Dermal-epidermal Junction Research Articles

Preliminary Evaluation of in vivo Reflectance Confocal Microscopy Features of Neonatal Lupus Erythematosus

Introduction: Neonatal lupus erythematosus (NLE) is a rare autoimmune disease, which needs to be distinguished from eczema, congenital syphilis, and tinea corporis in newborns. Reflectance confocal microscopy (RCM) could be a helpful noninvasive diagnostic tool, which has been used to evaluate several inflammatory skin conditions. The aim of this study was to describe the RCM characteristics of NLE. Methods: Eleven NLE patients were included in the study, and all patients were evaluated clinically with RCM. We also evaluated RCM images from 11 eczema patients as controls. Results: Some major key diagnostic features of NLE can be observed by RCM: an enlarged honeycomb pattern (9/11, 81.8%), round-to-oval cyst-like structures were present (6/11, 54.5%), the normal ring-like structures were totally or partially obliterated (11/11, 100%) at the level of the dermo-epidermal junction, medium refractivity collagen fibers that were disorganized (10/11, 90.9%), numerous high refractivity round cells (11/11, 100%) in the dermis. Conclusion: RCM allows the visualization of major key diagnostic features of NLE and serves as a complementary diagnostic tool for NLE.

Anti-aging and rejuvenating effects and mechanism of Dead Sea water in skin.

External environmental stressors and internal factors have a significant impact on the skin, causing inflammation, aging, reduced immunity and other adverse responses. Dead Sea Water (DSW) is well known for its dermatological benefits and has been widely used in dermatological therapy and skin care for conditions such as psoriasis, atopic dermatitis and photoaging. However, the anti-aging and rejuvenating effects of DSW and the related biological pathways involved, which have attracted increasing attention, are not fully understood. The aim of this study is to investigate the anti-aging and rejuvenating effects of DSW and to explore the related potential biological mechanisms of DSW under different environmental conditions. The effects of DSW were investigated using invitro human dermal cells and reconstructed skin models. Extracellular matrix (ECM) components and the morphological changes at the dermal-epidermal junction (DEJ) in a 3D human skin model were evaluated after DSW treatment. RNA sequencing (RNA-seq) analysis of human dermal fibroblast models after DSW treatment was performed to explore the potential mechanisms of action of DSW under normal and UV stress conditions. The novel findings in this work present the biological functions of DSW, including procollagen-1 and elastin secretion, hemidesmosome increase and the epidermal basal cell regeneration. In addition, GO, KEGG and Reactome analyses reveal the activation of pathways related to ion transmembrane transporter activity, ECM component biosynthesis, senescence-associated secretory phenotype (SASP), DNA repair and autophagy, which are associated with the anti-aging activities of DSW. Our work provides new perspectives for understanding the anti-aging and rejuvenating effects and mechanisms of DSW. The new findings also provide a theoretical basis for the further development of age-related strategies.

Líquen plano cutâneo extenso de início recente na infância após infecção assintomática por COVID-19: relato de caso

ABSTRACT Objective: The objective of this study was to describe a case of cutaneous lichen planus (LP) that appeared following COVID-19 infection. Case description: We report a case of extensive cutaneous classic familial LP in a 4-year-old male child after an asymptomatic serologically confirmed COVID-19 infection. The patient developed intensely itchy, purple, flat-topped papules and plaques, mainly on the dorsal surface of the hands, feet, forearms, and shins. Histopathological examination of the skin biopsy showed vacuolar and apoptotic degeneration of the basal cell layer with a band-like lymphocyte infiltrate at the dermo-epidermal junction and confirmed the diagnosis of LP. Comments: LP could be considered among the differential diagnoses of pediatric post-COVID inflammatory skin lesions, either in the patients recovering from COVID-19 infection or in the suspicious asymptomatic cases in close contact with COVID-19-infected patients.

