Destruction Of Hair Follicles Research Articles

Laser-Induced Koebner-Related Skin Reactions: A Clinical Overview.

The Koebner phenomenon (KP), also known as the isomorphic response, describes the process by which new lesions that are clinically and histologically identical to a patient's existing skin disease develop following trauma. Many skin diseases exhibit this characteristic, with variations that include possible, questionable, and pseudo-Koebner reactions, with the latter category occurring due to infectious agents seeding at a trauma site. Laser application, a type of controlled skin injury used for improving cutaneous lesions and skin rejuvenation, is also considered a form of trauma. This raises the question of whether controlled thermal injury can be regarded as a type of mechanical trauma capable of producing Koebner-related reactions. We conducted a literature review of cases or studies to identify laser-induced dermatoses that correspond to Koebner-related or pathergy reaction categories. As a whole, we identified nine case reports on true KPs, two cases on possible KPs, seventeen cases on laser-induced questionable KPs comprising cases of vasculitis, eczema or Meyerson reactions, and eruptive squamous atypia cases (ESA) as well as two pseudo-Koebner cases involving wart occurrences at laser application sites. Laser-induced Koebner reactions highlight several aspects of the KP. Firstly, the type of mechanical damage influences disease promotion, as different lasers are associated with different KPs. For example, hair removal lasers are linked with true and questionable KPs such as vasculitis while resurfacing lasers were found to be more connected with ESA occurrence. Secondly, the laser target is significant, with vascular laser application for port-wine stains tending to result in eczematous reactions, while hair follicle destruction can frequently lead to true KPs. Thirdly, the number of sessions matters; true KPs and eruptive squamous atypia questionable KPs typically appear after one to two sessions, whereas eczematous reactions require more sessions (at least four). Additionally, skin phototype is crucial, with darker phototypes showing a higher KP frequency as laser treatment for hypertrichosis relies on melanin absorption in the hair bulge or bulb for follicle destruction, as chromophore competes with the abundant melanin in the epidermis. Further research with larger-scale studies into trauma-specific Koebner reactions is vital for refining treatment protocols, minimizing post-laser adverse effects, and improving dermatological care outcomes.

Novel treatment of alopecia areata with shooting-type candlelit-dissolving microneedle

Alopecia areata (AA) is a T lymphocyte-mediated autoimmune disorder characterized by targeted hair follicle destruction that significantly affects the quality of life of patients. Conventional therapeutic strategies, including the topical application of triamcinolone acetonide (TA), face challenges owing to suboptimal cutaneous permeability and inconsistent intradermal injection techniques, which contribute to adverse effects and patient distress. In this study, we developed a shooting-type TA-encapsulated candlelit-dissolving microneedle (TCD) utilizing hyaluronic acid (HA) and polyvinylpyrrolidone (PVP) to address these limitations. In vitro evaluation using human outer root sheath cells demonstrated the ability of TCD to effectively reduce inflammation. Furthermore, in vivo analysis using a novel AA-induced C3H/HeJ mouse model revealed the efficacy of TCD in promoting hair growth and alleviating AA-related inflammatory processes. This innovative TCD applicator design overcomes the shortcomings of the prevailing TA treatments and provides a promising alternative approach for enhanced AA management. This study lays a foundation for future research focusing on optimizing TCD, assessing its long-term efficacy, and exploring its applicability in the treatment of other dermatological conditions. By integrating cutting-edge scientific discoveries, TCD can improve AA treatment outcomes.

1338 Epidermal growth factor receptor protects from immune privilege collapse and scarring hair follicle destruction

1338 Epidermal growth factor receptor protects from immune privilege collapse and scarring hair follicle destruction

SCARRING ALOPECIA DURING DISCOID LUPUS ERYTHEMATOSUS, CLINICAL CASE

Discoid Lupus Erythematosus is usually localized on the open areas. On the scalp it causes dilatation and plugging of hair follicles with adherent scales, this leads to destruction of hair follicles and permanent alopecia. Initial manifestation of disease can be difficult to recognize. Early visit to Dermatologist is recommended. Differential diagnosis of scarring alopecia include trauma, burn, tinea capitis, lichen planus, scalp psoriasis, sarcoidosis and alopecia areata.

Ox40-Cre-mediated deletion of BRD4 reveals an unexpected phenotype of hair follicle stem cells in alopecia.

