore, our data indicate that severity of TCS fear varies markedly between parents, ranging from parents with almost no fear to parents with high levels of fear. For effective education in clinical practice, the individual level of fear must be recognized and taken into account.

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.

Video-Based Education with Storytelling Reduces Parents' Fear of Topical Corticosteroid Use in Children with Atopic Dermatitis: A Randomized Controlled Trial (The EduDerm Study Part II).

OBJECTIVE: To investigate the efficacy of educational videos using storytelling to reduce parents' fear of topical corticosteroid (TCS) use in children affected by atopic dermatitis (AD). METHODS: Children aged 0 to 5 years who had AD were included. The primary outcome measures were parental fear of TCSs, as determined by Topical Corticosteroid Phobia score, and quality of life according to the Family Dermatology Life Quality Index. Disease severity, assessed by the Scoring Atopic Dermatitis tool, served as a secondary outcome measure. Assessments were performed at baseline (T1), 1 to 4 weeks later (T2), and at 3-month follow-up (T3). The intervention group was exposed to the videos between baseline and T2. RESULTS: Forty patients were recruited: 21 in the intervention group and 19 in the control group. A statistically significant decrease in parental TCS fear was found in the intervention group at T2 after video education as compared with the control group (P < .0001); this was maintained at T3 (P = .001). The groups did not significantly differ in FDLQI or SCORAD scores at any point. CONCLUSIONS: These findings suggest that video education based on the method of storytelling is effective in reducing TCS fear. Although the education did not impact disease severity or quality of life, effectively reducing TCS fear remains an important aspect for AD management.

Consensus guidelines for diagnosis and management of anemia in epidermolysis bullosa.

BACKGROUND: Anemia is a common complication of severe forms of epidermolysis bullosa (EB). To date, there are no guidelines outlining best clinical practices to manage anemia in the EB population. The objective of this manuscript is to present the first consensus guidelines for the diagnosis and management of anemia in EB. RESULTS: Due to the lack of high-quality evidence, a consensus methodology was followed. An initial survey exploring patient preferences, concerns and symptoms related to anemia was sent to EB patients and their family members. A second survey was distributed to EB experts and focused on screening, diagnosis, monitoring and management of anemia in the different types of EB. Information from these surveys was collated and used by the panel to generate 26 consensus statements. Consensus statements were sent to healthcare providers that care for EB patients through EB-Clinet. Statements that received more than 70% approval (completely agree/agree) were adopted. CONCLUSIONS: The end result was a series of 6 recommendations which include 20 statements that will help guide management of anemia in EB patients. In patients with moderate to severe forms of EB, the minimum desirable level of Hb is 100 g/L. Treatment should be individualized. Dietary measures should be offered as part of management of anemia in all EB patients, oral iron supplementation should be used for mild anemia; while iron infusion is reserved for moderate to severe anemia, if Hb levels of > 80-100 g/L (8-10 g/dL) and symptomatic; and transfusion should be administered if Hb is < 80 g/L (8 g/dL) in adults and < 60 g/L (6 g/dL) in children.

Kidney-Urinary Tract Involvement in Intermediate Junctional Epidermolysis Bullosa.

Importance: Kidney-urinary tract (KUT) manifestations cause substantial morbidity in patients with junctional epidermolysis bullosa (JEB), but the spectrum of disease severity and the clinical course have been poorly characterized. Objective: To examine in a large cohort of patients with intermediate JEB the KUT manifestations, diagnostic and therapeutic procedures, genotype-phenotype correlations, and outcomes as a basis for recommendations, prognosis, and management. Design, Setting, and Participants: In this retrospective, longitudinal case series study, 99 patients with a diagnosis of JEB based on clinical and genetic findings who were treated in a single dermatology department in Freiburg, Germany, were assessed during an 18-year period (January 1, 2003, to December 31, 2021). Clinical, laboratory, and molecular genetic parameters were extracted from patients' medical records. Main Outcomes and Measures: Clinical characteristics, natural history, management of KUT manifestations, and genotype-phenotype correlations of intermediate JEB. Results: Of the 183 patients with JEB, 99 (54%) had intermediate JEB and were included in this cohort. The cohort included 49 female patients and 50 male patients. None of 49 female patients and 15 of 50 male patients had KUT involvement affecting different levels of the urinary tract, resulting in a prevalence of 30% for males; thus, the overall prevalence was 15%. The mean age at onset of KUT manifestations was 6.9 years (range, first weeks of life to 20 years; age was not available for 1 patient). Median follow-up after diagnosis of KUT involvement was 13 years (range, 3 months to 54 years). Patients with laminin 332 or integrin ß4 deficiency had at least 1 missense or splice site genetic variant, leading to residual expression of laminin 332 or integrin α6ß4, respectively. Severity of KUT complications did not correlate with the extent of skin involvement but with the affected protein. Conclusions and Relevance: Physicians and patients with JEB should be aware of the risk for KUT involvement in intermediate JEB, and physicians should apply interdisciplinary and individualized diagnostic and therapeutic procedures for management of these complications. Because this disorder is so rare, multicenter studies are required to make general recommendations.