Histopathological Spectrum of Interface Dermatitis in a Tertiary Care Center

Background: Interface dermatitis (ID) is a histomorphological tissue reaction pattern that involves dermoepidermal junction of skin. Varieties of cutaneous lesions fall under primary ID which has to be differentiated from secondary ID. Aim: This study was undertaken to evaluate the histopathological spectrum of ID and compare them in relation to age, sex and anatomical site along with clinicopathological correlation. Material and method: This is a one year prospective cross sectional study done at Department of Pathology of Tribhuvan University Teaching Hospital, which included 69 cases of skin biopsies with histological features of ID. Results: Out of 650 skin biopsies, 69 cases were diagnosed as primary ID. Most common age of presentation was 21-40 years. Male to female ratio was 1:1.5. Lichen planus and variants were the commonest ID (63.8%) with widest anatomical distribution, followed by discoid lupus erythematosus (15.9%) and pityriasis lichenoides chronica (8.7%). The most consistent histopathological findings of IDs were basal layer vacuolation and interface inflammation. Clinicopathological concordance was seen in 79.7% of cases. Conclusion: Distinctive histopathological features of basal layer vacuolation and interface inflammation involving dermoepidermal junction were valuable in arriving at diagnosis of various lesions of interface dermatitis. However, histopathological categorization of ID should be done in a clinical context because of overlapping clinical and histological features and for guiding appropriate therapy.

Dermoscopy and reflectance confocal microscopy finding of different anatomic sites of Langerhans cell histiocytosis.

Recognizing Langerhans cell histiocytosis (LCH) might be a challenge due to its rarity. Reflectance confocal microscopy (RCM) and dermoscopy were emergent promising non-invasive technique as auxiliary tools in diagnosis of different skin conditions. However, the RCM and dermoscopic features of LCH had been less investigated. To reveal the common RCM and dermoscopic features of LCH. Forty cases of LCH were retrospectively analyzed according to age, locations, clinical, RCM, and dermoscopic features from September 2016 to December 2022. To reveal the differences and common in clinical, RCM, and dermoscopic features that occur in different anatomic location. In the study, sites of predilection include the trunk 31/40 (77.5%), extremity 21/40 (52.5%), face 14/40 (35%), scalp 11/40 (27.5%), vulvar 4/40 (10%), and nail 2/40 (5%). All LCHs had the common RCM features. There were significant differences in clinical and dermoscopic features for age and lesion anatomic site. The common dermoscopic features for scalp, face, trunk, and extremity were the erythematous scaly rash, purplish-red globules or patches, scar-like streaks with ectatic vessels. While the features for nail LCH were purpuric striae, onycholysis and purulent scaly rash, and the erosive erythematous plaque and purulent scaly rash for vulvar LCH. The common RCM features of all LCH showed a focal highly reflective dense image in the surface keratin layer, epidermis architectural disarray, obscuration of dermo-epidermal junction, numerous polygonal, large, medium reflective, short dendrites cells in the epidermis, and dermis. All LCH involving the vulvar and nail did not manifest skin lesions. RCM and dermoscopy showed promising value for diagnosis and differentiation of LCH.

Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update.

Bullous pemphigoid (BP) is a common autoimmune bullous disease affecting mainly the elderly, with rising incidence due to increased life expectancy. This disease is characterized by tense bullous lesions on normal or erythematous skin, accompanied by pruritus. BP pathogenesis involves autoantibodies against hemidesmosomal proteins BP180 and BP230, leading to detachment at the dermo-epidermal junction as well as blister formation. BP is associated with coexisting comorbidities and drug exposure, and its management often requires high doses or chronic use of systemic glucocorticoids, posing risks of adverse effects. This review focuses on novel treatment options for BP, exploring therapies targeting different immune pathways. Rituximab, a CD20 monoclonal antibody, depletes B-lymphocytes and has shown efficacy in severe cases. Dupilumab, targeting interleukin (IL)-4 receptor α and thus blocking IL-4 and IL-13, downregulates type 2 helper (Th2) responses and has demonstrated promising results. Targeting eosinophil-related molecules using bertilimumab and AKST4290 has yielded positive results in clinical trials. Omalizumab, an immunoglobulin (Ig)E antibody, can reduce disease severity and allows corticosteroid tapering in a number of cases. Complement inhibitors such as nomacopan and avdoralimab are being investigated. IL-17 and IL-23 inhibitors such as secukinumab and tildrakizumab have shown potential in a limited number of case reports. Neonatal Fc receptor antagonists such as efgartigimod are under investigation. Additionally, topical therapies and Janus kinase inhibitors are being explored as potential treatments for BP. These novel therapies offer promising alternatives for managing BP, with potential to improve outcomes and reduce high cumulative doses of systemic corticosteroids and related toxicities. Further research, including controlled clinical trials, is needed to establish their efficacy, safety, and optimal dosing regimens for BP management.

