Alopecia Areata Lesions Research Articles

Increased CRHR1 expression on monocytes from patients with AA enables a pro-inflammatory response to corticotrophin-releasing hormone.

Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (n = 54) and controls (n = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, p = 0.002, chi-squared test). AA incidence was correlated to elevated CD14+ monocyte numbers (R = 0.092, p = 0.036) and markedly independently correlated with increased CRHR1 expression (R = 0.215, p = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration >1 year; p = 0.003, chi-squared test), and large lesion area (AA area >25%; p = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16+ CD3- NK cell numbers in AA patients' PBMCs (p = 0.010; 0.025, respectively). Invitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.

Hair regrowth in alopecia areata and re-pigmentation in vitiligo in response to treatment: Commonalities and differences.

Both alopecia areata (AA) and vitiligo share common pathogenesis involving, interferon-γ (IFN-γ) and interleukin-15 (IL-15) signalling pathways that activate cytotoxic CD8+ T lymphocytes. These shared mechanisms may explain why both diseases respond to currently available treatments (e.g. topical/systemic corticosteroid) and emerging treatment modalities. As compared with the speed of re-pigmentation in vitiligo lesions, the regeneration of pigmented terminal hair follicles in AA lesions appears fast in response to treatments targeting the inhibition of the Janus kinases (JAKs) and other kinases. We summarize the commonalities and differences between AA and vitiligo focusing on the treatment modalities, followed by recent findings associated with hair follicle stem cells (HFSC) in hair bulge (HBg) and melanocyte stem cells (McSC) in HBg and hair germ (HGm). We then discuss how HFSC and HGm-McSC are involved in the initiation of anagen phase, followed by pigmented terminal hair regrowth in the recovering AA lesions in association with immunology. We also discuss how HBg-McSC contribute to the migration of fully dendritic mature melanocytes into interfollicular epidermis and the equal distribution of melanin in recovering vitiligo lesions. Finally, we present four hypotheses to elucidate the delayed distribution of melanin by mature melanocytes in depigmented vitiligo lesions from the aspects of stem cell biology, as compared with quick hair recovery in AA: (1) McSC are less abundant than HFSC. (2) McSC require a long travel, whereas HFSC reside close to hair regeneration trigger point. (3) Keratinocyte scaffold to accept melanin is not well preserved, whereas scaffold for hair regrowth is well preserved. (4) Inhibitors targeting JAKs and other kinases have less direct effects on melanocyte proliferation and differentiation in vitiligo than hair regrowth in AA. Our review provides an overview of treatment modalities and bridges the gap between scientific advancement and clinical practice in AA and vitiligo management.

Comparative Study of Trichoscopic Features of Alopecia Areata between Adults and Children and between Different Body Parts (Scalp, Beard, Eyebrow, and Moustache).

Round patches of baldness on the scalp or entire body are typically caused by the common, non-scarring hair loss condition known as alopecia areata (AA). Follicular units with two to four terminal hairs and one or two vellus hairs can be seen on a healthy, typical scalp trichoscopy. To compare trichoscopic features between adults and children and between different body parts. A cross-sectional observational study was performed on 90 patients; AA of the scalp and other body parts attended the dermatology out-patient clinic. A Gen Dermlite D100 Dermoscope was used to examine AA lesions and compare their features according to age and different body parts. Scalp was the most common area among all patients, 65.6% (among adults, it was 50%, and among children, it was 85%), with a significant difference, P = 0.001. The most common trichoscopic feature among all patients was empty follicular opening in 74 (82.2%) lesions; among children, it was honeycomb pigment in 35 (87.5%) lesions, while among adults, it was empty follicular opening in 40 (80%) lesions. Tulip hair was significantly higher among adults, P = 0.036. At the same time, honeycomb pigment patterns and pohlpinkus constriction were significantly higher among children, P = 0.044 and P < 0.001, respectively. The most common trichoscopic feature of adult lesions was empty follicular opening, while honeycomb pigment was dominant among children. Tulip hair was higher among adults, while honeycomb pigment patterns and pohlpinkus constriction were higher among children.

The Association between Number of Follicular Stelae and Severity and Treatment Response of Alopecia Areata Cases: A Retrospective Study.