Molecular and Clinical Outcomes After Intravenous Gentamicin Treatment for Patients With Junctional Epidermolysis Bullosa Caused by Nonsense Variants.

IMPORTANCE: Junctional epidermolysis bullosa (JEB) is an incurable blistering skin disorder with high infant mortality often caused by nonsense variants in the genes that encode laminin 332. OBJECTIVE: To evaluate the safety and outcomes following intravenous gentamicin readthrough therapy and subsequent laminin 332 expression in patients with JEB. DESIGN, SETTING, AND PARTICIPANTS: This open-label, pilot nonrandomized clinical trial assessed 1 course of low- or high-dose intravenous gentamicin, including follow-up at 30 and 90 days after treatment. Five pediatric patients with JEB (2 with intermediate JEB and 3 with severe JEB) and confirmed nonsense variants in LAMA3 or LAMB3 in 1 or 2 alleles and decreased expression of laminin 332 at the dermal-epidermal junction of their skin participated in the study, which was performed at a single institution in collaboration with physicians and home infusion services near the patients from April 1, 2019, to February 28, 2021, with follow-up until May 31, 2021. INTERVENTIONS: Three patients received gentamicin at 7.5 mg/kg daily for 14 days, and 2 patients received gentamicin at 10 mg/kg daily for 24 days. MAIN OUTCOMES AND MEASURES: Primary outcomes were change in expression of laminin 332 in patients' skin and assessments for safety (ototoxic effects, nephrotoxic effects, and autoimmune response). Secondary outcomes included wound healing in monitored wounds and Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) score. RESULTS: After gentamicin treatment, all 5 patients (age range, 3 months to 10 years, 4 [80%] female) exhibited increased laminin 332 in the dermal-epidermal junction. By 1 month, 7 of 9 wounds in patients receiving low-dose intravenous gentamicin and all wounds in patients receiving high-dose intravenous gentamicin exhibited at least 50% wound closure. By 3 months, 8 of 9 wounds in patients receiving low-dose gentamicin and all wounds in patients receiving high-dose intravenous gentamicin exhibited greater than 85% closure. All 3 patients who were evaluated with EBDASI showed a decrease in total activity scores that met minimal clinically important differences 1 month after treatment. All 5 patients completed the study, and no ototoxic effects, nephrotoxic effects, or anti-laminin 332 antibodies were detected. CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, intravenous gentamicin therapy was associated with induced readthrough of nonsense variants in patients with JEB, restored functional laminin 332 in their skin, and wound closure during the 3-month study period. Although long-term safety and efficacy requires further evaluation, a single cycle of intravenous gentamicin may be a safe and readily available therapy in the short term for this population of patients with JEB. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03526159 and NCT04140786.

Phänotypisches und genetisches Spektrum von Incontinentia pigmenti - eine große Fallserie.

