Scarring Alopecia Research Articles

JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia.

The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signaling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients revealed an active JAK-STAT1 signaling signature along with upregulation of antigen presentation and downregulation of key components of the EGFR pathway. Our findings offer molecular insights and highlight a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.

Efficacy and Safety of Laser Therapy and Phototherapy in Cicatricial and NonCicatricial Alopecia: A Systematic Review Study.

In recent years, the application of various light and laser devices in the treatment of different types of alopecia has been established. This systematic review aims to assess the efficacy and safety of laser therapy and phototherapy in cicatricial and non-cicatricial alopecia. A comprehensive search was conducted on PubMed, Scopus, Science Direct, and Google Scholar. Articles were evaluated across four subgroups: alopecia areata, androgenic alopecia, telogen effluvium, and cicatricial alopecia. Included studies were published in English or Persian between January 2010 and September 2023, focusing on interventional, cohort, or case series research that achieved a minimum score of 75% on the EBL checklist. Exclusion criteria encompassed animal and in vitro studies, review articles, case reports, duplicated or irrelevant research, as well as studies that did not meet the designated EBL score. Editorial letters and case studies were also excluded. Initially, 965 records were collected, resulting in the inclusion of 58 studies in the final review: 26 on alopecia areata, 26 on androgenic alopecia, five on cicatricial alopecia, and one on telogen effluvium. Narrow-band ultraviolet B, 308-nm excimer laser, and psoralen ultraviolet A therapy showed varying effectiveness; specifically, the excimer laser was notably effective for patients with shorter disease duration. In androgenic alopecia, erbium-glass and thulium lasers effectively increased hair density but showed a gradual decline posttreatment. Low-level light/laser therapy also increased hair density and diameter and exhibited potential benefits when used alongside minoxidil, but did not significantly enhance outcomes in telogen effluvium treatment. Light/laser therapy can serve as an additive treatment for cicatricial alopecia, particularly lichen planopilaris, but has limited efficacy in treating telogen effluvium. Overall, light/laser therapies exhibit a significant positive effect on increasing hair density and diameter across various alopecia types.

Responsiveness of the DLQI and the Colombian validated version of the Skindex-29 in scarring and non-scarring alopecia

Responsiveness of the DLQI and the Colombian validated version of the Skindex-29 in scarring and non-scarring alopecia

Cross-sectional study to evaluate the utility of elastic tissue staining in primary cicatricial alopecia

Background and aimsDiagnosing end-stage primary cicatricial alopecia (PCA) on routine histology is challenging since the major diagnostic feature (inflammatory infiltrate) may be minimal or absent. This study aimed to assess...

Association of lichen planopilaris with cardiovascular and metabolic disorders: A systematic review and meta-analysis.

Lichen planopilaris (LPP) is among the most common types of immune-mediated scarring alopecia. Observational studies have reported conflicting findings regarding the association of LPP with different comorbidities. We conducted a systematic review and meta-analysis to elucidate the association between LPP and different cardiovascular and metabolic disorders. We systematically searched four electronic databases-PubMed, Web of Science, Embase, and Cochrane Library-for relevant studies published from their inception to August 1, 2024. A random-effects model was used to perform a pooled analysis and calculate odds ratios or incidence rate ratios with 95% confidence intervals. The meta-analysis included 10 case-controls studies involving 7,516 patients with LPP and 64,719,097 controls. The results demonstrated no significant association between LPP and hypertension, diabetes mellitus, or hyperlipidemia. The pooled analysis results also revealed that patients with LPP did not have significantly higher risks of obesity and heart failure than did controls. All pooled analyses revealed high levels of heterogeneity across the studies, but no significant publication bias was detected. LPP is not significantly associated with most cardiovascular and metabolic disorders, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and heart failure.

Low-Level Laser and LED Therapy in Alopecia: A Systematic Review and Meta-Analysis.

Low-level laser/LED therapy (LLLT) has been described as a treatment option for alopecia, but no study has comprehensively reviewed its efficacy in multiple alopecia types. To review and evaluate LLLT for various alopecia types. A systematic search of PubMed/MEDLINE, Embase, and CENTRAL was conducted to identify studies assessing the effect of LLLT on patients diagnosed with alopecia. Prespecified outcome measure was the change in hair density. Meta-analysis was performed to calculate the standardized mean difference in hair density before and after LLLT compared with placebo. Thirty-eight studies were included that described 3,098 patients with androgenetic alopecia (2,930/3,098), scarring alopecia (49/3,098), alopecia areata (50/3,098), telogen effluvium (17/3,098), and chemotherapy-induced alopecia (32/3,098). The mean change in hair density increased significantly in androgenetic alopecia patients after LLLT for 4 to 26 weeks compared with placebo (<20 weeks: SMD = 1.14; 95% CI [0.51-1.78]; p = .000; I2 = 88.26%; >20 weeks: SMD = 1.44; 95% CI [0.97-1.91]; p = .000; I2 = 80.81%). Change in hair density was reported in 5 studies evaluating other alopecia types; however, statistical information was insufficient for meta-analysis. LLLT is a promising treatment option for patients with androgenetic alopecia, but future studies are needed to better understand its efficacy in other alopecia types.

