RARE DISEASE
Alopecia totalis
Alopecia totalis
Alopecia totalis
Drug discovery
4
drugs
With orphan designations
Overview
Alopecia totalis (AT) is a severe autoimmune subtype of alopecia areata characterized by complete scalp hair loss due to T-cell–mediated follicular destruction [6][13]. It affects 0.03% of the population, with <10% experiencing spontaneous regrowth [12][16]. Prognosis is poorer than localized AA, with frequent treatment resistance and relapses [6][11]. Management focuses on immune modulation, though sustained remission remains challenging [3][6].
Population
Affects ~0.03% globally, with rising prevalence [12][14]; 5%-10% of alopecia areata cases progress to AT/AU [2][9].
More common in children/young adults (mean onset <30 years) and those with family history (20% genetic link) [6][12][16].
Higher incidence in females (1.5–2:1 ratio) and Northeastern U.S. residents [2][14].
Burden
Psychological: 2–3x higher rates of depression/anxiety vs general population; social withdrawal common [4][9][10].
Economic: Annual healthcare costs ~70% higher than controls ($18,988 vs $11,030) [19]; frequent specialist visits (3.4 dermatology visits/year) [19].
Comorbidities: 20% have concurrent autoimmune disorders (thyroid disease, vitiligo, lupus) [6][9][13].
Therapies
First-line: Intralesional/topical corticosteroids ± adjunct minoxidil for maintenance [3][5].
Systemic agents: JAK inhibitors (baricitinib, ritlecitinib) show 50%+ regrowth in trials [3][8][18]; oral steroids for acute cases [5][11].
Advanced options: Contact immunotherapy (DPCP) or PUVA phototherapy, though relapse rates exceed 30% post-treatment [5][6].
Categories: rare skin diseases
Research Papers
541 drug discovery papers about Alopecia totalis, with 3 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
541 drug discovery papers about Alopecia totalis, with 3 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-17 | Alopecia areata: Emerging therapies and up-to-date management strategies.
Alopecia areata (AA) is an autoimmune hair disease with variable presentations necessitating individualized, stepwise management given patient age, extent of involvement, comorbidities, and treatment tolerability. Historically, severity was defined by percentage of scalp hair loss using the Severity of Alopecia Tool (SALT), with SALT≥50 defining severe disease and systemic therapy eligibility. Recently, severity assessment has expanded beyond scalp involvement with the AA Scale for Clinical Use (AASc), incorporating eyebrow/eyelash involvement, psychosocial impairment, and treatment response to better capture disease burden. First-line therapy for mild-to-moderate AA (SALT<50) includes topical or intralesional corticosteroids, often with topical or oral minoxidil. Observation may be appropriate in select cases given potential for spontaneous regrowth. FDA approval of oral Janus kinase inhibitors (JAKis) for severe AA (SALT≥50) has changed the therapeutic landscape. Selection among baricitinib, ritlecitinib, and deuruxolitinib is guided by patient age, safety considerations, comorbidities, laboratory monitoring, and insurance coverage. Switching between JAKis may still be beneficial after nonresponse to one agent. Adjunctive and alternative therapies include topical immunotherapy, systemic immunosuppressants, emerging biologic/targeted therapies, and procedural modalities, such as platelet-rich plasma, laser- and light-based therapies, and microneedling. This review synthesizes current evidence on AA treatment and offers a practical, contemporary framework for AA management.
2026-07-31 | Case Report: Repigmentation and complete hair regrowth in an 11-year-old preadolescent with alopecia totalis treated with a JAK inhibitor.
Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss. Janus kinase (JAK) inhibitors have emerged as effective therapeutic options for severe pediatric AA, though repigmentation of white hair during treatment remains rarely reported. Herein, we report an unusual case of complete hair regeneration with simultaneous white-to-black hair conversion in a child with severe AA following JAK inhibitor therapy. An 11-year-old girl presented with alopecia totalis (AT) persisting for two years. She initially received baricitinib for seven months, achieving SALT 65% with predominantly white and gray hair regrowth. After switching to ritlecitinib 50 mg/day, black hair emerged at 6 weeks, with complete hair regrowth and repigmentation at 6 months (SALT 0). The patient has now completed 12 months of ritlecitinib therapy with sustained response and stable pigmentation. Family Dermatology Life Quality Index (FDLQI) decreased from 18 to 4. No significant adverse effects were observed. This case suggests that prolonged JAK inhibition may facilitate both hair regrowth and pigment restoration in pediatric severe AA.
2026-07-29 | Efficacy and Safety of Oral Janus Kinase Inhibitors in Adults and Adolescents with Alopecia Areata: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
Alopecia areata is an autoimmune disorder characterised by T-cell-mediated damage of hair follicles, resulting in non-scarring hair loss that can progress to complete scalp (alopecia totalis) or body hair loss (alopecia universalis). While long-term systemic options were historically limited, the emergence of Janus kinase (JAK) inhibitors has revolutionised the treatment of alopecia areata, even in patients with moderate-to-severe disease. We aimed to evaluate the efficacy and safety of oral JAK inhibitors compared with placebo in adults and adolescents with moderate-to-severe alopecia areata. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases were searched from inception to 28 November, 2025. Randomised controlled trials evaluating oral JAK inhibitors in adolescents and adults (aged ≥12 years) with alopecia areata were included. Data extraction and risk of bias assessment were performed independently by multiple reviewers. Primary outcomes were the proportion of patients who achieved Severity of Alopecia Tool (SALT) scores of ≤10 and ≤20, and 50%, 75% and 90% reductions in SALT scores from baseline, as well as treatment-related adverse events (AEs). Data were synthesised using random-effects models to calculate odds ratios (ORs) and mean differences with 95% confidence intervals (CIs). Twelve randomised controlled trials involving 4141 participants (mean age 35.8 years, mean baseline SALT score 86.0) met the inclusion criteria. All trials enrolled adult participants, with the exception of one randomised controlled trial in which adolescents comprised 15% of the study population. Six trials were rated as having a low risk of bias, while six had "some concerns" primarily because of missing outcome data. Oral JAK inhibitors were significantly more effective than placebo across all primary efficacy endpoints. At week 24, the odds of achieving SALT ≤10 were 5.69 times higher for JAK inhibitors than placebo (95% CI 3.58-9.03); by week 36, this effect increased to an OR of 9.40 (95% CI 4.58-19.29). For SALT ≤20, the OR was 7.99 (95% CI 5.13-12.44) at week 24. Patients treated with oral JAK inhibitors were significantly more likely to achieve SALT50, SALT75 and SALT90 across all timepoints (weeks 12-36). Regarding safety, JAK inhibitors were associated with a higher risk of total AEs (OR 1.60; 95% CI 1.33-1.94), but no statistically significant difference was found for serious AEs (OR 1.04; 95% CI 0.69-1.57) or treatment discontinuation because of AEs (OR 1.22; 95% CI 0.84-1.76). Oral JAK inhibitors are effective in promoting scalp, eyebrow and eyelash hair regrowth in adults and adolescents with moderate-to-severe alopecia areata, with a trend of higher response rates at later timepoints across studies. The favourable safety profile of these agents is reassuring. Future research should prioritise head-to-head randomised controlled trials and long-term pharmacovigilance to define comparative efficacy and safety.
2026-06-30 | COMPARISON OF CLINICAL EFFICACY OF TOFACITINIB VERSUS METHOTREXATE IN SEVERE ALOPECIA AREATA, ALOPECIA TOTALIS, AND ALOPECIA UNIVERSALIS: A RANDOMIZED CONTROLLED TRIAL
Objective: To compare the 12-week clinical efficacy of oral tofacitinib with oral methotrexate in adults with severe alopecia areata, alopecia totalis, or alopecia universalis. Methods: This open-label, parallel-group randomized controlled trial was conducted in the Department of Dermatology, Medical Teaching Institution-Hayatabad Medical Complex, Peshawar, from 8 October 2024 to 8 March 2025. Seventy-eight adults aged 18-60 years were enrolled by consecutive non-probability sampling and allocated by blocked randomization (1:1) to tofacitinib 10 mg twice daily or methotrexate 0.2-0.4 mg/kg once weekly for 12 weeks. Participants receiving systemic alopecia therapy, pregnant or lactating women, and patients with renal, hepatic, or pulmonary disease were excluded. The trial was open-label; no allocation-concealment procedure was documented in the supplied records. Severity of Alopecia Tool (SALT) scores were measured at baseline and week 12. Efficacy was defined as a >50% reduction in SALT score. Ethical approval (No. 2141; 23 September 2024) and written informed consent were obtained. The trial was retrospectively registered (NCT07406204). Results: Baseline SALT scores were comparable between the tofacitinib and methotrexate groups (74.7 ± 9.5 vs 75.5 ± 8.7; p=0.68). At week 12, the mean SALT score was lower with tofacitinib (35.9 ± 11.2 vs 53.2 ± 9.5; p<0.001), and mean percentage improvement was greater (52.7 ± 10.2% vs 29.7 ± 9.5%; p<0.001). Efficacy was achieved by 23 (59.0%) and 1 (2.6%) participants, respectively (p<0.001). Conclusions: Oral tofacitinib demonstrated greater short-term efficacy than methotrexate over 12 weeks. The findings do not establish long-term safety, durability, relapse risk, or subtype-specific efficacy.