HINTERGRUND: Incontinentia pigmenti ist eine seltene X-chromosomal dominant vererbte Systemerkrankung, die vor allem die Haut, aber auch andere neuroektodermale Gewebe wie Zähne, Haare, Augen und das zentrale Nervensystem betrifft. PATIENTEN UND METHODIK: Diese multizentrische Fallserienstudie wurde an drei europäischen Hautkliniken durchgeführt und umfasste 30 Patienten mit Incontinentia pigmenti. Zwanzig Patienten wurden klinisch und genetisch untersucht, weitere zehn nur genetisch. ERGEBNISSE: Die Studie umfasste 28 Frauen und zwei Männer mit einem medianen Alter von drei Jahren. Kutane Manifestationen zeigten sich bei allen 20 Patienten mit klinischen Daten. Stadium I wurde in 90 % dieser Patienten beobachtet. Stadium IV wurde bereits im Alter von einem Jahr beobachtet. Zahn- (81 %), Haar- (78 %) und neurologische Anomalien (53 %) waren häufiger als in bisherigen Berichten. Vierzehn Hautbiopsien zeigten typische Merkmale des entsprechenden Stadiums. Genetische Tests wurden bei 24 Patienten durchgeführt, von denen 14 die häufige Exon 4-10-Deletion und sieben andere pathogene Varianten aufwiesen, darunter drei unveröffentlichte Mutationen. In drei weiteren Fällen wurden keine genetischen Veränderungen gefunden. SCHLUSSFOLGERUNGEN: In dieser Studie reichte der Phänotyp von lediglich subtil ausgeprägter Hautbeteiligung bis hin zu schweren Multisystemerkrankungen. Die extrakutane Beteiligung sollte zum Zeitpunkt der Diagnose und in regelmäßigen Abständen evaluiert werden, da sich einige Manifestationen erst mit der Zeit entwickeln. SUMMARY: Background and objectives Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system. Patients and methods This multicenter case series study was conducted at three European departments of Dermatology including 30 patients with incontinentia pigmenti. Twenty patients were evaluated clinically and genetically, another ten only genetically. Results The study included 28 females and two males with a median age of three years. Cutaneous manifestations were present in all 20 patients with clinical data. Stage I was observed in 90 % of those patients. Stage IV was observed as early as one year of age. Dental (81 %), hair (78 %) and neurological anomalies (53 %) were more frequent than previously reported. Fourteen skin biopsies showed typical features of the corresponding stage. Genetic testing of 24 patients revealed the common exon 4-10 deletion in 14 cases and seven other pathogenic variants, including three unpublished mutations. In another three cases, no genetic alterations were found. Conclusions In this study, the phenotype ranged from only subtle cutaneous involvement to severe multisystemic disorders. Extracutaneous involvement should be evaluated at the time of diagnosis and in regular intervals, as some manifestations may develop over time.

Phenotypic and genetic spectrum of incontinentia pigmenti - a large case series.

BACKGROUND AND OBJECTIVES: Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system. PATIENTS AND METHODS: This multicenter case series study was conducted at three European departments of Dermatology including 30 patients with incontinentia pigmenti. Twenty patients were evaluated clinically and genetically, another ten only genetically. RESULTS: The study included 28 females and two males with a median age of three years. Cutaneous manifestations were present in all 20 patients with clinical data. Stage I was observed in 90 % of those patients. Stage IV was observed as early as one year of age. Dental (81 %), hair (78 %) and neurological anomalies (53 %) were more frequent than previously reported. Fourteen skin biopsies showed typical features of the corresponding stage. Genetic testing of 24 patients revealed the common exon 4-10 deletion in 14 cases and seven other pathogenic variants, including three unpublished mutations. In another three cases, no genetic alterations were found. CONCLUSIONS: In this study, the phenotype ranged from only subtle cutaneous involvement to severe multisystemic disorders. Extracutaneous involvement should be evaluated at the time of diagnosis and in regular intervals, as some manifestations may develop over time.

Gianotti-Crosti Syndrom-ähnliche Reaktion bei Molluscum contagiosum -Klinische Charakteristika und Therapieansprechen.

HINTERGRUND UND ZIELE: Molluscum contagiosum (MC) ist eine häufige Virusinfektion der Haut. Bei gewissen Patienten mit MC kann eine Hypersensitivitätsreaktion ähnlich des Gianotti-Crosti-Syndroms beobachtet werden. Diese wird Gianotti-Crosti syndrome-like reaction (GCLR, Gianotti-Crosti-Syndrom-ähnliche Reaktion) genannt. Wir berichten über eine Kohorte von Patienten mit GCLR, um deren klinische Präsentation und Verlauf besser zu charakterisieren. PATIENTEN UND METHODIK: Retrospektive Studie mit Einschluss aller Kinder, welche sich zwischen 2015 und 2020 mit einer GCLR in unserem pädiatrischen Hautzentrum vorgestellt haben. RESULTATE: 26 Patienten (14 männlich) mit einem medianen Alter von 6.5 (3-11,3) Jahren wurden eingeschlossen. Die GCLR hat bei allen Patienten die Streckseiten der Extremitäten betroffen. Bei Kindern mit ausgedehntem Ausschlag waren bei 7 (27 %) auch der Stamm und bei 6 (23 %) auch das Gesicht mitbetroffen. Der Befall der Haut über der Achillessehne war ein auffälliges Phänomen bei 4 (15 %) Kindern. Juckreiz war das vorherrschende Symptom bei 20 (77 %) Patienten. Der Ausschlag hat gut auf die Behandlung mit topischen und/oder systemischen Kortikosteroiden angesprochen und ist innerhalb von 4 Wochen abgeklungen. Bei allen Patienten folgte innerhalb von 9 (4-24) Wochen nach der GCLR die Abheilung der MC. SCHLUSSFOLGERUNGEN: GCLR ist ein charakteristischer, akuter, ausgedehnter, juckender papulöser Ausschlag und führt häufig zu Notfallkonsultationen und Verunsicherung der betroffenen Patienten. Die GCLR spricht gut auf eine Behandlung mit Kortikosteroiden an, hat einen gutartigen Verlauf und geht der Abheilung der MC voraus.