Evaluation of the Environmental Risk Factors and Comorbidities in Patients with Lichen Planopilaris: A Case-Control Study

Introduction: Lichen planopilaris (LPP) is an uncommon cicatricial alopecia clinically characterized by follicular hyperkeratosis, perifollicular erythema, and permanent hair loss. The association of LPP with certain underlying diseases and environmental factors has been evaluated but there are limited data about this association. This study was designated to evaluate the environmental risk factors and comorbidities in LPP patients. Method: This case-control study was performed on LPP patients referred to two dermatology referral centers from 2019 to 2022. A group of non-LPP healthy individuals referring for cosmetic concerns was recruited as control group. Data collection was performed using two questionnaires: a general questionnaire, including demographic information, comorbidities, environmental risk factors, and disease-related information, and the lichen planopilaris activity index (LPPAI) questionnaire. Results: One hundred LPP patients as case group were compared with 100 healthy people without LPP as control group. Unemployment, history of major stressful events, thyroid disorder, history of hair dyeing, using face soaps, taking supplements, postmenopausal status, and family history of LPP or other types of alopecia had significant relationship with LPP (all p values <0.05). Conclusion: LPP has associations with environmental and non-environmental risk factors and, also, genetic component.

Evidence of IL-17-secreting mast cells in scalp lesions of folliculitis decalvans points to new therapeutic targets in recalcitrant lesions.

Folliculitis decalvans (FD) is a chronic neutrophilic scarring alopecia which exact pathogenesis remains unknown. The recent report on the successful use of a novel anti-IL17 biologic agent in FD and the presence of IL-17-secreting mast cells in other types of scarring alopecias point to a distinct pathogenic mechanism in this disease. Our aim was to study and correlate the expression of IL-17 and mast cells in lesional and non-lesional FD scalp, using immunohistochemical techniques. Increased expression in IL-17 and mast cells was found in lesional scalp compared to non-lesional scalp areas (p<.05). A significant positive correlation between IL-17 and Mast cell Tryptase immunolabeling in non-lesional scalp (r=.64) highlights the role of IL-17-secreting mast cells in "normal-appearing" sites of FD. These findings suggest that targeting both IL-17 and mast cells may be potentially beneficial to better control the chronic inflammatory status of the disease specially in recalcitrant cases of FD.

Vitamin D deficiency in non-scarring and scarring alopecias: a systematic review and meta-analysis.

Numerous studies have linked vitamin D deficiency (VDD) to the pathogenesis of various alopecia disorders. This study aimed to investigate whether patients with alopecia are more likely to have VDD or lower vitamin D levels than controls, and the prevalence of VDD among patients with certain alopecia disorders. Electronic searches were conducted using PubMed, Embase, Scopus, and Cochrane Library databases from the dates of their inception until September 2024. Studies that reported data allowing for the calculation of odds ratios, mean differences, or correlation coefficients related to vitamin D levels and alopecia were included, while studies without a confirmed diagnosis of alopecia or those involving patients taking vitamin D supplements were excluded. It was found that 51.94% of patients with alopecia areata (AA), 50.38% of patients with female pattern hair loss (FPHL), 47.38% of patients with male androgenic alopecia (MAGA), 53.51% of patients with telogen effluvium (TE), and 38.85% of patients with primary scarring alopecia had VDD. Compared to controls, AA patients had a pooled odds ratio (OR) of VDD of 2.84 (95% confidence interval: 1.89-4.26, I2 = 84.29%, p < 0.01) and a pooled unstandardized mean difference (UMD) of vitamin D levels of -8.20 (-10.28 - -6.12, I2 = 74.25%, p < 0.01) ng/mL. For FPHL patients, a pooled OR of VDD of 5.24 (1.50-18.33, I2 = 81.65%, p < 0.01) and a pooled UMD of vitamin D levels of -15.67 (-24.55 - -6.79, I2 = 91.60%, p < 0.01) ng/mL were found. However, for MAGA, a pooled VDD OR of 4.42 (0.53-36.61, I2 = 88.40%, p < 0.01), and a pooled UMD of vitamin D levels of -2.19 ng/mL (-4.07 - -0.31 ng/mL, I2 = 7.64%, p = 0.37) were found. For TE patients, pooled UMD of vitamin D levels of -5.71 (-10.10 - -1.32) ng/mL were found. People with alopecia frequently have VDD; however, only in patients with AA or FPHL was the association of VDD and decreased vitamin D levels statistically significant compared to control. The findings indicate screening for vitamin D could benefit patients with AA or FPHL, potentially addressing vitamin D deficiency. Further study on vitamin D supplementation as a treatment for alopecia is recommended.