Understanding the anatomy of dermoscopy of melanocytic skin tumours: Correlation invivo with line-field optical coherence tomography.

Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an invivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. LC-OCT permitted for the first time to perform an invivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.

Skin-protective biological activities of bio-fermented Aframomum angustifolium extract by a consortium of microorganisms.

Background: Aframomum sp. is a genus of plants in the Zingiberaceae family. It includes several species, some of which are used in cosmetics for their various properties, making them useful in skincare products, particularly for anti-aging, moisturizing, and brightening the skin. However, to date, there is no experimental evidence on its natural extracts obtained or modified using microorganisms (bio-fermentation) as an anti-aging agent. Objective: The present study aimed to evaluate the antiaging effect of a Bio-fermented Aframomum angustifolium (BAA) extract on 3D bioprinted skin equivalent. Methods: The consortium of microorganisms contained Komagataeibacter, Gluconobacter, Acetobacter, Saccharomyces, Torulaspora, Brettanomyces, Hanseniaspora, Leuconostoc, Lactobacillus, Schizosaccharomyces. It was developed on a media containing water, sugar, and infused black tea leaves. The seeds of Aframomum angustifolium previously grounded were mixed with the culture medium, and the ferments in growth; this fermentation step lasted 10 days. Then, the medium was collected and filtered (0.22µm) to obtain the BAA extract. To enhance our comprehension of the impact of BAA extract on skin aging, we developed skin equivalents using bio-printing methods with the presence or absence of keratinocyte stem cells (KSC). These skin equivalents were derived from keratinocytes obtained from both a middle-aged donor, with and without KSC. Moreover, we examined the effects of treating the KSC-depleted skin equivalents with Bio-fermented Aframomum angustifolium (BAA) extract for 5days. Skin equivalents containing KSC-depleted keratinocytes exhibited histological characteristics typical of aged skin and were compared to skin equivalents derived from young donors. Results: The BAA extract contained specific organic acids such as lactic, gluconic, succinic acid and polyphenols. KSC-depleted skin equivalents that were treated with BAA extract exhibited higher specular reflection, indicating better hydration of the stratum corneum, higher mitotic activity in the epidermis basal layer, improved dermal-epidermal connectivity, and increased rigidity of the dermal-epidermal junction compared to non-treated KSC-depleted equivalents. BAA extract treatments also resulted in changes at the dermis level, with an increase in total collagen and a decrease in global laxity, suggesting that this extract could help maintain youthful-looking skin. Conclusion: In summary, our findings indicated that BAA extract treatments have pleiotropic beneficial effects on skin equivalents and that the bio-fermentation provides new biological activities to this plant.

Line-field confocal optical coherence tomography for in vivo visualization of morphological characteristics of squamous cell carcinoma in a murine model.

Non-invasive imaging with line-field confocal optical coherence tomography (LC-OCT) can support the diagnosis of squamous cell carcinoma (SCC) through visualization of morphological characteristics specific to skin cancer. We aimed to visualize prominent morphological characteristics of SCC using LC-OCT in a well-established murine SCC model. Nine hairless mice were exposed to ultraviolet radiation three times weekly for 9 months to induce SCC development. Visible SCC tumors (n = 9) were imaged with LC-OCT and the presence of 10 well-described morphological characteristics of SCC were evaluated in the scans by two physicians with adjudication by a third. Overall, murine morphological characteristics resembled corresponding features previously reported in human SCCs. Interrupted dermal-epidermal junction occurred in 100% of tumors. In epidermis, the most frequently observed characteristics were severe epidermal dysplasia (100%) and tumor budding (89%). Common dermal characteristics included broad strands (100%) and collagen alterations (78%). LC-OCT imaging can be used to non-invasively visualize morphological characteristics specific to SCC in an in vivo preclinical model.