2026-06-25 | Alopecia totalis treated with constitutional medicine <i>Calcarea carbonica</i>: A case report
Introduction: Alopecia totalis is an autoimmune disease that causes hair loss anywhere in the body, but it most commonly affects the hair of the scalp. It occurs in people of all ages and affects 1–2% of the human population. The homoeopathic literature suggests that cases of alopecia totalis have been treated successfully with homoeopathic medicines. Case Summary: This case highlights the potential of the individualised homoeopathic remedy in promoting hair regrowth in alopecia totalis in a 14-yr old girl. The patient was prescribed Calcarea carbonica 200C, 2 doses on the basis of totality of symptoms and individualisation. This evidence-based case report shows how Homoeopathy can offer a promising alternative to conventional treatment in such cases.
cell therapies
2026-02-09 | Stem cell-based therapies for alopecia areata: a narrative review.
Alopecia Areata (AA) is a chronic inflammatory disorder characterized by non-scarring, patchy hair loss that may progress to the entire scalp (alopecia totalis) or body (alopecia universalis), significantly impairing patients' quality of life and psychological health. Although the exact pathogenesis of AA remains unclear, current evidence suggests that the breakdown of hair follicle immune privilege (IP) and subsequent autoimmune-mediated follicular attack play a pivotal role. Conventional therapeutic modalities, including corticosteroid and Janus kinase (JAK) inhibitors, are often limited by suboptimal efficacy in severe cases and high relapse rates following treatment cessation. In recent years, stem cell-based therapy has emerged as a novel treatment for AA, showing therapeutic potential through multiple mechanisms. Preliminary clinical trials have indicated significant efficacy in promoting hair regrowth among AA patients. However, comprehensive evaluation of long-term safety and therapeutic efficacy remains imperative. This review article aims to give a comprehensive overview of the recent advances in stem cell-based therapies for AA and explore their underlying mechanisms and clinical application prospects, hoping to provide a framework and reference for future research and clinical practice.
2026-01-10 | Exosome-Based Therapies for Alopecia Areata: A Systematic Review of Clinical and Experimental Evidence.
Alopecia areata (AA) is an autoimmune-mediated nonscarring alopecia with limited therapeutic options and frequent relapses. Exosomes, nanosized extracellular vesicles secreted by various cell types, have recently emerged as potential regenerative and immunomodulatory therapies. The aim of the study is to review the clinical and preclinical evidence regarding the efficacy and safety of EV-based therapies for alopecia areata. a systematic search of PubMed, Embase, Web of Science, and Cochrane Library was performed from 2020 to 2 October 2025. Inclusion criteria were original studies (clinical, preclinical, in vivo, in vitro) investigating exosome-derived interventions for AA. Outcomes of interest were hair regrowth, immune modulation, follicular regeneration, and safety. A total of 499 records were retrieved from electronic database searches. After deduplication and application of the inclusion/exclusion criteria, 40 studies met the eligibility criteria for the review. Of these, two were clinical studies (one retrospective cohort, one case report), while the remainder comprised five animal (in vivo) studies, six in vitro studies, and sixteen mixed translational studies (in vitro/in vivo ± clinical). Experimental studies reported hair coverage improvements of 50-99% and, in one instance, 30% regrowth in totalis and 16% in partialis, with nearly complete regrowth in incipient alopecia. Clinical reports noted density increases of 9-31 hairs per cm2 (e.g., from 121.7 to 146.6 hairs/cm2, p < 0.001) and improvements in hair count, length, and thickness. Several studies detailed activation of the Wnt/β-catenin pathway along with enhanced dermal papilla and hair follicle stem cell function, as well as anti-inflammatory effects. Reported safety profiles were favorable; when adverse events occurred, they were limited to mild, transient local reactions with no severe systemic issues. EV-based therapy is a novel and biologically plausible approach for AA, but robust randomized controlled trials (RCTs) are lacking. Standardization of small EV sources, doses, and delivery methods is essential before clinical translation.
2024-05-24 | Elucidating the role of T-Reg related cytokines: serum transforming growth factor beta and interleukin-35 in alopecia areata.
Previous studies demonstrated that Th1 cytokines like IL-2, IL-12 and IFN-γ have initiatory role in alopecia areata (AA) and positive correlation with disease severity. They informed that serum levels of Th17 cytokines, IL-17, IL-22, IL-23 increased in active AA patients and corelated, particularly IL-17, with disease severity. In recent reports it was showed the balance between Th17 and Treg cells is crucial for maintaining tolerance to self-antigens, and an imbalance towards Th17 may contribute to the development of autoimmune diseases like AA. But research on serum Treg markers in AA is limited. It was aimed to investigate whether the Treg cells have a role in the pathogenesis of AA analyzing the serum levels of Treg cytokines IL-35 and TGF-β in the patients with AA. 42 AA patients and 38 healthy controls were enrolled. Patient demographics, clinical data, disease severity assessed by Severity of Alopecia Tool (SALT) scores were recorded. Serum samples were collected and analyzed for TGF-β and IL-35 levels using ELISA kits. The cytokine levels in both groups were statistically compared. Their relation with parameters of demographic and severity of disease was evaluated. The patient and control groups had no statistically significant difference, there was 71.4% males and 28.6% females in patient group, while the control group had 63.2% males and 36.8% females, Severity analysis classified 18 patients with mild AA, 19 with moderate AA, and 5 with alopecia totalis/areata universalis. While TGF-β levels exhibited no significant difference between groups, IL-35 levels were significantly elevated in AA patients (p = 0.002). Logistic regression identified IL-35 as a significant parameter influencing disease status (OR = 1.055). Correlation analysis revealed a weak positive correlation between patient age and IL-35 levels (r = 0.436; p = 0.004). Notably, IL-35 levels displayed a significant decrease in individuals with antinuclear antibody (ANA) positivity. No correlations were identified between cytokine levels and disease severity, prognosis, or disease activity. Elevated IL-35 levels suggest that IL-35 and specific Treg cell subsets can play a role in AA pathogenesis. The nuanced roles of TGF-β and IL-35 highlight the need for comprehensive studies to interpret their implications in the complex immunopathogenesis of AA. These findings open avenues for further research, positioning IL-35 as a prospective target for investigating and potentially intervening in AA pathogenesis.
2023-12-22 | Study of effect of topical mometasone with intralesional platelet-rich plasma versus topical mometasone alone in the treatment of alopecia areata
Background: Alopecia areata (AA) is an autoimmune disorder and exhibits non scarring alopecia. Currently, there is no definitive cure, platelet rich plasma (PRP) has emerged as a newer modality for non-cicatricial alopecias such as AA. This study was conducted to compare the efficacy and adverse effects of topical mometasone with PRP versus topical mometasone alone in the treatment of patients of AA. Methods: This study was conducted on a total of 100 clinically diagnosed cases of AA. Patients in group A were subjected to intradermal injection of autologous PRP every 3 weeks along with topical mometasone cream 0.1% daily for 12 weeks. Group B was treated with topical mometasone cream 0.1% once a day locally over affected site for 12 weeks. Results: Baseline SALT score of group A was 6.05±5.36 while that of group B was 6.62±4.39. The mean SALT score of group A declined to 0.94±1.69 and that of group B 2.19±1.76 over a period of 20 weeks. Excellent response was observed by 12 and 5 patients of group A and group B respectively. Minor side effects like pain was seen in 10 patients (20%) in group A, while atrophy was seen in 2 patients of group B. Conclusions: This is the first ever study evaluating the additional benefit of intralesional PRP. In this study, it was found that adding intralesional PRP with topical mometasone 0.1% cream has higher efficacy and early improvement than topical mometasone alone, in the treatment of AA.