Alopecia areata (AA) is an autoimmune disease characterized by peribulbar lymphocytic infiltration, follicular miniaturization, catagen/telogen follicles, and increased follicular stelae (streamers) in skin biopsies. Our aim was to assess the number of follicular stelae of patients with AA and to evaluate their association with clinical type and severity and treatment response of AA. Histopathologic features including the number of follicular stelae were recorded in skin biopsies taken from lesions of AA in 142 patients who attended our dermatology clinic from 2011 to 2017. There was a statistically significant correlation between patient age and the number of follicular stelae (P = 0.001). There was a statistically significant correlation between the severity of disease and number of follicular stelae (P = 0.005). AA subtypes (0%-25% scalp hair loss) had a significantly lower number of follicular stelae than 75%-100% of scalp hair loss and alopecia universalis (7.92 ± 4.21 vs. 13.23 ± 7.28). There was no statistically significant correlation between treatment response and the number of follicular stelae (P = 0.75). Our results showed that the number of follicular stelae varied among AA clinical types and correlated with severity. This study was the first to evaluate the correlation between the number of follicular stelae and severity of AA.

Stability and instability in a three-component chemotaxis model for alopecia areata

This paper investigates the stability and instability of a generalized reaction–diffusion–advection system that describes the spatio-temporal dynamics of alopecia areata lesions. Using the spectral analysis, we investigate the effect of chemotactic strengths on the stability and instability of a linearized problem around the positive constant equilibrium. We then extend our analysis to the nonlinear system, utilizing higher-order energy estimates and bootstrap techniques to study its stability and instability based on the linearized results. Additionally, we provide numerical simulations to support our theoretical results.

Involvement of ILC1-like innate lymphocytes in human autoimmunity, lessons from alopecia areata.

Here, we have explored the involvement of innate lymphoid cells-type 1 (ILC1) in the pathogenesis of alopecia areata (AA), because we found them to be significantly increased around lesional and non-lesional HFs of AA patients. To further explore these unexpected findings, we first co-cultured autologous circulating ILC1-like cells (ILC1lc) with healthy, but stressed, organ-cultured human scalp hair follicles (HFs). ILClc induced all hallmarks of AA ex vivo: they significantly promoted premature, apoptosis-driven HF regression (catagen), HF cytotoxicity/dystrophy, and most important for AA pathogenesis, the collapse of the HFs physiological immune privilege. NKG2D-blocking or IFNγ-neutralizing antibodies antagonized this. In vivo, intradermal injection of autologous activated, NKG2D+/IFNγ-secreting ILC1lc into healthy human scalp skin xenotransplanted onto SCID/beige mice sufficed to rapidly induce characteristic AA lesions. This provides the first evidence that ILC1lc, which are positive for the ILC1 phenotype and negative for the classical NK markers, suffice to induce AA in previously healthy human HFs ex vivo and in vivo, and further questions the conventional wisdom that AA is always an autoantigen-dependent, CD8 +T cell-driven autoimmune disease.

IL-10‒Producing Potency from Blood B Cells Correlates with the Prognosis of Alopecia Areata

IL-10‒Producing Potency from Blood B Cells Correlates with the Prognosis of Alopecia Areata

368 Methods in Inflammatory Hair Disease Research: Enhanced Multiplex Imaging on Alopecia Areata Tissue Sections

Imaging Mass Cytometry (IMC) allows for the visualisation of up to 40 biomarkers on a single tissue section via the use of metal-tagged antibodies, permitting advanced multiplex imaging for detailed in situ analyses. To test whether this technique could be established to enhance the study of inflammatory hair diseases, we tested and optimised a panel of tissue architecture, immune infiltration, and immune activation markers on non-lesional and lesional alopecia areata (AA) frozen tissue sections.

The Association between the Number of Follicular Stelae and Severity and Treatment Response of Alopecia Areata Cases: A Retrospective Study.

Alopecia areata (AA) is an autoimmune disease characterized by peribulbar lymphocytic infiltration, follicular miniaturization, catagen/telogen follicles, and increased follicular stelae (streamers) in skin biopsies. Our aim was to assess the number of follicular stelae of patients with AA and to evaluate their association with clinical type and severity and treatment response of AA. Histopathologic features including number of follicular stelae were recorded in skin biopsies taken from lesions of AA in 142 patients who attended our dermatology clinic from 2011 to 2017. There was a statistically significant correlation between the patient age and the number of follicular stelae (P = 0.001). There was a statistically significant correlation between the severity of disease and the number of follicular stelae (P = 0.005). AA subtypes (0%-25% scalp hair loss) had a significantly lower number of follicular stelae than 75%-100% scalp hair loss and alopecia universalis (7.92 ± 4.21 vs. 13.23 ± 7.28). There was no statistically significant correlation between the treatment response and the number of follicular stelae (P = 0.75). Our results showed that number of follicular stelae varied among AA clinical types and correlated with severity. This study was the first to evaluate the correlation between the number of follicular stelae and severity of AA.

Gene Expression of CD70 and CD27 Is Increased in Alopecia Areata Lesions and Associated with Disease Severity and Activity.

