Dermal-epidermal Junction Research Articles

Non-Invasive Imaging Including Line-Field Confocal Optical Coherence Tomography (LC-OCT) for Diagnosis of Cutaneous Lymphomas

Background/Objectives: Primary cutaneous lymphomas (PCL) are a heterogeneous group of non-Hodgkin lymphomas arising from malignant T (CTCL) or B (CBCL) cells, often mimicking other skin conditions. Recently, non-invasive diagnostic imaging modalities, including dermoscopy, Reflectance Confocal Microscopy (RCM), and Line-field Optical Coherence Tomography (LC-OCT), have become increasingly important, supporting clinicians in clinical practice. Hence, our study aimed to describe dermoscopic, RCM, and LC-OCT features of PCL and to explore their role in PCL management. Methods: Between December 2022 and January 2024, 40 lesions of 25 patients with PCL were retrospectively analyzed at the Dermatologic Unit of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, and RCM criteria were assessed and their frequencies were calculated. Results: At dermoscopy, CTCL lesions were characterized by pinkish structureless areas (58,6%) and homogeneous distributed dotted vessels (35,7%), whereas 57.1% of CBCL presented with orange-yellow structureless areas. Considering CTCL, lymphocytes in the epidermis, dermal-epidermal junction, and dermis were detected by LC-OCT in 73.1%, 66.7%, and 51.9% and by RCM in 72.2%, 55.6%, and 61.1% of cases, respectively. The detection of lymphocytes was more precise using RCM than LC-OCT in CTCL (p < 0.001). Dermal infiltration of medium-reflective cells was visible in 80% and 40% of CBCL cases by LC-OCT and RCM, respectively. Conclusions: Non-invasive imaging techniques may support clinicians in managing PCL; however, further studies are mandatory in this field.

Superficial angiomyxoma-like myxofibrosarcoma

Abstract Introduction/Objective Myxofibrosarcoma comprises a spectrum of malignant fibroblastic neoplasms with variably myxoid stroma, pleomorphism, and a distinctive curvilinear vascular pattern. Herein we describe a case of myxofibrosarcoma with unusual histological features that could be deceptive, mimic superficial angiomyxoma and make the diagnosis challenging Methods/Case Report A 74-year-old female presented with a right upper arm lesion that had been present for 10-12 months and had significantly increased in size over this time and became painful. There was no history of trauma. Examination demonstrated approximately 3 cm multinodular mass along the anterior aspect of the proximal arm. There were no overlying skin discolorations or ecchymosis. The patient underwent a shave biopsy and then resection. Grossly, the lesion was gray-white firm with an ill-defined border covered with a tan-white skin ellipse. Histologically, the lesion was located in the dermis extending to the dermal-epidermal junction. The lesion comprised mainly of myxoid stroma, arborizing, and plexiform thin-walled blood vessels, stellate to spindled cells with enlarged hyperchromatic nuclei, and eosinophilic cytoplasm in addition to the presence of stromal neutrophils and hyperplastic overlying squamous epithelium. The morphologic appearance elicited the differential diagnosis of superficial angiomyxoma and low-grade myxofibrosarcoma. While many features were more suggestive of superficial angiomyxoma, the degree of atypia and mitotic activity (12/10 HPF) was outside the realm of angiomyxoma and warranted the diagnosis of myxofibrosarcoma Results (if a Case Study enter NA) NA Conclusion Although rare, myxofibrosarcoma may rarely extend to the dermal-epidermal junction and mimic superficial angiomyxoma. The presence of cytologic atypia and increased mitotic activity favors myxofibrosarcoma

Evaluating facial dermis aging in healthy Caucasian females with LC-OCT and deep learning