2023-12-16 | Effect of Topical Gel Administration of Secretome Hypoxia Mesenchymal Stem Cells (SH-MSCs) on IL-10 and TNF- α Gene Expression (In Vivo Experimental Study in Male Rats of Wistar Strains Model of Fluconazole-Induced Alopecia)
Alopecia is a dermatological disorder characterized by disturbances in the shorter anagen phase and longer telogen phase in the hair cycle. Therapy with irritant side effects and contact dermatitis, scalp allergies. causes increased hair loss. Alternative therapy using secretome hypoxia mesenchymal stem cells (SH-MSCs) which is safe and effective is an option. Objective to determine the effect of topical administration of SH-MSCs gel on IL-10 and TNF-α gene expression in Wistar rats with a fluconazole-induced alopecia-like model. In vivo experimental research using a Post Test Only Control Group Design research design. This study used 4 groups, namely 2 treatment groups and intervention with a topical SH-MSCs gel dose of 20 μL and a dose of 40 μL, 1 treatment group that did not receive intervention (base gel control) and 1 group of healthy mice. Skin tissue analysis was carried out on day 22 to assess IL-10 and TNF-α gene expression using the RT-PCR method. IL-10 gene expression using the One way Anova test obtained a value of 0.00 (p<0.05) so that there was a significant difference in IL-10 gene expression between groups in mice with the alopecia like model. The results of the TNF-α gene expression data with a value of 0.00 (p<0.05) showed significant differences between treatment groups. Administration of various doses of SH-MSCs topical gel increased IL-10 gene expression and decreased TNF-α gene expression in Wistar rats with a fluconazole-induced alopecia-like model, with the use of SH-MSCs topical gel at a dose of 40 μL having the greatest effect. most significant compared to other groups.
proteins
2023-10-23 | Allergen-specific immunotherapy improves alopecia totalis in a severe atopic dermatitis patient.
House dust mite (HDM) is the most common allergen exacerbating atopic dermatitis (AD), and allergen-specific immunotherapy (AIT) using HDM exhibited significant improvements in previous studies. Alopecia can occur as a complication of AD. Alopecia totalis (AT), a severe form of alopecia areata (AA), does not respond well to treatment and the chance of full recovery is less than 10%. For extensive hair loss, topical immunotherapy such as diphenylcyclopropenone (DPCP) is used as the first-line treatment. However, since DPCP is a kind of contact allergen, it has the potential to exacerbate AD. A 38-year-old man with AD and AA visited our clinic with symptoms worsening from 3 months ago. Although taking oral methylprednisolone (8 mg/day) and cyclosporine (100 mg/day) for 3 months, he has lost over 90% of his hair and the Eczema Area and Severity Index (EASI) was 43. Total serum immunoglobulin E (IgE) levels were 4454 kU/L (normal <100 kU/L) and the specific IgE levels for Dermatophagoides pteronyssinus and Dermatophagoides farinae following ImmunoCAP® were 20.8 and 37.4 kU/L, respectively. This patient did not respond well to previous treatment and was reluctant to use long-term steroids, so subcutaneous AIT using HDM was administered along with oral cyclosporine (100 mg/day). Topical tacrolimus was also applied to the AD lesions throughout the body. To reduce itching, nonsedative antihistamines were used if necessary. Hair loss was almost completely improved 1 year after the AIT initiation and the skin lesions of AD also improved (EASI 2.4). The specific IgE levels for D. pteronyssinus and D. farinae were 3.73 and 7.16 kU/L, respectively. Herein, we report a patient with promising results following AIT for AT with severe AD. In severe alopecic patients with AD refractory to conventional treatment, including immunosuppressants, AIT could be considered as a treatment option.
2018-08-01 | Hair Regrowth Outcomes of Contact Immunotherapy for Patients With Alopecia Areata
Contact immunotherapy with diphenylcyclopropenone or squaric acid dibutyl ester is a preferred treatment for severe alopecia areata; however, the defined criteria for therapeutic hair regrowth and regrowth rate have been highly heterogeneous across studies.To summarize the clinical outcomes of contact immunotherapy for alopecia areata according to standardized criteria for therapeutic hair regrowth and several prognostic factors.A database search of MEDLINE, Embase, and Cochrane Library was performed for articles published before November 20, 2017, using the search terms areata, totalis, universalis, sensitizer, sensitization, immunotherapy, DPCP, diphenylcyclopropenone, diphencyprone, SADBE, and squaric.Clinical trials or observational studies that investigated contact immunotherapy for alopecia areata and subgrouped the disease into patchy alopecia or alopecia totalis/universalis and reported their hair regrowth rates were included, whereas studies that investigated combination therapy or nonconventional protocol and case series or reviews were excluded.The following data were extracted from each of the studies included in this meta-analysis: study year and setting, sensitizer type, study population, study population composition by disease subtype, defined criteria for therapeutic hair regrowth, and regrowth rate of contact immunotherapy. The incidence of adverse effects and recurrence rate were also recorded. A random effects model was used for data synthesis because of the expected high heterogeneity of the included studies.The main outcome was therapeutic hair regrowth rate according to the 4-grade criteria for therapeutic regrowth. Secondary outcomes included incidence of treatment-related adverse effects and recurrence rate.Forty-five studies comprising 2227 patients were analyzed. The overall rate of any hair regrowth was 65.5% among patients with alopecia areata (74.6% in the patchy alopecia and 54.5% in the alopecia totalis/universalis subgroups). However, the complete regrowth rate was 32.3% (24.9% in the patchy alopecia and 32.3% in the alopecia totalis/universalis subgroups). Disease extent of 50% or greater (odds ratio [OR], 3.05; 95% CI, 2.26-4.12), atopic history (OR, 1.61; 95% CI, 1.03-2.50), and nail involvement (OR, 2.06; 95% CI. 1.26-3.36) were associated with poorer therapeutic outcome. Recurrence rates were 38.3% among patients receiving maintenance treatment and 49.0% among those not receiving maintenance treatment.Various factors were associated with the clinical outcomes of contact immunotherapy for alopecia areata, with significant differences in hair regrowth rates according to the level of expected therapeutic regrowth. Quantitative summarization may improve patient education and lead to better therapeutic adherence and outcomes.
2017-04-12 | 846 Human scalp-derived fibroblasts alter FGF expression profile upon WNT activation: implication of their role to provide folliculogenetic microenvironment
Hair follicle (HF) morphogenesis is enabled by epithelial-mesenchymal interactions in which WNT signaling plays key roles. Recent studies demonstrated that dermal fibroblasts surrounding HF enhanced HF regeneration via FGF9 secretion in mice. However, whether human dermal fibroblasts are capable of providing folliculogenetic environment by similar machinery remains elusive. The aim of this study is to assess if human scalp-derived dermal fibroblasts (hsFBs) are able to modulate their FGF expression profile in response to WNT activation. In isolated culture, hsFBs were distinguished from dermal papilla (DP) and dermal sheath cells by relatively-high expression of FGF5 and 18, potential inducers of hair cycle retardation or catagen phase. Interestingly, when exposed to WNT activator CHIR99021, cultured hsFBs down-regulated FGF7 whlile up-regulating FGF9, a positive regulator of HF morphogenesis, and FGF16 and 20 belonging to the same FGF subfamily. In addition, CHIR99021 dose-dependently modulated FGF7 and 9 expression. Supplementation of FGF9 to co-culture of human DP cell and keratinocytes resulted in up-regulation of DP biomarkers, implying a role of FGF9 in the maintenance of DP properties. When administered subcutaneously into immunodeficient mice co-transplanted with mice keratinocytes and dermal cells, FGF9 increased both of the number and the diameter of newly formed HFs, while FGF7 decreased HF diameter. These findings suggested that hsFBs may support HF formation by modulating regional FGF expression profile responding to WNT activation.
2015-12-17 | Treatment of Alopecia Areata in Mice by Stimulating the Hair Follicles Using Parathyroid Hormone Agonists Linked to a Collagen Binding Domain
Abstract Alopecia Areata is a patchy hair loss from autoimmune-mediated destruction of hair follicles, for which there is no adequate therapy. PTH-CBD is a fusion protein of parathyroid hormone and a bacterial collagen-binding domain, providing targeted delivery of a hair cycle stimulator to skin and promoting hair growth. Objectives: We tested the effects of PTH-CBD on hair growth in an established animal model for alopecia areata, the C3H/HeJ engrafted mouse. Methods: C3H/HeJ engrafted mice (Jackson Laboratories, Bar Harbor, ME) were treated subcutaneously for 8 weeks with either vehicle or different doses of PTH-CBD (320 mcg/kg x1, 1000 mcg/kg x1 or 1000 mcg/kg/wk). Results: Vehicle animals showed progressive hair loss, as expected. In PTH-CBD treated animals, grey scale quantification showed a greater proportion of PTH-CBD treated animals without significant hair loss at the end of the 2 month period (18/22 PTH-CBD vs. 4/11 vehicle), with no observed differences between the different PTH-CBD treatment regimens. Histological examination revealed no change in CD8+ cells, but there was a marked increases in the number of anagen VI hair follicles in PTH-CBD treated animals. There were also increased levels of betacatenin, a known initiator of the hair cycle, observed around the bulge region of hair follicles. Conclusions: C3H/HeJ engrafted animals treated with PTH-CBD showed rapid and persistent improvements in hair growth in the majority of tested animals. There were marked increases in anagen hair follicles despite an ongoing immune reaction. Increased beta catenin levels suggest that PTH-CBD stimulates hair growth by activating the Wnt pathway.