Background Alopecia areata (AA) is an acquired hair loss disorder induced by a cell-mediated autoimmune attack against anagen hair follicles. CD27-CD70 is a receptor-ligand complex which enhances T helper and cytotoxic T cell activation, survival, and proliferation. The overstimulation of this complex can lead to a lack of tolerance and the development of autoimmunity. Objectives This study aimed to assess the gene expression of CD27 and CD70 in patients with AA. Methods CD70 and CD27 mRNA expressions were evaluated by a quantitative real-time polymerase chain reaction in scalp biopsies from 40 AA patients (both AA lesions and non-lesional areas) and 40 healthy controls (HCs). The Severity of Alopecia Tool (SALT) score was used to assess AA severity. Patients were evaluated for signs of AA activity, including a positive hair pull test and dermoscopic features of black dots, broken hairs, and tapering hairs. Results The gene expression of CD70 and CD27 was significantly higher in AA lesions than in non-lesional areas (p < 0.001 for both) and HCs (p=0.004, p=0.014, respectively). There were significant positive correlations between AA severity and gene expression of CD70 (p < 0.001) and CD27 (p=0.030) in AA lesions. Significant associations were detected between signs of AA activity and lesional gene expression of CD70 and CD27. Additionally, CD70 and CD27 gene expression was significantly lower in non-lesional biopsies compared to HCs (p < 0.001). Conclusion Gene expression of CD70 and CD27 was increased in AA lesions and was associated with disease severity and activity. Thus, both molecules can be a predictor of AA severity and activity. Furthermore, the expression was reduced in non-lesional scalp areas. Thus, a lack of CD27 and CD70 expression may initially predispose to immunological dysregulation and the development of AA.

Combined effects of nonlinear proliferation and logistic damping in a three-component chemotaxis system for alopecia areata

This work considers the zero Neumann initial–boundary problem to the chemotaxis system ut=Δu−χ1∇⋅(u∇w)+w−μ1u2,vt=Δv−χ2∇⋅(v∇w)+w+ruv−μ2v2,0=Δw+u+v−w,in a bounded domain Ω⊂Rn,n≥1, with smooth boundary, which was initially proposed by Dobreva et al. (2020) to describe the process of alopecia areata lesions that involves the complicated interplay between CD4+ T cells, CD8+ T cells and interferon-gamma. Compared with the well-known Keller–Segel-type systems, the appearance of the nonlinear proliferation term ruv constituted by the product of two immune cell densities along with a new production term w activated by the chemical in the first two equations forms a novel feature of this model.For any given suitably regular initial data, it is firstly shown that if the positive parameters χ1,χ2, μ1,μ2 and r satisfy the assumptions μ1−r2>(n−2)+n(2χ1+χ22)andμ2−r>(n−2)+n(2χ2+χ12),then the problem admits a global and bounded classical solution. Moreover, we identify a set of parameter conditions: μ1<μ2<3μ1,r=μ2−μ1andχ12+χ22<2μ1(3μ1−μ2),under which any global smooth solution will stabilize to the constant coexistence equilibrium as the time goes to infinity. In addition, in the case of μ1>μ2, the nonlinear stability of the unique positive stationary solution to the corresponding ODE system is also discussed.

LB709 Therapeutic effect of γδTregs cells in Alopecia Areata

Regulatory γδ T cells (γδTregs) may exert therapeutic effects under some experimental autoimmune disease (AID) conditions. This encouraged us to explore whether this this also applies to alopecia areata (AA), one of the most common human AIDs. Triple immunofluorescence (IF) staining was performed to determine the distribution of γδTregs in human skin presence of γδTregs on skin sections of AA patients. Autologous circulating human γδ Tregs were expanded and either co-cultured with organ-cultured, stressed human scalp hair follicles (HFs) ex vivo or injected into experimentally induced AA lesions on human scalp skin xenotransplants on SCID mice.

Efficacy of intralesional methotrexate in the treatment of alopecia areata

Background Alopecia areata (AA) treatment is still challenging as multiple treatment options are available, but there is no fully curative or preventive treatment. Aim To evaluate the efficacy and safety of intralesional methotrexate (MTX) in the treatment of localized AA both clinically and dermoscopically. Patients and methods A total of 30 patients aged 18–55 years with localized AA were enrolled in this study. Each patient was treated by intralesional MTX (25 mg/ml) at 2-week intervals for four sessions and followed up for 3 months. The target lesions were evaluated clinically using regrowth scale and dermoscopically at the end of sessions, 1, 2, and 3 months after treatment. Results At the end of study, the response rate to intralesional MTX was ∼93.3%, and 15 (50.0%) patients showed a score of 4 (regrowth ≥75%). There was a statistically significant difference in regrowth scale between end of sessions, 4, 8, and 12 weeks of follow-up. There was also statistically significant reduction in dermoscopic parameters at the end of sessions, 4, 8, and 12 weeks of follow-up with a significant clinicodermoscopic relation between regrowth scale and dermoscopic findings. No patient (0.0%) showed recurrence. Conclusion Intralesional MTX can be an effective and safe therapeutic option for localized AA with no significant adverse effects. Dermoscopy can be used for evaluating the response of AA lesion to treatment.