Efficacy of human living skin equivalent in the treatment of inherited epidermolysis bullosa

Background: inherited epidermolysis bullosa is a group of genetic skin disorders caused by mutations in genes encoding structural proteins of epidermis and dermo-epidermal junction. Clinical manifestations are characterized by spontaneous or trauma-induced skin and/or mucosal blistering, and extensive wounds. Cell therapy is considered to be a perspective therapeutic approach in improving wound healing process.
 Aims: to assess safety and efficacy of human skin equivalent in the treatment of inherited epidermolysis bullosa patients
 Materials and methods: 7 patients (5 female and 2 male subjects from the age of 20 to 55) with inherited epidermolysis bullosa with different clinical subtypes were enrolled in the study: 3 patients with intermediate recessive dystrophic epidermolysis bullosa, 2 patients with severe recessive dystrophic epidermolysis bullosa, 1 patient with dominant dystrophic epidermolysis bullosa and 1 patient with junctional epidermolysis bullosa. Transplantation of composite allogeneic living skin equivalent comprising allogeneic keratinocytes and fibroblasts in low concentration (5 mg/ml) embedded within a type I collagen gel matrix was performed. The living skin equivalent was developed at N.K. Koltsov Institute of Developmental Biology. 19 erosions and ulcers with a surface area between 0,4 cm2 and 120 cm2 were evaluated. At day 14 clinical assessment was performed. To assess level of expression immunofluorescence antigen mapping was used.
 Results: at day 14 complete erosion closure was achieved in 10 (53%) erosions. 4 (21%) erosions reduced in size 75%. Size reduction between 25% and 75% was shown in a single (5%) case. No clinical efficacy was demonstrated in 4 (21%) cases. Collagen VII expression increased comparing to baseline level and accompanied clinical improvement.
 Conclusions: the obtained data showed clinical efficacy of topical treatment with living skin equivalent, although no statistically significant difference was seen between living skin equivalent and atraumatic non-adhesive dressings.
 Keywords: inherited epidermolysis bullosa, junctional epidermolysis bullosa, recessive dystrophic epidermolysis bullosa, erosions, healing, topical treatment.

Monocyte populations are involved in the pathogenesis of experimental epidermolysis bullosa acquisita.

Monocytes play a significant role in the pathogenesis of most inflammatory diseases, including autoimmune diseases. Herein, different subpopulations of monocytes often play differential, partially antagonistic roles, in the regulation of tissue populations. Pemphigoid diseases constitute a group of autoimmune blistering skin diseases featuring a marked infiltration of the dermis with immune cells, including monocytes. The monocyte subsets infiltrating the skin, however, have largely remained elusive. Monocyte adhesion and recruitment into the inflamed tissues are regulated by chemokine receptors, most prominently by CCR2 and CX3CR1. To delineate the involvement of monocyte populations in autoimmune blistering skin diseases, we spatiotemporally monitored the dynamic spectrum of monocyte populations that infiltrate the inflamed skin using multiphoton intravital imaging and reporter mice for chemokine receptors. Experimental epidermolysis bullosa acquisita (EBA) was induced by injection of anti-murine type VII collagen (amCOLVII) IgG into the Csf1rEGFP-reporter mice, where circulating myeloid cells, such as monocytes and neutrophils, express an EGFP. EGFP+ cells, including neutrophils and monocytes, were present in the skin, immediately after the deposition of the amCOLVII antibody at the dermal-epidermal junction. To investigate the recruitment and involvement of different monocyte-derived cell populations in the disease course further, EBA was induced in CCR2RFP/+-reporter and CX3CR1GFP/+-reporter mice. A comparable distribution of red fluorescent protein (RFP)+ or green fluorescent protein (GFP)+ was found in both diseased mice and their respective controls over time, indicating the similar recruitment of monocytes into the skin following the binding of autoantibodies. Experiments were extended to the CCR2RFP/RFP-deficient and CX3CR1GFP/GFP-deficient mice to determine whether monocyte recruitment and disease severity are compromised in the absence of the receptor. A comparable pattern was seen in the recruitment of monocytes into the skin in both reporter and deficient mice. However, in contrast to similar disease severity between CX3CR1-deficient and reporter mice, CCR2-deficient mice developed significantly less disease than CCR2-reporter mice, as indicated by the percentage of affected area of ears. Collectively, our observations indicate that while CCR2 and CX3CR1 receptors are not involved in the recruitment of monocytes into the skin, CCR2 deficiency is associated with improved disease outcomes in experimental EBA in mice.