2015-11-01 | Therapy for Alopecia Areata in Mice by Stimulating the Hair Cycle with Parathyroid Hormone Agonists Linked to a Collagen-Binding Domain
Alopecia areata is a common disorder in which autoimmune destruction of hair follicles results in patchy hair loss. Currently there is no adequate therapy, although immune modulator therapies are currently in development. Parathyroid hormone (PTH) is a hair cycle stimulator which shows promise in treating various forms of alopecia, although its short half-life limits its clinical use. PTH-CBD is a PTH analog which binds collagen, prolonging retention in skin. We tested effects of PTH-CBD in C3H/HeJ-engrafted mice, the animal model for alopecia areata, on hair growth and found that a significant proportion of animals had reduced hair loss (PTH-CBD: 13/21, 62% vs.3/10, 30%; P<0.01). Histological analysis showed no change in immune response, but there was increased number of anagen hair follicles and increased production of beta-catenin, a factor which initiates the anagen phase of the hair cycle. PTH-CBD thus shows promise as a therapy for alopecia areata, either alone or in conjunction with immune modulation therapy.
antibodies
2026-03-04 | From Bald to Bold: Reversal of Alopecia Totalis in an Adolescent Using Dupilumab Monotherapy.
Alopecia areata (AA) is an autoimmune condition marked by non-scarring, patchy hair loss of the scalp which progresses in <10% of cases to alopecia totalis (AT), which is marked by complete hair loss from the scalp, eyebrows, and eyelashes. AA is prevalent in pediatric patients and is associated with atopic dermatitis (AD). The interleukin (IL)-4 and IL-13 antagonist dupilumab is approved for use in both pediatric and adult patients with AD and asthma. However, in some cases, dupilumab has shown promising results in regrowing hair in patients with concurrent AA. We report a 13-year-old male patient with a past medical history of AD and food atopy, who presented with AA to the scalp. The patient's hormonal lab work-up was within normal limits, and he was treated and failed typical therapies for AA. Within nine months of treatment, the hair loss progressed to AT of the scalp and eyebrows. Dupilumab was then initiated as monotherapy for the patient's AD and AT, leading to regrowth of hair on the scalp and eyebrows within several months and sustained complete hair regeneration after 17 months post dupilumab initiation. This case demonstrates the potential use of dupilumab, which has a well-established safety profile, for pediatric patients with AA and its ability to initiate and sustain hair growth for the long term. Dermatologists may consider dupilumab for patients with AA and comorbid AD that have failed a variety of treatments from several drug classes. .
2025-04-09 | Cytokine-Targeting Biologic Therapies for Alopecia Areata: A Comprehensive Review of Mechanism of Action, Clinical Efficacy, and Adverse Events
Background: Alopecia areata (AA) is an autoimmune disease affecting 2% of the global population, often causing localized scalp hair loss that can progress to alopecia totalis or universalis. While corticosteroids and JAK inhibitors are effective, their significant side effects highlight the need for safer, more targeted treatments. Recently, biologics have gained attention as potential treatments for AA. Methods: A review of clinical trials, case series, and case reports published on PubMed was conducted to assess the efficacy of cytokine-targeting biologics for the treatment of AA. Data on the mechanism of action, treatment outcomes, and safety were extracted and analyzed. Results: Cytokine-targeting biologics identified included Dupilumab, Secukinumab, Tralokinumab, Etanercept, Ustekinumab, Infliximab, Adalimumab, and Tildrakizumab. Dupilumab and ustekinumab demonstrated strong efficacy, with dupilumab showing significant regrowth in 89% of cases and ustekinumab in all patients. Tralokinumab demonstrated a 33.75% improvement, with no patients achieving SALT50. Limited efficacy was observed with secukinumab, tildrakizumab, and adalimumab, with 71.4%, 77.8%, and 50% of patients, respectively, showing no response. Disease worsening was observed in patients who received etanercept (29%) and infliximab (50%). Conclusions: Further research is necessary to optimize treatment protocols, identify predictive biomarkers, and, crucially, discover novel and more effective cytokine targets to advance biologics as a cornerstone therapy for AA.
2024-11-12 | Managing Azathioprine-Induced Myelosuppression and Alopecia Totalis: Lessons from a SLE Patient
Introduction Azathioprine (AZA), an immunosuppressant and mercaptopurine analog, is used to manage rheumatological and immunological conditions. Although effective, AZA can cause myelosuppression, sometimes necessitating dose adjustments or discontinuation. While severe pancytopenia or alopecia is rare, these issues can arise. This report describes a case of severe myelosuppression and alopecia totalis following AZA treatment in a patient with systemic lupus erythematosus (SLE). Case Report A 27-year-old healthy female presented with an 8-month history of fever, cough with pleuritic chest pain, and hemoptysis. Clinical and biochemical evaluations diagnosed her with SLE and secondary pulmonary vasculitis. She was initially treated with systemic steroids, followed by AZA. AZA was started at 25 mg daily (0.8 mg/kg) and increased to 75 mg daily (2 mg/kg) over three months. After dose escalation, she developed increased hair loss, feverishness, and lethargy, prompting her admission to a medical facility. Examination revealed significant non-scarring alopecia, (Figure 1) but no clinical signs of an SLE flare. Laboratory tests showed pancytopenia: hemoglobin 8.4 g/dL, white blood cells 880/[Formula: see text]L, platelets 130K/[Formula: see text]L, and absolute neutrophil count 38/[Formula: see text]L. Inflammatory markers, complement levels, and septic screening were normal. AZA was discontinued, and she was treated for neutropenic sepsis with high-dose steroids and GM-CSF. Despite these measures, blood parameters did not improve as expected. After 25 days of treatment, hair loss ceased, and cytopenias began to recover. Bone marrow analysis was not performed during the acute phase. Upon discharge, her blood counts were WBC 6,130/[Formula: see text]L, hemoglobin 10.9 g/dL, and platelets 85K/[Formula: see text]L. Given her SLE and lung pathology, she continued immunosuppressive therapy but was switched from AZA to IV Rituximab. Six weeks later, her blood counts had improved (WBC 10K/[Formula: see text]L, hemoglobin 10.9 g/dL, platelets 289K/[Formula: see text]L), and hair regrowth was observed. (Figure 2) Conclusion This case underscores the need for clinicians to be vigilant for early signs of severe myelosuppression, such as alopecia, in patients receiving azathioprine. Awareness of these uncommon side effects is crucial for effective management.
2023-10-09 | Case report: Dupilumab therapy for alopecia areata in a 4-year-old patient resistant to baricitinib
Alopecia areata (AA) is a non-scarring hair loss disorder. Alopecia totalis (AT) and alopecia universalis (AU) are the severe subtypes of AA. Age of onset before 6 years of age, disease duration of more than 1 year, and extensive alopecia involving more than 50% of the scalp (including AT or AU) suggest a poorer prognosis. Topical corticosteroids are the preferred first-line treatment for pediatric AA. While some treatments, such as intralesional corticosteroids, systemic steroids, contact immunotherapy with squaric acid dibutyl ester, and JAK inhibitors, showed efficacy in adults with AA, their safety profiles limit their use in pediatric AA patients. Dupilumab is a biologic that effectively addresses the patho-physiology of Th2 allergic diseases, and treats atopic diseases by inhibiting the helper Th2 immune axis. AA has been reported to be significantly improved with dupilumab for atopic dermatitis (AD) in children and adults. We report hair regrowth over all of the scalp, eyebrows, and eyelashes after 10 months of dupilumab therapy in a 4-year-old AU patient resistant to baricitinib.
2022-08-08 | [Hair growth with dupilumab in alopecia areata universalis and atopic dermatitis].
We report the case of a 46-year-old woman who has suffered from severe atopic dermatitis since early childhood and from alopecia areata totalis since she was 18 years old, which has now developed into alopecia areata universalis. After the introduction of therapy with the monoclonal antibody dupilumab, renewed hair growth of the scalp, face and lower legs was observed. Dupilumab blocks the α‑subunit of interleukin (IL)-4 receptor and prevents the signaling cascade of IL‑4 and IL-13. This leads to a reduction of Th2 immune response. The severe eczema and itching with difficulties falling and staying asleep decreased after just 14 days. The patient tolerates the drug without significant side effects and has a significantly improved quality of life. Patients with severe atopic dermatitis and alopecia areata could benefit twice from the use of dupilumab in the future. Berichtet wird über eine 46-jährige Patientin, die seit ihrer frühen Kindheit unter einer schweren atopischen Dermatitis leidet und seit ihrem 18. Lebensjahr unter einer Alopecia areata totalis, die mittlerweile in eine Alopecia areata universalis übergegangen ist. Durch die Einleitung einer Therapie mit dem monoklonalen Antikörper Dupilumab wurde erneutes Haarwachstum am Kapillitium, im Gesicht und an den Unterschenkeln beobachtet. Dupilumab blockiert die α‑Untereinheit des IL(Interleukin)-4-Rezeptors, unterbindet die Signalkaskade von IL‑4 und IL-13 und führt so zu einer reduzierten Th2-Immunantwort. Die schwere Ausprägung der Ekzeme und der Juckreiz mit Ein- und Durchschlafstörungen sind bereits 14 Tage nach Beginn der Einnahme zurückgegangen. Die Patientin verträgt das Medikament ohne wesentliche Nebenwirkungen, ihre Lebensqualität ist deutlich verbessert. Patienten mit einer schweren atopischen Dermatitis und einer Alopecia areata könnten von Dupilumab in Zukunft doppelt profitieren.
small molecules
2026-08-17 | Alopecia areata: Emerging therapies and up-to-date management strategies.