Clinical efficacy of adipocyte-derived stem cells conditioned media combined with micro-injury in refractory patch of alopecia areata.

Management of alopecia areata (AA) is often challenging especially when patients have AA lesion refractory to conventional treatments such as corticosteroids, contact immunotherapy, and systemic therapy. Reports indicate adipocyte-derived stem cell conditioned media (ASC-CM) can activate hair growth and micro-injury using fractional laser or microneedling can also induce wound healing and hair regeneration, which suggests ASC-CM combined with fractional laser or microneedling might provide alternative therapeutic option for a refractory patch of AA. This study aimed to evaluate the clinical efficacy and safety of ASC-CM combined with 10,600nm carbon dioxide fractional laser or microneedling for the treatment of refractory patch of AA. This retrospective study was based on evaluations of 14 patients with a refractory patch of AA treated with ASC-CM, combined with a 10,600nm carbon dioxide fractional laser, or microneedling from March 2017 to August 2020. The efficacy of treatment was assessed by extents of hair regrowth percentages of involved areas. Of the 14 enrolled patients, 9 (64.3%) showed > 50% hair regrowth and 6 patients (42.9%) showed complete recovery. In the responder group (n = 9), mean period to achieve > 50% hair regrowth was 11.3weeks (range 8-16weeks). In the non-responder group (n = 5), 4 patients (28.6%) showed < 25% of hair regrowth and 1 patient show slight hair regrowth (7.1%) after 3months of treatment. This study showed ASC-CM combined with 10,600nm carbon dioxide fractional laser or microneedling may offer effective and safe treatment options for a refractory patch of AA.

CCL13 is upregulated in alopecia areata lesions and is correlated with disease severity.

Alopecia areata (AA) is a multi-factors disease characterized by non-scarring hair loss. AA could be classified into three main clinical phenotypes including patchy type AA (AAP), alopecia totalis (AT) and alopecia universalis (AU) based on the severity and areas of hair loss. Recent studies suggested immunological factor was critical in AA, but the precise aetiology and pathogenesis of AA still need exploration. In the work, we screened two gene expression profiles (GSE45512 and GSE68801) from Gene Expression Omnibus (GEO). Based on the two data sets, 10 upregulated genes and 107 downregulated genes in AA skin biopsies were identified. CCL13, as one of the remarkably upregulated genes, was found to have potential biological functions in aberrant immune response of AA according to the GO and KEGG analyses. The PPI network showed CCL13 was associated with multiple immune-related genes. The expression of CCL13 was increased depending on the severity of disease in AA patients. Cytotoxic lymphocytes, T cells and myeloid dendritic cells accumulated remarkably in scalp tissue depending on the severity of AA, and CCL13 was significantly correlated to cytotoxic lymphocytes, T cells and myeloid dendritic cells in AA patients. Our RT-PCR and ELISA results found CCL13 was upregulated in skin biopsy and serum of AA patients, and the immunohistochemistry (IHC) detection showed CCL13 was expressed by both the hair follicle epithelium and infiltrating immune cells. In conclusion, the upregulated of CCL13 and subsequent immune cell infiltration was related to AA, which could be a promising target for diagnosis and therapy in AA patients.

Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata.

Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4+IL-4+ cells and CD4+IFN-γ+ cells to CD4+IL-13+ cells were higher than those in AA patients with extrinsic AD. Meanwhile, the ratio of CD8+IFN-γ+ cells to CD8+IL-13+ cells was significantly higher in the non-atopic AA than in the healthy controls. In AA patients with extrinsic AD, the skin AA lesion showed dense infiltration of not only CXCR3+ cells but also CCR4+ cells around hair bulb before dupilumab treatment. However, after the treatment, the number of CXCR3+ cells had no remarkable change while the number of CCR4+ cells significantly decreased. These results indicate that the immunological condition of AA may be different between atopic and non-atopic patients and between extrinsic and intrinsic AD patients. Our study provides an important notion that type 2 immunity may participate in the development of AA in extrinsic AD patients. It may be considered that the immunological state of non-atopic AA is different from that of atopic AA.