Recent advancements in high-resolution imaging have significantly improved our understanding of microstructural changes in the skin and their relationship to the aging process. Line Field Confocal Optical Coherence Tomography (LC-OCT) provides detailed 3D insights into various skin layers, including the papillary dermis and its fibrous network. In this study, a deep learning model utilizing a 3D ResNet-18 network was trained to predict chronological age from LC-OCT images of 100 healthy Caucasian female volunteers, aged 20 to 70 years. The AI-based protocol focused on regions of interest delineated between the segmented dermal-epidermal junction and the superficial dermis, exploiting complex patterns within the collagen network for age prediction. The model achieved a mean absolute error of 4.2 years and exhibited a Pearson correlation coefficient of 0.937 with actual ages. Furthermore, there was a notable correlation (r = 0.87) between quantified clinical scoring, encompassing parameters such as firmness, elasticity, density, and wrinkle appearance, and the ages predicted by deep learning model. This strong correlation underscores how integrating emerging imaging technologies with deep learning can accelerate aging research and deepen our understanding of how alterations in skin microstructure are related to visible signs of aging.

Borderline Lepromatous Leprosy Masquerading as Granuloma Annulare: A Case Report

Background: Leprosy is a chronic granulomatous disease caused by Mycobacterium Leprae. Leprosy is a great imitator with its various atypical, unusual and varying clinical presentations which can be confused with many infectious and non-infectious diseases. Case Report: A 46-year-old female presented to the dermatology department with complaints of painful raised lesions over face, upper back, upper limbs, lower legs and feet for 12 months. Clinically suspected as a case of Granuloma annulare. Punch biopsy was taken which revealed epidermis with dermis showing nodules of histiocytes and lymphocytes with grenz zone at the dermoepidermal junction. Acid fast stain and Fite Faraco stain was performed which revealed the presence of leprae bacilli with bacteriological index of 4+. Conclusion: Detailed history taking and correlating clinical picture with morphology is required to diagnose atypical presentations of leprosy. Early diagnosis helps to provide appropriate treatment and thus prevent from devastating complications.

Concomitant melanoma and keratoma affecting the equine digit: clinical, pathological, and long-term follow-up findings

BackgroundThis case report details a long-term follow-up of a hoof melanoma with dermo-epidermal activity (resembling Spreading Superficial Melanoma (SSM)) in a bay horse with a history of a right front hoof keratoma. Melanomas involving the horse's foot are seldom reported and usually diagnosed as anaplastic melanomas based on signalment and post-mortem examination. The clinical-pathological characteristics of the foot melanoma in this bay horse are consistent with SSM-like described in humans, which is considered an intermediate malignant tumour attending their biological behaviour. However, a definitive diagnosis is limited by the single case and the lack of references in horses.Case presentationA 12-year-old bay Andalusian gelding underwent keratoma removal on the lateral aspect of the hoof wall. A partial resection of the hoof wall was performed for this purpose. Additionally, a plaque-like, hyperkeratotic pigmented lesion, 2 × 2X0,4 cm in size, was observed at the lateral aspect of the coronary band and was also resected for histopathological examination. Microscopically, a melanocytic tumour, characterised by small nests of large polygonal or epithelioid cells infiltrating the basal and suprabasal epidermis, the dermo – epidermal junction, and the superficial dermis, was observed. The neoplastic cells exhibited large euchromatic nuclei, prominent nucleoli, moderate pleomorphism and 4 mitotic figures per 2,37mm2; variable amounts of dark granules (melanin) were present in the cytoplasm, as well as in numerous peritumoral macrophages. The immunophenotype of the tumour cells was PNL2 + + + , S100 + + , AE1/AE3-. A diagnosis of melanoma with dermo-epidermal junction and marked intraepidermal activity (consistent with superficial spreading melanoma) was made.A magnetic resonance imaging (MRI) performed, revealed no further invasion into surrounding structures. Treatment was based on surgical resection and multiple local chemotherapy sessions with cisplatin were applied. The biopsies obtained after treatment showed partial regression of the tumour and different stages of healing. After 26 months of follow-up, there was no signs of malignant spreading into surrounding structures including the pedal bone and distal metastasis but a dark – coloured area persists over the lateral aspect of the coronary band.ConclusionsThis case presents a concomitant keratoma and melanoma with dermo – epidermal activity, resembling a spreading superficial melanoma. After a follow – up of 26 months the horse remains healthy and sound providing new information for clinicians and pathologists. Despite the poor prognosis associated with foot malignant melanocytic tumours, it is important that an early and accurate diagnosis is reached through different diagnostic modalities such as advanced imaging techniques and histopathology. Additionally, these findings demonstrate that the current classification and prognosis for equine foot melanomas are insufficient.