Alopecia areata (AA) is an autoimmune hair disease with variable presentations necessitating individualized, stepwise management given patient age, extent of involvement, comorbidities, and treatment tolerability. Historically, severity was defined by percentage of scalp hair loss using the Severity of Alopecia Tool (SALT), with SALT≥50 defining severe disease and systemic therapy eligibility. Recently, severity assessment has expanded beyond scalp involvement with the AA Scale for Clinical Use (AASc), incorporating eyebrow/eyelash involvement, psychosocial impairment, and treatment response to better capture disease burden. First-line therapy for mild-to-moderate AA (SALT<50) includes topical or intralesional corticosteroids, often with topical or oral minoxidil. Observation may be appropriate in select cases given potential for spontaneous regrowth. FDA approval of oral Janus kinase inhibitors (JAKis) for severe AA (SALT≥50) has changed the therapeutic landscape. Selection among baricitinib, ritlecitinib, and deuruxolitinib is guided by patient age, safety considerations, comorbidities, laboratory monitoring, and insurance coverage. Switching between JAKis may still be beneficial after nonresponse to one agent. Adjunctive and alternative therapies include topical immunotherapy, systemic immunosuppressants, emerging biologic/targeted therapies, and procedural modalities, such as platelet-rich plasma, laser- and light-based therapies, and microneedling. This review synthesizes current evidence on AA treatment and offers a practical, contemporary framework for AA management.
2026-07-31 | Case Report: Repigmentation and complete hair regrowth in an 11-year-old preadolescent with alopecia totalis treated with a JAK inhibitor.
Alopecia areata (AA) is an autoimmune disease characterized by non-scarring hair loss. Janus kinase (JAK) inhibitors have emerged as effective therapeutic options for severe pediatric AA, though repigmentation of white hair during treatment remains rarely reported. Herein, we report an unusual case of complete hair regeneration with simultaneous white-to-black hair conversion in a child with severe AA following JAK inhibitor therapy. An 11-year-old girl presented with alopecia totalis (AT) persisting for two years. She initially received baricitinib for seven months, achieving SALT 65% with predominantly white and gray hair regrowth. After switching to ritlecitinib 50 mg/day, black hair emerged at 6 weeks, with complete hair regrowth and repigmentation at 6 months (SALT 0). The patient has now completed 12 months of ritlecitinib therapy with sustained response and stable pigmentation. Family Dermatology Life Quality Index (FDLQI) decreased from 18 to 4. No significant adverse effects were observed. This case suggests that prolonged JAK inhibition may facilitate both hair regrowth and pigment restoration in pediatric severe AA.
2026-07-29 | Efficacy and Safety of Oral Janus Kinase Inhibitors in Adults and Adolescents with Alopecia Areata: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
Alopecia areata is an autoimmune disorder characterised by T-cell-mediated damage of hair follicles, resulting in non-scarring hair loss that can progress to complete scalp (alopecia totalis) or body hair loss (alopecia universalis). While long-term systemic options were historically limited, the emergence of Janus kinase (JAK) inhibitors has revolutionised the treatment of alopecia areata, even in patients with moderate-to-severe disease. We aimed to evaluate the efficacy and safety of oral JAK inhibitors compared with placebo in adults and adolescents with moderate-to-severe alopecia areata. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases were searched from inception to 28 November, 2025. Randomised controlled trials evaluating oral JAK inhibitors in adolescents and adults (aged ≥12 years) with alopecia areata were included. Data extraction and risk of bias assessment were performed independently by multiple reviewers. Primary outcomes were the proportion of patients who achieved Severity of Alopecia Tool (SALT) scores of ≤10 and ≤20, and 50%, 75% and 90% reductions in SALT scores from baseline, as well as treatment-related adverse events (AEs). Data were synthesised using random-effects models to calculate odds ratios (ORs) and mean differences with 95% confidence intervals (CIs). Twelve randomised controlled trials involving 4141 participants (mean age 35.8 years, mean baseline SALT score 86.0) met the inclusion criteria. All trials enrolled adult participants, with the exception of one randomised controlled trial in which adolescents comprised 15% of the study population. Six trials were rated as having a low risk of bias, while six had "some concerns" primarily because of missing outcome data. Oral JAK inhibitors were significantly more effective than placebo across all primary efficacy endpoints. At week 24, the odds of achieving SALT ≤10 were 5.69 times higher for JAK inhibitors than placebo (95% CI 3.58-9.03); by week 36, this effect increased to an OR of 9.40 (95% CI 4.58-19.29). For SALT ≤20, the OR was 7.99 (95% CI 5.13-12.44) at week 24. Patients treated with oral JAK inhibitors were significantly more likely to achieve SALT50, SALT75 and SALT90 across all timepoints (weeks 12-36). Regarding safety, JAK inhibitors were associated with a higher risk of total AEs (OR 1.60; 95% CI 1.33-1.94), but no statistically significant difference was found for serious AEs (OR 1.04; 95% CI 0.69-1.57) or treatment discontinuation because of AEs (OR 1.22; 95% CI 0.84-1.76). Oral JAK inhibitors are effective in promoting scalp, eyebrow and eyelash hair regrowth in adults and adolescents with moderate-to-severe alopecia areata, with a trend of higher response rates at later timepoints across studies. The favourable safety profile of these agents is reassuring. Future research should prioritise head-to-head randomised controlled trials and long-term pharmacovigilance to define comparative efficacy and safety.
2026-06-30 | COMPARISON OF CLINICAL EFFICACY OF TOFACITINIB VERSUS METHOTREXATE IN SEVERE ALOPECIA AREATA, ALOPECIA TOTALIS, AND ALOPECIA UNIVERSALIS: A RANDOMIZED CONTROLLED TRIAL
Objective: To compare the 12-week clinical efficacy of oral tofacitinib with oral methotrexate in adults with severe alopecia areata, alopecia totalis, or alopecia universalis. Methods: This open-label, parallel-group randomized controlled trial was conducted in the Department of Dermatology, Medical Teaching Institution-Hayatabad Medical Complex, Peshawar, from 8 October 2024 to 8 March 2025. Seventy-eight adults aged 18-60 years were enrolled by consecutive non-probability sampling and allocated by blocked randomization (1:1) to tofacitinib 10 mg twice daily or methotrexate 0.2-0.4 mg/kg once weekly for 12 weeks. Participants receiving systemic alopecia therapy, pregnant or lactating women, and patients with renal, hepatic, or pulmonary disease were excluded. The trial was open-label; no allocation-concealment procedure was documented in the supplied records. Severity of Alopecia Tool (SALT) scores were measured at baseline and week 12. Efficacy was defined as a >50% reduction in SALT score. Ethical approval (No. 2141; 23 September 2024) and written informed consent were obtained. The trial was retrospectively registered (NCT07406204). Results: Baseline SALT scores were comparable between the tofacitinib and methotrexate groups (74.7 ± 9.5 vs 75.5 ± 8.7; p=0.68). At week 12, the mean SALT score was lower with tofacitinib (35.9 ± 11.2 vs 53.2 ± 9.5; p<0.001), and mean percentage improvement was greater (52.7 ± 10.2% vs 29.7 ± 9.5%; p<0.001). Efficacy was achieved by 23 (59.0%) and 1 (2.6%) participants, respectively (p<0.001). Conclusions: Oral tofacitinib demonstrated greater short-term efficacy than methotrexate over 12 weeks. The findings do not establish long-term safety, durability, relapse risk, or subtype-specific efficacy.
2026-06-25 | Alopecia totalis treated with constitutional medicine <i>Calcarea carbonica</i>: A case report
Introduction: Alopecia totalis is an autoimmune disease that causes hair loss anywhere in the body, but it most commonly affects the hair of the scalp. It occurs in people of all ages and affects 1–2% of the human population. The homoeopathic literature suggests that cases of alopecia totalis have been treated successfully with homoeopathic medicines. Case Summary: This case highlights the potential of the individualised homoeopathic remedy in promoting hair regrowth in alopecia totalis in a 14-yr old girl. The patient was prescribed Calcarea carbonica 200C, 2 doses on the basis of totality of symptoms and individualisation. This evidence-based case report shows how Homoeopathy can offer a promising alternative to conventional treatment in such cases.
cell therapies
2026-02-09 | Stem cell-based therapies for alopecia areata: a narrative review.