Prognostic markers for severity, activity, and recurrence of alopecia areata

Background Alopecia areata (AA) is considered an autoimmune disorder caused by altered T-cell-mediated immunity. MicroRNAs (miR) are important translational regulators of genes in various tissues and biological processes involved in autoimmune responses and have been identified in autoimmune diseases such as rheumatoid arthritis and type I diabetes mellitus. However, little is known about their role in pathogenesis of AA.Objective To assess serum levels of miR-155 and miR-146a in patients with AA and to correlate them with different clinical variables. Patients and methods MiR-155 and miR-146a serum levels were identified by real-time PCR in 50 patients with AA and 50 healthy age-matched and sex-matched patients as controls. Disease severity in the patients was assessed by Severity of Alopecia Tool score. Results There was a statistically significant increase in serum miR-155 and miR-146a levels in patients with AA than in controls. A significant increase in serum levels of miR-155 was found in patients with active disease and recurrent lesions of AA, whereas significant increase in serum level of miR-146a was found in patients with recurrent disease only. Significant positive correlations were found between serum miR-155 and miR-146a levels and disease severity. Conclusion Serum levels of miR-155 and miR-146a seem to have an essential role in the etiopathogenesis of AA and could be markers for severity and early detection of recurrent AA. In addition, serum miR-155 could be a marker of activity in AA, whereas serum miR-146a could be a marker of multiplicity. Further understanding of the function and regulation of miR-155 and miR-146a could be of great value for the introduction of new therapeutic approaches for AA.

Clinical significance of serum prolactin levels in patients with alopecia areata

Objectives To assess the value of elevated serum prolactin levels as a diagnostic marker in alopecia areata (AA). Background AA is characterized by areas of nonscarring hair loss that ranges from a single oval patch to multiple patches. Immunological, environmental, psychological, and genetic factors may play a role in the pathogenesis of AA. Prolactin is a polypeptide hormone secreted from the anterior pituitary gland that has a variety of physiological actions including growth promoting activity and exerts a proliferative effect on human keratinocytes. Prolactin may therefore play an important role in the pathogenesis of AA, through its immunomodulatory function. Several studies have shown that prolactin and AA are positively correlated. Patients and methods This case–control study was conducted on 50 patients: 25 AA patients and 25 age-matched and sex-matched healthy controls during the period from November 2017 to March 2018. All patients were subjected to full history taking, clinical examination, and laboratory investigations. Serum prolactin levels were measured by chemiluminescence through an immunoassay-automated access 2 Beckman coulter. Results Serum prolactin levels were significantly elevated in AA patients (mean ± SD, 16.8 ± 2.3) compared with healthy controls (mean ± SD, 9.7 ± 3.00). There was significant positive correlation between serum prolactin level and size of the AA lesion (r = 0.661, P Conclusion Serum prolactin levels were higher in AA patients compared with healthy controls. The levels were correlated with clinical severity in patients with AA. Therefore, serum prolactin level can be used as a diagnostic biomarker for evaluating the clinical status of AA.

Identification and verification of EOMEs regulated network in Alopecia areata

Alopecia areata (AA) is a common alopecia characterized by non-scarring hair loss with the dysregulated immunity. However, the pathogenesis of AA remains to be elucidated. In this study, we identified gene signatures and then analyzed transcription factor-immune regulatory network in AA using integrated bioinformatics methods. Finally, we verified potential target genes in lesions of AA patients using qPCR and immunohistochemistry. Here, 74 differentially expressed genes (DEGs) were identified in AA, which were enriched in immune-related signaling pathway. The immune analysis revealed the infiltration of γδT cells and Macrophages M1 in AA lesion. Next, the expression correlation analysis and ChIP-seq results revealed a transcription factor (EOMEs) regulated network. We found that EOMEs, a T-box transcription factor, may be involved in the immunoregulation in AA via targeting CD8A and BMP2, and it may affect keratinocytes function via regulating GZMK, LYPD6, RNF182, KRTAP5-9 and KRT73 expression. Finally, the mRNA expression of these network genes in AA lesions was confirmed using qPCR. And the increase expression of EOMEs was identified at inflammatory cells at the periphery of hair follicles and partial keratinocytes in AA tissue using immunohistochemistry. In conclusions, our research demonstrated that EOMEs may play a key role in the progression of AA via regulating immune cell infiltration and keratinocytes function, indicating EOMEs as a promising therapeutic target of AA.

Local secretion of stress hormones increases in alopecia areata lesions after treatment with UVA-1 phototherapy.

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P=.037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P=.032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P=.013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P=.626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.