BRD4 is a bromodomain extraterminal domain family member and functions primarily as a chromatin reader regulating genes involved in cell-fate decisions. Here, we bred Brd4fl/fl Ox40-Cre mice in which Brd4 was conditionally deleted in OX40-expressing cells to examine the role of BRD4 in regulating immune responses. We found that the Brd4fl/fl Ox40-Cre mice developed profound alopecia and dermatitis, while other organs and tissues were not affected. Surprisingly, lineage-tracing experiments using the Rosa26fl/fl-Yfp mice identified a subset of hair follicle stem cells (HFSCs) that constitutively express OX40, and deletion of Brd4 specifically in such HFSCs resulted in cell death and a complete loss of skin hair growth. We also found that death of HFSCs triggered massive activation of the intradermal γδ T cells, which induced epidermal hyperplasia and dermatitis by producing the inflammatory cytokine IL-17. Interestingly, deletion of Brd4 in Foxp3+ Tregs, which also constitutively express OX40, compromised their suppressive functions, and this, in turn, contributed to the enhanced activation of γδ T cells, as well as the severity of dermatitis and hair follicle destruction. Thus, our data demonstrate an unexpected role of BRD4 in regulating skin follicle stem cells and skin inflammation.

Demodicosis

A 75-year-old female presented with swelling and redness on the left lower lid away from the lid margin since 10 days. The best corrected visual acuity in both eyes is 6/6 and N6. On examination, an erythematous ulcerative lesion with rolled edges and central necrosis on the left malar area was seen clinically mimicking basal cell carcinoma. Excision biopsy was performed, and the histopathology report revealed an inflamed follicle with intra-follicular demodex folliculorum with ulceration and suppurative abscess with necrotizing destruction of hair follicles. The patient was treated with topical ciprofloxacin ointment. Follow-up after 3 weeks showed complete resolution of the lesion with no recurrence at 3 months.

HSD120 Real-World Treatment Patterns Among US Adults with Alopecia Areata: A Retrospective Claims Analysis

Alopecia areata (AA) is an autoimmune disorder causing destruction of hair follicles resulting in non-scarring hair loss. This study aimed to characterize treatment patterns among adult patients with AA in the US who received treatment.

Topical immunotherapy for alopecia areata: A successful diphenylcyclopropenone protocol

Alopecia areata (AA) is an autoimmune disorder that involves the destruction of anagenic hair follicles, resulting in non-scarring patchy hair loss. The patient presented in the following case had not seen improvement by use of conventional treatments and was started on topical immunotherapy, diphenylcyclopropenone (DPCP). This agent is commonly left as a last resort due to its constant need for follow-up, clinician-required administration, and risk of adverse effects. The following case presents a titration schedule using DPCP, resulting in minimal adverse effects and dramatic improvement in hair regeneration.

Clinical, Dermoscopic and Histopathologic Features of Cicatricial AlopeciaA Prospective Cohort Study

Introduction: Cicatricial Alopecia (CA) is a scarring form that arises due to permanent hair follicle destruction. It can either primarily affect the follicles or by an external process leads to secondary alopecia causing scarring and considerable disfigurement of the scalp. Hence initial diagnosis, aetiology of the contributing factors and earlier intervention are vital. Aim: To identify the diagnostic features of CA based on clinical, dermoscopic and histopathological (HP) findings and the underlying aetiological causes. Materials and Methods: This prospective cohort study was conducted in a tertiary care centre of Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India from November 2016 to September 2017. Total 50 clinically diagnosed CA cases were randomly selected and case history, related skin findings, predisposing factors and other findings associated with scarring were documented. Dermatological examination and Hair pull test was done. Trichoscopic examination was done using a non polarized dermoscopy with specific emphasis on the follicular ostia and morphological patterns. Scalp biopsy was done. The collected data were analysed in terms of frequency and percentage and Chi-square test was also performed with p-value <0.05 as statistically significant. Results: Out of total 50 patients, 22 (44%) were males, and 28 (56%) females with the mean age of 35.46±15.03 years. Total 29 (58%) patients had multiple lesions and 21 (42%) had localized involvement of alopecia in the scalp. Focal type was noted in 86%, and diffuse type in 14%. In this study, 80% of CA were of primary causes with only 20% secondary causes. Lichen Plano Pilaris (LPP) and trauma were the most common primary and secondary causes. The dermoscopic features of absent follicular orifice, arborising thicker blood vessel and pustule formation were statistically significant (p-value <0.001) for the diagnosis of CA. The most common histopathological feature was basal cell vacuolization (54%), followed by hyperkeratosis (52%), and follicular plugging (46%). Conclusion: The clinical, dermoscopic and histopathological findings of this study were consistent for diagnosis and differentiating primary CA. Histopathology is the final confirmatory diagnostic tool when characteristic clinical and dermoscopic features are absent.

