Long-term follow-up outcomes of laser-treated port wine stain patients: A double-blinded retrospective study.

BACKGROUND: Port wine stains (PWS) can be effectively treated with lasers. However, complete clearance is rarely observed, and data from long-term studies are limited. The study aimed to evaluate the efficacy and complications of long-term laser treatment in patients with PWS. METHODS: We performed a 25-year double-blinded retrospective chart review of patients diagnosed with PWS who underwent laser treatment at Ramathibodi Hospital, Thailand, between June 1995 and June 2021. The scores for improvement and color were independently evaluated by two dermatologists. RESULTS: A total of 129 patients were included. Most patients were male (70.54%). A total of 4141 laser treatment sessions were reviewed, with a median of 49 (interquartile range, 27-66) sessions per patient. A total of 1070 photographic records were reviewed. Overall, 53% of the patients achieved statistically significant (50%) improvement, after six treatment sessions. However, none of these patients achieved complete clearance. Due to the nonuniform treatments, we could not evaluate the efficacy of each laser type. However, this study illustrates the outcomes of a real-world setting in which various laser types were selected specifically for each patient to obtain the best result. CONCLUSIONS: Vascular lasers are a promising treatment for PWS. Although laser treatment is applicable to most patients, multiple treatment sessions are required to achieve excellent results.

Epidermolysis Bullosa With Congenital Absence of Skin: Congenital Corneal Cloudiness and Esophagogastric Obstruction Including Extended Genotypic Spectrum of PLEC, LAMC2, ITGB4 and COL7A1.

Epidermolysis bullosa (EB) is a rare and genetically heterogeneous disorder characterized by skin fragility and blister formation occurring spontaneously or after minor trauma. EB is accompanied by congenital absence of skin (EB with CAS) in some patients. Pathogenic variants of COL7A1 are responsible for EB with CAS in the vast majority of cases. Type and subtype diagnosis of EB with CAS generally requires specific immunohistological examinations that are not widely available plus targeted gene analysis. The present study aimed to determine the clinical features of five patients affected by EB with CAS and to identify the underlying genetic defects using whole exome sequencing (WES) followed by focused analysis of the target genes. Four patients had generalized skin involvement and one had localized defects. Two patients exhibited extremely severe skin manifestations and congenital cloudy cornea along with pyloric atresia, and one had partial esophagogastric obstruction and anuria due to vesicoureteric obstruction. In the WES analysis, the average coverage of the target exons was 99.05% (726 of 733 exons), with a range of 96.4-100% for individual genes. We identified four novel and two known pathogenic/likely pathogenic variants of five distinct genes in the examined families: PLEC:c.2536G > T (p.Glu846Ter); LAMC2:c.3385C > T (p.Arg1129Ter); KRT5:c.429G > A (p.Glu477Lys); ITGB4:c.794dupC (p.Ala266SerfsTer5); COL7A1:c.5440C > T (p.Arg1814Cys); and COL7A1:c.6103delG. All alleles were inherited from the parents, except for the KRT5 variant as a de novo finding. The findings reveal extremely rare phenotypes found in EB with CAS, namely congenital cloudy cornea, esophagogastric obstruction, and anuria, and extend the genotypic spectrum of EB-related genes. The data confirm that WES provides very high coverage of coding exons/genes and support its use as a reasonable alternative method for diagnosis of EB. The present data from an underrepresented population in Southeast Asia could further broaden the knowledge and research on EB.

Transcriptomic Repositioning Analysis Identifies mTOR Inhibitor as Potential Therapy for Epidermolysis Bullosa Simplex.

Expression-based systematic drug repositioning has been explored to predict novel treatments for a number of skin disorders. In this study, we utilize this approach to identify, to our knowledge, previously unreported therapies for epidermolysis bullosa simplex (EBS). RNA sequencing analysis was performed on skin biopsies of acute blisters (<1 week old) (n = 9) and nonblistered epidermis (n = 11) obtained from 11 patients with EBS. Transcriptomic analysis of blistered epidermis in patients with EBS revealed a set of 1,276 genes dysregulated in EBS blisters. The IL-6, IL-8, and IL-10 pathways were upregulated in the epidermis from EBS. Consistent with this, predicted upstream regulators included TNF-α, IL-1ß, IL-2, IL-6, phosphatidylinositol 3-kinase, and mTOR. The 1,276 gene EBS blister signature was integrated with molecular signatures from cell lines treated with 2,423 drugs using the Connectivity Map CLUE platform. The mTOR inhibitors and phosphatidylinositol 3-kinase inhibitors most opposed the EBS signature. To determine whether mTOR inhibitors could be used clinically in EBS, we conducted an independent pilot study of two patients with EBS treated with topical sirolimus for painful plantar keratoderma due to chronic blistering. Both individuals experienced marked clinical improvement and a notable reduction of keratoderma. In summary, a computational drug repositioning analysis successfully identified, to our knowledge, previously unreported targets in the treatment of EBS.