Clinicopathologic features, demographics, disease burden, and therapeutics in alopecic sarcoidosis: a case series and systematic review.

Alopecic sarcoidosis is an uncommon cutaneous manifestation of sarcoidosis. Scarring and nonscarring alopecic sarcoidosis have been reported; however, information on the epidemiology, systemic disease associations, and treatment efficacy is limited. To address these gaps, we conducted a retrospective chart review and systematic literature review of alopecic sarcoidosis cases. Full-text English publications from PubMed, Scopus, and Google Scholar from inception to August 2023 were analyzed. Treatment evidence quality was assessed using the modified Oxford Centre for Evidence-Based Medicine rating scale. Three patients with biopsy-proven alopecic sarcoidosis were included as a case series, all demonstrating systemic sarcoidosis and 2 requiring multiple therapies. Among 1778 search results, 60 articles representing 77 cases of alopecic and scalp sarcoidosis were included. Patients were categorized into 4 distinct alopecic subgroups. Black patients constituted the majority of all subgroups. Extracutaneous sarcoidosis burden was high across all alopecic subgroups, with ocular disease appearing overrepresented. Topical and oral corticosteroids were the main treatments. Though scarring alopecia patients had poor outcomes despite receiving immunomodulators/cx, limited data suggest potential efficacy of tumor necrosis factor-alpha inhibitors. This study has a small sample size. Our findings underscore the importance of evidence-based strategies for improving alopecic sarcoidosis management. Prompt diagnosis and systemic evaluation, especially for scarring alopecia, are essential for timely intervention to optimize patient outcomes.

Early-Onset Graham-Little-Piccardi-Lasseur Syndrome with Cutaneous Lichen Planus – A Rare Case Report and Review of Literature

Graham-Little-Piccardi-Lasseur syndrome (GLPLS) is a rare condition characterized by lichen planopilaris with scarring alopecia of the scalp and nonscarring alopecia of the axilla, groin, and pubis with keratosis pilaris. It usually affects middle-aged women more than men. The onset of scarring alopecia is usually reported in middle age. We report a case of GLPLS from South India, having early onset of alopecia in childhood, associated with cutaneous lichen planus.

A phase 2a trial of brepocitinib for cicatricial alopecia

BackgroundCicatricial alopecias (CA) are chronic, progressive scarring hair-loss conditions. Molecular dysregulation is not fully understood, hindering treatment development. Th1/IFNγ signaling and JAK dysregulation has shown involvement, providing rationale for this phase 2a trial with TYK2/JAK1 inhibitor brepocitinib. MethodsRandomized, placebo-controlled phase 2a trial spanning 52 weeks. Adults (18≥years of age) with lichen planopilaris, frontal fibrosing alopecia, or central centrifugal cicatricial alopecia diagnosis were randomized 3:1 to brepocitinib 45mg daily or placebo for 24 weeks, after which all patients received brepocitinib for another 24 weeks, with a safety follow up 4 weeks later. Lesional scalp biopsies were collected at baseline, week 24, and week 48. Co-primary endpoints were changes in lesional expression of CCL5, changes in lesional expression of fibrosis-related markers, and safety at week 24. ResultsPatients receiving brepocitinib showed significant downregulation in CCL5 expression at week 24 (p=0.004). Enrichment analysis of a subset of fibrosis markers showed trending upregulation in placebo patients (p<0.1). Brepocitinib was well tolerated and improved clinical severity scores. LimitationsSingle-dose regimen, small placebo group. ConclusionBrepocitinib significantly reduces CCL5 expression and was well tolerated at week 24, meeting co-primary endpoints. Brepocitinib reduces inflammatory biomarker expression and improves clinical severity, while maintaining favorable safety profile.