Dissecting the Roles of Innate Cells in the Skin and Intractable Skin Diseases.

The skin is not merely a physical barrier but also an active immunological interface, exposed to various external stimuli including microbes. Over the recent years, our laboratory has defined hair follicles as control towers that regulates immune cells residing in the skin. Hair follicles produce chemokines and cytokines that are crucial for the localization and tissue-residency of immune cells including the Langerhans cells, resident memory T cells, and innate lymphoid cells. We also discovered that disruption of the ADAM17-EGF receptor axis and ADAM10-Notch signaling axis leads to dysbiosis on the skin surface and in the hair follicles, respectively. The former leads to microbiome predominance of Staphylococcus aureus and results in atopic skin inflammation, whereas the latter leads to Corynebacterium species predominance that trigger irreversible hair follicle destruction. These findings highlight the distinct mechanisms that regulate the microbiome in different compartments of the skin. In this talk, I will focus on the deeper layers of the skin-the hypodermis (a.k.a subcutaneous tissue), a common site for cellulitis, which we found to be enriched with macrophages. We enabled layer-specific depletion of macrophages, which had prominent effects on the organization of the extracellular matrix, counterintuitively rendering mice highly protected against S. aureus-mediated cellulitis. I will also introduce our ongoing efforts to understand the histology and pathophysiology of Degos disease, an extremely rare and highly fatal disease of unknown etiology.

English

BACKGROUND Cicatricial alopecia is the term used for permanent areas of hair loss due to destruction of hair follicles. It may occur due to a disease that primarily affects hair follicles or due to external causes that damages hair follicle secondarily. The common causes of primary cicatricial alopecia include discoid lupus erythematosus, lichen plano pilaris, pseudopelade of Brocq, folliculitis decalvans and folliculitis keloidalis. Exact diagnosis at an early stage will help to provide disease specific management at the earliest thus, preventing further progression of the disease. We conducted this study to assess the role of clinico-pathological correlation to find out the exact aetiology of primary scarring alopecia in our patients. METHODS We conducted a descriptive cross sectional study to find out aetiology of primary cicatricial alopecia based on clinical and histopathological findings of 50 patients who attended the outpatient department of Dermatology in our hospital. After a detailed history and clinical examination of scalp, biopsy of lesional scalp skin was taken in all patients. In relevant cases direct immunofluorescence study was also done. RESULTS Age of the patients ranged from 16-75 years. M: F ratio was 1:1.5. Hair loss, itching, scaling and scalp pain were the reported symptoms. Commonly affected sites were parietal and temporal areas. 76 % of patients had multiple lesions. Absent follicular ostia, follicular plugging, atrophy, pigmentary changes, scaling and telangiectasias were the commonly observed clinical scalp findings. 88 % of cases showed lymphocytic infiltrate on histopathology. After clinico-pathological correlation, 48% patients had discoid lupus erythematosus followed by follicular lichen planus in 28% and pseudopelade of Brocq in 20 % cases. Folliculitis decalvans and folliculitis keloidalis each were observed in 2 % cases of primary scarring alopecia. CONCLUSIONS Clinicopathological correlation is highly useful to make an early diagnosis in primary cicatricial alopecia. In our patients discoid lupus erythematosus was found to be the predominant cause. KEY WORDS Cicatricial Alopecia, Clinicopathological Correlation, Discoid Lupus Erythematosus, Lichen Planus

Scarring Alopecias: Pathology and an Update on Digital Developments.

Primary cicatricial alopecias (PCA) represent a challenging group of disorders that result in irreversible hair loss from the destruction and fibrosis of hair follicles. Scalp skin biopsies are considered essential in investigating these conditions. Unfortunately, the recognised complexity of histopathologic interpretation is compounded by inadequate sampling and inappropriate laboratory processing. By sharing our successes in developing the communication pathway between the clinician, laboratory and histopathologist, we hope to mitigate some of the difficulties that can arise in managing these conditions. We provide insight from clinical and pathology practice into how diagnoses are derived and the key histological features observed across the most common PCAs seen in practice. Additionally, we highlight the opportunities that have emerged with advances in digital pathology and how these technologies may be used to develop clinicopathological relationships, improve working practices, enhance remote learning, reduce inefficiencies, optimise diagnostic yield, and harness the potential of artificial intelligence (AI).