Successful Medical Management of Life-threatening Hepatic Hemangioma in Neonates.

Hepatic hemangioma (HH) is a common asymptomatic, self-limiting benign vascular tumor of the liver in neonates. Although complicated HHs are rare, they have significant risks of morbidity and mortality, especially during the perinatal period. Because of the high risks of complications from surgical interventions, there is an unmet need for effective medical therapy. We report 2 neonates with life-threatening HH who were evaluated for a liver transplant before being treated successfully with combined medical therapy, which included sirolimus, corticosteroids, and propranolol.

Successful treatment of spindle cell hemangiomas in a patient with Maffucci syndrome and review of literatures.

Maffucci syndrome is a rare genetic disease due to somatic mutation of IDH1 gene. Currently there is no medical treatment available for spindle cell hemangioma associated with this disorder. Here we report successful management of these hemangiomas using sirolimus in combination with surgery.

Alterations of the MEK/ERK, BMP, and Wnt/ß-catenin pathways detected in the blood of individuals with lymphatic malformations.

Lymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/ß-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development.

Cutaneous manifestations of nutritional deficiency.

PURPOSE OF REVIEW: Childhood malnutrition is a major global health issue. It is often thought of as a developing world problem and therefore, underdiagnosed or misdiagnosed in developed countries. The delay in diagnosis and treatment can lead to increased morbidity and mortality. Cutaneous manifestations are often the initial presenting signs of nutritional deficiency. Early recognition is essential in timely initiation of the necessary interventions. This article will review pertinent cutaneous findings and systemic manifestations associated with common nutritional deficiencies. RECENT FINDINGS: Malnutrition has historically been associated with poverty in developing countries. However, recent literatures suggest that the incidence of nutritional deficiencies continuous to rise among infants from developed countries, as a result of dietary restrictions because of perceived food allergies or intolerance. It is also an emerging finding in children with complicated medical problems. SUMMARY: It is very important to raise awareness about cutaneous manifestations of nutritional deficiency as early and appropriate treatment results in excellent prognosis.

Randomized, controlled trial split-faced study of 595-nm pulsed dye laser in the treatment of acne vulgaris and acne erythema in adolescents and early adulthood.

The high prevalence of acne vulgaris in teenagers has increased comorbidities. Lasers offer alternative options for acne treatment because they have rapid action, low systemic adverse effects, and do not require everyday treatment. To study the efficacy and patients' satisfaction of 595-nm pulse dye laser (PDL) treatment of acne vulgaris and acne erythema in adolescents and early adulthood, we designed a blocked-randomized, split-faced 595-nm PDL (fluence 8 J/cm3 pulse duration 10 ms, spot size 7 mm, 2 session every 2 weeks) study in patients with mild to moderate acne by comparing the laser-treated and non-treated side. The acne lesion counts, acne erythema grading, and acne severity grading were evaluated at baseline and 2, 4, and 8 weeks. Thirty patients were recruited. The results showed no statistically significant difference except the papule count at week 4 which was -1.828 on the treated side and 0.103 on the non-treated side of the face, P-value 0.0018. There was no statistically significant difference of acne severity grading and acne erythema grading between both sides of the face. The mean scores of patients' satisfaction on the laser-treated side were 75, 81, and 81%, respectively. The PDL treatment in this study reveals no significant improvement in acne therapy; however, the patients were satisfied with this laser treatment.

Nail Scabies: An Unusual Presentation Often Overlooked and Mistreated.

Nail scabies is an interesting clinical presentation of scabies. Although it is usually found concomitant with characteristic dermatologic manifestations, it may present as an isolated finding in the immunocompromised host. This condition is commonly mistaken with other diseases such as nail dystrophy, nail psoriasis and onychomycosis. We report two cases of unusual nail presentations that provide clues to diagnosis. Also, literature on unusual nail and dermatologic presentations was reviewed to recognize dermatologist consideration for appropriate treatment options.