An overview of bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune bullous skin disease that causes blistering due to the presence of immunoglobulin G antibody/antigen complexes at the dermal-epidermal junction. Primarily seen in people over the age of 60, BP can be triggered by medications, infections, comorbidities, and environmental skin stressors. The clinical presentation of BP begins with non-bullous patches that may resemble eczema or urticaria; this stage is followed by the development of tense vesiculobullous lesions in flexural areas that usually heal without scarring. Erosions sometimes develop on mucous membranes such as the oral cavity or genitalia. The diagnosis is made by using direct immunofluorescence on punch biopsy samples taken from perilesional skin, which will show the linear deposits of immunoglobulin G antibody/antigen complexes along the dermal-epidermal junction. Salt-split skin testing can also confirm the direct immunofluorescence results. Treatment options include the removal of any triggering factors and the use of topical or oral corticosteroids. If prolonged treatment is required, steroid-sparing medications such as immunosuppressants, immunoglobulins, monoclonal antibody agents, or doxycycline can be combined to achieve satisfactory results. BP causes an increased risk of developing pulmonary emboli or stroke, but most patients will be able to achieve remission after 6–60 months of treatment without further complications.

Brein en blaren: een bijzondere band

Bullous pemphigoid (BP) is a dermatological autoimmune disease characterized by itch and blisters. Sometimes the blisters are preceded by years of itching and eczematous patches, which can cause a delay in recognition of BP. The disease is caused by production of autoantibodies against the hemidesmosomal proteins BP180 and BP230 at the dermal-epidermal junction. An association between BP and neurodegenerative disorders, such as Parkinson’s disease, is known. However, this association is not commonly known amongst health care professionals, but is of clinical significance. Neurodegenerative disorders (including Parkinson’s disease) are thought to disrupt the blood brain barrier, resulting in exposure of neuronally located BP180 and BP230 to the immune system. In most studies that have examined the association between BP and Parkinson’s disease (and other neurodegenerative disease), BP develops several years after the diagnosis of Parkinson’s. We present a case of a patient with proven bullous pemphigoid who developed clinical features of Parkinson’s disease during follow-up at the dermatology outpatient clinic. After neurological analysis, the patient most likely suffered from long-standing Parkinson’s disease.

A New TGF-β Mimetic, XEP™-716 Miniprotein™, Exhibiting Regenerative Properties Objectivized by Instrumental Evaluation.