Disruption of the endopeptidase ADAM10-Notch signaling axis leads to skin dysbiosis and innate lymphoid cell-mediated hair follicle destruction

Hair follicles (HFs) function as hubs for stem cells, immune cells, and commensal microbes, which must be tightly regulated during homeostasis and transient inflammation. Here we found that transmembrane endopeptidase ADAM10 expression in upper HFs was crucial for regulating the skin microbiota and protecting HFs and their stem cell niche from inflammatory destruction. Ablation of the ADAM10-Notch signaling axis impaired the innate epithelial barrier and enabled Corynebacterium species to predominate the microbiome. Dysbiosis triggered group 2 innate lymphoid cell-mediated inflammation in an interleukin-7 (IL-7) receptor-, S1P receptor 1-, and CCR6-dependent manner, leading to pyroptotic cell death of HFs and irreversible alopecia. Double-stranded RNA-induced ablation models indicated that the ADAM10-Notch signaling axis bolsters epithelial innate immunity by promoting β-defensin-6 expression downstream of type I interferon responses. Thus, ADAM10-Notch signaling axis-mediated regulation of host-microbial symbiosis crucially protects HFs from inflammatory destruction, which has implications for strategies to sustain tissue integrity during chronic inflammation.

100 Pathogenic CD8+ T cells form cytolytic immune synapses to mediate hair follicle destruction in Alopecia Areata

100 Pathogenic CD8+ T cells form cytolytic immune synapses to mediate hair follicle destruction in Alopecia Areata

Needle-nerve interaction in acupuncture: A morphological study.

Some acupuncture effects are considered to be caused by interaction with nerve structures in and around the acupoints. The aim of the present study was to investigate the nerve structures that interact with the needle in acupuncture and to present their distribution in acupoint tissues. To do this, the microscopic anatomy and its alterations in the vicinity of the needle tract formed after experimental acupuncture in ST36 acupoint in rats were described by histological and immunohistochemical methods. Free nerve endings were seen in the epidermis, and surrounding hair follicles and sebaceous glands in the dermis. Muscle spindles and larger nerve fibres close to blood vessels were also observed deeper, in the muscular plane. Needling of the acupoint caused destruction and displacement of hair follicles together with their free nerve endings. Deeper, some muscle spindles and smaller nerves were displaced and disrupted. Larger nerves were not destroyed, but rather pushed aside by the needle. Furthermore, needle impact also caused degranulation of mast cells near the needle tract. The findings suggest multiple ways of interaction between acupuncture needle and the nerve structures of the acupoint. Acupuncture combines destruction, disruption and displacement of nerve structures, together with additional interaction with mast cells. Those mechanisms are involved in eliciting the needling sensation and are possibly associated with the systemic effect of acupuncture.

Cicatricial alopecia: do clinical, trichoscopic, and histopathological diagnosis agree?

Cicatricial alopecia (CA) results from irreversible destruction and fibrosis of hair follicles. Trichoscopy offers a noninvasive method for diagnosis. Thirty-two patients clinically diagnosed with CA were subjected to trichoscopy and histopathology assessment. The sensitivity and specificity of clinical and trichoscopic diagnoses were compared to histopathology. Thirty-two patients were clinically diagnosed as follows: 12 with discoid lupus erythematosus, four with lichen planopilaris (LPP), two with frontal fibrosing alopecia (FFA), three with folliculitis decalvans (FD), nine with central cicatricial centrifugal alopecia (CCCA), and two with long-term alopecia areata. Trichocopy revealed discoid lupus in 13 patients, LPP in nine, FFA in two, FD in three, central centrifugal alopecia in four, and pseudopelade in one. Histopathology confirmed discoid lupus in 13 patients, LPP in five, FFA in two, FD in three, CCCA in six, pseudopelade in two, and sarcoidosis in one. The sensitivity and specificity of clinical diagnosis were 69.2% and 84.2% in discoid lupus, 40.0% and 92.6% in LPP, 100.0% and 100.0% in FFA, 66.7% and 96.6% in FD, and 66.7% and 80.8% in central centrifugal alopecia. The sensitivity and specificity of trichoscopy were 84.6% and 89.5% in discoid lupus, 100.0% and 85.2% in LPP, 100.0% and 100.0% in FFA and FD, 66.7% and 100.0% in central centrifugal alopecia, and 50.0% and 100.0% in pseudopelade. Trichoscopy can be equivalent to histopathology for diagnosing some cases of CA.