Inheritance of the Epidermolysis Bullosa Subtypes

Epidermolysis bullosa (EB) is a group of inherited disorders that cause skin to blister and tear easily. The disease is caused by mutations in structural proteins that are key for maintaining the integrity of the skin’s basement membrane zone or dermoepidermal junction. EB can be inherited in two ways: autosomal dominant and autosomal recessive. The most common form of EB, epidermolysis bullosa simplex (EBS), as well as some forms of dystrophic epidermolysis bullosa (DEB) are inherited in an autosomal dominant pattern. This means they are passed down from an affected parent to half of his or her children. Other forms of EB, such as junctional epidermolysis bullosa (JEB) and some forms of DEB, are inherited in an autosomal recessive pattern. This means that two copies of the mutated gene, one from each parent, are required to develop the condition.

Immediate diagnosis of cutaneous metastases with optical coherence tomography, line‐field confocal optical coherence tomography and dermoscopy: A case series

AbstractBackgroundCutaneous metastases (CM) are a frequent finding in the follow‐up of malignant tumours.ObjectivesCM were examined with dermoscopy, optical coherence tomography (OCT), dynamic OCT and line‐field confocal OCT (LC‐OCT) to describe common findings.MethodsIn the University Hospital Carl Gustav Carus Dresden, Germany, 18 patients with 61 CM were examined with dermoscopy. CM (n = 43, 31 melanoma metastases, two metastases of renal carcinoma, five metastases of cutaneous squamous cell carcinoma and five metastases of pleomorphic dermal sarcoma) were examined with OCT (VivoSight® Michelson Diagnostics). Additional 18 melanoma metastases were examined with LC‐OCT (deepLive™; Damae Medical).ResultsCM were localized on the head, trunk, neck and limbs. Dermoscopy patterns were angioma‐like, nevus‐like nonglobular, nevus‐like globular, blue nevus‐like and unspecific. CM showed an ulceration, hyperkeratosis with increased entrance signal and disturbed architecture of the epidermis in OCT. In deeper metastases, the dermoepidermal junction (DEJ) was normal; in most cases it was disturbed. CM were visible as subepidermal hyporeflective roundish area, with septae, with either clear margin and shadowing or blurred margin. DOCT showed dot, coiled, serpiginous and branched vessels; there was a disarray in size and distribution and vessels were converging on the centre of the metastasis. In LC‐OCT, CM showed enhanced entrance signal and disturbed architecture of a thinned epidermis, ulceration, atypical honeycomb or cobblestone pattern as well as a broken DEJ. In the dermis, a hyporeflective roundish area with clusters of hyporeflective cells with septae, clear margin and clefting or blurred margin was visible; the hyporeflective area was surrounded by bundles of connective tissue. Subepidermal vessels differentiated in size and distribution. Inflammatory, dendritic and pagetoid cells were visible.ConclusionsOCT and LC‐OCT may be useful tools for immediate diagnosis, localization of CM and monitoring under treatment in addition to conventional methods like ultrasound and histopathology.

From Molecular Insights to Clinical Perspectives in Drug-Associated Bullous Pemphigoid

Bullous pemphigoid (BP), the most common autoimmune blistering disease, is characterized by the presence of autoantibodies targeting BP180 and BP230 in the basement membrane zone. This leads to the activation of complement-dependent and independent pathways, resulting in proteolytic cleavage at the dermoepidermal junction and an eosinophilic inflammatory response. While numerous drugs have been associated with BP in the literature, causality and pathogenic mechanisms remain elusive in most cases. Dipeptidyl peptidase 4 inhibitors (DPP4i), in particular, are the most frequently reported drugs related to BP and, therefore, have been extensively investigated. They can potentially trigger BP through the impaired proteolytic degradation of BP180, combined with immune dysregulation. DPP4i-associated BP can be categorized into true drug-induced BP and drug-triggered BP, with the latter resembling classic BP. Antineoplastic immunotherapy is increasingly associated with BP, with both B and T cells involved. Other drugs, including biologics, diuretics and cardiovascular and neuropsychiatric agents, present weaker evidence and poorly understood pathogenic mechanisms. Further research is needed due to the growing incidence of BP and the increasing identification of new potential triggers.