Alopecia Areata (AA) is a chronic inflammatory disorder characterized by non-scarring, patchy hair loss that may progress to the entire scalp (alopecia totalis) or body (alopecia universalis), significantly impairing patients' quality of life and psychological health. Although the exact pathogenesis of AA remains unclear, current evidence suggests that the breakdown of hair follicle immune privilege (IP) and subsequent autoimmune-mediated follicular attack play a pivotal role. Conventional therapeutic modalities, including corticosteroid and Janus kinase (JAK) inhibitors, are often limited by suboptimal efficacy in severe cases and high relapse rates following treatment cessation. In recent years, stem cell-based therapy has emerged as a novel treatment for AA, showing therapeutic potential through multiple mechanisms. Preliminary clinical trials have indicated significant efficacy in promoting hair regrowth among AA patients. However, comprehensive evaluation of long-term safety and therapeutic efficacy remains imperative. This review article aims to give a comprehensive overview of the recent advances in stem cell-based therapies for AA and explore their underlying mechanisms and clinical application prospects, hoping to provide a framework and reference for future research and clinical practice.
2026-01-10 | Exosome-Based Therapies for Alopecia Areata: A Systematic Review of Clinical and Experimental Evidence.
Alopecia areata (AA) is an autoimmune-mediated nonscarring alopecia with limited therapeutic options and frequent relapses. Exosomes, nanosized extracellular vesicles secreted by various cell types, have recently emerged as potential regenerative and immunomodulatory therapies. The aim of the study is to review the clinical and preclinical evidence regarding the efficacy and safety of EV-based therapies for alopecia areata. a systematic search of PubMed, Embase, Web of Science, and Cochrane Library was performed from 2020 to 2 October 2025. Inclusion criteria were original studies (clinical, preclinical, in vivo, in vitro) investigating exosome-derived interventions for AA. Outcomes of interest were hair regrowth, immune modulation, follicular regeneration, and safety. A total of 499 records were retrieved from electronic database searches. After deduplication and application of the inclusion/exclusion criteria, 40 studies met the eligibility criteria for the review. Of these, two were clinical studies (one retrospective cohort, one case report), while the remainder comprised five animal (in vivo) studies, six in vitro studies, and sixteen mixed translational studies (in vitro/in vivo ± clinical). Experimental studies reported hair coverage improvements of 50-99% and, in one instance, 30% regrowth in totalis and 16% in partialis, with nearly complete regrowth in incipient alopecia. Clinical reports noted density increases of 9-31 hairs per cm2 (e.g., from 121.7 to 146.6 hairs/cm2, p < 0.001) and improvements in hair count, length, and thickness. Several studies detailed activation of the Wnt/β-catenin pathway along with enhanced dermal papilla and hair follicle stem cell function, as well as anti-inflammatory effects. Reported safety profiles were favorable; when adverse events occurred, they were limited to mild, transient local reactions with no severe systemic issues. EV-based therapy is a novel and biologically plausible approach for AA, but robust randomized controlled trials (RCTs) are lacking. Standardization of small EV sources, doses, and delivery methods is essential before clinical translation.
2024-05-24 | Elucidating the role of T-Reg related cytokines: serum transforming growth factor beta and interleukin-35 in alopecia areata.
Previous studies demonstrated that Th1 cytokines like IL-2, IL-12 and IFN-γ have initiatory role in alopecia areata (AA) and positive correlation with disease severity. They informed that serum levels of Th17 cytokines, IL-17, IL-22, IL-23 increased in active AA patients and corelated, particularly IL-17, with disease severity. In recent reports it was showed the balance between Th17 and Treg cells is crucial for maintaining tolerance to self-antigens, and an imbalance towards Th17 may contribute to the development of autoimmune diseases like AA. But research on serum Treg markers in AA is limited. It was aimed to investigate whether the Treg cells have a role in the pathogenesis of AA analyzing the serum levels of Treg cytokines IL-35 and TGF-β in the patients with AA. 42 AA patients and 38 healthy controls were enrolled. Patient demographics, clinical data, disease severity assessed by Severity of Alopecia Tool (SALT) scores were recorded. Serum samples were collected and analyzed for TGF-β and IL-35 levels using ELISA kits. The cytokine levels in both groups were statistically compared. Their relation with parameters of demographic and severity of disease was evaluated. The patient and control groups had no statistically significant difference, there was 71.4% males and 28.6% females in patient group, while the control group had 63.2% males and 36.8% females, Severity analysis classified 18 patients with mild AA, 19 with moderate AA, and 5 with alopecia totalis/areata universalis. While TGF-β levels exhibited no significant difference between groups, IL-35 levels were significantly elevated in AA patients (p = 0.002). Logistic regression identified IL-35 as a significant parameter influencing disease status (OR = 1.055). Correlation analysis revealed a weak positive correlation between patient age and IL-35 levels (r = 0.436; p = 0.004). Notably, IL-35 levels displayed a significant decrease in individuals with antinuclear antibody (ANA) positivity. No correlations were identified between cytokine levels and disease severity, prognosis, or disease activity. Elevated IL-35 levels suggest that IL-35 and specific Treg cell subsets can play a role in AA pathogenesis. The nuanced roles of TGF-β and IL-35 highlight the need for comprehensive studies to interpret their implications in the complex immunopathogenesis of AA. These findings open avenues for further research, positioning IL-35 as a prospective target for investigating and potentially intervening in AA pathogenesis.
2023-12-22 | Study of effect of topical mometasone with intralesional platelet-rich plasma versus topical mometasone alone in the treatment of alopecia areata
Background: Alopecia areata (AA) is an autoimmune disorder and exhibits non scarring alopecia. Currently, there is no definitive cure, platelet rich plasma (PRP) has emerged as a newer modality for non-cicatricial alopecias such as AA. This study was conducted to compare the efficacy and adverse effects of topical mometasone with PRP versus topical mometasone alone in the treatment of patients of AA. Methods: This study was conducted on a total of 100 clinically diagnosed cases of AA. Patients in group A were subjected to intradermal injection of autologous PRP every 3 weeks along with topical mometasone cream 0.1% daily for 12 weeks. Group B was treated with topical mometasone cream 0.1% once a day locally over affected site for 12 weeks. Results: Baseline SALT score of group A was 6.05±5.36 while that of group B was 6.62±4.39. The mean SALT score of group A declined to 0.94±1.69 and that of group B 2.19±1.76 over a period of 20 weeks. Excellent response was observed by 12 and 5 patients of group A and group B respectively. Minor side effects like pain was seen in 10 patients (20%) in group A, while atrophy was seen in 2 patients of group B. Conclusions: This is the first ever study evaluating the additional benefit of intralesional PRP. In this study, it was found that adding intralesional PRP with topical mometasone 0.1% cream has higher efficacy and early improvement than topical mometasone alone, in the treatment of AA.
2023-12-16 | Effect of Topical Gel Administration of Secretome Hypoxia Mesenchymal Stem Cells (SH-MSCs) on IL-10 and TNF- α Gene Expression (In Vivo Experimental Study in Male Rats of Wistar Strains Model of Fluconazole-Induced Alopecia)
Alopecia is a dermatological disorder characterized by disturbances in the shorter anagen phase and longer telogen phase in the hair cycle. Therapy with irritant side effects and contact dermatitis, scalp allergies. causes increased hair loss. Alternative therapy using secretome hypoxia mesenchymal stem cells (SH-MSCs) which is safe and effective is an option. Objective to determine the effect of topical administration of SH-MSCs gel on IL-10 and TNF-α gene expression in Wistar rats with a fluconazole-induced alopecia-like model. In vivo experimental research using a Post Test Only Control Group Design research design. This study used 4 groups, namely 2 treatment groups and intervention with a topical SH-MSCs gel dose of 20 μL and a dose of 40 μL, 1 treatment group that did not receive intervention (base gel control) and 1 group of healthy mice. Skin tissue analysis was carried out on day 22 to assess IL-10 and TNF-α gene expression using the RT-PCR method. IL-10 gene expression using the One way Anova test obtained a value of 0.00 (p<0.05) so that there was a significant difference in IL-10 gene expression between groups in mice with the alopecia like model. The results of the TNF-α gene expression data with a value of 0.00 (p<0.05) showed significant differences between treatment groups. Administration of various doses of SH-MSCs topical gel increased IL-10 gene expression and decreased TNF-α gene expression in Wistar rats with a fluconazole-induced alopecia-like model, with the use of SH-MSCs topical gel at a dose of 40 μL having the greatest effect. most significant compared to other groups.
proteins
2023-10-23 | Allergen-specific immunotherapy improves alopecia totalis in a severe atopic dermatitis patient.
