Laser in surgical scar clearance: An update review.

AbstractScar formation is a consequence of wound healing that developed from damaged tissue either from physical injury or surgical incision. A hypertrophic scar develops due to an abnormal healing response to trauma. It might lead to serious functional and cosmetic disability. There are numerous methods mentioned in the literature to treat such scars but to date, no single method has been known to cure them. In this review, we focused on differences between various types of nonsurgical management of hypertrophic scar focusing on the indication, mechanism of action, and efficacy of the pulsed dye laser (PDL), fractional carbon dioxide laser (fCO2), Er‐YAG laser, and intense pulse light (IPL). The literature research included peer‐reviewed articles (clinical trials or scientific reviews) which were identified by searching electronic databases like PubMed till January 2021 and reference lists of respective articles. Only articles published in the English language were included

Further insights in trichothiodistrophy: a clinical, microscopic, and ultrastructural study of 20 cases and literature review

Background: Trichothiodistrophy (TTD) is a rare autosomal recessive condition that is characterized by a specific congenital hair shaft dysplasia caused by deficiency of sulfur associated with a wide spectrum of multisystem abnormalities. In this article, we study clinical, microscopic, and ultrastructural findings of 20 patients with TTD with the aim to add further insights regarding to this rare condition. Additionally, analyses of our results are compared with those extracted from the literature in order to enhance its comprehensibility. Materials and Methods: Twenty cases of TTD were included: 7 from Mexico and 14 from Spain. Clinical, microscopic, scanning electron microscopy (SEM) studies and X-ray microanalysis (XrMa) were carried out in all of them. Genetic studies were performed in all seven Mexican cases. Patients with xeroderma pigmentosum and xeroderma pigmentosum/TTD-complex were excluded. Results: Cuticular changes and longitudinal crests of the hair shaft were demonstrated. These crests were irregular, disorganized, following the hair longest axis. Hair shaft sulfur deficiency was disposed discontinuously and intermittently rather than uniformly. This severe decrease of sulfur contents was located close to the trichoschisis areas. Only five patients did not show related disturbances. Micro-dolichocephaly was observed in five cases and represented the most frequent facial dysmorphism found. It is also remarkable that all patients with urologic malformations also combined diverse neurologic disorders. Moreover, three Mexican sisters demonstrated the coexistence of scarce pubic vellus hair, developmental delay, onychodystrophy, and maxillar/mandibullar hypoplasia. Conclusions: TTD phenotype has greatly varied from very subtle forms to severe alterations such as neurologic abnormalities, blindness, lamellar ichthyosis and gonadal malformations. Herein, a multisystem study should be performed mandatorily in patients diagnosed with TTD

Mutations in the Cholesterol Transporter Gene ABCA5 Are Associated with Excessive Hair Overgrowth

Inherited hypertrichoses are rare syndromes characterized by excessive hair growth that does not result from androgen stimulation, and are often associated with additional congenital abnormalities. In this study, we investigated the genetic defect in a case of autosomal recessive congenital generalized hypertrichosis terminalis (CGHT) (OMIM135400) using whole-exome sequencing. We identified a single base pair substitution in the 5′ donor splice site of intron 32 in the ABC lipid transporter gene ABCA5 that leads to aberrant splicing of the transcript and a decrease in protein levels throughout patient hair follicles. The homozygous recessive disruption of ABCA5 leads to reduced lysosome function, which results in an accumulation of autophagosomes, autophagosomal cargos as well as increased endolysosomal cholesterol in CGHT keratinocytes. In an unrelated sporadic case of CGHT, we identified a 1.3 Mb cryptic deletion of chr17q24.2-q24.3 encompassing ABCA5 and found that ABCA5 levels are dramatically reduced throughout patient hair follicles. Collectively, our findings support ABCA5 as a gene underlying the CGHT phenotype and suggest a novel, previously unrecognized role for this gene in regulating hair growth

Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa–Associated Squamous Cell Carcinoma

PURPOSE: Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need. EXPERIMENTAL DESIGN: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo. RESULTS: ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib. CONCLUSIONS: These data support a “first in RDEB” phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC

Mutations in EDA and EDAR Genes in a Large Mexican Hispanic Cohort with Hypohidrotic Ectodermal Dysplasia

