Glucagon-like peptide1 receptor agonists (GLP-1RAs) and dual gastric inhibitory polypeptide (GIP)/GLP-1RAs are used to improve glycaemic control in patients with type2 diabetes mellitus; some of these drugs are also used to help with weight loss. In recent years, safety signals concerning a possible link between GLP-1RA therapies and hair loss have been emerging in the USA. The volume of prescriptions for these drugs in Europe is now increasing, and it can be expected that the number of cases of GLP-1RA-associated hair loss will therefore also increase in Europe over the coming years. In this commentary, we consider the pharmacological context and market expansion for GLP-1RAs, examine the evidence for an association between GLP-1RAs and hair loss, explore potential pathophysiological mechanisms, and propose clinical recommendations. Most evidence suggesting a potential association between GLP-1RAs and hair loss comes from pharmacovigilance database analyses and retrospective cohort studies. No prospective, controlled studies have specifically evaluated this issue. The evidence suggesting an increased risk of hair loss is strongest for semaglutide and tirzepatide. However, although cases of hair loss have been noted across diverse settings and multiple analyses, causality has not been established. One potential underlying mechanism is the rapid weight loss seen with these drugs, which could induce telogen effluvium. Further research is needed to evaluate causality, underlying mechanisms, the role of dosing and route of administration, and patient factors that may increase the risk. Clinicians need to be aware of the possibility of hair loss occurring with GLP-1RAs and patients should be informed about the potential risk and monitored for hair loss.

Glucagon-like peptide-1 receptor agonists and hair loss: A systematic review and meta-analysis.

Hair follicle cycling is regulated by complex signaling networks that coordinate stem cell activation and quiescence. Although transient receptor potential vanilloid 4 (TRPV4) is expressed in the skin and implicated in cutaneous physiology, its role in hair growth remains unclear. Here, we investigated the contribution of TRPV4 activation to hair growth and its relationship with thymic stromal lymphopoietin (TSLP). Pharmacological activation of TRPV4 using GSK1016790A significantly promoted hair regrowth and elongation in mice, whereas TRPV4 inhibition attenuated these effects. Consistently, Trpv4⁻/⁻ mice exhibited spontaneous hair loss, supporting a role for TRPV4 in maintaining hair homeostasis. TRPV4 activation increased TSLP production in the skin, and exogenous TSLP recapitulated the pro-growth effects of TRPV4 activation. These effects were suppressed by pharmacological blockade of the TSLP receptor, indicating TSLP-dependent signaling. Notably, TSLP restored hair growth in Trpv4⁻/⁻ mice, whereas TRPV4 activation did not, supporting the notion that TSLP acts downstream of TRPV4. In contrast, activation of TRPV3, another TRP channel abundantly expressed in the skin, did not significantly affect hair growth, highlighting the specific role of TRPV4 in this process. Overall, these findings identify a TRPV4-TSLP signaling axis that promotes hair growth and regulates hair follicle function, suggesting a potential therapeutic target for hair loss disorders.

Alopecia areata (AA) is an immune-mediated disorder increasingly recognised for its systemic metabolic associations. Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, shares common inflammatory and metabolic pathways with AA. However, the association between AA and NAFLD remains under-explored.

Ritlecitinib, an oral, selective dual inhibitor of Janus kinase (JAK) 3 and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinases, is approved for treating severe alopecia areata (AA) in patients aged ≥ 12years in the USA. This study describes characteristics, treatment satisfaction, and success among adults initiating ritlecitinib. A sample of US dermatologists treating adults who received ritlecitinib for severe AA were surveyed between November 2023 and June 2024. Demographics, clinical characteristics, treatment history, satisfaction, and health-related quality of life were analyzed overall, among recent initiators, and stratified by treatment duration. A total of 123 adults were included (mean age 37.1years; 57% male; 79% white; 88% commercial insurance). Mean disease duration was 2.1years. At ritlecitinib initiation (n = 93), mean scalp hair loss was 71% and 73% had worsening AA. The proportion of patients with hair regrowth increased with longer treatment duration, 49% among those with < 3months of treatment (n = 18/37) to 82% with > 6months (n = 28/34). Physicians reported many recent initiators (n = 26) felt moderate/severe embarrassment (84%), frustration (73%), and anxiety (65%) due to their AA. Among patients with available data (n = 102), ritlecitinib was the first AA treatment for 46%. Treatment goals (n = 123) included reducing hair loss (94%), improving quality-of-life (41%), and achieving long-term control (32%). Reasons for selecting ritlecitinib (n = 113) included its ability to reduce scalp hair loss (38%), cost-benefit ratio (28%), and safety profile (25%). Satisfaction with AA control was 54%, 68%, and 85% after < 3 (n = 20/37), 3-6 (n = 27/40), and > 6months (n = 29/34), respectively, of ritlecitinib treatment. Many patients experienced psychological burden due to their AA around the start of treatment. Ritlecitinib was chosen for its efficacy, safety, and cost-effectiveness. Hair regrowth, disease stability, and treatment satisfaction increased with longer ritlecitinib treatment duration suggesting sustained treatment is important for achieving treatment goals.