Histopathological characteristics analysis of giant melanocytic naevi in children.

The major diagnostic criterion for the giant congenital melanocytic nevus (GCMN) is a size larger than 20 cm in diameter. However, the histopathological origin, pathogenesis, and GCMN progression are not yet completely clear. Unlike other medium or small superficial lesions, histomorphological evaluation is significant for GCMN pathological classification, malignant transformation assessment, and early detection of prognosis. This study aimed to investigate the pathological features of GCMN, including its satellite lesions. Twenty-three giant naevi and seventeen "satellite lesions" were collected from children aged 1 to 10 in Shanghai Ninth People's Hospital from 2018 to 2020. A histological study was conducted to evaluate their histological appearance. All the data observed and recorded data were statistically analyzed. In 23 cases of GCMN primary nevus, nevus cells were mainly distributed in the dermal region, with melanocyte proliferation and the presence of nevus nests at the dermal-epidermal junction. However, in satellite nevus, a junctional growth pattern was noted. Additionally, other histopathologic features, including epidermal contour, cell morphology, and architecture disorder also showed significant differences between primary nevus and satellite nevus. We demonstrated that the congenital pattern of the main nevus is more obvious than one of the satellite nevus, suggesting that the satellite nevus and the main nevus may occur slightly later than the main nevus. "Satellite nevus" happens as a result of a separate genetic event.

Differences in the microanatomy of skin of sole and palm in humans

Background: The prevalence of skin diseases has increased over the last few decades and they contribute to a significant burden on the health-care systems all across the world. In some forms of reconstructive or plastic surgery, palm skin has successfully been replaced with sole skin, removed to form a full-thickness graft that covered almost the entire palm of the hand without impairing the weight-bearing areas of the feet or encumbering the gait. In cases such as these, the skin of the palm and sole is preferred for grafts. Aims and Objectives: The study was conducted to learn the microanatomy of palm and sole. Materials and Methods: The present observational study was carried out in the Department of Anatomy, King George Medical University, Lucknow, from the period of September 2017 to August 2018. Ethical clearance was obtained from Institutional Ethics Committee (Ref. code:63/Ethics/R-Cell-18). For the present study, skin was procured from the palm and sole of six freshly embalmed human cadavers (three males and three females). The mean age of the cadavers was 67 years. Tissues were preserved in 10% of formaldehyde for 48 h, fixed, Stained in H and E, and observed under light microscope. Results: The study showed that the thickness of epidermis and ratio of epidermis to stratum corneum (Edp: sc) of the sole are greater than palm, dermoepidermal junctions were more in sole. Thickness of dermis both papillary and reticular dermis was more in sole than palm. Conclusion: The values of thickness of skin of palm and sole region provide data for plastic surgeons to plan cosmetic surgeries.

Advancing Treatment in Bullous Pemphigoid: A Comprehensive Review of Novel Therapeutic Targets and Approaches.

Bullous pemphigoid is one of the most common autoimmune bullous diseases occurring primarily in the elderly. Pathogenic autoantibodies against BP180 and BP230 at the dermal-epidermal junction cause subepidermal blisters, erosions, and intense pruritus, all of which adversely affect the patients' quality of life and may increase their morbidity and mortality. Current systemic treatment options for bullous pemphigoid are limited to corticosteroids and immunosuppressants, which can have substantial side effects on these vulnerable patients that even exceed their therapeutic benefits. Therefore, more precisely, targeting therapies to the pathogenic cells and molecules in bullous pemphigoid is an urgent issue. In this review, we describe the pathophysiology of bullous pemphigoid, focusing on autoantibodies, complements, eosinophils, neutrophils, proteases, and the T helper 2 and 17 axes since they are crucial in promoting proinflammatory environments. We also highlight the emerging therapeutic targets for bullous pemphigoid and their latest discoveries in clinical trials or experimental studies. Further well-designed studies are required to establish the efficacy and safety of these prospective therapeutic options.