Difficulties in differential diagnosis of alopecia in the practice of dermatologists: Clinical cases

Background. All types of alopecia fall into two main categories: scarring and non-scarring alopecias. Among these, certain types frequently pose challenges in differential diagnosis due to their similar clinical manifestations, thus necessitating specific examinations to be made for confirmation of the diagnosis. For instance, trichotillomania may be easily confused with alopecia areata. Description of clinical cases. The paper presents three clinical observations of patients with both scarring and non-scarring alopecia and highlights the challenges in establishing a definitive diagnosis due to the similarities in clinical presentations. The study emphasized the importance of thorough examination and close attention to patients with long-standing areas of hair thinning, along with the necessity for meticulous differential diagnostic efforts. In addition, the significance of pathological examination is considered as an indispensable tool for the evaluation of most similar cases of scarring and non-scarring alopecias. Conclusion. Early verification of the diagnosis and timely initiation of therapy for hair disorders appear crucial, both for the potential restoration of hair growth and for the prevention of further hair loss.

Low-Dose Metformin and Profibrotic Signature in Central Centrifugal Cicatricial Alopecia

Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia predominantly affecting Black female individuals. Current conventional treatments target inflammation but not the underlying fibrotic processes, often leading to permanent hair loss. To investigate the associations of low-dose oral metformin, an antidiabetic medication with antifibrotic properties, with clinical symptoms and scalp gene expression patterns in patients with CCCA. This retrospective clinical case series and transcriptomic analysis included patients treated at a single tertiary academic medical center between January 2023 and March 2024. All patients had biopsy-confirmed CCCA refractory to standard treatments. Transcriptomic analysis was performed on patients with previously banked, paired scalp biopsies before and after treatment with adjuvant metformin for at least 6 weeks. Extended-release metformin, 500 mg, once daily was added to participants' baseline CCCA treatment regimens. Clinical assessments included pruritus, inflammation, scalp resistance, and hair regrowth. Gene expression profiling via bulk RNA sequencing analysis evaluated differential gene expression and pathway enrichment. A total of 12 Black female participants were included in the study, and transcriptomic analysis was performed in 4 participants. After at least 6 months of metformin treatment, 9 participants experienced improvement in disease, including scalp pain, inflammation, and/or pruritus, and 6 demonstrated clinical evidence of hair regrowth. The addition of metformin led to reversal of many prominent gene pathways previously identified in CCCA. Transcriptomic analysis revealed upregulation of pathways and genes (keratin-associated proteins [KRTAPs]) involved in keratinization, epidermis development, and the hair cycle (absolute log2-fold change > 4), with concomitant downregulation of fibrosis-related pathways and genes (eg, MMP7, COL6A1) (fold change >1.5; all false discovery rate <.05). Gene set analysis showed reduced expression of helper T cell 17 and epithelial-mesenchymal transition pathways and elevated adenosine monophosphate kinase signaling and KRTAPs after metformin treatment. In this case series of patients with treatment-refractory CCCA, low-dose oral metformin was associated with symptomatic improvement and dual modulation of gene expression, stimulating hair growth pathways while suppressing fibrosis and inflammation markers. These findings provide a rationale for future clinical trials studying metformin as a targeted therapy for CCCA and other cicatricial alopecias.

Actualización de la tricodinia, un reto para los dermatólogos

Trichodynia is the sensation of pain in the scalp, which, in most cases, is associated with certain types of alopecia. Despite being a term coined by Rebora back in 1996 to described patients with diffuse alopecia consistent with telogen effluvium, this symptom has currently been reported in other entities. Androgenic alopecia, scarring alopecia, alopecia areata, trichotillomania, and chemotherapy-induced alopecia are common causes of trichodynia. Similarly, its association with psychiatric comorbidities, including depression, anxiety, obsessive-compulsive disorder and somatoform disorders has been reported with a higher prevalence among women. Although its pathogenesis is still to be elucidate, some factors involved are substanceP, psychiatric comorbidities and perifollicular inflammation. Clinically it exhibits pain or discomfort of the scalp, almost always in association with hair los. The sensation of pain can occur throughout the scalp or locally in some specific areas. Diagnosis is clinical and one of exclusion. Regarding treatment, there are no specific therapies for trichodynia. However, the use of botulinum toxinA, antidepressants, neuromodulators, propranolol, topical corticosteroids, oral corticosteroids and topical cannabinoids are therapeutic alternatives that should be taken into consideration. Since treatment of trichodynia is still therapeutically challenging for dermatologists more prospective studies are needed to evaluate new therapies.