Gianotti-Crosti syndrome-like reaction to molluscum contagiosum-Clinical characteristics and response to treatment.

BACKGROUND AND OBJECTIVES: Molluscum contagiosum (MC) is a common viral infection. Hypersensitivity reactions reminiscent of Gianotti-Crosti syndrome, termed Gianotti-Crosti syndrome-like reaction (GCLR), have been reported in a subset of patients. We report a series of patients with GCLR, better delineating its clinical presentation and course. PATIENTS AND METHODS: Retrospective chart review of all children presenting with GCLR at our Pediatric Skin Center between 2015 and 2020. RESULTS: 26 children (14 boys) with a median age of 6.5 (3-11.3) years were included. GCLR involved the extensor surfaces of the extremities in all patients. More widespread eruptions also affected the trunk and face in 7 (27 %) and 6 (23 %) children respectively. Involvement of the skin overlying the Achilles tendons was a new finding in 4 (15 %) children. Itch was the predominant symptom in 20 (77 %) patients. The rash responded to topical and/or systemic corticosteroids and resolved within four weeks. GCLR was followed by clearance of MC in all patients within 9 (4-24) weeks. CONCLUSIONS: GCLR is a characteristic acute, wide-spread, pruritic papular eruption, which often leads to emergency consultations and anxiety in affected patients. GCLR responds well to corticosteroid treatment, has a benign course, and heralds the healing of MC.

Subcutaneous fat necrosis associated with hypercalcemia in neonates with neonatal encephalopathy treated with therapeutic hypothermia.

Subcutaneous fat necrosis of the newborn (SFNN) is a rare, self-resolving panniculitis. The onset of skins lesions occurs within the first week of life, with a median age of onset around day 6 of life (range 1-70). About 50% of neonates with SFNN will develop hypercalcemia in the first month though some present later. Typically, SFNN develops prior to hypercalcemia. Only half of the neonates have classic symptoms of hypercalcemia; routine screening for hypercalcemia is recommended for neonates with SFNN or at-risk. The mechanism for hypercalcemia is usually aberrant 1,25-dihydroxyvitamin D synthesis in the necrotic tissue increasing intestinal absorption of calcium. Prompt recognition and treatment is required, often in hospital. Treatment options are low calcium-vitamin D formula or sometimes intravenous bisphosphonates. Regular monitoring post-intervention is required when normalizing the diet. Outcomes are good with routine surveillance and interventions. A multidisciplinary team approach (neonatologists, pediatric endocrinologists and nephrologists, dieticians) is optimal.

Sleep behavior of infants with infantile hemangioma treated with propranolol-a cohort study.

Sleep problems are frequently reported in infants treated with propranolol for infantile hemangiomas, possibly serving as a marker for a negative impact on central nervous system function. In this cohort study, we objectively investigate the sleep behavior of infants with infantile hemangiomas on propranolol compared to a healthy, untreated control group. Sleep of propranolol-treated infants and controls was investigated using ankle actigraphy and a 24-h diary for 7-10 days at ages 3 and 6 months. The main outcome measures were the Number of Nighttime Awakenings and Sleep Efficiency. The main secondary outcome measures included 24-hour Total Sleep, daytime sleep behavior, and parent-rated infant sleep quality and behavioral development based on the Brief Infant Sleep Questionnaire (BISQ) and the age-appropriate Ages-and-Stages Questionnaire (ASQ), respectively. Fifty-four term-born infants were included in each cohort. No group difference in any investigated parameter was seen at age 3 months. At age 6 months, the propranolol group exhibited a decrease in Sleep Efficiency and a trend towards an increased Number of Nighttime Awakenings compared to the control group. Treated infants at 6 months also had shorter daytime waking periods. 24-hour Total Sleep was unaffected by propranolol. No negative impact of propranolol on subjective sleep quality and behavioral development was noted.Conclusion: Propranolol exerts a measurable yet mild impact on objectively assessed infants' sleep measures. Behavioral developmental scores were unaffected. Our results support propranolol as first-line therapy for complicated infantile hemangiomas. What is Known: • Sleep disorders are frequently reported in infants with infantile hemangiomas treated with propranolol and often lead to treatment discontinuation. • Investigations of the sleep pattern in this patient group using objective measures are lacking. What is New: • The sleep pattern of propranolol-treated infants is assessed using actigraphy and a 24-h sleep diary and compared to healthy, untreated controls. • Propranolol leads to a decreased sleep efficiency at night and an increased demand of daytime sleep, yet effects are mild overall.