Exosomes in Hair Restoration.

Venlafaxine reverses chemotherapy-induced alopecia through epithelial and dermal reprogramming at single-cell resolution.

Alopecia areata (AA) is a chronic, immune-mediated disorder characterized by nonscarring hair loss. Emerging evidence suggests that AA is associated with systemic inflammation, metabolic dysregulation, and coagulation abnormalities. However, data on these associations in the Indian population remain limited. To evaluate coagulation parameters, metabolic profiles, and inflammatory markers in Indian patients with AA and assess their correlation with disease severity. A case-control study was conducted at a tertiary care center in North India, including 110 AA patients and 110 age- and sex-matched healthy controls. Coagulation parameters (D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time), metabolic markers [fasting blood glucose, lipid profile, body mass index (BMI)], and inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)] were analyzed. Disease severity was assessed using the Severity of Alopecia Tool (SALT) score. Correlation and multivariate regression analyses were performed to identify predictors of severe AA. AA patients exhibited significantly elevated D-dimer ( P < 0.001) and fibrinogen levels ( P < 0.001) compared to controls, indicating a hypercoagulable state. The prothrombin time was also prolonged ( P = 0.03). Metabolic abnormalities, including higher fasting blood glucose ( P < 0.001) and total cholesterol ( P = 0.008), were observed. Inflammatory markers (CRP and ESR) were significantly elevated in AA patients. A strong positive correlation was found between SALT scores and D-dimer levels (r = 0.64, P < 0.001). Multivariate regression analysis identified D-dimer (95% CI: 1.58-4.20), fibrinogen (95% CI: 1.41-3.11), CRP (95% CI: 1.23-2.97), and BMI (95% CI: 1.18-2.46) as independent predictors of severe AA. Cross-sectional study design and lack of longitudinal follow-up. Indian AA patients exhibit significant coagulation abnormalities, metabolic dysregulation, and systemic inflammation, with these factors correlating with disease severity. These findings suggest that AA extends beyond a localized dermatological disorder and may have systemic implications. These associations imply a link rather than causality due to the cross-sectional nature of the study. Further research is warranted to explore the role of targeted therapies in mitigating these risks.

Emerging evidence suggests that G-protein-coupled receptor family C group 6 member A (GPRC6A) and Dual oxidase 1 (Duox1) mediate a non-classical testosterone signaling pathway. However, the molecular mechanism in which testosterone mediates the GPRC6A-Duox1 cascade in the hair cycle was unclear. Therefore, this study aimed to elucidate the molecular role of the testosterone-GPRC6A-Duox1 signaling axis in regulating hair cycle progression and testosterone-mediated hair loss. GPRC6A-deficient and Duox1-deficient keratinocytes were prepared and stimulated with testosterone to assess hydrogen peroxide (H2O2) generation. Apoptosis was evaluated in primary keratinocytes from GPRC6A knockout (KO), Duox1 KO, and wild-type (WT) mice. Hair growth cycle progression was examined by measuring anagen phase duration and hair length. Ki-67 expression was analyzed as a marker of the anagen phase. To validate the testosterone-GPRC6A-Duox1 signaling network in androgenetic alopecia, testosterone was topically applied for one week to the back skin of WT, Duox1 KO, and GPRC6A KO mice on postnatal day 31 (P31). GPRC6A-deficient and Duox1-deficient keratinocytes failed to induce H2O2 generation in response to testosterone. Testosterone-dependent apoptosis in primary keratinocytes from GPRC6A KO and Duox1 KO mice was suppressed compared to keratinocytes from WT. The anagen phase of the hair growth cycle and hair lengths in GPRC6A KO and Duox1 KO mice were longer than WT consistent with the GPRC6A-Duox1 axis stimulating the anagen-to-catagen transition. The expression of Ki-67, a hallmark of the anagen phase, in GPRC6A KO and Duox1 KO mice was higher than that in WT. Duox1 KO and GPRC6A KO mice were resistant to testosterone-mediated hair loss, unlike WT. Taken together, these results suggest that the GPRC6A-Duox1 axis regulates natural hair cycles and testosterone-mediated hair loss.