Skin aging, which results from intrinsic and extrinsic factors, is characterized by a rough, uneven and wrinkled appearance of the skin at the macroscopic level. At the microscopic level, aging shows lowered keratinocyte turnover, flattened dermal-epidermal junction and reduced collagen fiber density; however, use of skin biopsies to evaluate characteristic properties of these microscopic changes is too limiting for panelists and rarely used. The development of non-invasive techniques is an opportunity to be considered for such evaluations. Our objective was to demonstrate the rejuvenating effects of XEP™-716 Miniprotein™ on skin, a miniprotein having TGF-β beta-like properties, in vitro on normal human fibroblasts and at the clinical level. In vitro, the skin rejuvenation properties of XEP™-716 Miniprotein™ were studied by quantification of well-known dermal components such as collagen type I, hyaluronic acid and elastin. At the clinical level, we used a non-invasive technique, the confocal laser scanning microscopy (CLSM) system, which enabled non-invasive morphological characterization of skin structures (stratum corneum thickness, viable epidermis, full epidermis, dermal-epidermal junction, papillae, dermal collagen density) and high-frequency ultrasonography to quantify the dermal density and thickness, which are useful parameters for quantifying rejuvenating effects on skin. Lastly, a cutometer was used to assess the skin's biomechanical properties, mainly firmness and elasticity. This monocentric double-blind, split-face, randomized, placebo-controlled clinical trial compared the active ingredient XEP™-716 Miniprotein™ in a vehicle on one hemiface versus vehicle alone on the other (placebo) and enrolled panelists aged 40 to 60years old. All measurements were carried out on the malar area before and after 28 and 56days of twice daily application of a cosmetic cream formulation containing either 2.5% or 5% XEP™-716 Miniprotein™. The skin rejuvenating properties were demonstrated by studying dermo-epidermal junction (DEJ) flattening reduction using the measure of two parameters by CLSM: the DEJ length and number of edged papillae. Dermis rejuvenation was assessed by measuring the collagen fiber perimeters (CLSM), dermal density and dermal thickness (ultrasonography). The in vitro results confirmed the ability of XEP™-716 Miniprotein™ to stimulate the key extracellular macromolecules, namely collagen type I, hyaluronic acid and elastin, at a level comparable to that induced by TGF beta growth factor. The clinical data showed that after 28 and 56days of topical XEP™-716 Miniprotein™ application, there was a statistically significant increase of DEJ length, number of edged papillae and collagen fiber perimeters. At the same time point, the B-scan images of facial skin showed a statistically significant increase of dermal density and thickness. These results reveal that the DEJ became more undulated and tightly attached to the dermis, while the papillary dermis was densified, both traits being typical characteristic of younger skin. Rejuvenation was also confirmed by an improvement of skin firmness and elasticity. The in vitro and clinical results presented in this article show that XEP™-716 Miniprotein™ is a potent ingredient to rejuvenate the DEJ and dermis of mature skin.

Exosomes, peptides and peri-procedure management – comparative investigations

Introduction: Exosome technology is a promising new advancement in therapeutic options but is still in its early stages, leading to uncertainties. A small pilot study compared traditional peptide technology (Regenerating Skin Nectar with TriHex Technology® and TriHex Technology® peptide + Octapeptide) to two leading exosome products (Stem cell derived Lyophilized exosomes and Platelet derived exosomes) for post-procedure use. These studies were carried out on pre-clinical (ex vivo) and clinical front to investigate effects on the extracellular matrix, dermo-epidermal junction, and skin tolerance as post-procedure outcomes. Methods and materials: The ex vivo model study was conducted by 3D Genomics using photodamaged skin from facelift patients. The skin was divided, processed under BSL2 conditions and cultured in transwells with specific media. Treatments, including peptides and platelet-derived products, were applied daily for 7 days, while stem cell-derived exosomes were applied as a single application as per the described usage. One set was left untreated as a control. Skin samples were treated and analyzed using immunohistochemistry staining for tropoelastin and CD44. RNA was isolated after treatments and sequenced to assess changes in gene expression. The study aimed to compare the effects of different treatments on skin regeneration and tolerance. Clinically, the participants underwent microneedling of the face and applied exosomes and peptides on each side of the face as comparisons. Participants completed questionnaires on Day 0. On Days 0,1,2,3 and 4 participants completed their self-healing ratings and were also assessed by an assessor on their healing rating on a 5-point scale. Results: The plated exosome products exhibited significant toxicity in the ex vivo model and neither of the exosome products produced relevant changes in gene expression or regenerative effects in this model. Participants in the small clinical series experienced unpleasant burning and stinging in keeping with the effects seen in the ex vivo model. In contrast, the peptide technology showed favorable gene expression upregulation and histological changes in the extracellular matrix and was well-tolerated and comfortable for post-procedure use, as has been demonstrated in multiple clinical trials. Conclusion: The overall impression from these pilot studies suggests that peptide formulations are better tolerated and more effectively target ECM regenerative effects. Conversely, exosome preparations appear to be prone to skin reactions and lack clear targeting of skin regenerative pathways.