The effects of topical mafenide acetate application on skin graft survival in bacterial contaminated wounds

BackgroundInfection related skin graft loss still remains as a common problem even with the use of systemic antibiotics. Mafenide acetate (Sulfamylon) is a topical antimicrobial agent with a wide spectrum of antimicrobial activity. Since mafenide acetate has the ability to penetrate the burn eschar, it was preferred in the treatment of infected full-thickness skin grafts. We investigated the effects of topical Mafenide acetate application on graft survival in an experimental model of contaminated wound beds in rats. Materials and methodsTwenty-eight male Wistar albino rats were included in the study. A full-thickness skin graft (FTSG) was harvested from the back region and the wound bed was inoculated with Pseudomonas aeruginosa. The same FTSG was sutured in place. Rats were divided into 4 groups. In groups 1 and 2, wound care was performed with gauze and hydrofiber dressings respectively. In groups 3 and 4, Mafenide acetate soaked hydrofiber and Mafenide acetate soaked gauze dressings were used respectively. The dressings were closed for 4 days in all groups. The rats in groups 1 and 2 received dressing changes every day. The dressing of the rats in group 3 was changed once every two days. The dressing of the rats in group 4 was changed twice a day. ResultsIn groups 3 and 4, the graft survival rates decreased significantly from day 7 to day 14 in all groups. Histologically, detachment at the dermoepidermal junction, disorganization of collagen along with increased numbers of fibroblasts and a decrease in graft adhesion to the wound bed were determined in Mafenide acetate-treated groups. ConclusionIn rats treated with Mafenide acetate, graft survival was higher on day 7 and gradually decreased towards day 14. Application of a 2.5% solution of Mafenide acetate longer than 7 days on inoculated skin grafts in a rat model causes significant cytotoxicity and graft loss.

Reflectance confocal microscopy as a complementary diagnostic tool for greyish-brown dermatoses in children.

Mastocytosis, lichen planus pigmentosus (LPP), fixed drug eruption (FDE) and café-au-lait macules (CALM) have a similar appearance, often lead to misdiagnosis and missed diagnoses. At the outpatient clinic at Tianjin Children's Hospital in 21 patients with mastocytosis, 18 with LPP, 11 with FDE and 12 with CALM we evaluated the characteristics and distinguishing features of their dermatoses using reflectance confocal microscopy (RCM). In mastocytosis, the dermal papillary rings generally had a significantly increased bright refractive index and the superficial dermis was filled with moderate refractive flocculent material. In LPP, the dermal papillary rings were absent and numerous different-sized cellular structures were densely distributed in the superficial dermis. In FDE, the dermal papillary rings were intact with a significantly increased bright refractive index. In CALM, normal dermal papillary rings were detected with a uniformly slightly increased refractive index and no obvious abnormality in the superficial dermis. RCM allows for real-time visualization of the major key diagnostic and distinguishing features of four greyish-brown dermatoses in children.

Rare variants of pemphigoid diseases

Pemphigoid diseases comprise aheterogeneous group of subepidermal autoimmune blistering dermatoses characterized by autoantibodies against structural proteins of the dermal-epidermal junction. Recent decades have witnessed asignificant surge in the incidence of these diseases, which, in addition to general aging of the population, can be attributed to the availability of precise diagnostic methods and improved knowledge of the clinical and immunopathological spectrum. While bullous pemphigoid, mucous membrane pemphigoid, and linear IgA disease account for most pemphigoid disorders, less frequent, presumably underdiagnosed variants are increasingly becoming relevant for clinicians. These include epidermolysis bullosa acquisita, anti-p200 pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, and recently defined entities such as IgM pemphigoid and Orf-induced pemphigoid. Accurate characterization and differentiation of these subtypes are not only of diagnostic relevance but may also be associated with therapeutic and prognostic implications for affected individuals. Due to the rarity of these diseases, no controlled prospective clinical trials currently exist, making their diagnosis and therapy challenging.