Alopecia areata (AA) is an autoimmune disorder characterized by hair loss due to immune-mediated destruction of hair follicles. The polygenic nature of AA, influenced by genetic and environmental factors, complicates its pathogenesis. Advances in bioinformatics have facilitated understanding of AA's genetic basis, providing insights into key molecular pathways and regulatory mechanisms. This study utilized the GEO database (dataset GSE111061) to analyze differentially expressed genes (DEGs) between healthy controls and AA patients. Functional enrichment and protein-protein interaction (PPI) network analyzes identified hub genes, transcription factors (TFs), and miRNAs. Tools such as STRING, Cytoscape, and KEGG were employed to uncover key interactions and pathways. An aggregate of 5134 DEGs was discovered, with 2576 elevated genes constituting a PPI network. Key pathways included chemokine signaling and cytokine-cytokine receptor interactions. Ten hub genes (e.g., CCL5, CCR7, and CXCL9) and top TFs (ZNF683, FOXP3, and TBX21) were identified. Additionally, 49 miRNAs were predicted to regulate AA-related genes. This work focuses on critical molecular regulators involved in AA pathogenesis, such as TFs and miRNAs. These findings suggest possible treatment targets and shed light on the molecular mechanisms of AA.

Alopecia, or hair loss, is a multifactorial condition that may arise from genetic, hormonal, or autoimmune causes. This review outlines the major types of alopecia and discusses their underlying etiologies, along with the limitations associated with current therapeutic approaches, including poor efficacy, adverse effects, and low patient adherence. In recent years, lipid-based nanoparticles have emerged as promising carriers for improving the delivery of therapeutic agents to the scalp and hair follicles. The present review summarizes different treatment strategies for alopecia while highlighting the potential role of lipid-based nanocarriers in enhancing drug delivery. The review critically summarizes recent advances in the use of these nanocarriers for alopecia management, with focus on their ability to improve skin penetration, follicular targeting, drug stability, and sustained release characteristics. In addition, the advantages and limitations of different lipid-based systems are comparatively discussed, together with current challenges related to formulation stability, large-scale production, safety, and regulatory considerations in dermatological nanomedicine. Overall, this review provides an updated perspective on the therapeutic potential and translational prospects of lipid based nanocarriers as emerging platforms for alopecia treatment, while highlighting the need for further preclinical and clinical validation.

Androgenetic alopecia (AGA) imposes a significant psychosocial burden, yet current treatments such as minoxidil and finasteride often yield suboptimal responses or adverse effects. Exosomes, nanoscale extracellular vesicles derived from mesenchymal stem cells and dermal papilla cells (DPCs), offer a promising regenerative alternative by modulating key hair-growth pathways. This systematic review evaluates the efficacy, mechanisms, and translational challenges of exosome-based therapies for hair restoration in AGA. A comprehensive search was conducted across Google Scholar, Embase, PubMed, Scopus, and Web of Science for studies published from 2019 to 2025. The search strategy prioritized AGA-related terminology, including androgenetic alopecia, male pattern hair loss, female pattern hair loss, baldness, exosomes, extracellular vesicles, and hair regrowth. Following duplicate removal, 39 studies meeting Population, Intervention, Comparison, Outcome, and Study design criteria were included for qualitative synthesis. Preclinical data demonstrate that exosomes promote hair regeneration through multiple synergistic mechanisms: activation of the Wnt/beta-catenin and Sonic Hedgehog pathways, suppression of transforming growth factor beta (TGF-beta)/SMAD3 signaling, delivery of anti-inflammatory cytokines (e.g., IL-10), and rejuvenation of senescent DPCs via microRNA cargo (e.g., miR-122-5p). Early clinical studies report improvements in hair density (8-20%) and shaft thickness; however, the evidence base remains limited by small sample sizes, retrospective designs, lack of control groups, and inconsistent outcome measures. Emerging delivery systems, such as thermoresponsive hydrogels and microneedle patches, show promise in enhancing follicular penetration but require further validation. Exosome therapy represents a multi-target regenerative approach for AGA with a favorable preliminary safety profile. However, widespread clinical adoption is hindered by critical gaps in manufacturing standardization, scalability, regulatory frameworks, and robust long-term efficacy data. Future research must prioritize large-scale randomized controlled trials with standardized endpoints and Good Manufacturing Practice (GMP)-compliant production protocols to validate these findings and establish exosomes as a mainstream therapeutic option for AGA.