House dust mite (HDM) is the most common allergen exacerbating atopic dermatitis (AD), and allergen-specific immunotherapy (AIT) using HDM exhibited significant improvements in previous studies. Alopecia can occur as a complication of AD. Alopecia totalis (AT), a severe form of alopecia areata (AA), does not respond well to treatment and the chance of full recovery is less than 10%. For extensive hair loss, topical immunotherapy such as diphenylcyclopropenone (DPCP) is used as the first-line treatment. However, since DPCP is a kind of contact allergen, it has the potential to exacerbate AD. A 38-year-old man with AD and AA visited our clinic with symptoms worsening from 3 months ago. Although taking oral methylprednisolone (8 mg/day) and cyclosporine (100 mg/day) for 3 months, he has lost over 90% of his hair and the Eczema Area and Severity Index (EASI) was 43. Total serum immunoglobulin E (IgE) levels were 4454 kU/L (normal <100 kU/L) and the specific IgE levels for Dermatophagoides pteronyssinus and Dermatophagoides farinae following ImmunoCAP® were 20.8 and 37.4 kU/L, respectively. This patient did not respond well to previous treatment and was reluctant to use long-term steroids, so subcutaneous AIT using HDM was administered along with oral cyclosporine (100 mg/day). Topical tacrolimus was also applied to the AD lesions throughout the body. To reduce itching, nonsedative antihistamines were used if necessary. Hair loss was almost completely improved 1 year after the AIT initiation and the skin lesions of AD also improved (EASI 2.4). The specific IgE levels for D. pteronyssinus and D. farinae were 3.73 and 7.16 kU/L, respectively. Herein, we report a patient with promising results following AIT for AT with severe AD. In severe alopecic patients with AD refractory to conventional treatment, including immunosuppressants, AIT could be considered as a treatment option.
2018-08-01 | Hair Regrowth Outcomes of Contact Immunotherapy for Patients With Alopecia Areata
Contact immunotherapy with diphenylcyclopropenone or squaric acid dibutyl ester is a preferred treatment for severe alopecia areata; however, the defined criteria for therapeutic hair regrowth and regrowth rate have been highly heterogeneous across studies.To summarize the clinical outcomes of contact immunotherapy for alopecia areata according to standardized criteria for therapeutic hair regrowth and several prognostic factors.A database search of MEDLINE, Embase, and Cochrane Library was performed for articles published before November 20, 2017, using the search terms areata, totalis, universalis, sensitizer, sensitization, immunotherapy, DPCP, diphenylcyclopropenone, diphencyprone, SADBE, and squaric.Clinical trials or observational studies that investigated contact immunotherapy for alopecia areata and subgrouped the disease into patchy alopecia or alopecia totalis/universalis and reported their hair regrowth rates were included, whereas studies that investigated combination therapy or nonconventional protocol and case series or reviews were excluded.The following data were extracted from each of the studies included in this meta-analysis: study year and setting, sensitizer type, study population, study population composition by disease subtype, defined criteria for therapeutic hair regrowth, and regrowth rate of contact immunotherapy. The incidence of adverse effects and recurrence rate were also recorded. A random effects model was used for data synthesis because of the expected high heterogeneity of the included studies.The main outcome was therapeutic hair regrowth rate according to the 4-grade criteria for therapeutic regrowth. Secondary outcomes included incidence of treatment-related adverse effects and recurrence rate.Forty-five studies comprising 2227 patients were analyzed. The overall rate of any hair regrowth was 65.5% among patients with alopecia areata (74.6% in the patchy alopecia and 54.5% in the alopecia totalis/universalis subgroups). However, the complete regrowth rate was 32.3% (24.9% in the patchy alopecia and 32.3% in the alopecia totalis/universalis subgroups). Disease extent of 50% or greater (odds ratio [OR], 3.05; 95% CI, 2.26-4.12), atopic history (OR, 1.61; 95% CI, 1.03-2.50), and nail involvement (OR, 2.06; 95% CI. 1.26-3.36) were associated with poorer therapeutic outcome. Recurrence rates were 38.3% among patients receiving maintenance treatment and 49.0% among those not receiving maintenance treatment.Various factors were associated with the clinical outcomes of contact immunotherapy for alopecia areata, with significant differences in hair regrowth rates according to the level of expected therapeutic regrowth. Quantitative summarization may improve patient education and lead to better therapeutic adherence and outcomes.
2017-04-12 | 846 Human scalp-derived fibroblasts alter FGF expression profile upon WNT activation: implication of their role to provide folliculogenetic microenvironment
Hair follicle (HF) morphogenesis is enabled by epithelial-mesenchymal interactions in which WNT signaling plays key roles. Recent studies demonstrated that dermal fibroblasts surrounding HF enhanced HF regeneration via FGF9 secretion in mice. However, whether human dermal fibroblasts are capable of providing folliculogenetic environment by similar machinery remains elusive. The aim of this study is to assess if human scalp-derived dermal fibroblasts (hsFBs) are able to modulate their FGF expression profile in response to WNT activation. In isolated culture, hsFBs were distinguished from dermal papilla (DP) and dermal sheath cells by relatively-high expression of FGF5 and 18, potential inducers of hair cycle retardation or catagen phase. Interestingly, when exposed to WNT activator CHIR99021, cultured hsFBs down-regulated FGF7 whlile up-regulating FGF9, a positive regulator of HF morphogenesis, and FGF16 and 20 belonging to the same FGF subfamily. In addition, CHIR99021 dose-dependently modulated FGF7 and 9 expression. Supplementation of FGF9 to co-culture of human DP cell and keratinocytes resulted in up-regulation of DP biomarkers, implying a role of FGF9 in the maintenance of DP properties. When administered subcutaneously into immunodeficient mice co-transplanted with mice keratinocytes and dermal cells, FGF9 increased both of the number and the diameter of newly formed HFs, while FGF7 decreased HF diameter. These findings suggested that hsFBs may support HF formation by modulating regional FGF expression profile responding to WNT activation.
2015-12-17 | Treatment of Alopecia Areata in Mice by Stimulating the Hair Follicles Using Parathyroid Hormone Agonists Linked to a Collagen Binding Domain
Abstract Alopecia Areata is a patchy hair loss from autoimmune-mediated destruction of hair follicles, for which there is no adequate therapy. PTH-CBD is a fusion protein of parathyroid hormone and a bacterial collagen-binding domain, providing targeted delivery of a hair cycle stimulator to skin and promoting hair growth. Objectives: We tested the effects of PTH-CBD on hair growth in an established animal model for alopecia areata, the C3H/HeJ engrafted mouse. Methods: C3H/HeJ engrafted mice (Jackson Laboratories, Bar Harbor, ME) were treated subcutaneously for 8 weeks with either vehicle or different doses of PTH-CBD (320 mcg/kg x1, 1000 mcg/kg x1 or 1000 mcg/kg/wk). Results: Vehicle animals showed progressive hair loss, as expected. In PTH-CBD treated animals, grey scale quantification showed a greater proportion of PTH-CBD treated animals without significant hair loss at the end of the 2 month period (18/22 PTH-CBD vs. 4/11 vehicle), with no observed differences between the different PTH-CBD treatment regimens. Histological examination revealed no change in CD8+ cells, but there was a marked increases in the number of anagen VI hair follicles in PTH-CBD treated animals. There were also increased levels of betacatenin, a known initiator of the hair cycle, observed around the bulge region of hair follicles. Conclusions: C3H/HeJ engrafted animals treated with PTH-CBD showed rapid and persistent improvements in hair growth in the majority of tested animals. There were marked increases in anagen hair follicles despite an ongoing immune reaction. Increased beta catenin levels suggest that PTH-CBD stimulates hair growth by activating the Wnt pathway.
2015-11-01 | Therapy for Alopecia Areata in Mice by Stimulating the Hair Cycle with Parathyroid Hormone Agonists Linked to a Collagen-Binding Domain
Alopecia areata is a common disorder in which autoimmune destruction of hair follicles results in patchy hair loss. Currently there is no adequate therapy, although immune modulator therapies are currently in development. Parathyroid hormone (PTH) is a hair cycle stimulator which shows promise in treating various forms of alopecia, although its short half-life limits its clinical use. PTH-CBD is a PTH analog which binds collagen, prolonging retention in skin. We tested effects of PTH-CBD in C3H/HeJ-engrafted mice, the animal model for alopecia areata, on hair growth and found that a significant proportion of animals had reduced hair loss (PTH-CBD: 13/21, 62% vs.3/10, 30%; P<0.01). Histological analysis showed no change in immune response, but there was increased number of anagen hair follicles and increased production of beta-catenin, a factor which initiates the anagen phase of the hair cycle. PTH-CBD thus shows promise as a therapy for alopecia areata, either alone or in conjunction with immune modulation therapy.
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2026-03-04 | From Bald to Bold: Reversal of Alopecia Totalis in an Adolescent Using Dupilumab Monotherapy.