Interobserver agreement on line-field confocal optical coherence tomography image markers in keratinocyte carcinomas and precursor lesions

Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association between reported image markers and lesion types, was determined. Six evaluators blinded to histopathologic diagnoses, assessed 75 LC-OCT images of KC (21 SCC; 21 BCC), CIS (12), and AK (21). For each image, evaluators independently reported the presence or absence of 10 predefined key image markers of KCs and precursors described in an LC-OCT literature review. Evaluators were stratified by experience-level as experienced (3) or novices (3) based on previous OCT and reflectance confocal microscopy usage. IOA was tested for all groups, using Conger’s kappa coefficient (κ). The frequency of reported image marker and their association with lesion-types, were calculated as proportions and odds ratios (OR), respectively. Overall IOA was highest for the image markers lobules (κ = 0.68, 95% confidence interval (CI) 0.57;0.78) and clefting (κ = 0.63, CI 0.52;0.74), typically seen in BCC (94%;OR 143.2 and 158.7, respectively, p < 0.001), followed by severe dysplasia (κ = 0.42, CI 0.31;0.53), observed primarily in CIS (79%;OR 7.1, p < 0.001). The remaining seven image-markers had lower IOA (κ = 0.06–0.32) and were more evenly observed across lesion types. The lowest IOA was noted for a well-defined (κ = 0.07, CI 0;0.15) and interrupted dermal-epidermal junction (DEJ) (κ = 0.06, CI -0.002;0.13). IOA was higher for all image markers among experienced evaluators versus novices. This study shows varying IOA for 10 key image markers of KC and precursors in LC-OCT images among evaluators new to the technology. IOA was highest for the assessments of lobules, clefting, and severe dysplasia while lowest for the assessment of the DEJ integrity.

Comparison of facial skin ageing in healthy Asian and Caucasian females quantified by in vivo line-field confocal optical coherence tomography 3D imaging.

Quantitative biomarkers of facial skin aging were investigated in 109 healthy Asian female volunteers, aged 20 to 70 years. In vivo 3D Line-field Confocal Optical Coherence Tomography (LC-OCT) imaging, enhanced by Artificial Intelligence (AI)-based quantification algorithms, was utilized to compute various metrics, including stratum corneum thickness (SC), viable epidermal (VE) thickness, and Dermal-Epidermal Junction (DEJ) undulation along with cellular metrics for the temple, cheekbone, and mandible. Comparison with data from a cohort of healthy Caucasian volunteers revealed similarities in the variations of stratum corneum and viable epidermis layers, as well as cellular shape and size with age in both ethnic groups. However, specific findings emerged, such as larger, more heterogeneous nuclei in both layers, demonstrated by an increase in nuclei volume and their standard deviation, and increased network atypia, all showing significant age-related variations. Caucasian females exhibited a flatter and more homogeneous epidermis, evidenced by a decreased standard deviation of the number of layers, and a less dense cellular network with fewer cells per layer, indicated by a decrease in cell surface density. Ethnicity-wise comparisons highlighted distinct biological features specific to each population. Asian individuals showed significantly higher DEJ undulation, higher compactness, and lower cell network atypia compared to their Caucasian counterparts across age groups. Differences in stratum corneum and viable epidermal thickness on the cheekbone were also significant. LC-OCT 3D imaging provides valuable insights into the aging process in different populations and underscores inherent biological differences between Caucasian and Asian female volunteers.

Paxbp1 Is Indispensable for the Maintenance of Epidermal Homeostasis

The mammalian epidermis is a structurally complex tissue that serves critical barrier functions, safeguarding the organism from the external milieu. The development of the epidermis is governed by sophisticated regulatory processes. However, the precise mechanism maintaining epidermal homeostasis remains incompletely elucidated. Recent studies have identified Paxbp1, an evolutionarily conserved protein, as being involved in the developmental regulation of various cells, tissues, and organs. Nonetheless, its role in skin development has not been explored. Here, we report that the targeted deletion of Paxbp1 in epidermal keratinocytes mediated by Keratin14-Cre leads to severe disruption in skin architecture. Mice deficient in Paxbp1 exhibited a substantially reduced epidermal thickness and pronounced separation at the dermo-epidermal junction upon birth. Mechanistically, we demonstrate that the absence of Paxbp1 hinders cellular proliferation, marked by a halt in cell cycle transition, suppressed gene expression of proliferation, and a compromised DNA replication pathway in basal keratinocytes, resulting in the thinning of the skin epidermis. Moreover, molecules and pathways associated with hemidesmosome assembly were impaired in Paxbp1-deficient keratinocytes, culminating in the detachment of the skin epidermal layer. Therefore, our study highlights an indispensable role of Paxbp1 in the maintenance of epidermal homeostasis.