Hair follicles, the organs that produce hair, go through a constant cycle composed of phases of growth, regression, and rest. During this cycle, matrix keratinocytes (MKs), the cells responsible for hair fiber synthesis, proliferate for several years and then undergo spontaneous apoptosis. Damage to MKs and perturbations in their normal dynamics result in a shortened growth phase of the hair cycle, leading to hair loss. The most common factors causing such disruption are hormonal imbalance and attacks by the immune system. Androgenetic alopecia (AGA) is a form of hair loss caused by high sensitivity to androgens, and alopecia areata (AA) is a condition where hair loss is caused by an autoimmune reaction against MKs. In this study, we inform a mathematical model for the human hair cycle with experimental data for the lengths of hair cycle phases available from male control subjects and subjects with AGA. We also connect a mathematical model for AA with estimates for the duration of hair cycle phases obtained from the literature. Subsequently, with each model we perform parameter screening, uncertainty quantification, and global sensitivity analysis, and we compare the results across control, AGA, and AA conditions. The findings reveal that, in AGA subjects, there is greater uncertainty associated with the duration of hair growth than in control subjects. Additionally, compared to control and AGA conditions, in AA it is more certain that longer hair growth phase could not be expected. The global sensitivity analysis results show that, in AGA conditions, synthesis of regulatory molecules in the dermal papilla and stem cell input to the MK population have high impact on hair growth duration, which agrees with physiological understanding for the effect of androgens on hair follicles in AGA.

Trichodynia significantly impairs quality of life in patients with hair loss, for which effective treatments remain limited. This study evaluates the use of intradermal botulinum toxin type A (BTA) in patients with trichodynia unresponsive to conventional therapies. We retrospectively analyzed 21 patients with trichodynia and with alopecia who had discontinued or refused systemic treatments. BTA was administered using the Nappage technique. Symptom severity and disease activity were assessed using the Visual Analogue Scale (VAS) and the Lichen Planopilaris Activity Index (LPPAI), respectively. Most patients (90.5%) reported symptomatic improvement within 18.3days on average. Mean VAS scores declined from 8.0 to 2.0 at 3months and reached 0.0 by 6months. In cicatricial alopecia, LPPAI scores showed significant reduction. Treatment was well tolerated, with only minor adverse effects. The clinical improvement observed may be explained by the neuromodulatory effects of BTA on neurogenic inflammation, including inhibition of substance P and CGRP release. Notably, patients with inflammatory scarring alopecias showed a more pronounced response than those with noncicatricial alopecias, suggesting that BTA may be particularly beneficial in conditions where pain is linked to active perifollicular inflammation. Intradermal BTA appears to be a safe and potentially effective treatment for trichodynia, particularly in patients with scarring alopecia who are not candidates for systemic therapy. These findings warrant further validation in controlled studies.

The camel has received very little attention in contrast to other domesticated animals, especially in developing nations such as Ethiopia. As a result, camels are susceptible to several illnesses, including mange mites. In the present study, a camel whose main complaint was itching, rubs against an object and is kept extensively was treated clinically at Kombolcha City Administration Veterinary Clinic, Northeast, Ethiopia. Upon physical examination, the body temperature was 37.2°C. The camel was emaciated, and the hair was rough. The clinical manifestations of the camel mange in the present study included hair loss on the head, with skin crust around the lower flank, hand quarters and the head and inside of the thigh and thickening and corrugation of the skin of the inguinal area, including the skin of the prepuce. The patient was clinically diagnosed with camel mange and not confirmed by laboratory diagnosis. However, therapeutic diagnosis based on three subcutaneous injections of ivermectin (1ml/50 kg body weight) administered at ten-day intervals, together with two topical applications of amitraz applied midway between consecutive injections, this treatment was followed by the disappearance of clinical signs. Additionally, the owner was instructed to separate healthy camels from those that were contaminated, clean the fomites before and after usage, and treat the herds whenever one or more camels had clinical symptoms. There was no recurrence of infestation within five months of follow-up. Therefore, the combination of ivermectin and topical amitraz appeared effective in the clinical management of camel mange in this case. Detailed epidemiological and therapeutic investigations are warranted.