Ectodermal dysplasias (ED) encompass nearly 200 different genetic conditions identified by the lack, or dysgenesis, of at least two ectodermal derivatives, such as hair, nails, teeth, and sweat glands. Hypohidrotic/anhidrotic ED (HED) is the most frequent form of ED and it can be inherited as an X-linked (XL)-HED (MIM 305100), autosomal recessive (AR)-HED (MIM 224900), or autosomal dominant (AD)-HED (MIM 229490) condition. HED is caused by mutations in any of the three ectodisplasin pathway genes: ectodisplasin (EDA), which encodes a ligand for the second gene, the EDA receptor (ectodysplasin A-receptor, EDAR), and EDARADD, an intracellular signaling for this pathway. HED is characterized by a triad of clinical features including absent or diminished eccrine sweat glands, missing and/or malformed teeth, and thin, sparse hair. It also includes dryness of the skin, eyes, airways, and mucous membranes, as well as other ectodermal defects and, in some cases, fever, seizures, and rarely, death. XL-HED is caused by mutations in the EDA gene, located on chromosome Xq12-q13.1, which encodes a signaling molecule of the tumor necrosis factor (TNF) superfamily. AR- and AD-HED are caused by mutations in the EDAR gene, located on chromosome 2q11.q13 or the EDARAssociated Death Domain encoding gene, EDARADD, located on chromosome 1q42-q431. Several mutations in the EDA, EDAR, and EDARADD genes have been described as causing HED in different populations. The XL-HED form is the most common and is responsible for 90% of all HED cases2-6. The three forms of HED are clinically indistinguishable. To date, a comprehensive evaluation of HED in the Mexican Hispanic population has not been undertaken. In the present study, we aimed to characterize the mutations in EDA, EDAR, and EDARADD genes present in Mexican Hispanic patients with HED. Male and female patients (35 families) from different geographical regions of Mexico with features suggestive of HED were enrolled in the study (Fig. 1). Index cases and their parents were screened for missing or malformed teeth, thin or sparse hair, and nail changes; all subjects answered questions about sweating, heat intolerance, fever, seizures, and family history of siblings deceased due to unknown feve

Lysyl hydroxylase 3 localizes to epidermal basement membrane and Is reduced in patients with Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

Funder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; doi: http://dx.doi.org/10.13039/501100002322Funder: Radiumhemmets Forskningsfonder; doi: http://dx.doi.org/10.13039/501100007232Funder: Swedish Cancer SocietyFunder: Lunds Universitet Paulsson TrustFunder: CIBER de Enfermedades Raras of the Instituto de Salud Carlos IIIFunder: European Regional Development Fund; doi: http://dx.doi.org/10.13039/501100008530Funder: DiagnopticsFunder: CERCA Programme Generalitat de CatalunyaFunder: Esther Koplowitz Center, Barcelona, SpainFunder: Comision Honoraria de Lucha Contra el Cancer, CSIC, Fundacion Manuel Perez, Montevideo, UruguayBACKGROUND: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. METHODS: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. RESULTS: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. CONCLUSIONS: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families

Innate sensing of microbial products promotes wound-induced skin cancer

The association between tissue damage, chronic inflammation and cancer is well known. However, the underlying mechanisms are unclear. Here we characterize a mouse model in which constitutive epidermal extracellular-signal-regulated kinase-MAP-kinase signalling results in epidermal inflammation, and skin wounding induces tumours. We show that tumour incidence correlates with wound size and inflammatory infiltrate. Ablation of tumour necrosis factor receptor (TNFR)-1/-2, Myeloid Differentiation primary response gene 88 or Toll-like receptor (TLR)-5, the bacterial flagellin receptor, but not other innate immune sensors, in radiosensitive leukocytes protects against tumour formation. Antibiotic treatment inhibits, whereas injection of flagellin induces, tumours in a TLR-5-dependent manner. TLR-5 is also involved in chemical-induced skin carcinogenesis in wild-type mice. Leukocytic TLR-5 signalling mediates upregulation of the alarmin HMGB1 (High Mobility Group Box 1) in wound-induced papillomas. HMGB1 is elevated in tumours of patients with Recessive Dystrophic Epidermolysis Bullosa, a disease characterized by chronic skin damage. We conclude that in our experimental model the combination of bacteria, chronic inflammation and wounding cooperate to trigger skin cancer