Cytokine Profiling in Primary Cicatricial Alopecia: Androgenic Alopecia and Leptin Connections

Primary Cicatricial Alopecias (PCA) are a group of autoimmune inflammatory disorder which cause permanent destruction of hair follicles, mainly affected by the inflammatory cells such as lymphocytes, neutrophils, or combination of these. The management of PCA has become one of the most challenging clinical issues among dermatologists. The specific treatment of any form of the PCAs is currently unknown. We aim to identify the cytokine biomarkers in each type of PCA and study cytokine signatures’ (role) in alopecia’s pathogenesis and therapeutic aspects. Total protein from affected individuals scalp biopsy was extracted using the total protein extraction kit. For the cytokine detection, we used RayBio ® C- Series Human Cytokine Antibody Array C5 with the help of a chemiluminescence detector. A total of 42 cytokines were analyzed and found significant differences in the diseased states’ ratio compared to normal and unaffected samples. The inflammatory cells and associated cytokines are essential to develop a thorough understanding of alopecia’s autoimmune nature. The cytokines can be incorporated with current therapeutics for the better management of alopecia.

Correlation between serum granulysin level and clinical activity in patients with alopecia areata before and after tofacitinib therapy.

Alopecia areata (AA) is a common immune-mediated disorder. Destruction of anagen hair follicles by cytotoxic T cells (CTL) plays a major role in the pathogenesis of AA. Serum granulysin has been shown to reflect overall activity of CTLs. In this study, we aimed to compare serum granulysin levels in patients with AA before and after therapy and to analyze correlation between serum granulysin levels and disease severity. We evaluated the Severity of Alopecia Tool (SALT) score and serum granuysin levels of 38 AA patients at baseline and at 6th month of therapy. Thirty-three patients were treated with tofacitinib 5mg b.i.d, and five patients were treated with topical immunotherapy. Serum granulysin levels were measured by enzyme-linked immunosorbent assay. A moderate correlation was found between SALT scores and serum granulysin level at baseline (r=.378, P=.019). Baseline serum granulysin levels were significantly higher in patients with alopecia totalis/universalis compared with patients with patchy AA (P=.004, Z=2.778). Serum granulysin levels significantly decreased in patients treated with tofacitinib compared to baseline (P=.001). The reduction in serum granulysin levels after tofacitinib therapy correlated with the reduction in SALT scores (P=.001). Our results suggest serum granulysin levels to be a good correlate of immunological activity of AA. We also assume granulysin to be a potential mediator of follicle attack, the effects of which is blocked by tofacitinib therapy. Therefore, changes in serum granulysin levels under therapy can reflect the downregulation of immunological activity of AA.

Destruction of the stem cell Niche, Pathogenesis and Promising Treatment Targets for Primary Scarring Alopecias.

The Primary Scarring Alopecias are characterised by the irreversible destruction and fibrosis of hair follicles, leading to permanent and often disfiguring loss of hair. The pathophysiology of these diseases is not well understood. However, follicular-fibrosis and loss of the stem-cell niche appears to be a common theme. This review explores the pathogenesis of primary scarring alopecias, asking what happens to the stem cells of the hair follicle and how they may contribute to the progression of these diseases. Bulge-resident cells are lost (leading to loss of capacity for hair growth) from the follicle either by inflammatory-mediate apoptosis or through epigenetic reprogramming to assume a mesenchymal-like identity. What proportion of bulge cells is lost to which process is unknown and probably differs depending on the individual PCA and its specific inflammatory cell infiltrate. The formation of fibroblast-like cells from follicular stem cells may also mean that the cells of the bulge have a direct role in the pathogenesis. The identification of specific cells involved in the pathogenesis of these diseases could provide unique diagnostic and therapeutic opportunities to prevent disease progression by preventing EMT and specific pro-fibrotic signals.

Primary Cicatricial Alopecia among Lybian patients: A Clinicopathological and Epidemiological study

Introduction: Cicatricial alopecias are a group of disorders characterized by hair follicle destruction with the consequence of permanent hair loss. The current study was conducted to evaluate the epidemiological and clinicopathological characteristics of cicatricial alopecia in Libyan community. Methods: Thirty-one patients with confirmed diagnosis of cicatricial alopecia by biopsy and tricoscopy during Jan 2018 to Dec 2019 were included in this study. Data were collected by filling a pre-designed questionnaire by all included patients. Descriptive statistics were used for analyzing the results. Chi-squared test was performed to test the relationship between different variables using SPSS 22. Results: Out of 31 cases, 16.1% of patients suffered from lichen planopilaris (LPP), 25.8% discoid lupus erythematosus (DLE), 6% Folliculitis decalvans, 6.45% pseudopelade of brocq, and 16.12% Frontal fibrosing alopecia. Conclusions: Cicatricial alopecia was found to affect mainly middle-aged individuals, particularly females. Early diagnosis and treatment can decrease the burden of this concern.