ABSTRACTMultiple carboxylase deficiency (MCD) is a rare, treatable inborn error of biotin metabolism that may present in children in the first year of life with life‐threatening metabolic crises. We report a 4‐month‐old child presenting with persistent seizures, eczematous rash near the orifices, unjustified loss of hair with baldness, and severe metabolic acidosis, initially mimicking septicemia. Urine organic acid investigation showed elevated levels of 3‐hydroxyisovaleric acid, 3‐methylcrotonylglycine, 3‐hydroxypropionic acid, methylcitrate, and lactate that lead towards MCD. This diagnosis remains unconfirmed, as confirmatory testing (serum biotinidase activity and genetic analysis) was not available at our center. Early initiation of biotin (10 mg/day) led to rapid clinical and biochemical recovery. This particular case depicts the importance of biotin‐responsive metabolic disorders in the first year of a child presenting with the classic triad of seizures, dermatitis, and alopecia with metabolic acidosis. Early recognition and prompt initiation of biotin therapy can result in rapid clinical recovery. Timely diagnosis is crucial to prevent avoidable morbidity and long‐term neurological sequelae. This case highlights the importance of considering MCD in children. In the first year of life, unexplained metabolic acidosis as timely treatment can be lifesaving.

Condition-specific outcome measure instruments (OMIs) are essential for assessing severity and evaluating response to emerging treatments. This scoping review identified OMIs used in assessing and treating androgenetic alopecia (AGA). Among 317 studies involving 194,158 individuals, 12 clinician-reported OMIs were identified, used in 51.7% of studies, including 31% of clinical trials. Hamilton-Norwood (23.9%) and Ludwig (20%) were the most used ClinROMs in AGA clinical trials, for male-pattern and female-pattern hair loss, respectively. The Men Hair Growth Questionnaire (MHGQ) was the most frequently used patient-reported severity assessment instrument in clinical trials (4.1%). The Women's Androgenetic Alopecia Quality of Life (WAA-QoL) and Hairdex were the only identified HRQoL instruments, used in 5.9% and 1.4% of clinical trials, respectively. Condition-specific OMIs are inconsistently applied across AGA clinical trials. Patient-reported instruments have remained underutilized. Our results underscore the need for consensus-based harmonization towards standardized assessment of AGA. Psychometric evaluation of existing instruments is also essential.

The spectrum defining T-cell-mediated alopecias is an expression of autoimmune, innate, regenerative, and effete pathophysiological pathways. Four main folliculotropic T-cell patterns can be integrated into clinicopathologic aspects and define the majority of these alopecias. Lymphocytic inflammation targeting bulbs defines alopecia areata, and pan follicular lymphocytes sparing the hair bulbs and perifollicular concentric fibrosis define lichen planopilaris. Non-destructive lymphocytic folliculitis localized to the bulge modulating stem cell function is introduced as an unrecognized spectrum without defined alopecia. Pan follicular lymphocytic alopecia targets all levels of the follicle, including the bulb and sebaceous glands, and occurs in lupus erythematosus, follicular mucinosis, folliculotropic T-cell dyscrasia, and lymphoma. These form an evidence-based platform due to their inherent programmed pathways. Major advances have occurred in defining inducible mesenchymal skin associated with lymphoid tissue incorporating the pleiotropic functions of regulatory T cells integrated into the JAK/STAT activating transducer pathway. Beyond immunology, the integrated Tregs have non-immunologic functions that modulate stem cell pathways, regulate follicular cycles and follicular inflammation, and repair. In all T-cell alopecias, the central role of both CD8+ and Treg memory cells is pivotal in creating local, multifocal, and diffuse patterns of hair loss. The relationship between the stem cell niche localized to the bulge and supported by the stem cell niche forming progenitor bulbs that induce rapid transit amplifying basaloid cells and trichogenesis are explored in reference to both physiologic and pathogenic pathways. The expanding evidence-based studies defining the pleiotropic functions of the iSALT incorporated Treg/JAK/STAT pathways have led to the development of a conceptual framework to address T-cell alopecias.

Association between hair loss and cardiometabolic diseases in Chinese adults: a cross-sectional analysis in Tianning Cohort.

Alopecia areata (AA) is achronic autoimmune condition characterized by relapsing, non-scarring hair loss. Approximately 80% of patients experience limited patchy hair loss with potential for spontaneous recovery, while others progress to more extensive forms, such as alopecia totalis or alopecia universalis, both of which carry aprofound psychosocial burden. Advances in research have identified immune privilege collapse of the hair follicle, Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway activation and genetic predisposition as key mechanisms driving disease onset and progression. These insights have advanced therapeutic strategies, shifting from nonspecific treatment towards targeted interventions. Conventional treatment, including topical agents and light-based approaches, remain important options, particularly for mild or localized disease, while the advent of oral Janus kinase inhibitors, such as baricitinib and ritlecitinib, offers the first U.S. Food and Drug Administration (FDA)-approved systemic treatment for severe AA. In this review, we summarize current concepts in epidemiology, pathogenesis, diagnosis, comorbidities and treatment, highlighting emerging therapies and discussing future directions for improving patient outcomes.