Epidermal renewal during the treatment of atopic dermatitis lesions: A study coupling line‐field confocal optical coherence tomography with artificial intelligence quantifications

AbstractObjectiveThis study explores the application of Line‐field Confocal Optical Coherence Tomography (LC‐OCT) imaging coupled with artificial intelligence (AI)‐based algorithms to investigate atopic dermatitis (AD), a common inflammatory dermatosis.Materials and methodsAD acute and chronic lesions (ADL) were compared to clinically healthy‐looking skin (ADNL). LC‐OCT was used noninvasively and in real‐time to image the skin of AD patients during flare‐ups and monitor remissions under topical steroid treatment for 2 weeks. Quantitative parameters were extracted from the images, including morphological and cellular‐level markers of epidermal architecture. A novel cellular‐level parameter, nuclei “atypia,” which quantifies the orderliness of epidermal renewal, was used to highlight abnormal maturation processes.ResultsCompared to healthy skin, AD lesions exhibited significant increases in both epidermal and stratum corneum (SC) thickness, along with a more undulated dermo‐epidermal junction (DEJ). Additionally, keratinocyte nuclei (KN) were larger, less compact, and less organized in lesional areas, as indicated by the atypia parameter. A higher degree of atypia was observed in chronic lesions compared to acute ones. Following treatment, all the parameters normalized to levels observed in healthy skin within 2 weeks, mirroring clinical improvements.ConclusionThis study provides insights into the quantification of epidermal renewal using a noninvasive imaging technique, highlighting differences between ADL/ADNL and acute/chronic lesions. It also presents the AD treatment mechanism, paving the way for future investigations on AD and other skin barrier function‐related conditions.

Anti-Laminin β4 IgG Drives Tissue Damage in Anti-p200 Pemphigoid and Shows Interactions with Laminin α3 and γ1/2 Chains

Laminin β4 was recently identified as a structural component of the dermal-epidermal junction and autoantigen of anti-p200 pemphigoid. In this study, we provided further evidence of the pathogenic effect of anti-laminin β4 IgG and identified potential binding partners of laminin β4. We showed that laminin β4 immune complexes led to activation of normal leukocytes and dose-dependent ROS release. Using cryosections of normal skin, we demonstrated that anti-laminin β4 patient serum IgG but not anti-laminin γ1 IgG, which are also detectable in patients with anti-p200 pemphigoid, cause dermal-epidermal separation in the presence of leukocytes. Proximity ligation assay and indirect immunofluorescence staining suggested that laminin β4 localizes closely to laminin α3 and γ2 in primary keratinocytes. Subsequent coimmunoprecipitation experiments using epidermal extracts confirmed the interaction of laminin β4 with the α3 and γ2 chains and indicated additional affinity to laminin γ1. The laminin β4-α3/β4-γ1 protein complexes were also detected using mass spectrometry. In conclusion, this study showed that anti-laminin β4 IgG can exert tissue damage in the skin, supporting their pathogenic role in anti-p200 pemphigoid. Our data further provide strong evidence for an interaction of laminin β4 with laminin α3, whereas its association to the laminin γ1 and γ2 chains is ambiguous.

Novel readthrough agent suppresses nonsense mutations and restores functional type VII collagen and laminin 332 in epidermolysis bullosa