53299 Efficacy of oral retinoids as a maintenance therapy in primary cicatricial alopecia: a retrospective study

53299 Efficacy of oral retinoids as a maintenance therapy in primary cicatricial alopecia: a retrospective study

A retrospective clinical and laboratory analysis including vitamin D and antinuclear antibodies in central centrifugal cicatricial alopecia and nonscarring alopecia in African Americans

A retrospective clinical and laboratory analysis including vitamin D and antinuclear antibodies in central centrifugal cicatricial alopecia and nonscarring alopecia in African Americans

52069 Effect of primary cicatricial alopecia on cardiovascular disease: A nationwide cohort study

52069 Effect of primary cicatricial alopecia on cardiovascular disease: A nationwide cohort study

Evaluation of hair surface structure and morphology of patients with lichen planopilaris (LPP) by atomic force microscopy (AFM).

Lichen planopilaris (LPP) is a chronic lymphocytic skin disease manifested by progressive scarring alopecia. The diagnosis of LPP is made based on histopathological examination, although it is not always definite. The current study evaluates the effectiveness of non-invasive atomic force microscopy (AFM) hair examination in detecting morphological differences between healthy and diseased hair. Here, three to five hairs from lesional skin of 10 LPP patients were collected and examined at nine locations using AFM. At least four images were taken at each of the nine sites. Metric measurements were taken and metric (length, width, and scale step height) and morphological features (striated and smooth surface of scales, the presence of endocuticle and cortex, shape of scales edges, scratches, pitting, cracks, globules, and wavy edge) were compared with hair from healthy controls. In addition, areas on diseased hair where the process of pathological, unnatural delamination of the hair fiber occurs are described. There was a statistically significant difference in the number of scratches in the initial sections of the LPP hair, in the intensity of wavy edges along the entire length of the tested hair, and in the number of scales with pitting in the middle section of the hair. In addition, a statistically significant higher number of scales with striated surface was found in LPP group starting at 3.5cm from the root continuing towards the free end of the hair. Other morphological changes such as presence of cortex, globules, oval indentations, and rod-like macrofibrillar elements were also assessed, however, detailed results are not presented, as the differences shown in the number of these morphological changes were not significantly different. This publication outlines the differences between virgin, healthy Caucasian hair, and the hair of LPP patients. The results of this study can be used for further research and work related to LPP. This is the first attempt to characterize the hair of LPP patients using AFM.

Treatment of Lichen Planopilaris and Frontal Fibrosing Alopecia: A Retrospective, Real-Life Analysis in a Tertiary Center in Germany.

Background: Lichen planopilaris (LPP) is an inflammatory cicatricial alopecia characterized by an irreversible destruction of the hair follicle resulting in its permeant destruction. The clinical presentation of LPP is a progressive patchy scarring alopecia. A variety of systemic agents is used to treat LPP with varying success. The aim of this retrospective, real-life analysis was to evaluate the treatment of hydroxychloroquine for LPP. Method: In this retrospective, single-center study, we analyzed 110 patients with LPP and frontal fibrosing alopecia (FFA) who received treatment over a 12-month period from March 2014 to March 2021 at the Department of Dermatology, University of Mainz Medical Center. Patient records were analyzed for response to treatment, co-morbidities, disease progression-free survival (DPFS), and safety. Clinical parameters associated with treatment response were determined with Cox regression modelling and logistic regression. Results: Overall, 77 of 110 patients were treated with a systemic agent. There was a clear association between LPP and the occurrence of Hashimoto thyroiditis. Topical treatment with corticosteroids did not improve clinical symptoms in the majority of patients (15 out of 101). In 71% of patients treated with systemic cyclosporine A and 62% of patients treated with hydroxychloroquine, we observed a significant resolution of the inflammatory process, which correlated with a robust durable clinical response (p < 0.001). Toxicity was observed in 17% (n = 9) of patients receiving systemic treatment with hydroxychloroquine and correlated with the duration of systemic treatment (p < 0.001). Treatment discontinuation was associated with a flare-up of clinical symptoms (29%), which required the re-initiation of second-line therapy in 13 out of 51 patients. Overall, the initiation of second-line treatment, either hydroxychloroquine or Cyclosporine A (CsA), yielded positive results, especially in the patient cohort treated with hydroxychloroquine (overall response rate, ORR = 100%), who showed disease progression during CsA or retinoids. Conclusions: Our results from this contemporary cohort of patients with LPP and FFA indicate that hydroxychloroquine and cyclosporine are effective systemic agents in decreasing clinical symptoms. However, our data also show that the discontinuation of treatment is often associated with the exacerbation of clinical symptoms. Response rates to second-line treatment were especially favorable in the patient cohort with hydroxychloroquine.