Case Report: Pansclerotic Morphea-Clinical Features, Differential Diagnoses and Modern Treatment Concepts.

Pansclerotic morphea (PSM) is a rare skin disease characterized by progressive stiffening of the skin with or without the typical superficial skin changes usually seen in morphea (localized scleroderma). Standard therapy, consisting of a combination of systemic glucocorticoids and methotrexate or mycophenolate mofetil, does rarely stop disease progression, which may lead to severe cutaneous sclerosis and secondary contractures. Little is known about the efficacy of newer biologicals such as abatacept, a fusion protein antibody against CTLA-4, or tocilizumab, a fully humanized IL-6R antibody, in the treatment of this pathology. We present the case of an 8 years old girl with an unusual, progressive stiffening of the skin, which was eventually diagnosed as pansclerotic morphea. A treatment with systemic glucocorticoids and methotrexate combined with tocilizumab led to a good clinical response within 2 months after initiation. In this paper, we discuss differential diagnoses to be considered and this new promising treatment option based on a case review of the literature.

Negative pressure wound treatment in a neonate with epidermolysis bullosa simplex severe generalized: A case report.

Negative pressure wound treatment (NPWT) is very useful for the treatment of chronic or deep wounds and in the setting of skin grafting. Due to the need for adhesive dressings, this treatment is rarely attempted in patients with skin fragility secondary to hereditary epidermolysis bullosa (EB). We present a neonate with EB simplex, severe generalized in a critical clinical state where NPWT was successfully applied and describe the measures taken to avoid any further skin damage. This case is of clinical importance to physicians and health care staff treating patients with this rare disease where additional therapeutic measures for the treatment of chronic wounds are scarce.

Secukinumab Therapy for Netherton Syndrome.

Importance: Netherton syndrome (NS) is a rare, severe genetic disorder of cornification with high morbidity. Treatment for NS has been notoriously difficult. Recent studies showed an upregulated helper T cell (TH) 17/interleukin 23 (IL-23) pathway in NS, suggesting the possibility of treatment strategies that target IL-17. Objective: To evaluate the clinical response of NS to treatment with the IL-17 antagonist secukinumab. Design, Setting, and Participants: This case series study reports the experience of compassionate use therapy with secukinumab in 4 patients with severe NS, including 2 children, from December 1, 2018, to December 1, 2019, with 3 patients still undergoing treatment at the time of final analysis. Data were analyzed from December 1, 2018, to December 1, 2019. Main Outcomes and Measures: Expression of IL-17 in the skin was evaluated by immunohistochemical analysis, and serum cytokine concentrations were measured using a commercially available assay. Treatment response was assessed using the Ichthyosis Area and Severity Index (IASI) total score, including measures of erythema and scaling, the Dermatology Life Quality Index (DLQI), and the 5-D itch scale. Results: In all 4 patients (age range, 9-27 years; 3 male and 1 female), immunostaining with an IL-17A antibody showed an increased number of positive cells in lesional skin. Cytokine assessment in serum samples revealed increased levels of CCL20. Treatment duration with secukinumab was 3 to 12 months at the time of this report. After 3 months of therapy, IASI scores were reduced by 44% to 88%, DLQI scores were reduced by 40% to 76%, and 5-D itch scale scores were reduced by 27% to 62%. This outcome was sustained at the 6-month follow-up. Two patients with an erythrodermic phenotype showed marked improvement of all parameters. A refractory palmoplantar eczematous eruption occurred in 2 patients, and a candidal nail infection developed in 2 patients. No severe adverse events were reported. Conclusions and Relevance: This initial case series reporting the use of anti-IL-17 therapy in NS demonstrated marked cutaneous improvement, particularly in 2 pediatric patients with erythrodermic phenotypes. Further studies are needed to evaluate the long-term benefit of this potential treatment modality.