Recessive Dystrophic Epidermolysis Bullosa (RDEB) and Junctional Epidermolysis Bullosa (JEB) are lethal blistering skin disorders resulting from mutations in genes coding for type VII collagen (COL7A1) and laminin 332 (LAMA3, LAMB3, or LAMC2), respectively. In RDEB, 25% of patients harbor nonsense mutations causing premature termination codons (PTCs). In JEB, a majority of mutations in LAMB3 are nonsense mutations (80%). ELX-02, an aminoglycoside analog, has demonstrated superior PTC readthrough activity and lower toxicity compared to gentamicin in various genetic disorders. This study investigated ELX-02's ability to suppress PTCs and promote the expression of C7 and laminin 332 in primary RDEB keratinocytes/fibroblasts and primary JEB keratinocytes harboring nonsense mutations. ELX-02 induced a dose-dependent production of C7 or laminin β3 that surpassed the results achieved with gentamicin. ELX-02 reversed RDEB and JEB cellular hypermotility and improved poor cell-substratum adhesion in JEB cells. Importantly, ELX-02-induced C7 and laminin 332 localized to the dermal-epidermal junction. This is the first study demonstrating that ELX-02 can induce PTC readthrough and restore functional C7 and laminin 332 in RDEB and JEB caused by nonsense mutations. Therefore, ELX-02 may offer a novel and safe therapy for RDEB, JEB, and other inherited skin diseases caused by nonsense mutations.

Diagnosis of autoimmune bullous dermatoses: Comparative analysis of immunohistochemical staining using C4d, C3d, IgG, and IgG4 in lesional tissues and perilesional frozen skin samples

Immunohistochemical staining with immunoglobulins and complements may aid the diagnosis of patients whose clinical and histological findings are consistent with autoimmune bullous dermatoses (AIBD). We aimed to investigate the diagnostic value of immunohistochemical markers in lesional biopsy and perilesional frozen samples in AIBD. We included 136 cases from whom lesional biopsies and perilesional samples for direct immunofluorescence (DIF) examination were collected with a preliminary diagnosis of AIBD between January 2019 and January 2023. All diagnoses were reconfirmed by evaluating the clinical, histopathological, and serological findings and DIF results (C3, IgG, IgA, or IgM positivity compatible with the clinical diagnosis) altogether, although DIF results were considered a priority. After confirming the diagnoses, the samples were categorized as AIBD or the others. The perilesional tissues obtained for DIF simultaneously with skin biopsy and stored at −80 °C were thawed, and FFPE tissues were prepared. We performed immunohistochemical staining (C4d, C3d, IgG, and IgG4) on FFPE tissues of both lesional and perilesional samples. Strong, linear, or granular staining patterns at the dermoepidermal junction or the intraepidermal blistering space were considered positive in line with the diagnosis of the case. Cases other than AIBD were used as negative control tissues to assess the specificity of immunohistochemical markers. Of the 136 cases, 52 were diagnosed with AIBD. In lesional samples, the sensitivity of C4d, C3d, IgG, and IgG4 was 80.6 %, 69.4 %, 75 %, and 5.7 % with corresponding specificity of 100 %, 98.7 %, 89.6 %, and 97.4 %, respectively in pemphigoid diseases compared to a sensitivity of 18.2 %, 9.1 %, 70 %, and 9.1 % and specificity of 98.7 %, 100 %, 89.6 %, and 97.4 %, respectively in pemphigus diseases. In frozen samples, we detected expression in a limited number of cases. The sensitivity of C4d, C3d, IgG, and IgG4 was 8.7 %, 2.2 %, 19.4 %, and 2.2 %, with corresponding specificity of 100 %, 100 %, 98.5 %, and 98.6, respectively. There was a none to slight concordance rate between the IHC results of lesional tissues and perilesional frozen samples. Kappa coefficients for C4d, C3d, IgG, and IgG4 were 0.120 (P = 0.029), 0.111 (P = 0.050), 0.203 (P = 0.003), and - 0.15 (P = 0.846), respectively. Immunohistochemical staining with C4d, C3d, IgG, and IgG4 on biopsy samples collected from lesions may guide the diagnosis of AIBD, thereby eliminating the need for an additional biopsy and accelerating the diagnostic process.

Novel Thermus thermophilus and Bacillus subtilis mixed-culture ferment extract provides potent skin benefits invitro and protects skin from aging.