Alopecia areata (AA) is an autoimmune condition marked by non-scarring, patchy hair loss of the scalp which progresses in <10% of cases to alopecia totalis (AT), which is marked by complete hair loss from the scalp, eyebrows, and eyelashes. AA is prevalent in pediatric patients and is associated with atopic dermatitis (AD). The interleukin (IL)-4 and IL-13 antagonist dupilumab is approved for use in both pediatric and adult patients with AD and asthma. However, in some cases, dupilumab has shown promising results in regrowing hair in patients with concurrent AA. We report a 13-year-old male patient with a past medical history of AD and food atopy, who presented with AA to the scalp. The patient's hormonal lab work-up was within normal limits, and he was treated and failed typical therapies for AA. Within nine months of treatment, the hair loss progressed to AT of the scalp and eyebrows. Dupilumab was then initiated as monotherapy for the patient's AD and AT, leading to regrowth of hair on the scalp and eyebrows within several months and sustained complete hair regeneration after 17 months post dupilumab initiation. This case demonstrates the potential use of dupilumab, which has a well-established safety profile, for pediatric patients with AA and its ability to initiate and sustain hair growth for the long term. Dermatologists may consider dupilumab for patients with AA and comorbid AD that have failed a variety of treatments from several drug classes. .
2025-04-09 | Cytokine-Targeting Biologic Therapies for Alopecia Areata: A Comprehensive Review of Mechanism of Action, Clinical Efficacy, and Adverse Events
Background: Alopecia areata (AA) is an autoimmune disease affecting 2% of the global population, often causing localized scalp hair loss that can progress to alopecia totalis or universalis. While corticosteroids and JAK inhibitors are effective, their significant side effects highlight the need for safer, more targeted treatments. Recently, biologics have gained attention as potential treatments for AA. Methods: A review of clinical trials, case series, and case reports published on PubMed was conducted to assess the efficacy of cytokine-targeting biologics for the treatment of AA. Data on the mechanism of action, treatment outcomes, and safety were extracted and analyzed. Results: Cytokine-targeting biologics identified included Dupilumab, Secukinumab, Tralokinumab, Etanercept, Ustekinumab, Infliximab, Adalimumab, and Tildrakizumab. Dupilumab and ustekinumab demonstrated strong efficacy, with dupilumab showing significant regrowth in 89% of cases and ustekinumab in all patients. Tralokinumab demonstrated a 33.75% improvement, with no patients achieving SALT50. Limited efficacy was observed with secukinumab, tildrakizumab, and adalimumab, with 71.4%, 77.8%, and 50% of patients, respectively, showing no response. Disease worsening was observed in patients who received etanercept (29%) and infliximab (50%). Conclusions: Further research is necessary to optimize treatment protocols, identify predictive biomarkers, and, crucially, discover novel and more effective cytokine targets to advance biologics as a cornerstone therapy for AA.
2024-11-12 | Managing Azathioprine-Induced Myelosuppression and Alopecia Totalis: Lessons from a SLE Patient
Introduction Azathioprine (AZA), an immunosuppressant and mercaptopurine analog, is used to manage rheumatological and immunological conditions. Although effective, AZA can cause myelosuppression, sometimes necessitating dose adjustments or discontinuation. While severe pancytopenia or alopecia is rare, these issues can arise. This report describes a case of severe myelosuppression and alopecia totalis following AZA treatment in a patient with systemic lupus erythematosus (SLE). Case Report A 27-year-old healthy female presented with an 8-month history of fever, cough with pleuritic chest pain, and hemoptysis. Clinical and biochemical evaluations diagnosed her with SLE and secondary pulmonary vasculitis. She was initially treated with systemic steroids, followed by AZA. AZA was started at 25 mg daily (0.8 mg/kg) and increased to 75 mg daily (2 mg/kg) over three months. After dose escalation, she developed increased hair loss, feverishness, and lethargy, prompting her admission to a medical facility. Examination revealed significant non-scarring alopecia, (Figure 1) but no clinical signs of an SLE flare. Laboratory tests showed pancytopenia: hemoglobin 8.4 g/dL, white blood cells 880/[Formula: see text]L, platelets 130K/[Formula: see text]L, and absolute neutrophil count 38/[Formula: see text]L. Inflammatory markers, complement levels, and septic screening were normal. AZA was discontinued, and she was treated for neutropenic sepsis with high-dose steroids and GM-CSF. Despite these measures, blood parameters did not improve as expected. After 25 days of treatment, hair loss ceased, and cytopenias began to recover. Bone marrow analysis was not performed during the acute phase. Upon discharge, her blood counts were WBC 6,130/[Formula: see text]L, hemoglobin 10.9 g/dL, and platelets 85K/[Formula: see text]L. Given her SLE and lung pathology, she continued immunosuppressive therapy but was switched from AZA to IV Rituximab. Six weeks later, her blood counts had improved (WBC 10K/[Formula: see text]L, hemoglobin 10.9 g/dL, platelets 289K/[Formula: see text]L), and hair regrowth was observed. (Figure 2) Conclusion This case underscores the need for clinicians to be vigilant for early signs of severe myelosuppression, such as alopecia, in patients receiving azathioprine. Awareness of these uncommon side effects is crucial for effective management.
2023-10-09 | Case report: Dupilumab therapy for alopecia areata in a 4-year-old patient resistant to baricitinib
Alopecia areata (AA) is a non-scarring hair loss disorder. Alopecia totalis (AT) and alopecia universalis (AU) are the severe subtypes of AA. Age of onset before 6 years of age, disease duration of more than 1 year, and extensive alopecia involving more than 50% of the scalp (including AT or AU) suggest a poorer prognosis. Topical corticosteroids are the preferred first-line treatment for pediatric AA. While some treatments, such as intralesional corticosteroids, systemic steroids, contact immunotherapy with squaric acid dibutyl ester, and JAK inhibitors, showed efficacy in adults with AA, their safety profiles limit their use in pediatric AA patients. Dupilumab is a biologic that effectively addresses the patho-physiology of Th2 allergic diseases, and treats atopic diseases by inhibiting the helper Th2 immune axis. AA has been reported to be significantly improved with dupilumab for atopic dermatitis (AD) in children and adults. We report hair regrowth over all of the scalp, eyebrows, and eyelashes after 10 months of dupilumab therapy in a 4-year-old AU patient resistant to baricitinib.
2022-08-08 | [Hair growth with dupilumab in alopecia areata universalis and atopic dermatitis].
We report the case of a 46-year-old woman who has suffered from severe atopic dermatitis since early childhood and from alopecia areata totalis since she was 18 years old, which has now developed into alopecia areata universalis. After the introduction of therapy with the monoclonal antibody dupilumab, renewed hair growth of the scalp, face and lower legs was observed. Dupilumab blocks the α‑subunit of interleukin (IL)-4 receptor and prevents the signaling cascade of IL‑4 and IL-13. This leads to a reduction of Th2 immune response. The severe eczema and itching with difficulties falling and staying asleep decreased after just 14 days. The patient tolerates the drug without significant side effects and has a significantly improved quality of life. Patients with severe atopic dermatitis and alopecia areata could benefit twice from the use of dupilumab in the future. Berichtet wird über eine 46-jährige Patientin, die seit ihrer frühen Kindheit unter einer schweren atopischen Dermatitis leidet und seit ihrem 18. Lebensjahr unter einer Alopecia areata totalis, die mittlerweile in eine Alopecia areata universalis übergegangen ist. Durch die Einleitung einer Therapie mit dem monoklonalen Antikörper Dupilumab wurde erneutes Haarwachstum am Kapillitium, im Gesicht und an den Unterschenkeln beobachtet. Dupilumab blockiert die α‑Untereinheit des IL(Interleukin)-4-Rezeptors, unterbindet die Signalkaskade von IL‑4 und IL-13 und führt so zu einer reduzierten Th2-Immunantwort. Die schwere Ausprägung der Ekzeme und der Juckreiz mit Ein- und Durchschlafstörungen sind bereits 14 Tage nach Beginn der Einnahme zurückgegangen. Die Patientin verträgt das Medikament ohne wesentliche Nebenwirkungen, ihre Lebensqualität ist deutlich verbessert. Patienten mit einer schweren atopischen Dermatitis und einer Alopecia areata könnten von Dupilumab in Zukunft doppelt profitieren.
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Drug Discovery Landscape
4 orphan drug designations for Alopecia totalis.
4 orphan drug designations for Alopecia totalis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
trafermin in combination with plasma and platelet rich plasma | other | FDA | 2017-12-21 | — | HCell, Inc. |
Diphencyprone | small molecules | EMA | 2006-06-29 | — | [INACTIVE] Orfagen |
Diphencyprone | small molecules | EMA | 2006-06-29 | — | [INACTIVE] Orfagen |
diphenylcyclopenone | small molecules | FDA | 2003-06-13 | — | Lloyd E. King, Jr. |
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