Skin aging is one of the most abundant aging-related disorders that can be accelerated by excessive exposure to ultraviolet irradiation. Topically applied fermented skincare ingredients have gained mounting attentions due to their high concentration of various skin nourishing nutrients and bioactive components and low skin irritation potency. In the present study, we aim to fully demonstrate the skin-related benefits of a novel extract of Thermus thermophilus and Bacillus subtilis mixed-culture ferment (TBFE). TBFE was prepared through an innovative mixed-culture fermentation process. The contents of nutrients and bioactive ingredients were quantified by different methods accordingly. Both invitro tests and randomized controlled human trial were utilized to further demonstrate multifaceted beneficial effects on human skin, as well as the potential mechanisms. Our results showed that TBFE upregulated the expression of type IV collagen, elastin, aquaporin-3, and dermal-epidermal junction markers, while inhibited production of melanin, in different skin cell models. Moreover, TBFE inhibited the generation of reactive oxygen species and pro-inflammatory mediators induced by ultraviolet irradiation in normal human keratinocytes, while stimulated autophagy in senescent keratinocytes. Results from clinical studies confirmed those invitro findings, demonstrating that TBFE at 5% and 20% concentration provides anti-aging properties in subjects with sensitive skin, in terms of improving wrinkles, moisturization, and skin lightening. In summary, we demonstrate that a novel mixed-culture ferment extract has promising anti-aging effects, which may be attributed to anti-oxidation, anti-inflammation, and promotion of autophagy in skin cells.

Cosmetic retinoid use in photoaged skin: A review of the compounds, their use and mechanisms of action.

The inevitable attrition of skin due to ultraviolet radiation, termed photoaging, can be partially restored by treatment with retinoid compounds. Photoaged skin in lightly pigmented individuals, clinically presents with the appearance of wrinkles, increased laxity, and hyper- and hypopigmentation. Underlying these visible signs of ageing are histological features such as epidermal thinning, dermal-epidermal junction flattening, solar elastosis and loss of the dermal fibrillin microfibrillar network, fibrillar collagen and glycosaminoglycans. Retinoid compounds are comprised of three main generations with the first generation (all-trans retinoic acid, retinol, retinaldehyde and retinyl esters) primarily used for the clinical and cosmetic treatment of photoaging, with varying degrees of efficacy, tolerance and stability. All-trans retinoic acid is considered the 'gold standard' for skin rejuvenation; however, it is a prescription-only product largely confined to clinical use. Therefore, retinoid derivatives are readily incorporated into cosmeceutical formulations. The literature reported in this review suggests that retinol, retinyl esters and retinaldehyde that are used in many cosmeceutical products, are efficacious, safe and well-tolerated. Once in the skin, retinoids utilize a complex signalling pathway that promotes remodelling of photoaged epidermis and dermis and leads to the improvement of the cutaneous signs of photoaging.

An overview of S100 proteins and their functions in skin homeostasis, interface dermatitis conditions and other skin pathologies.

S100 proteins comprise a family of structurally related proteins that are calcium-sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti-microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal-epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies.

Anti-IL-17 monoclonal antibodies and bullous pemphigoid: treatment or causal agents? A case series and review of the literature.

Bullous pemphigoid (BP) is an autoimmune bullous disease, typically affecting the elderly, characterized by the production of autoantibodies directed against structural components of the dermal-epidermal junction. An association between BP and psoriasis has been described several times, but the mechanisms underlying this association have yet to be clearly defined. The pathophysiological mechanism underlying psoriasis may be implicated in the pathogenesis of BP, as psoriasis precedes BP in most cases; in particular, a promoting role has been hypothesized by biologic therapies, which may induce a switch from a T helper 1 (TH1)/TH17-dominant cytokine milieu, typical of patients with psoriasis, to a TH2-dominant one, typical of patients with BP. IL-17 inhibitors, in particular, have also been successfully used to treat BP in patients with psoriasis. The use of these drugs in these patients has been based on in vitro studies. However, cases of new-onset BP or relapses of BP already diagnosed in patients with psoriasis treated with biologic drugs have also been reported, and they occurred mainly in patients on anti-TNF drugs, yet very few cases with anti-IL-17A drugs have been described. We hereby describe two cases of new-onset BP in two patients treated with anti-IL-17 drugs for psoriasis.